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33868369

RRM2B Is Frequently Amplified Across Multiple Tumor Types: Implications for DNA Repair, Cellular Survival, and Cancer Therapy.

RRM2B plays a crucial role in DNA replication, repair and oxidative stress. While germline RRM2B mutations have been implicated in mitochondrial disorders, its relevance to cancer has not been established. Here, using TCGA studies, we investigated RRM2B alterations in cancer. We found that RRM2B is highly amplified in multiple tumor types, particularly in MYC-amplified tumors, and is associated with increased RRM2B mRNA expression. We also observed that the chromosomal region 8q22.3-8q24, is amplified in multiple tumors, and includes RRM2B, MYC along with several other cancer-associated genes. An analysis of genes within this 8q-amplicon showed that cancers that have both RRM2B-amplified along with MYC have a distinct pattern of amplification compared to cancers that are unaltered or those that have amplifications in RRM2B or MYC only. Investigation of curated biological interactions revealed that gene products of the amplified 8q22.3-8q24 region have important roles in DNA repair, DNA damage response, oxygen sensing, and apoptosis pathways and interact functionally. Notably, RRM2B-amplified cancers are characterized by mutation signatures of defective DNA repair and oxidative stress, and at least RRM2B-amplified breast cancers are associated with poor clinical outcome. These data suggest alterations in RR2MB and possibly the interacting 8q-proteins could have a profound effect on regulatory pathways such as DNA repair and cellular survival, highlighting therapeutic opportunities in these cancers.

['Iqbal|Waleed|W|', 'Demidova|Elena V|EV|', 'Serrao|Samantha|S|', 'ValizadehAslani|Taha|T|', 'Rosen|Gail|G|', 'Arora|Sanjeevani|S|']

2021

23810776

Effect of soft and semirigid ankle orthoses on Star Excursion Balance Test performance in patients with functional ankle instability.

OBJECTIVES To evaluate the effect of soft and semirigid ankle orthoses on dynamic balance assessed using Star Excursion Balance Test in patients with functional ankle instability compared with healthy individuals. DESIGN Non-experimental, observational study with multiple-factor design, including group (functional ankle instability and healthy) as the between-subjects factor and orthotics condition (no orthosis, soft orthosis and semirigid orthosis) as the within-subjects factor. METHODS Sixteen unilateral functional ankle instability patients and a group of 16 healthy control individuals, matched for age, height and weight, participated in the study. Dynamic balance was tested with and without wearing ankle orthosis. Reach distance of participants in 3 bracing conditions were measured in anteromedial, medial and posteromedial directions of Star Excursion Balance Test. Average of 3 trials in 3 measured directions, normalized to leg length of each participant, was used for statistical analysis. RESULTS There were no differences among orthotics conditions in healthy people. However, normalized reach distance increased from no-orthosis to semirigid to soft orthoses in FAI patients. Differences were significant between soft and no-orthosis (13% in anteromedial, 14% in medial and 15% in posteromedial direction p=0.01) and between semirigid and no-orthosis (10% in anteromedial, 8.5% in medial and 8.5% in posteromedial direction, p=0.01) conditions in all 3 measured directions. The difference between soft and semirigid orthoses was significant (6% difference, p<0.05) only in PM direction. CONCLUSIONS Ankle orthoses improve reach distance in functional ankle instability patients in various reach directions. Soft orthosis has a more pronounced effect on dynamic balance, especially in posteromedial direction, compared with semirigid orthosis.

['Hadadi|Mohammad|M|', 'Mousavi|Mohammad Ebrahim|ME|', 'Fardipour|Shima|S|', 'Vameghi|Roshanak|R|', 'Mazaheri|Masood|M|']

2014

31951199

Do progenitors play dice?

The wide range of cell types produced by single progenitors in the neocortex of mice may result from stochastic rather than deterministic processes.

['Klingler|Esther|E|0000-0002-6577-1362', 'Jabaudon|Denis|D|0000-0003-2438-4769']

2020

30263837

High fibre tiger nut pasta and xanthan gum: cooking quality, microstructure, physico-chemical properties and consumer acceptance.

The feasibility of replacing wheat semolina by tiger nut flour (20 and 40%) and xanthan gum (1%) in order to obtain high fibre dry pappardelle with fair techno-functional, structural and sensory attributes, was assessed. The cooking properties, texture, colour and sensory acceptance of uncooked and cooked pasta were evaluated. The proximate chemical composition of the raw materials, and the microstructure of the dry pasta were also assessed. The results in this manuscript address the improved nutritional value in terms of its dietary fibre, mineral content, oleic and linoleic acids, and the positive effects on the textural characteristics and cooking behaviour achieved on dry tiger nut based pappardelle using 1% of xanthan gum as a structural agent. Micrographs revealed in fact that the gluten network was better formed when xanthan gum was used. Furthermore, the obtained results seem to support that consumers would prefer pappardelle with 40% tiger nut flour.

['Martín-Esparza|M E|ME|0000-0002-0066-6748', 'Raigón|M D|MD|', 'Raga|A|A|', 'Albors|A|A|']

2018

30341600

Biophysical and Spectroscopic Methods for Monitoring Protein Misfolding and Amyloid Aggregation.

Proteins exhibit a remarkable structural plasticity and may undergo conformational changes resulting in protein misfolding both in a biological context and upon perturbing physiopathological conditions. Such nonfunctional protein conformers, including misfolded states and aggregates, are often associated to protein folding diseases. Understanding the biology of protein folding diseases thus requires tools that allow the structural characterization of nonnative conformations of proteins and their interconversions. Here we present detailed procedures to monitor protein conformational changes and aggregation based on spectroscopic and biophysical methods that include circular dichroism, ATR-Fourier-transformed infrared spectroscopy, fluorescence spectroscopy and dynamic light scattering. To illustrate the application of these methods we report to our previous studies on misfolding, aggregation and amyloid fibril formation by superoxide dismutase 1 (SOD1), a protein whose toxic deposition is implicated in the neurodegenerative disease amyotrophic lateral sclerosis (ALS).

['Cristóvão|Joana S|JS|', 'Henriques|Bárbara J|BJ|', 'Gomes|Cláudio M|CM|']

2019

29584711

Proteomics Analysis to Assess the Role of Mitochondria in BRCA1-Mediated Breast Tumorigenesis.

Mitochondria are the organelles deputed to energy production, but they are also involved in carcinogenesis, cancer progression, and metastasis, playing a role in altered energy metabolism in cancer cells. Mitochondrial metabolism is connected with several mitochondrial pathways such as ROS signaling, Ca2+ homeostasis, mitophagy, and mitochondrial biogenesis. These pathways are merged in an interactive super-network that seems to play a crucial role in cancer. Germline mutations of the BRCA1 gene account for 5-10% of breast cancers and confer a risk of developing the disease 10- to 20-fold much higher than in non-carriers. By considering metabolic networks that could reconcile both genetic and non-genetic causal mechanisms in BRCA1 driven tumorigenesis, we herein based our study on the hypothesis that BRCA1 haploinsufficiency might drive metabolic rewiring in breast epithelial cells, acting as a push toward malignant transformation. Using 2D-DIGE we analyzed and compared the mitochondrial proteomic profile of sporadic breast cancer cell line (MCF7) and BRCA1 mutated breast cancer cell line (HCC1937). Image analysis was carried out with Decider Software, and proteins differentially expressed were identified by LC-MS/MS on a quadrupole-orbitrap mass spectrometer Q-Exactive. Ingenuity pathways analysis software was used to analyze the fifty-three mitochondrial proteins whose expression resulted significantly altered in response to BRCA1 mutation status. Mitochondrial Dysfunction and oxidative phosphorylation, and energy production and nucleic acid metabolism were, respectively, the canonical pathway and the molecular function mainly affected. Western blotting analysis was done to validate the expression and the peculiar mitochondrial compartmentalization of specific proteins such us HSP60 and HIF-1α. Particularly intriguing is the correlation between BRCA1 mutation status and HIF-1α localization into the mitochondria in a BRCA1 dependent manner. Data obtained led us to hypothesize an interesting connection between BRCA1 and mitochondria pathways, capable to trigger metabolic changes, which, in turn, sustain the high energetic and anabolic requirements of the malignant phenotype.

['Concolino|Antonio|A|', 'Olivo|Erika|E|', 'Tammè|Laura|L|', 'Fiumara|Claudia Vincenza|CV|', 'De Angelis|Maria Teresa|MT|', 'Quaresima|Barbara|B|', 'Agosti|Valter|V|', 'Costanzo|Francesco Saverio|FS|', 'Cuda|Giovanni|G|0000-0001-6313-1866', 'Scumaci|Domenica|D|0000-0002-8117-834X']

2018

23204616

Homology modeling a fast tool for drug discovery: current perspectives.

Major goal of structural biology involve formation of protein-ligand complexes; in which the protein molecules act energetically in the course of binding. Therefore, perceptive of protein-ligand interaction will be very important for structure based drug design. Lack of knowledge of 3D structures has hindered efforts to understand the binding specificities of ligands with protein. With increasing in modeling software and the growing number of known protein structures, homology modeling is rapidly becoming the method of choice for obtaining 3D coordinates of proteins. Homology modeling is a representation of the similarity of environmental residues at topologically corresponding positions in the reference proteins. In the absence of experimental data, model building on the basis of a known 3D structure of a homologous protein is at present the only reliable method to obtain the structural information. Knowledge of the 3D structures of proteins provides invaluable insights into the molecular basis of their functions. The recent advances in homology modeling, particularly in detecting and aligning sequences with template structures, distant homologues, modeling of loops and side chains as well as detecting errors in a model contributed to consistent prediction of protein structure, which was not possible even several years ago. This review focused on the features and a role of homology modeling in predicting protein structure and described current developments in this field with victorious applications at the different stages of the drug design and discovery.

['Vyas|V K|VK|', 'Ukawala|R D|RD|', 'Ghate|M|M|', 'Chintha|C|C|']

2012

26232335

Structure and function of cardiac troponin C (TNNC1): Implications for heart failure, cardiomyopathies, and troponin modulating drugs.

In striated muscle, the protein troponin complex turns contraction on and off in a calcium-dependent manner. The calcium-sensing component of the complex is troponin C, which is expressed from the TNNC1 gene in both cardiac muscle and slow-twitch skeletal muscle (identical transcript in both tissues) and the TNNC2 gene in fast-twitch skeletal muscle. Cardiac troponin C (cTnC) is made up of two globular EF-hand domains connected by a flexible linker. The structural C-domain (cCTnC) contains two high affinity calcium-binding sites that are always occupied by Ca(2+) or Mg(2+) under physiologic conditions, stabilizing an open conformation that remains anchored to the rest of the troponin complex. In contrast, the regulatory N-domain (cNTnC) contains a single low affinity site that is largely unoccupied at resting calcium concentrations. During muscle activation, calcium binding to cNTnC favors an open conformation that binds to the switch region of troponin I, removing adjacent inhibitory regions of troponin I from actin and allowing muscle contraction to proceed. Regulation of the calcium binding affinity of cNTnC is physiologically important, because it directly impacts the calcium sensitivity of muscle contraction. Calcium sensitivity can be modified by drugs that stabilize the open form of cNTnC, post-translational modifications like phosphorylation of troponin I, or downstream thin filament protein interactions that impact the availability of the troponin I switch region. Recently, mutations in cTnC have been associated with hypertrophic or dilated cardiomyopathy. A detailed understanding of how calcium sensitivity is regulated through the troponin complex is necessary for explaining how mutations perturb its function to promote cardiomyopathy and how post-translational modifications in the thin filament affect heart function and heart failure. Troponin modulating drugs are being developed for the treatment of cardiomyopathies and heart failure.

['Li|Monica X|MX|', 'Hwang|Peter M|PM|']

2015

34820326

Efficacy and Safety of First-Line Treatment Strategies for Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: A Bayesian Network Meta-Analysis.

Background Targeted therapies have led to significant improvement in the management and prognosis of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). We performed a network meta-analysis of frontline treatment options of ALK-positive NSCLC to provide clinical guidance. Methods PubMed, Embase, ClinicalTrials.gov, and international conference databases were searched to identify relevant trials from inception to June 30, 2021. Phase III randomized controlled trials (RCTs) comparing treatments for patients with ALK-positive advanced NSCLC in the first-line setting were included in a Bayesian network meta-analysis. Eligible studies reported at least one of the following clinical outcomes: progression-free survival (PFS), overall survival (OS), risk of the central nervous system (CNS) progression, adverse events (AEs) of grade (G) 3 or higher (G3 AEs), or serious AEs (SAEs). Hazard ratios (HRs) and CI for primary outcome of PFS and secondary outcome of OS and risk of CNS progression were obtained. A multivariate, consistency model, fixed-effects analysis was used in the network meta-analysis. Data on G3 AEs and SAEs were abstracted and meta-analyzed. Risk of bias (RoB) was assessed using the Cochrane Collaboration's tool. Results Nine RCTs comprising 2,484 patients were included with seven treatments: alectinib, brigatinib, ceritinib, crizotinib, ensartinib, lorlatinib, and chemotherapy. Compared with chemotherapy, ALK-tyrosine kinase inhibitors (TKIs) significantly prolong PFS and reduced risk of CNS progression except for ceritinib. Lorlatinib appears superior at reducing risk of CNS progression. None of the ALK-TKIs have a significantly prolonged OS as compared with chemotherapy. Lorlatinib increases the risk of G3 AEs as compared with alectinib (odds ratio 4.26 [95% CrI 1.22 to 15.53]), while alectinib caused the fewest G3 AEs. Conclusions Lorlatinib is associated with the highest PFS benefit and lowest risk of CNS progression benefits for patients with advanced ALK-positive NSCLC, compared with other first-line treatments, but with higher toxicity. The implementation of a newer generation of ALK-TKIs in the first-line treatment of ALK-positive NSCLC into current clinical practice is evolving rapidly.

['Peng|Ling|L|', 'Lu|Dafeng|D|', 'Xia|Yang|Y|', 'Hong|Shaodong|S|', 'Selvaggi|Giovanni|G|', 'Stebbing|Justin|J|', 'Sun|Yilan|Y|', 'Liang|Fei|F|']

2021

29729290

Anticonvulsant evaluation of novel non-imidazole histamine H3R antagonists in different convulsion models in rats.

Novel non-imidazole histamine H3 receptor (H3R) antagonists (2-8) were developed and assessed for in-vitro antagonist binding affinities at the human histamine H1-H4R. These novel H3R antagonists (2-8) were examined in-vivo for anticonvulsant effects in three different convulsion models in male adult rats. Compound 6 significantly and dose-dependently exhibited decreased duration of tonic hind limb extension (THLE) in the maximal electroshock (MES)- and fully protected animals against pentylenetetrazole (PTZ)-induced convulsion, following acute systemic administration (5, 10, and 20 mg/kg, i.p.). Contrary, all compounds 2-8 showed moderate protection in the strychnine (STR)-induced convulsion model following acute pretreatment (10 mg/kg, i.p.). Moreover, the acute systemic administration of H3R antagonist 6 (10 mg/kg, i.p.) significantly prolonged latency time for MES convulsions. Furthermore, the anticonvulsant effect observed with compound 6 in MES-model was entirely abrogated when rats were co-injected with the brain penetrant H1R antagonist pyrilamine (PYR) but not the brain penetrant H2R antagonist zolantidine (ZOL). However, PYR and ZOL failed to abolish the full protection provided by the H3R antagonist 6 in PTZ- and STR-models. No mutagenic or antiproliferative effects or potential metabolic interactions were shown for compound 6 when assessing its antiproliferative activities and metabolic profiling applying in-vitro methods. These findings demonstrate the potential of non-imidazole H3R antagonists as novel antiepileptic drugs (AEDs) either for single use or in addition to currently available epilepsy medications.

['Alachkar|Alaa|A|', 'Latacz|Gniewomir|G|', 'Siwek|Agata|A|', 'Lubelska|Annamaria|A|', 'Honkisz|Ewelina|E|', 'Gryboś|Anna|A|', 'Łażewska|Dorota|D|', 'Handzlik|Jadwiga|J|', 'Stark|Holger|H|', 'Kiec-Kononowicz|Katarzyna|K|', 'Sadek|Bassem|B|']

2018

23796236

Variability and consistency in lung inflammatory responses to particles with a geogenic origin.

BACKGROUND AND OBJECTIVE Particulate matter <10 μm (PM10 ) is well recognized as being an important driver of respiratory health; however, the impact of PM10 of geogenic origin on inflammatory responses in the lung is poorly understood. This study aimed to assess the lung inflammatory response to community sampled geogenic PM10 . METHODS This was achieved by collecting earth material from two regional communities in Western Australia (Kalgoorlie-Boulder and Newman), extracting the PM10 fraction and exposing mice by intranasal instillation to these particles. The physicochemical characteristics of the particles were assessed and lung inflammatory responses were compared to control particles. The primary outcomes were cellular influx and cytokine production in the lungs of the exposed mice. RESULTS The physical and chemical characteristics of the PM10 from Kalgoorlie and Newman differed with the latter having a higher concentration of Fe and a larger median diameter. Control particles (2.5 μm polystyrene) caused a significant influx of inflammatory cells (neutrophils) with little production of proinflammatory cytokines. In contrast, the geogenic particles induced the production of MIP-2, IL-6 and a significant influx of neutrophils. Qualitatively, the response following exposure to particles from Kalgoorlie and Newman were consistent; however, the magnitude of the response was substantially higher in the mice exposed to particles from Newman. CONCLUSIONS The unique physicochemical characteristics of geogenic particles induced a proinflammatory response in the lung. These data suggest that particle composition should be considered when setting community standards for PM exposure, particularly in areas exposed to high geogenic particulate loads.

['Zosky|Graeme R|GR|', 'Boylen|Catherine E|CE|', 'Wong|Russell S|RS|', 'Smirk|Michael N|MN|', 'Gutiérrez|Lucia|L|', 'Woodward|Robert C|RC|', 'Siah|W Shan|WS|', 'Devine|Brian|B|', 'Maley|Fiona|F|', 'Cook|Angus|A|']

2014

27288810

Neurogenomics in Africa: Perspectives, progress, possibilities and priorities.

The understanding of the genetic basis of neurological disorders has grown rapidly in the last two decades. Despite the genomic heterogeneity within African populations, large-scale candidate gene or linkage and exome studies are lacking. However, current knowledge on neurogenetics in African populations is limited and geographically very uneven. Isolated reports indicate the existence of autosomal dominant or recessive conditions incorporating cerebrovascular, movement, neuromuscular, seizure and motor neuron disorders in Africans. In addition, few African families with neurodegenerative disorders associated with dementia have been characterized in North, West and South Africa. The current insurgency in genomic research triggered by among others the Human Health and Heredity (H3) Africa Initiative indicates that there are unique opportunities to advance our knowledge and understanding of the influence of genomic variation on the pattern, presentations and prognosis of neurological disorders in Africa. These have enormous potential to unmask novel genes and molecular pathways germane to the neurobiology of brain disorders. It would facilitate the development of novel diagnostics, preventative and targeted treatments in the new paradigm of precision medicine. Nevertheless, it is crucial to strike a balance between effective traditional public health strategies and personalized genome based care. The translational barriers can be overcome through robust stakeholder engagement and sustainable multilevel, multigenerational and multidisciplinary capacity building and infrastructural development for genomic medicine in Africa.

['Akinyemi|Rufus O|RO|', 'Owolabi|Mayowa O|MO|', 'Oyeniyi|Tolulope|T|', 'Ovbiagele|Bruce|B|', 'Arnett|Donna K|DK|', 'Tiwari|Hemant K|HK|', 'Walker|Richard|R|', 'Ogunniyi|Adesola|A|', 'Kalaria|Raj N|RN|', '|||']

2016

25477915

Evaluation of tests to predict metallo-β-lactamase in cystic fibrosis (CF) and non-(CF) Pseudomonas.

Double disks synergy test (DDST) and combined disks test (CD) were evaluated to predict the presence of metallo-β-lactamase in 70 Pseudomonas aeruginosa isolates recovered from cystic fibrosis and non-cystic fibrosis patients. DDST(CAZ-EDTA 1 cm) and CD(IMP-EDTA) tests showed the best accuracy (94.3%). Furthermore, for other combinations, accuracy unsatisfactory was obtained.

['Perez|Leandro Reus Rodrigues|LR|', 'Limberger|Mariana Fagundes|MF|', 'Costi|Ricardo|R|', 'Dias|Cícero Armídio Gomes|CA|', 'Barth|Afonso Luís|AL|']

2014

22928074

An ecological study of cancer mortality rates in California, 1950-64, with respect to solar UVB and smoking indices.

UNLABELLED <u> PURPOSE </u> This paper addresses whether nonmelanoma skin cancer (NMSC) mortality rates can serve as a useful index of population ultraviolet-B (UVB) irradiance and vitamin D production in a manner that affects the risk of internal cancers <u> METHODS </u> This analysis uses the ecological study approach with cancer mortality rate data from 19 state economic areas in California. This paper uses age-adjusted data for those aged 40 y or older. Two additional indices for solar UVB doses were also used: latitude and surface UVB doses for July 1992 from the total ozone mapping spectrometer. Lung cancer mortality rates served as the index of the health effects of smoking<u> RESULTS </u> Significant inverse correlations with NMSC mortality rate in multiple linear regression analyses were found during the period 1950-64 for eight types of cancer for males: bladder, brain, colon, gastric, prostate, and rectal cancer; multiple myeloma; and non-Hodgkin lymphoma. No similar results emerged for females with respect to all three UVB indices. Their NMSC mortality rates averaged 60% lower than those for males. Lung cancer mortality rates were directly correlated with three types of cancer for males: laryngeal, oral, and renal. No significant correlations with NMSC mortality rates appeared for later periods<u> CONCLUSIONS </u> NMSC mortality rates were found inversely correlated with internal cancers for males in the period 1950-64. After that period, no further such correlations were found. The reasons may hypothetically include reduced NMSC mortality rates, high immigration rates, movement from rural to urban locations and reduced solar UVB irradiance.

['Grant|William B|WB|']

2012

28933258

Dignity in nursing care: What does it mean to nursing students?

BACKGROUND: Despite growing interest in the potential of nursing education to enhance dignity in nursing care, relatively little is known about what dignity means to nursing students. RESEARCH QUESTION: What meaning does dignity in nursing care have for nursing students? RESEARCH DESIGN: Photo-elicitation was embedded within a Nominal Group Technique and responses were analysed by qualitative and quantitative content analysis. PARTICIPANTS AND RESEARCH CONTEXT: Participants were recruited from each year of a 3-year undergraduate preregistration adult nursing programme in Scotland. In total, 31 nursing students participated in the study. ETHICAL CONSIDERATIONS: The study was approved by the Ethics Committee of the School of Health, Nursing and Midwifery, University of the West of Scotland. FINDINGS: Participants articulated the meaning of dignity in nursing care in terms of the relationships and feelings involved. A total of 10 categories of meaning were identified. DISCUSSION: The significance of the nature of the nurse-patient interaction to preserving dignity in nursing care is highlighted. CONCLUSION: Understanding the meaning of dignity for nursing students may help prepare future nurses more able to preserve dignity in nursing care.

['Mullen|Rosemary F|RF|', 'Kydd|Angela|A|', 'Fleming|Anne|A|', 'McMillan|Laura|L|']

2019

34294133

Optimizing cisplatin delivery to triple-negative breast cancer through novel EGFR aptamer-conjugated polymeric nanovectors.

BACKGROUND Management of triple-negative breast cancer (TNBC) is still challenging because of its aggressive clinical behavior and limited targeted treatment options. Cisplatin represents a promising chemotherapeutic compound in neoadjuvant approaches and in the metastatic setting, but its use is limited by scarce bioavailability, severe systemic side effects and drug resistance. Novel site-directed aptamer-based nanotherapeutics have the potential to overcome obstacles of chemotherapy. In this study we investigated the tumor targeting and the anti-tumorigenic effectiveness of novel cisplatin-loaded and aptamer-decorated nanosystems in TNBC. METHODS Nanotechnological procedures were applied to entrap cisplatin at high efficacy into polymeric nanoparticles (PNPs) that were conjugated on their surface with the epidermal growth factor receptor (EGFR) selective and cell-internalizing CL4 aptamer to improve targeted therapy. Internalization into TNBC MDA-MB-231 and BT-549 cells of aptamer-decorated PNPs, loaded with BODIPY505-515, was monitored by confocal microscopy using EGFR-depleted cells as negative control. Tumor targeting and biodistribution was evaluated by fluorescence reflectance imaging upon intravenously injection of Cyanine7-labeled nanovectors in nude mice bearing subcutaneous MDA-MB-231 tumors. Cytotoxicity of cisplatin-loaded PNPs toward TNBC cells was evaluated by MTT assay and the antitumor effect was assessed by tumor growth experiments in vivo and ex vivo analyses. RESULTS We demonstrate specific, high and rapid uptake into EGFR-positive TNBC cells of CL4-conjugated fluorescent PNPs which, when loaded with cisplatin, resulted considerably more cytotoxic than the free drug and nanovectors either unconjugated or conjugated with a scrambled aptamer. Importantly, animal studies showed that the CL4-equipped PNPs achieve significantly higher tumor targeting efficiency and enhanced therapeutic effects, without any signs of systemic toxicity, compared with free cisplatin and untargeted PNPs. CONCLUSIONS Our study proposes novel and safe drug-loaded targeted nanosystems for EGFR-positive TNBC with excellent potential for the application in cancer diagnosis and therapy.

['Agnello|Lisa|L|', 'Tortorella|Silvia|S|', "d'Argenio|Annachiara|A|", 'Carbone|Clarissa|C|', 'Camorani|Simona|S|', 'Locatelli|Erica|E|', 'Auletta|Luigi|L|', 'Sorrentino|Domenico|D|', 'Fedele|Monica|M|', 'Zannetti|Antonella|A|', 'Franchini|Mauro Comes|MC|', 'Cerchia|Laura|L|']

2021

24592367

Determination of the best position and site for color Doppler ultrasonographic evaluation of the testicular vein to define the clinical grades of varicocele ultrasonographically.

BACKGROUND There are no generally accepted criteria for the ultrasonographic diagnosis and grading of varicocele. We aimed to determine the best position and site for color Doppler ultrasonographic (CDUS) evaluation of the testicular vein to define the clinical grades of varicocele ultrasonographically. MATERIALS AND METHODS This study consisted of 103 men (44 normal and 59 with clinical varicocele). First, WHO clinical grade of varicocele was determined by physical examination. Then, the diameter of largest testicular vein at four different sites was measured in both upright and supine positions with or without Valsalva maneuver. Finally, the cut-off points of venous diameter for different clinical grades were determined using the values of the position and sites that had the strongest correlation with the clinical grades. RESULTS The strongest correlation between venous diameter and clinical grade of varicocele was observed when the venous diameter was measured at the level of epididymal head in the upright position with Valsalva maneuver (r: 0.87, P-value < 0.0001). In aforementioned conditions, venous diameter of 2.35 mm (sensitivity 87%, specificity 87%) can distinguish normal subjects from grade 1 varicocele, venous diameter of 3.15 mm (sensitivity 58%, specificity 70%) can discriminate grade 1 from grade 2, and venous diameter of 3.75 mm (sensitivity 83%, specificity 70%) can differentiate grade 2 from grade 3. Furthermore, venous diameter of 2.65 mm (sensitivity 91%, specificity 89%) can distinguish normal subjects from patients with clinical varicocele. CONCLUSION The best position for CDUS examination of patients suspected of having varicocele is the upright position with Valsalva maneuver, and the best site for venous diameter measurement is at the level of epididymal head.

['Karami|Mehdi|M|', 'Mazdak|Hamid|H|', 'Khanbabapour|Saeid|S|', 'Adibi|Atoosa|A|', 'Nasr|Nafiseh|N|']

2014

24215675

Antiproliferation activity of Devil's club (Oplopanax horridus) and anticancer agents on human pancreatic cancer multicellular spheroids.

Devil's club (DC, Oplopanax horridus) is an important medicinal herb of the Pacific Northwest which has significant antiproliferation activity against a variety of human tumor cell lines in vitro. This study compared the antiproliferation activity of DC extract alone, and in combination with chemotherapeutic agents gemcitabine (GEM), cisplatin (CDDP), and paclitaxel (PTX) on human pancreatic cancer PANC-1 3D spheroids and 2D monolayer cells. 3D tumor spheroids were prepared with a rotary cell culture system. PANC-1 3D spheroids were significantly more resistant to killing by DC extract, GEM and PTX compared to 2D cells, with IC50 levels closer to that observed in vivo. DC extract significantly enhanced the antiproliferation activity of CDDP and GEM at some concentrations. The bioactive compound identified as a polyacetylene showed strong antiproliferation activity against PANC-1 2D cells and 3D spheroids with IC50 at 0.73±0.04 and 3.15±0.16μM, respectively. 3D spheroids and 2D cells differentially expressed a number of apoptosis related genes. Cell cycle analysis showed that the proportion of cells in S phase was increased and in G2/M phase reduced in 3D spheroids compared to 2D cells. DC extract can potentially be used to enhance the activity of chemotherapeutic agents against pancreatic cancer cells. Use of 3D spheroid model for screening of natural products can potentially increase the efficiency in discovering in vivo bioactive compounds.

['Tai|J|J|', 'Cheung|S S C|SS|', 'Ou|D|D|', 'Warnock|G L|GL|', 'Hasman|D|D|']

2014

30414347

Global soil nitrous oxide emissions since the preindustrial era estimated by an ensemble of terrestrial biosphere models: Magnitude, attribution, and uncertainty.

Our understanding and quantification of global soil nitrous oxide (N2 O) emissions and the underlying processes remain largely uncertain. Here, we assessed the effects of multiple anthropogenic and natural factors, including nitrogen fertilizer (N) application, atmospheric N deposition, manure N application, land cover change, climate change, and rising atmospheric CO2 concentration, on global soil N2 O emissions for the period 1861-2016 using a standard simulation protocol with seven process-based terrestrial biosphere models. Results suggest global soil N2 O emissions have increased from 6.3 ± 1.1 Tg N2 O-N/year in the preindustrial period (the 1860s) to 10.0 ± 2.0 Tg N2 O-N/year in the recent decade (2007-2016). Cropland soil emissions increased from 0.3 Tg N2 O-N/year to 3.3 Tg N2 O-N/year over the same period, accounting for 82% of the total increase. Regionally, China, South Asia, and Southeast Asia underwent rapid increases in cropland N2 O emissions since the 1970s. However, US cropland N2 O emissions had been relatively flat in magnitude since the 1980s, and EU cropland N2 O emissions appear to have decreased by 14%. Soil N2 O emissions from predominantly natural ecosystems accounted for 67% of the global soil emissions in the recent decade but showed only a relatively small increase of 0.7 ± 0.5 Tg N2 O-N/year (11%) since the 1860s. In the recent decade, N fertilizer application, N deposition, manure N application, and climate change contributed 54%, 26%, 15%, and 24%, respectively, to the total increase. Rising atmospheric CO2 concentration reduced soil N2 O emissions by 10% through the enhanced plant N uptake, while land cover change played a minor role. Our estimation here does not account for indirect emissions from soils and the directed emissions from excreta of grazing livestock. To address uncertainties in estimating regional and global soil N2 O emissions, this study recommends several critical strategies for improving the process-based simulations.

['Tian|Hanqin|H|0000-0002-1806-4091', 'Yang|Jia|J|0000-0003-2019-9603', 'Xu|Rongting|R|0000-0001-7292-9271', 'Lu|Chaoqun|C|0000-0002-1526-0513', 'Canadell|Josep G|JG|0000-0002-8788-3218', 'Davidson|Eric A|EA|0000-0002-8525-8697', 'Jackson|Robert B|RB|', 'Arneth|Almut|A|', 'Chang|Jinfeng|J|', 'Ciais|Philippe|P|', 'Gerber|Stefan|S|', 'Ito|Akihiko|A|0000-0001-5265-0791', 'Joos|Fortunat|F|', 'Lienert|Sebastian|S|', 'Messina|Palmira|P|', 'Olin|Stefan|S|', 'Pan|Shufen|S|0000-0001-7920-1427', 'Peng|Changhui|C|0000-0003-2037-8097', 'Saikawa|Eri|E|0000-0003-3166-8620', 'Thompson|Rona L|RL|', 'Vuichard|Nicolas|N|', 'Winiwarter|Wilfried|W|0000-0001-7131-1496', 'Zaehle|Sönke|S|0000-0001-5602-7956', 'Zhang|Bowen|B|']

2019

27336837

Enhancing stress growth traits as well as phytochemical and antioxidant contents of Spiraea and Pittosporum under seaweed extract treatments.

Seaweed extracts (SWE) might play an important role in enhancing growth and phytochemical composition of medicinal shrubs. In this study, we investigate the morphological, physiological and biochemical effects of irrigation levels (100% and 50% of the evapotranspiration rate) coupled with a weekly treatment of SWE of Ascophyllum nodosum at 5 and 7 mL L(-1) as a soil drench or foliar spray on Spiraea nipponica "Snowmound" and Pittosporum eugenioides "Variegatum" grown in containers under controlled greenhouse conditions. In addition, the phenolic and flavonoid content, antioxidant capacity and lipid peroxidation in both plant species was largely enhanced while the proline accumulation was reduced. After 8 weeks of treatments, drought condition reduced plant vegetative growth and gas exchange, as well as leaf water potential, but increased the phenolic and flavonoid contents in leaves, their antioxidant capacities and proline content. The application of SWE enhanced the performance of both species during mild drought conditions by means of increasing leaf number and area, dry weights, plant height, gas exchange and leaf water potential. The maximum vegetative growth, physiological performance and phytochemical composition of both species was achieved using the drench SWE treatments (5 and 7 mL L(-1)) in moderate drought conditions, which improved the plant water status, stomatal conductance, and photosynthetic rate. SWE enhanced plant growth and the phytochemical composition and antioxidant capacity of plant leaves of both species during moderate drought conditions.

['Elansary|Hosam O|HO|', 'Skalicka-Woźniak|Krystyna|K|', 'King|Ian W|IW|']

2016

30584284

Immunosuppressive therapy related adherence, beliefs and self-management in kidney transplant outpatients.

Purpose Kidney transplant (KTx) recipients should strictly adhere to their lifelong complex therapeutic regimen, and any barriers to medication adherence can weaken correct patient behavior. This study aimed to determine the adherence to immunosuppressive therapy (IS) in KTx adult outpatients in the Czech Republic, and attempted to gain a greater insight into their attitudes toward IS and self-management tasks. Materials and methods Pharmacist-led structured interviews were conducted to assess self-reported adherence to IS using the Czech version of the Medication Adherence Report Scale, in the context of attitudes toward IS in terms of necessity and concern scale of the Beliefs about Medicines Questionnaire. A specific questionnaire was developed to target IS self-management tasks. Medication records were also reviewed for IS serum levels, reflecting direct adherence measurement. Descriptive statistics were used to calculate adherence and self-management variables, and were analyzed by univariate and multivariate correlations, including the decision-tree method. Results The interview was completed by 211 (male 123; mean age 55.0±12.4 years, mean time 6.6±5.9 years after KTx) of the total of 235 patients. Full adherence to IS was reported by 173 (82.0%) patients. Most of them had IS serum levels within the therapeutic range, however, cyclosporine was associated with the highest variability (P<0.001). Non-adherence and concerns increased over time after KTx (P<0.05). Despite the more common unintentional non-adherence (P<0.001), relatively high concerns signified the risk of not taking IS as prescribed. Concerns also correlated with the perception of impaired health status (P<0.01), as well as the occurrence of IS-related adverse effects (P<0.001). The patients' awareness of their therapy was insufficient, and main gaps in self-management comprised inadequate sun protection, incorrect administration of IS, and unfamiliarity with the IS name, or their indications. Conclusion Although self-reported adherence to IS therapy was satisfactory, the comprehensive evaluation enabled the detection of greater concerns about IS, as well as underestimated self-management tasks that posttransplant interventions should target in the future.

['Vankova|Barbora|B|', 'Mala-Ladova|Katerina|K|', 'Kubena|Ales Antonin|AA|', 'Maly|Josef|J|', 'Sulkova|Sylvie Dusilova|SD|']

2018

21716881

Giant unilateral hydrocele "en-bisac" with right hydronephrosis in an adult: A rare entity.

Abdominoscrotal hydrocele consists of two large sacs; the abdominal and scrotal, both are connected via the inguinal canal. The diagnosis is made by clinical examination and can be confirmed with ultrasound scan. Surgical treatment is considered mandatory since spontaneous resolution is extremely rare. Herein, we report a case of giant unilateral hydrocele en-bisac who presented with spontaneous rupture of the sac.

['Singh|Dharamveer|D|', 'Aga|Pallavi|P|', 'Goel|Apul|A|']

2011

27956330

Magnetic Fe3O4 nanoparticles induced effects on performance and microbial community of activated sludge from a sequencing batch reactor under long-term exposure.

The performance and microbial community of activated sludge from a sequencing batch reactor (SBR) were investigated under long-term exposure of magnetic Fe3O4 nanoparticles (Fe3O4 NPs). The COD removal showed a slight decrease at 5-60mg/L Fe3O4 NPs compared to 0mg/L Fe3O4 NPs, whereas the NH4+-N removal had no obvious variation at 0-60mg/L Fe3O4 NPs. It was found that 10-60mg/L Fe3O4 NPs improved the denitrification process and phosphorus removal of activated sludge. The microbial enzymatic activities of activated sludge could be affected by Fe3O4 NPs, which had similar variation trends to the nitrogen and phosphorus removal rates of activated sludge. The reactive oxygen species (ROS) production and lactate dehydrogenase (LDH) release demonstrated that Fe3O4 NPs led to the toxicity to activated sludge and destroyed the integrity of microbial cytomembrane. High throughput sequencing indicated that Fe3O4 NPs could obviously affect the microbial richness and diversity of activated sludge.

['Ma|Bingrui|B|', 'Wang|Sen|S|', 'Li|Zhiwei|Z|', 'Gao|Mengchun|M|', 'Li|Shanshan|S|', 'Guo|Liang|L|', 'She|Zonglian|Z|', 'Zhao|Yangguo|Y|', 'Zheng|Dong|D|', 'Jin|Chunji|C|', 'Wang|Xuejiao|X|', 'Gao|Feng|F|']

2017

30880894

Diabetics have Inferior Long-Term Survival and Quality of Life after CABG.

A prevalence of diabetes is increasing among the patients undergoing coronary artery bypass grafting (CABG). Data on whether health-related quality of life improves similarly after CABG in diabetics and nondiabetics are limited. We assessed long-term mortality and changes in quality of life (RAND-36 Health Survey) after CABG. Seventy-four of the 508 patients (14.6%) operated on in a single institution had a history of diabetes and were compared with nondiabetics. The RAND-36 Health Survey was used as an indicator of quality of life. Assessments were made preoperatively and repeated 1 and 12 years later. Thirty-day mortality was 2.7 versus 1.6 ( p  = 0.511) in the diabetics and nondiabetics. One- and 10-year survival rates in the diabetics and nondiabetics were 94.6% versus 97.0% ( p  = 0.287) and 63.5% versus 81.6% ( p  < 0.001), respectively. After 1 year, diabetics improved significantly ( p  < 0.005) in seven, and nondiabetics ( p  < 0.001) in all eight RAND-36 dimensions. Despite an ongoing decline in quality of life over the 12-year follow-up, an improvement was maintained in four out of eight dimensions among diabetics and in seven dimensions among nondiabetics. Physical and mental component summary scores on the RAND-36 improved significantly ( p  < 0.001) in both groups after 1 year, and at least slight improvement was maintained during the 12-year follow-up time. Diabetics have inferior long-term survival after CABG as compared with nondiabetics. They gain similar improvement of quality of life in 1 year after surgery, but they have a stronger decline tendency over the years.

['Järvinen|Otso|O|', 'Hokkanen|Matti|M|', 'Huhtala|Heini|H|']

2019

30362023

Trimethylamine N-Oxide and Risk of Cardiovascular Disease and Mortality.

PURPOSE OF REVIEW Trimethylamine N-oxide (TMAO) is a gut microbiota-dependent metabolite produced from choline and phosphatidylcholine. Trimethylamine N-oxide was found associated with enhanced atherosclerosis and thrombosis in vitro and in vivo. We summarized available clinical studies which investigated TMAO's role in predicting prognostic outcomes, including mortality, in patients with cardiovascular diseases. RECENT FINDINGS In chronic kidney disease cohorts, higher TMAO levels were significantly associated with higher mortality from 1.18 to 4.32 folds. Higher TMAO levels were not significantly associated with mortality in patient undergoing dialysis. In patients with peripheral artery disease, higher TMAO levels were associated with higher overall mortality from 1.38 to 2.06 folds. In patients with type 2 diabetes, higher TMAO levels were significantly associated with higher overall mortality 2.07 to 2.7 folds. In patients with heart failure, higher TMAO levels were associated with higher mortality or cardiac transplantation 1.18 to 1.79 folds. TMAO levels could potentially be integrated to existed risk stratification tools and could lead to novel prevention and treatment approaches to cardiovascular disease. Nonetheless, more studies would be needed to clarify predictive value of TMAO to specific groups of patients. Mechanisms how TMAO affect atherosclerosis and confounding effects of TMAO with traditional cardiovascular parameters should also be further investigated.

['Kanitsoraphan|Chanavuth|C|', 'Rattanawong|Pattara|P|', 'Charoensri|Suranut|S|', 'Senthong|Vichai|V|']

2018

34684103

Associations of Spiritual Well-Being and Hope with Health Anxiety Severity in Patients with Advanced Coronary Artery Disease.

Background and Objectives: Health anxiety is one of the most common problems in patients with coronary artery disease. The present study tested whether health anxiety severity could be predicted by spiritual well-being and hope in patients with advanced coronary artery disease. Materials and Methods: In a cross-sectional study, 100 patients with advanced coronary artery disease were recruited from hospitals and healthcare centers in Iran. Patients completed self-report scales, including the Spiritual Well-Being Scale, Adult Hope Scale, and Short Health Anxiety Inventory. Hierarchical multiple regression analyses were used to empirically explore the relations among variables. Results: Results indicated that patients who reported higher levels of hope (β = 0.42, p < 0.01) and spiritual well-being (β = 0.20, p < 0.05) reported lower levels of health anxiety. Agency (β = 0.58, p < 0.01) scores were a significant negative predictor of health anxiety severity. Additionally, religious spirituality scores (β = 0.28, p < 0.01) were shown to significantly negatively predict health anxiety level. However, the pathways components of hope and existential spirituality were not significant predictors. Conclusion: The findings of the present study indicate that spiritual well-being and hope could be important factors in determining health anxiety for adults with coronary artery disease, and their role is worthy of further exploration to help improve health anxiety for patients with coronary artery disease.

['Heshmati|Rasoul|R|0000-0003-2418-8821', 'Jafari|Eisa|E|', 'Salimi Kandeh|Tahereh|T|', 'Caltabiano|Marie L|ML|']

2021

31461624

Advancing cancer diagnostics with artificial intelligence and spectroscopy: identifying chemical changes associated with breast cancer.

Background: Artificial intelligence (AI) and machine learning (ML) approaches in combination with Raman spectroscopy (RS) to obtain accurate medical diagnosis and decision-making is a way forward for understanding not only the chemical pathway to the progression of disease, but also for tailor-made personalized medicine. These processes remove unwanted affects in the spectra such as noise, fluorescence and normalization, and help in the optimization of spectral data by employing chemometrics. Methods: In this study, breast cancer tissues have been analyzed by RS in conjunction with principal component (PCA) and linear discriminate (LDA) analyses. Tissue microarray (TMA) breast biopsies were investigated using RS and chemometric methods and classified breast biopsies into luminal A, luminal B, HER2, and triple negative subtypes. Results: Supervised and unsupervised algorithms were applied on biopsy data to explore intra and inter data set biochemical changes associated with lipids, collagen, and nucleic acid content. LDA predicted specificity accuracy of luminal A, luminal B, HER2, and triple negative subtypes were 70%, 100%, 90%, and 96.7%, respectively. Conclusion: It is envisaged that a combination of RS with AI and ML may create a precise and accurate real-time methodology for cancer diagnosis and monitoring.

['Talari|Abdullah C S|ACS|', 'Rehman|Shazza|S|', 'Rehman|Ihtesham U|IU|']

2019

34532305

Case Report: Clinical Features of a Chinese Boy With Epileptic Seizures and Intellectual Disabilities Who Carries a Truncated NUS1 Variant.

The mental retardation-55 with seizures (MRD55) is a rare genetic disease characterized by developmental delay, intellectual disability, language delay and multiple types of epileptic seizures. It is caused by pathogenic variants of the NUS1 gene, which encodes Nogo-B receptor (NgBR), a necessary subunit for the glycosylation reactions in mammals. To date, 25 disease-causing mutations of NUS1 have been reported, which are responsible for various diseases, including dystonia, Parkinson's disease, developmental and epileptic encephalopathy as well as congenital disorder of glycosylation. In addition, only 9 of these mutations were reported with detailed clinical features. There are no reports about Chinese cases with MRD55. In this study, a novel, de novo pathogenic variant of NUS1 (c.51_54delTCTG, p.L18Tfs*31) was identified in a Chinese patient with intellectual disability and epileptic seizures. This pathogenic variant resulted in truncated NgBR proteins, which might be the cause of the clinical features of the patient. Oxcarbazepine was an effective treatment for improving speech and movement of the patient, who consequently presented with no seizure. With this novel pathogenic variant found in NUS1, we expand the genotype spectrum of MRD55 and provide valuable insights into the potential genotype-phenotype correlation.

['Zhang|Pingli|P|', 'Cui|Di|D|', 'Liao|Peiyuan|P|', 'Yuan|Xiang|X|', 'Yang|Nuan|N|', 'Zhen|Yuanyuan|Y|', 'Yang|Jing|J|', 'Huang|Qikun|Q|']

2021

32019189

The Use of Different Commercial Mineral Water Brands to Produce Oil-In-Water Nanoemulsions.

Nanoemulsions are submicron-size colloidal systems that have the ability to encapsulate, protect, and deliver active ingredients. They have been used in the pharmaceutical, cosmetics, and food industries to improve the absorption of drugs by the skin or via the gastrointestinal tract, aide in food conservation, and treat skin problems. To proper formulate a nanoemulsion, it is important to know the characteristics of its components (aqueous and oil phases, surfactants and additives), as well as the influence on the production method that will be used. This study investigates the influence of aqueous phase composition, stability and particle size in an oil-and-water nanoemulsion formation. By using a low energy method, the purified water was exchanged for different commercial mineral water and saline solutions, and the results of stability, particle size, pH and conductivity tests, were compared. These results show that the minerals present in commercial waters may alter the particle size, pH and conductivity values of nanoemulsions, as well as their stability.

['Rocha-Filho|Pedro A|PA|0000-0001-7424-5447', 'Monteiro|Antonio D|AD|', 'Agostinho|Luciana C|LC|', 'Oliveira|Marina P A|MPA|']

2020

25255474

MRI evaluation of not complicated Tailgut cyst: Case report.

INTRODUCTION The Tailgut cyst (cystic hamartoma) is an uncommon congenital disease of presacral retrorectal space and is embryologically part of some forms of enteric cysts. It is a benign malformation, although cases have been described in neoplastic degeneration. PRESENTATION OF CASE A caucasian 24 year old female presented shortly after childbirth with hypogastric abdominal discomfort associated with rectal tenderness, bleeding and moderate urinary symptoms for about three weeks. No previous similar episodes were reported. The patient was not suffering from haemorrhoids or inflammatory disease of the gastrointestinal tract. Clinical examination revealed no significant abnormalities or in the perianal area and gluteal surface. Digital rectal examination was suspicious of the presence of a presacral retrorectal mass. However, it could not exclude a trans-sphinteric perianal fistula. There was no fistulous communication with the exterior and the pain seemed to be more pronounced in the rectum. MRI, which has a diagnostic accuracy of 76-100% for the detection of any perianal fistulae, was performed and demonstrated the presence of a retrorectal cystic hamartoma (Tailgut cyst). DISCUSSION The most common retrorectal space cystic lesions includes epidermoid cysts, dermoid cysts and enteric cysts. It presents with pelvic pain, and sometimes with local abscess, secondary to a sinus cyst. There can also be a communication between Tailgut cyst and fistula; in the absence of primary infection may develop postinflammatory fibrosis. Radiological investigation is carried out by TRUS, CT and MRI. During MRI, on T1-weighted images, the signal intensity may change from hypointense to hyperintense as protein concentration increases, as well as in the case of bleeding. On T2-weighted images, signal intensity of mucinous fluids can decrease from highly hyperintense to hypointense with increasing protein concentration and viscosity. CONCLUSION MRI is a non-invasive useful imaging investigation with high diagnostic accuracy when a retrorectal cyst is suspected. Despite its rarity, Tailgut cyst should be considered, both for acute complications, like infection or bleeding, and for the risk, however infrequent, of neoplastic degeneration.

['Saba|Luca|L|', 'Fellini|Federica|F|', 'Greco|Francesca Gabriella|FG|', 'Leonzio|Annelise|A|', 'Cionci|Giovanni|G|', 'Consolo|Dina|D|', 'Ariozzi|Irene|I|', 'Zambrini|Eleonora Ivelize|EI|', 'Bocchi|Carlo|C|', 'Concari|Giorgio|G|', 'Rossi|Cristina|C|', 'De Filippo|Massimo|M|']

2014

34627060

Haematological and radiological-based prognostic markers of COVID-19.

BACKGROUND Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has emerged in 2019 and caused a global pandemic in 2020, manifesting in the coronavirus disease 2019 (COVID-19). The majority of patients exhibit a mild form of the disease with no major complications; however, moderate to severe and fatal cases are of public health concerns. Predicting the potential prognosis of COVID-19 could assist healthcare workers in managing cases and controlling the pandemic in an effective way. Therefore, the objectives of the study were to search for biomarkers associated with COVID-19 mortality and predictors of the overall survival (OS). METHODS Here, clinical data of 6026 adult COVID-19 patients admitted to two large centers in Saudi Arabia (Riyadh and Hafar Al-Batin cities) between April and June 2020 were retrospectively analysed. RESULTS More than 23% of the study subjects with available data have died, enabling the prediction of mortality in our cohort. Markers that were significantly associated with mortality in this study were older age, increased d-dimer in the blood, higher counts of WBCs, higher percentage of neutrophil, and a higher chest X-ray (CXR) score. The CXR scores were also positively associated with age, d-dimer, WBC count, and percentage of neutrophil. This supports the utility of CXR scores in the absence of blood testing. Predicting mortality based on Ct values of RT-PCR was not successful, necessitating a more quantitative RT-PCR to determine virus quantity in samples. Our work has also identified age, d-dimer concentration, leukocyte parameters and CXR score to be prognostic markers of the OS of COVID-19 patients. CONCLUSION Overall, this retrospective study on hospitalised cohort of COVID-19 patients presents that age, haematological, and radiological data at the time of diagnosis are of value and could be used to guide better clinical management of COVID-19 patients.

['Alsagaby|Suliman A|SA|', 'Aljouie|Abdulrhman|A|', 'Alshammari|Talal H|TH|', 'Mir|Shabir Ahmad|SA|', 'Alhumaydhi|Fahad A|FA|', 'Al Abdulmonem|Waleed|W|', 'Alshaalan|Hesham|H|', 'Alomaish|Hassan|H|', 'Daghistani|Rayyan|R|', 'Alsehawi|Ali|A|', 'Alharbi|Naif Khalaf|NK|']

2021

29399248

The Efficacy of Handheld Resistive Exercise Device (HRED) Training on Wellness Outcome in Older Adults.

The primary purpose of this study was to examine the efficacy of Handheld Resistive Exercise Device (HRED) training on wellness outcomes in older adults. A secondary purpose was to assess the utilization of an HRED in older adult fitness program. A group of healthy, active older adults (N=28, 76.6 ± 6.7 years old) volunteered to complete a 10-week HRED training program. Pre- and post-intervention changes were evaluated for muscular strength, static balance, mobility, fall-efficacy, and self-efficacy for activities of daily living. Significant improvement was seen in muscular strength (grip strength, p < 0.01), mobility (TUG time, p <0.01), and self-efficacy for jogging (p = 0.036) and push-ups (p = 0.045). Most of participants (92.9%) indicated that they would like to continue exercising with the HRED. A 10-week HRED exercise program produced some improvement on wellness outcomes in older adults and the HRED is an acceptable fitness device for this population.

['Clocksin|Brian D|BD|', 'Harrison|Ryan N|RN|', 'Douglas|Andrew|A|']

2017

28560359

Analysis of plastic residues in maple sap and syrup collected from tubing systems sanitized with isopropyl alcohol.

A plastic tubing system operated under vacuum is usually used to collect sap from maple trees during spring time to produce maple syrup. This system is commonly sanitized with isopropyl alcohol (IPA) to remove microbial contamination colonizing the system during the sugar season. Questions have been raised whether IPA would contribute to the leaching of plastic residues in maple sap and syrup coming from sanitized systems. First, an extraction experiment was performed in the lab on commercial plastic tubing materials that were submitted to IPA under harsh conditions. The results of the GC-MS analysis revealed the presence of many compounds that served has target for further tests. Secondly, tests were done on early and mid-season maple sap and syrup coming from many sugarbushes using IPA or not to determine potential concentrations of plastic residues. Results obtained from sap and syrup samples showed that no quantifiable (< 1-75 μg/L) concentration of any plastic molecules tested was determined in all samples coming from IPA treated or not treated systems. However, some samples of first sap run used as a rinse solution to be discarded before the season start and that were coming from non sanitized or IPA sanitized systems, showed quantifiable concentrations of chemical residue such as ultraviolet protector (octabenzone). These results show that IPA can be safely used to sanitize maple sap collection system in regards to the leaching of plastic residues in maple sap and syrup and reinforced the need to thoroughly rinse the tubing system at the beginning of the season for both sanitized and non sanitized systems.

['Lagacé|Luc|L|', 'Charron|Carmen|C|', 'Sadiki|Mustapha|M|']

2017

28940378

Potential risk of weed outbreak by increasing biochar's application rates in slow-growth legume, lentil (Lens culinaris Medik.).

BACKGROUND Biochar amendment is a promising tool to improve the soil quality and, consequently, higher crop yield has received more attention during last decades. The positive effects of biochar have been attracting more attention especially in the areas with low precipitation rates, such as the Middle East, due to low soil organic carbon content, higher drought intensity, and increasing demands for food production. However, biochar can lead to lower herbicide efficacy, resulting in higher consumption of herbicides. In this study, the impact of two biochars on soil properties, plant growth, and fomesafen efficacy under rain-fed condition was investigated. RESULTS Biochar amendment at the rate of 5 t ha-1 improved soil quality and plant growth by 40-200% and 46-57%, respectively, compared to the control. The increase of biochar application rate from 5 t ha-1 to 15 t ha-1 showed small additional positive effects on soil and lentil as the tested crop plant, whereas the growth of weeds elevated by 200% in this case. CONCLUSION Albeit biochar application could be an effective way to improve the soil fertility, the potential risk of weed outbreak in the long term should be evaluated carefully before the use of biochar amendment at field scale. © 2017 Society of Chemical Industry.

['Safaei Khorram|Mahdi|M|', 'Fatemi|Akram|A|http://orcid.org/0000-0002-1675-8006', 'Khan|Md Asaduzzaman|MA|', 'Kiefer|Rudolf|R|', 'Jafarnia|Sasan|S|']

2018

34155483

A diagnostic prediction model for colorectal cancer in elderlies via internet of medical things.

Internet of Medical Things (IoMT) and embedded systems have improved the healthcare systems by enabling remote monitoring the patients' health conditions anywhere and anytime especially during novel COVID-19 pandemic. In this paper, an IoT-based predicting model is proposed to predict colorectal cancer (CRC) in elderlies. It provides a CRC predicting model for the involved medical team to continuously trace an elderly's biological indicators using smart wearable embedded systems and medical IoT devices. In this model, vital medical data is collected by IoMT devices and sensors, then analytical information is derived via machine learning (ML) methods for early CRC diagnosis and elderly's health parameters changes. The experimental results confirm that the suggested model meets the proper accuracy of predicting the CRC in aged people.

['Asghari|Parvaneh|P|0000-0002-5969-6896']

2021

25732371

Far Space Remapping by Tool Use: A rTMS Study Over the Right Posterior Parietal Cortex.

BACKGROUND In previous studies, rTMS has been successfully employed to interfere with the right posterior parietal cortex (rPPC) inducing neglect-like behavior in healthy subjects. Several studies have shown that the use of tools can modulate the boundaries between near and far space: indeed when far space is reached by the stick, far space can be remapped as near. OBJECTIVE The aim of the present study was to investigate whether once that rTMS on the rPPC has selectively induced neglect-like bias in the near space (but not in the far space), neglect can appears also in the far space when the subjects used a tool to perform the task. METHODS Fifteen right-handed healthy subjects executed a line length judgment task in two different spatial positions (60 cm: near space and 120 cm: far space), with or without rPPC on-line rTMS. In the far space condition, subjects performed the perceptual task while holding or not a tool. RESULTS During rTMS, visuospatial performance significantly shifted toward right when the task was performed in the near space and in the far space when the tool was used. No significant effect was found when rTMS was delivered in the far space condition without tool use. CONCLUSIONS Our results demonstrate that the application of rTMS on rPPC, specifically affect the representation of near space because it caused neglect both when the subjects acted in the near space and when they acted in a far space that was remapped as near by the use of a tool.

['Giglia|Giuseppe|G|', 'Pia|Lorenzo|L|', 'Folegatti|Alessia|A|', 'Puma|Angela|A|', 'Fierro|Brigida|B|', 'Cosentino|Giuseppe|G|', 'Berti|Anna|A|', 'Brighina|Filippo|F|']

2015

31907247

Knowledge, Attitudes, and Practice Patterns of Health Professionals Toward Medical and Non-medical Stimulant Use by Young Adults.

BACKGROUND The role of family physicians (FPs) and college health professionals (CHPs) in stimulant treatment and nonmedical use of stimulants is not clear. OBJECTIVE To investigate the current practices, concerns, needs, beliefs, barriers, and facilitators to appropriate pharmacological treatment of teens and young adults with attention deficit hyperactivity disorder (ADHD) and prevention of nonmedical use and diversion. METHODS A cross-sectional survey developed by the project team and experts in the field, delivered to national sample of FPs and CHPs. RESULTS A total of 794 completed surveys were analyzed. The average age of respondents was 51.6 ± 10.3 years; 50.6% of the respondents were female. The majority of CHPs (80.6%) reported they spend 75% to 100% of their time with patients age 17 to 24 years and 74.0% of FPs reported they spend less than 25% of their time with this age group. The majority (91.7%) of the respondents indicated that untreated ADHD affects quality of life, and 76.4% indicated untreated ADHD is often associated with risky behaviors. More CHPs than FPs always refer out for ADHD diagnosis (70.7% vs 52.1%; P < .001). Most respondents (81.2%) were concerned with ADHD medication diversion, and 84.2% believed that diversion or abuse is a problem overall. Respondents indicated they are unprepared to provide patient education on decisions about pharmacotherapy or behavioral therapy choices for adult ADHD. CONCLUSION There is an opportunity to enhance safety and effectiveness of ADHD management in young adults. Additional resources and interventions are needed to improve medication management, reduce misuse, and ensure safe and appropriate use of stimulants.

['Loskutova|Natalia Y|NY|', 'Waterman|Jason|J|', 'Callen|Elisabeth|E|', 'Staton|Elizabeth W|EW|', 'Bullard|Emily|E|', 'Shields|Joel|J|']

2020

26276966

Alemtuzumab as Remission Induction Therapy in Behçet Disease: A 20-year Experience.

OBJECTIVE To study the efficacy and safety of anti-CD52 antibody (alemtuzumab) in the treatment of refractory and relapsing Behçet disease (BD). METHODS Thirty-two patients (22 women) with BD received 60 courses of alemtuzumab between 1994 and 2013. Three-dose regimens were used: 134 mg in 21 courses (Group 1), 95 mg in 18 courses (Group 2), and 60 mg in 21 courses (Group 3). Immunosuppressive drugs were stopped at the time of alemtuzumab, and prednisolone was reduced according to clinical response. Treatment response was assessed by clinical status, inflammatory activity, prednisolone dose, and the need for subsequent immunosuppressive drugs and disease relapse. RESULTS After the first alemtuzumab course, 27 of 32 patients (84%) achieved partial or complete remission (CR). Fifty of 60 courses (83%) resulted in remission (66% CR) without differences in remission rates between dosing regimens. Profound lymphocyte depletion occurred after all courses. Relapse-free survival rates were 83.6% at 6 months and 52.8% at 12 months, and were higher among Group 1 patients (Group 1: 100% and 77.8%, Group 2: 81.3% and 37.5%, and Group 3: 65.0% and 37.1%, p < 0.001). Mild to moderate infusion reactions occurred after 16 courses (27%). Eight patients (25%) developed symptomatic thyroid disease. CONCLUSION Alemtuzumab led to remission in the majority of patients with difficult-to-treat BD. Relapse was common and may be associated with lower dosing. Adverse events included infusion reactions and new autoimmunity. Achieving complete lymphocyte depletion did not affect the remission rate or duration.

['Mohammad|Aladdin J|AJ|', 'Smith|Rona M|RM|', 'Chow|Yok W|YW|', 'Chaudhry|Afzal N|AN|', 'Jayne|David R W|DR|']

2015

33958083

How Radiology Leaders Can Address Burnout.

The 2018 Annual Workforce Survey conducted by the ACR Commission on Human Resources demonstrated that, although the majority of radiology practice leaders acknowledge radiologist burnout as a significant problem, only about one in five leaders responded that their practices were either extremely or very effective at addressing physician burnout. Moving forward, leaders will be increasingly held accountable and expected to describe to their teams their reasons for not addressing burnout. In this article, common misperceptions that may contribute to radiology practice leaders not addressing burnout are described, followed by outlining practical skills that leaders should develop to effectively address burnout.

['Parikh|Jay R|JR|', 'Bender|Claire E|CE|']

2021

28658619

Peripheral Sensory Deprivation Restores Critical-Period-like Plasticity to Adult Somatosensory Thalamocortical Inputs.

Recent work has shown that thalamocortical (TC) inputs can be plastic after the developmental critical period has closed, but the mechanism that enables re-establishment of plasticity is unclear. Here, we find that long-term potentiation (LTP) at TC inputs is transiently restored in spared barrel cortex following either a unilateral infra-orbital nerve (ION) lesion, unilateral whisker trimming, or unilateral ablation of the rodent barrel cortex. Restoration of LTP is associated with increased potency at TC input and reactivates anatomical map plasticity induced by whisker follicle ablation. The reactivation of TC LTP is accompanied by reappearance of silent synapses. Both LTP and silent synapse formation are preceded by transient re-expression of synaptic GluN2B-containing N-methyl-D-aspartate (NMDA) receptors, which are required for the reappearance of TC plasticity. These results clearly demonstrate that peripheral sensory deprivation reactivates synaptic plasticity in the mature layer 4 barrel cortex with features similar to the developmental critical period.

['Chung|Seungsoo|S|', 'Jeong|Ji-Hyun|JH|', 'Ko|Sukjin|S|', 'Yu|Xin|X|', 'Kim|Young-Hwan|YH|', 'Isaac|John T R|JTR|', 'Koretsky|Alan P|AP|']

2017

25151550

High definition plus colonoscopy combined with i-scan tone enhancement vs. high definition colonoscopy for colorectal neoplasia: A randomized trial.

BACKGROUND High definition endoscopy is the accepted standard in colonoscopy. However, an important problem is missed polyps. AIMS Our objective was to assess the additional adenoma detection rate between high definition colonoscopy with tone enhancement (digital chromoendoscopy) vs. white light high definition colonoscopy. METHODS In this prospective randomized trial patients were included to undergo a tandem colonoscopy. The first exam was a white light colonoscopy with removal of all visualized polyps. The second examination was randomly assigned in a 1:1 ratio as either again white light colonoscopy (Group A) or colonoscopy with tone enhancement (Group B). Primary endpoint was the adenoma detection rate during the second withdrawal (sample size calculation - 40 per group). RESULTS 67 lesions (Group A: n=34 vs. Group B: n=33) in 80 patients (mean age 61 years, male 64%) were identified on the first colonoscopy. The second colonoscopy detected 78 additional lesions: n=60 with tone enhancement vs. n=18 with white light endoscopy (p<0.001). Tone enhancement found more additional adenomas (A n=20 vs. B n=6, p=0.006) and identified significantly more missed adenomas per subject (0.5 vs. 0.15, p=0.006). CONCLUSIONS High definition plus colonoscopy with tone enhancement detected more adenomas missed by white light colonoscopy.

['Hoffman|Arthur|A|', 'Loth|Linn|L|', 'Rey|Johannes Wilhelm|JW|', 'Rahman|Fareed|F|', 'Goetz|Martin|M|', 'Hansen|Torsten|T|', 'Tresch|Achim|A|', 'Niederberger|Theresa|T|', 'Galle|Peter Robert|PR|', 'Kiesslich|Ralf|R|']

2014

34658579

Clinico-histopathological Profile of Primary Paediatric Intra-abdominal Tumours: a Multi-hospital-Based Study.

Paediatric cancers are gradually on the rise in India. Its proportion among children aged < 15 years constitutes close to 5% of the total cancer affected population. A high proportion of this constitutes intra-abdominal tumours. This study was done to study the demographic profile, clinical features and management of intra-abdominal tumours among children. Data of all histopathologically confirmed patients aged < 15 years with various primary intra-abdominal tumours diagnosed from 2009 to 2019 were included in this study. The median age of the patients (n = 50) was 3 years (IQR 1.4, 6). The median age at diagnosis of cancer (n = 23) was 2.5 years (IQR 1, 4). Tumours were more common among males (70%). The most common tumour in this study was Wilm's tumour (17 (34%)). Forty-eight (96%) patients had malignant tumours. Fever was present among the majority (27 (54%)) of the patients. The most common anti-cancer drug used for management was Vincristine, used among 23 patients. Remission was more among infants with Wilm's tumour (P = 0.0221) and among patients with Hodgkin's lymphoma (HL) (P = 0.0444). Default with treatment was more among patients with stage 4 malignancy (P = 0.0186). Recovery following treatment was more among patients with germ cell tumour (P = 0.0082). Reasons for default with treatment in the late stages of malignancies need to be identified in future research studies. Supplementary Information The online version contains supplementary material available at 10.1007/s13193-021-01365-x.

['Joseph|Nitin|N|0000-0002-3639-510X', 'Rai|Sharada|S|', 'Singhal|Kshitiz|K|', 'Saha|Sreejita|S|', 'Chakraborty|Deboshruti|D|', 'Badoni|Gauri|G|', 'Revanth|Thella|T|', 'Lobo|Flora D|FD|']

2021

27554049

Prevalence and clinical features of Fabry disease in Japanese male patients with diagnosis of hypertrophic cardiomyopathy.

BACKGROUND The prevalence of Fabry disease (FD) in Japanese patients presenting with unexplained left ventricular hypertrophy (LVH) has remained unclear. METHODS We measured plasma α-galactosidase A activity in 177 men with a diagnosis of hypertrophic cardiomyopathy (HCM) (maximum LV wall thickness ≥15mm). RESULTS Two patients (1.1%) showed very low α-galactosidase A activity [0.0 and 0.3nmol/hr/ml (normal range: 3.6-17.6nmol/hr/ml)], and a clinical diagnosis of cardiac variant of FD was finally made. One patient was a 55-year-old man who came to our hospital because of abnormal results of electrocardiography and showed concentric LVH in echocardiography. A missense mutation, R112L, was identified. The other was a 74-year-old man who had been diagnosed with HCM at the age of 60 years in another hospital and was referred for evaluation of repeated hospitalization for heart failure. Although echocardiography revealed asymmetric septal hypertrophy (ASH) with interventricular septal wall thickness of 16mm and posterior wall thickness of 11mm and reduced LV ejection fraction with hypokinetic posterior wall motion, his echocardiographic findings at the initial diagnosis of HCM were not ASH but concentric LVH with normal LV systolic function. A splicing mutation, IVS4+919G>A, was identified. CONCLUSIONS The prevalence of FD in Japanese male patients with a clinical diagnosis of HCM was found to be 1.1%. These patients showed late onset and concentric LVH at initial presentation.

['Kubo|Toru|T|', 'Ochi|Yuri|Y|', 'Baba|Yuichi|Y|', 'Hirota|Takayoshi|T|', 'Tanioka|Katsutoshi|K|', 'Yamasaki|Naohito|N|', 'Yoshimitsu|Makoto|M|', 'Higuchi|Koji|K|', 'Takenaka|Toshihiro|T|', 'Nakajima|Kimiko|K|', 'Togawa|Tadayasu|T|', 'Tsukimura|Takahiro|T|', 'Sano|Shigetoshi|S|', 'Tei|Chuwa|C|', 'Sakuraba|Hitoshi|H|', 'Kitaoka|Hiroaki|H|']

2017

33061848

The emerging roles of non-coding competing endogenous RNA in hepatocellular carcinoma.

Accumulating evidence has emerged revealing that noncoding RNAs (ncRNAs) play essential roles in the occurrence and development of hepatocellular carcinoma (HCC). However, the complicated regulatory interactions among various ncRNAs in the development of HCC are not entirely understood. The newly discovered mechanism of competing endogenous RNAs (ceRNAs) uncovered regulatory interactions among different varieties of RNAs. In recent years, a growing number of studies have suggested that ncRNAs, including long ncRNAs, circular RNAs and pseudogenes, play major roles in the biological functions of the ceRNA network in HCC. These ncRNAs can share microRNA response elements to affect microRNA affinity with target RNAs, thus regulating gene expression at the transcriptional level and both physiological and pathological processes. The ncRNAs that function as ceRNAs are involved in diverse biological processes in HCC cells, such as tumor cell proliferation, epithelial-mesenchymal transition, invasion, metastasis and chemoresistance. Based on these findings, ncRNAs that act as ceRNAs may be promising candidates for clinical diagnosis and treatments. In this review, we discuss the mechanisms and research methods of ceRNA networks. We also reviewed the recent advances in studying the roles of ncRNAs as ceRNAs in HCC and highlight possible directions and possibilities of ceRNAs as diagnostic biomarkers or therapeutic targets. Finally, the limitations, gaps in knowledge and opportunities for future research are also discussed.

['Xu|Gang|G|', 'Xu|Wei-Yu|WY|', 'Xiao|Yao|Y|', 'Jin|Bao|B|', 'Du|Shun-Da|SD|0000-0002-9357-3259', 'Mao|Yi-Lei|YL|', 'Zhang|Zhong-Tao|ZT|']

2020

34189178

Fecal Microbiota Functional Gene Effects Related to Single-Dose Antibiotic Treatment of Travelers' Diarrhea.

Background Travelers' diarrhea (TD) is common among military personnel deployed to tropical and subtropical regions. It remains unclear how TD and subsequent antibiotic treatment impact the resident microflora within the gut, especially given increased prevalence of antibiotic resistance among enteric pathogens and acquisition of multidrug-resistant organisms. We examined functional properties of the fecal microflora in response to TD, along with subsequent antibiotic treatment. Methods Fecal samples from US and UK military service members deployed to Djibouti, Kenya, and Honduras who presented with acute watery diarrhea were collected. A sample was collected at acute presentation to the clinic (day 0, before antibiotics), as well as 7 and/or 21 days following a single dose of antibiotics (azithromycin [500 mg], levofloxacin [500 mg], or rifaximin [1650 mg], all with loperamide). Each stool sample underwent culture and TaqMan reverse transcription polymerase chain reaction analyses for pathogen and antibiotic resistance gene detection. Purified DNA from each sample was analyzed using the HumiChip3.1 functional gene array. Results In total, 108 day 1 samples, 50 day 7 samples, and 94 day 21 samples were available for analysis from 119 subjects. Geographic location and disease severity were associated with distinct functional compositions of fecal samples. There were no overt functional differences between pre- and postantibiotic treatment samples, nor was there increased acquisition of antibiotic resistance determinants for any of the antibiotic regimens. Conclusions These results indicate that single-dose antibiotic regimens may not drastically alter the functional or antibiotic resistance composition of fecal microflora, which should inform clinical practice guidelines and antimicrobial stewardship. Clinical Trials Registration Number NCT01618591.

['Johnson|Ryan C|RC|', 'Van Nostrand|Joy D|JD|', 'Tisdale|Michele|M|', 'Swierczewski|Brett|B|', 'Simons|Mark P|MP|', 'Connor|Patrick|P|', 'Fraser|Jamie|J|', 'Melton-Celsa|Angela R|AR|', 'Tribble|David R|DR|', 'Riddle|Mark S|MS|https://orcid.org/0000-0002-0607-7880']

2021

32652581

Investigating mentor commitment in youth mentoring relationships: The role of perceived program practices.

Highly committed mentors may be less likely to end their mentoring relationships with their mentees. Theory suggests commitment is predicted by relationship satisfaction, investment, and perceptions of available alternatives. Mentoring program practices may influence commitment, but little research has investigated potential mechanisms. Using data from 537 mentors representing 55 mentoring programs, this study examined a theoretical path model in which mentor perceptions of program practices, specifically setting expectations, prematch mentor training, and matching based on mentor preferences, predict mentor satisfaction, investment, perceptions of available alternatives, and ultimately, relationship commitment. As expected, commitment was associated positively with satisfaction and investment and negatively with available alternatives. Perceptions of the program setting clear expectations, the amount of prematch training, and matching by preferences predicted mentor commitment. These associations were mediated by relationship satisfaction, investment, and available alternatives, respectively. These findings identify program practices that can support mentor commitment.

['Drew|Alison L|AL|0000-0002-3590-1269', 'Keller|Thomas E|TE|0000-0002-9198-5073', 'Spencer|Renée|R|0000-0002-2876-2918', 'Herrera|Carla|C|']

2020

32705352

IoT Architecture for Smart Control of an Exoskeleton Robot in Rehabilitation by Using a Natural User Interface Based on Gestures.

This paper describes a system for allowing a therapist to record specific motions, as a part of a rehabilitation program, mainly aimed at the elderly people, by using a Natural User Interface based on gestures. Motions are sent to an exoskeleton robot which reproduces them in the patient's lower limbs. The proposed system is an early prototype implemented as a set of interconnected components, which run independently and remotely, under a distributed software architecture. Such prototype has been properly validated through different tests in a controlled environment. The obtained results and a discussion about benefits and drawbacks are also presented, together with preliminary ideas about future research for overcoming such drawbacks and transforming the prototype into a functional system to be tested in a real scenario with real patients.

['Pavón-Pulido|Nieves|N|http://orcid.org/0000-0001-9561-1151', 'López-Riquelme|Juan Antonio|JA|', 'Feliú-Batlle|Jorge J|JJ|']

2020

31993951

Use of an Argentinean Wildlife Tissue Collection for Epidemiological Studies of Histoplasmosis.

Histoplasmosis is a worldwide systemic endemic mycosis caused by several cryptic species included within the Histoplasma capsulatum complex. Domestic and wild mammals are susceptible to infection by this fungus and could be used as indicators of its presence in the environment. The aim of the study was to identify the natural reservoirs of H. capsulatum in the Argentinean Humid Pampas eco-region analyzing a wildlife frozen-tissue collection and trace its distribution patterns over time and space. Tissue samples from 34 small wild mammals caught in the Humid Pampas were analyzed using two molecular markers: 100 kDa protein coding gene (Hcp100) and ITS1 rDNA. Results showed that 32.4% of them were infected with H. capsulatum and its DNA was detected in 5/17 Calomys laucha; 3/6 Calomys musculinus; 1/5 Akodon azarae, 1/3 Monodelphis dimidiata; and 1/2 Didelphis albiventris. In the single specimen studied of Cavia aperea, no H. capsulatum DNA was detected. This is the first H. capsulatum infection report in C. laucha and C. musculinus rodents and M. dimidiate opossum which proves that tissue collections are an important source of material for epidemiological studies of endemic disease over time.

['Canteros|Cristina E|CE|', 'Toranzo|Adriana I|AI|', 'Levis|Silvana|S|', 'Salas|Héctor D|HD|', 'López-Joffre|María C|MC|', 'Suárez-Alvarez|Roberto Osvaldo|RO|http://orcid.org/0000-0003-0571-8380']

2020

31573322

Single-Molecule Characterization of Drug Delivery Systems.

Delivery of the drug to a desired point of body and controlled release of the therapeutic agent are important features, provided by drug delivery systems (DDSs), for development of today's effective medicines. A variety of nanomaterials or nanomolecules such as lipids/liposomes, nucleic acids, peptides/proteins, composites, polymers, or carbon nanotubes can be used as DDSs. Single-molecule characterization of these small materials in terms of their size, shape, surface, encapsulation efficiency, as well as interaction with the drug-receiving cell has importance for their efficiency. The loading, distribution, or leakage of the drug as well as its interaction with DDS should also be characterized. Although diverse techniques are present for characterization of specific DDS material, methods such as electron microscopy and fluorescence microscopy are widely used. In this review, the current methodologies utilized for the single-molecule characterization of mostly preferred DDS materials were presented.

['Okay|Sezer|S|']

2020

31535068

Superior Canal Dehiscence: A Comparative Postmortem Multislice Computed Tomography Study.

Objective Superior canal dehiscence is defined by missing bony coverage of the superior canal against the middle cranial fossa. The gold standard in diagnosis is high-resolution computed tomography (CT). A false-positive CT scan, identifying a dehiscence when one is not present, could lead to unnecessary surgical therapy. This study aims to compare postmortem CT scans with autopsy findings with regard to superior canal dehiscence. Study Design Postmortem study. Setting Tertiary referral center. Subjects and Methods Twenty-two nontraumatic death cases within a 3-month period (January to March 2017) were included with 44 temporal bones. Each body underwent postmortem head CT prior to medicolegal autopsy. The middle fossa floor was exposed, and if present, the superior semicircular canal dehiscence was identified and measured. In each case, 3 comparable photographs were taken during the autopsy (left temporal bone, right temporal bone, overview). Results Autopsy findings revealed bony dehiscences in 11% of the temporal bones, whereas CT scan revealed bony dehiscences in 16%. The length of the dehiscences were longer when measured by CT imaging. Conclusion The diagnosis of superior canal dehiscence syndrome requires high-resolution CT with clinical symptoms and physiologic evidence of a third mobile window. Our study underlines a mismatch between multislice CT imaging in the coronal plane and the presence of a dehiscence on autopsy.

['Mittmann|Philipp|P|', 'Ernst|Arne|A|', 'Seidl|Rainer|R|', 'Skulj|Anna-Felicitas|AF|', 'Mutze|Sven|S|', 'Windgassen|Marc|M|', 'Buschmann|Claas|C|']

2018

28339775

Mining non-lattice subgraphs for detecting missing hierarchical relations and concepts in SNOMED CT.

Objective Quality assurance of large ontological systems such as SNOMED CT is an indispensable part of the terminology management lifecycle. We introduce a hybrid structural-lexical method for scalable and systematic discovery of missing hierarchical relations and concepts in SNOMED CT. Material and Methods All non-lattice subgraphs (the structural part) in SNOMED CT are exhaustively extracted using a scalable MapReduce algorithm. Four lexical patterns (the lexical part) are identified among the extracted non-lattice subgraphs. Non-lattice subgraphs exhibiting such lexical patterns are often indicative of missing hierarchical relations or concepts. Each lexical pattern is associated with a potential specific type of error. Results Applying the structural-lexical method to SNOMED CT (September 2015 US edition), we found 6801 non-lattice subgraphs that matched these lexical patterns, of which 2046 were amenable to visual inspection. We evaluated a random sample of 100 small subgraphs, of which 59 were reviewed in detail by domain experts. All the subgraphs reviewed contained errors confirmed by the experts. The most frequent type of error was missing is-a relations due to incomplete or inconsistent modeling of the concepts. Conclusions Our hybrid structural-lexical method is innovative and proved effective not only in detecting errors in SNOMED CT, but also in suggesting remediation for these errors.

['Cui|Licong|L|', 'Zhu|Wei|W|', 'Tao|Shiqiang|S|', 'Case|James T|JT|', 'Bodenreider|Olivier|O|', 'Zhang|Guo-Qiang|GQ|']

2017

34339719

Widespread theta coherence during spatial cognitive control.

Cognitive control allows humans to process relevant sensory information while minimizing distractions from irrelevant stimuli. The neural basis of cognitive control is known to involve frontal regions of the brain such as the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC), but the temporal dynamics of larger scale networks is unclear. Here we used EEG with source localization to identify how the neural oscillations localized to the mPFC and ACC coordinate with parietal, sensory, and motor areas during spatial cognitive control. Theta coherence (3-8 Hz) between the mPFC and ACC increased with task difficulty and predicted individual differences in reaction time. Individual differences in accuracy were predicted by earlier activation of ACC-motor coherence, highlighting the relationship between processing speed and task performance. Our results provide evidence that successful cognitive control requires dynamic coordination between a widespread network of brain regions. Long range theta coherence may be a key mechanism for efficient cognitive control across the neocortex.

['Myers|John C|JC|', 'Chinn|Lisa K|LK|', 'Sur|Sandeepa|S|', 'Golob|Edward J|EJ|']

2021

34887349

Demographics and incidence of anal squamous cell carcinoma in people living in high HIV prevalence geographical areas.

OBJECTIVES Anal squamous cell carcinoma (ASCC) is an uncommon cancer that is rapidly increasing in incidence. HIV is a risk factor in the development of ASCC, and it is thought that the rapidly increasing incidence in men is related to increasing numbers of people living with HIV (PLWH). We undertook a population-based study comparing the demographics and incidence of ASCC in patients residing high HIV prevalence areas in England to patients living in average HIV prevalence areas in England. METHODS This is a cross-sectional study following the 'Strengthening the Reporting of Observational Studies in Epidemiology' statement. Demographic data and incidence rates of ASCC within Clinical Commissioning Groups (CCGs) between 2013 and 2018 were extracted from the Cancer Outcomes and Services Dataset. CCGs were then stratified by HIV prevalence from data given by Public Health England, and high HIV prevalence geographical areas were compared with average HIV geographical areas. RESULTS Patients in high HIV areas were more likely to be young and male with higher levels of social deprivation. Incidence rates in men between 2013 and 2017 were higher in high HIV areas than average HIV areas with a rapidly increasing incidence rates in early-stage disease and a 79.1% reduction in incidence of metastatic stage 4 disease.Whereas women in high HIV areas had lower ASCC incidence than the national average and a low incidence of early-stage disease; however, metastatic disease in women had quintupled in incidence in high HIV areas since 2013. CONCLUSIONS Patients presenting with ASCC in high HIV geographical areas have different demographics to patients presenting in average HIV geographical areas. This may be related to screening programmes for PLWH in high HIV areas.

['Brogden|Danielle Rebecca Louise|DRL|http://orcid.org/0000-0002-4837-0321', 'Kontovounisios|Christos|C|', 'Mandalia|Sundhiya|S|', 'Tekkis|Paris|P|', 'Mills|Sarah Catherine|SC|']

2021

33650072

What Can the Chemical Hold?: The Politics of Efficacy in the Psychedelic Renaissance.

Drawing from ethnographic research with psychedelic therapists and researchers, this article explores political tensions between two sources of efficacy within psychedelic therapy: the self and the chemical. At times researchers and therapists emphasize the specificity of chemical effects in relationship to the neurobiology of particular diagnoses. And at other times they foreground the self as the true source of an experience which is not tied to that same biochemistry. Anthropologists have long emphasized that efficacy is a historically and socially embedded category and practice. Those conversations have new valence in light of recent theorization of the chemicals as material-semiotic structures shaped by their experimental contexts. This article argues that while the empirical claims embedded in these two efficacies can and do mutually include each other, a fundamental political tension remains between the efficacious ends envisioned by each. As clinical trials develop these drugs as therapeutic agents, they do so through linking the specific effects of the chemical to particular diagnostic populations, which may enfranchise these chemicals, but not all their efficacies.

['Hendy|Katherine|K|http://orcid.org/0000-0003-4128-1649']

2021

26594168

Fifty-Three Years after a Pencil Puncture Wound.

A pencil core with an intact pencil tip was excised from the thigh of a 60-year-old male 53 years after a puncture wound. Histologic examination of the excised pencil core and the surrounding tissue revealed a foreign body reaction with abundant entrapped dark black pigment and chronic reparative changes, including dense sclerosis and focal granulation tissue formation.

['Aswani|Vijay H|VH|', 'Kim|Seung Lae|SL|']

2015

25772212

A randomized controlled trial of birth simulation for medical students.

OBJECTIVE The objective of the study was to evaluate the effectiveness of a high-fidelity birth simulator (Noelle; Gaumard Scientific, Coral Gables, FL) compared with a lower-cost, low-tech, birth simulator (MamaNatalie; Laerdal Medical, Stavanger, Norway) in teaching medical students how to perform a spontaneous vaginal delivery (SVD). STUDY DESIGN Prior to the obstetrics-gynecology clerkship, students were randomly assigned to 2 groups. The MamaNatalie group (MG) completed 45 minutes of SVD simulation using an obstetrical abdominal-pelvic model worn by an obstetrics-gynecology faculty member. The Noelle group (NG) completed 45 minutes of SVD simulation using a high-fidelity, computer-controlled mannequin facilitated by an obstetrics-gynecology faculty member. The primary outcome was student performance during his or her first SVD as rated by supervising preceptors. Surveys were also completed by students on confidence in performing steps of a SVD (secondary outcome). RESULTS One hundred ten medical students (95% of those eligible) participated in this research study. The final postclerkship survey was completed by 93 students (85% follow-up rate). There were no significant differences in performance of SVD steps between MG and NG students as rated by preceptors. The SVD step with the least involvement by students was controlling the head (20.5% in MG, 23.3% in NG performed step with hands-off supervision). Delivery of the placenta was the SVD step with the most involvement (65.9% in MG, 52.3% in NG performed step with hands-off supervision). Baseline presimulation confidence levels were similar between MG and NG. On the immediate postsimulation survey of confidence, MG students were significantly more confident in their ability to deliver the abdomen and legs and perform fundal massage with hands-off supervision (P < .05) than NG students. Following the clerkship, MG students were significantly more confident in their ability to control the head and deliver the abdomen and legs (P < .05) than NG students. CONCLUSION MamaNatalie is as effective as Noelle in training medical students how to perform a SVD and may be a useful, lower-cost alternative in teaching labor and delivery skills to novice learners. Because birth simulation interventions involve both a simulation model and facilitator, research is required to further determine the effect of human interaction on learning outcomes.

['DeStephano|Christopher C|CC|', 'Chou|Betty|B|', 'Patel|Silka|S|', 'Slattery|Rebecca|R|', 'Hueppchen|Nancy|N|']

2015

33528682

Preparation, characterization, and applications of polyacrylonitrile/ball clay nanocomposite synthesized by gamma radiation.

Elimination of hazardous metals is of extreme worry for their toxicity at trace levels and accumulation in the biosystem. Polyacrylonitrile ball clay nanocomposite was prepared by gamma irradiation at 20 kGy. Different analytical tools were applied to prove morphology, functional groups, and chemical structure for prepared composite; SEM, TEM, IR, XRD, and XRF. From TEM and XRD data expose the studied composite has nanoscale and crystalline. The adsorption of Cs+, Co2+ and Fe3+ onto studied material took place after 24 h. Second order was preceded by the kinetic system. The capacity and effect of pH on kd reflect selectivity sequence; Co2+  > Fe3+  >  > Cs+. Both Freundlich and Langmuir are applicable for investigated material. Finally, PAN/BC nanocomposite is suitable for the column technique.

['Abass|M R|MR|http://orcid.org/0000-0002-1766-0449', 'El-Masry|E H|EH|', 'Ibrahim|A B|AB|']

2021

30036747

Negative cues lead to more inefficient search than positive cues even at later stages of visual search.

Observers can focus their attention on task-relevant items in visual search when they have prior knowledge about the target's properties (i.e., positive cues). However, little is known about how negative cues, which specify the features of task-irrelevant items, can be used to guide attention away from distractors and how their effects differ from those of positive cues. It has been proposed that when a distractor color is cued, people would first select the to-be-ignored items early in search and then inhibit them later. The present study investigated how the effects of positive and negative cues differ throughout the visual search process. The results showed that positive cues sped up the early stage of visual search and that negative cues led to initial selection for inhibition. We further found that visual search with negative cues was more inefficient than that with positive cues even at later stages, suggesting that sustained inhibition is needed throughout the visual search process. Taken together, the results indicate that positive and negative cues have different functions: prior knowledge about target features can weight task-relevant information at early stages of visual search, and negative cues are used more inefficiently even at later stages of visual search.

['Kawashima|Tomoya|T|', 'Matsumoto|Eriko|E|']

2018

32821607

Hospital Course of a Man With Viral Pneumonia Caused by COVID-19.

The authors present a case of a man with pneumonia caused by COVID-19. There is currently no FDA-approved medical treatment or vaccine for COVID-19, so a variety of drugs and medicinal therapies have been repurposed for use in hospital settings and clinical studies while the medical community waits for a medication to be approved and standardized. Pneumonia is a common outcome of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), so cases of it are rapidly spreading around the world as the novel coronavirus continues to spread.

['Solomon|Matthew|M|', 'Ganti|Latha|L|']

2020

32135293

Multi-scale characterisation of stream nutrient and carbon dynamics in sandy near coastal catchments of south-western Australia.

Managers tasked with repairing degraded stream ecosystems require restoration strategies that are tailored to local and regional characteristics. Emerging evidence suggests that local reach-scale approaches may be as effective, if not more so, than catchment-scale actions in highly permeable coastal landscapes, particularly if there is hydraulic connectivity to shallow groundwater and where recharge is strongly seasonal. This study assessed the relative influence of catchment-scale land use and reach-scale vegetation structure on the distribution of carbon and nutrient concentrations of streams within urban and agricultural catchments of the Perth region of south-western Australia. We used linear mixed-effects models to evaluate the extent to which phosphorus, nitrogen and carbon concentrations in different stream zones (streamwater, and fluvial and parafluvial sediments) were explained by catchment and reach-scale attributes and moderated by high versus low-flow periods, i.e., in wet versus dry months. We found that reach-scale vegetation (woody plant cover, annual plant cover) was a better predictor of nutrient concentrations than catchment-scale land use, particularly total imperviousness, a common measure of urbanisation. Flow was also important, with carbon and nutrient concentrations better described by reach- or catchment-scale attributes during the low flow period. The extent to which individual catchment and reach attributes influenced the distribution of nutrients in different stream zones was complex. However, our results suggest that planting woody vegetation can reduce nitrogen concentrations in surface water and fluvial sediments. Reducing the abundance of weedy annual species and restoring woody perennial species may further reduce phosphorus concentrations in surface water. We conclude that local riparian restoration can be a cost-effective strategy for managing excess nutrients and carbon in flat and permeable urban landscapes, particularly during low flow periods.

['Middleton|Jen A|JA|', 'Grierson|Pauline F|PF|', 'Pettit|Neil E|NE|', 'Kelly|Liam N|LN|', 'Gwinn|Daniel C|DC|', 'Beesley|Leah S|LS|']

2020

27504306

A Retrospective Study of the Treatment Outcome of Drug Therapies used in Heart Failure Patients with Associated Co-morbidities in a Tertiary Care Hospital.

INTRODUCTION Heart failure is one of the most common heart problems seen in the Indian population. There are various drugs used to prevent further progression of the disease. In India, there are few studies in relation to treatment outcome in a tertiary care hospital. AIM To study the treatment outcome of drug therapies used in heart failure patients with associated co-morbidities in a tertiary care hospital. MATERIALS AND METHODS This was an observational study conducted on 250 patients with heart failure. Details collected using the proforma were demography (age, gender); medical history; medication history for heart failure patients on admission and discharge; ejection fraction; median length of stay in hospital; number of readmissions & in-hospital mortality. RESULTS One hundred and twenty eight patients categorized into LVSD group (ejection fraction <40%) and 122 patients in PSF group (ejection fraction > 40%). Medical history of coronary artery disease (54%) was significantly higher in LVSD group (p<0.05) and anaemia (19%) was significantly higher in PSF group (p<0.05). On admission, inotropes (30%), digoxin (59%) and statins (54%) were prescribed more in LVSD patients (p<0.05) while calcium channel blockers (20%) were prescribed more in PSF group (p<0.05). At discharge, patients with LVSD were receiving ACE inhibitors (51%), beta blockers (30%), digoxin (67%) and statins (59%) (p<0.05) while calcium channel blockers (20%) was prescribed more in PSF group. The median length of stay was slightly higher in patients with PSF (7 days) as compared to LVSD (6 days). In-hospital mortality was lower in patients with PSF (6%) than patients with LVSD (20%). The percentage of readmissions within one month was slightly higher in patients with PSF (15%) compared to LVSD (14%). CONCLUSION Length of stay in hospital was 6-7 days in heart failure patients. In hospital mortality in LVSD patients (20%) was higher compared to PSF patients (6%). A 15% heart failure patient were readmitted within 1month of discharge.

['Thanusubramanian|Harish|H|', 'Kishore|Meena Kumari Kamal|MK|', 'Shetty|Ranjan|R|', 'Amberkar|Mohan Babu|MB|']

2016

26161355

Churg-Strauss Syndrome as an Unusual Cause of Dysphagia: Case Report.

Systemic vasculitis is a rare disease, and the diagnosis is very difficult when patient shows atypical symptoms. We experienced an unusual case of dysphagia caused by Churg-Strauss syndrome with lower cranial nerve involvement. A 74-year-old man, with a past history of sinusitis, asthma, and hearing deficiency, was admitted to our department for evaluation of dysphagia. He also complained of recurrent bleeding of nasal cavities and esophagus. Brain magnetic resonance imaging did not show definite abnormality, and electrophysiologic findings were suggestive of mononeuritis multiplex. Dysphagia had not improved after conventional therapy. Biopsy of the nasal cavity showed extravascular eosinophilic infiltration. All these findings suggested a rare form of Churg-Strauss syndrome involving multiple lower cranial nerves. Dysphagia improved after steroid therapy.

['Park|Jihye|J|', 'Im|Sun|S|', 'Moon|Su-Jin|SJ|', 'Park|Geun-Young|GY|', 'Jang|Yongjun|Y|', 'Kim|Yeonjin|Y|']

2015

28780927

White matter microstructure predicts longitudinal social cognitive outcomes after paediatric traumatic brain injury: a diffusion tensor imaging study.

BACKGROUND Deficits in social cognition may be among the most profound and disabling sequelae of paediatric traumatic brain injury (TBI); however, the neuroanatomical correlates of longitudinal outcomes in this domain remain unexplored. This study aimed to characterize social cognitive outcomes longitudinally after paediatric TBI, and to evaluate the use of sub-acute diffusion tensor imaging (DTI) to predict these outcomes. METHODS The sample included 52 children with mild complex-severe TBI who were assessed on cognitive theory of mind (ToM), pragmatic language and affective ToM at 6- and 24-months post-injury. For comparison, 43 typically developing controls (TDCs) of similar age and sex were recruited. DTI data were acquired sub-acutely (mean = 5.5 weeks post-injury) in a subset of 65 children (TBI = 35; TDC = 30) to evaluate longitudinal prospective relationships between white matter microstructure assessed using Tract-Based Spatial Statistics and social cognitive outcomes. RESULTS Whole brain voxel-wise analysis revealed significantly higher mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) in the sub-acute TBI group compared with TDC, with differences observed predominantly in the splenium of the corpus callosum (sCC), sagittal stratum (SS), dorsal cingulum (DC), uncinate fasciculus (UF) and middle and superior cerebellar peduncles (MCP & SCP, respectively). Relative to TDCs, children with TBI showed poorer cognitive ToM, affective ToM and pragmatic language at 6-months post-insult, and those deficits were related to abnormal diffusivity of the sCC, SS, DC, UF, MCP and SCP. Moreover, children with TBI showed poorer affective ToM and pragmatic language at 24-months post-injury, and those outcomes were predicted by sub-acute alterations in diffusivity of the DC and MCP. CONCLUSIONS Abnormal microstructure within frontal-temporal, limbic and cerebro-cerebellar white matter may be a risk factor for long-term social difficulties observed in children with TBI. DTI may have potential to unlock early prognostic markers of long-term social outcomes.

['Ryan|N P|NP|', 'Genc|S|S|', 'Beauchamp|M H|MH|', 'Yeates|K O|KO|', 'Hearps|S|S|', 'Catroppa|C|C|', 'Anderson|V A|VA|', 'Silk|T J|TJ|']

2018

34442721

Culture-Independent and Culture-Dependent Characterization of the Black Soldier Fly Gut Microbiome Reveals a Large Proportion of Culturable Bacteria with Potential for Industrial Applications.

Black soldier fly larvae (BSFL) are fast-growing, resilient insects that can break down a variety of organic substrates and convert them into valuable proteins and lipids for applications in the feed industry. Decomposition is mediated by an abundant and versatile gut microbiome, which has been studied for more than a decade. However, little is known about the phylogeny, properties and functions of bacterial isolates from the BSFL gut. We therefore characterized the BSFL gut microbiome in detail, evaluating bacterial diversity by culture-dependent methods and amplicon sequencing of the 16S rRNA gene. Redundant strains were identified by genomic fingerprinting and 105 non-redundant isolates were then tested for their ability to inhibit pathogens. We cultivated representatives of 26 genera, covering 47% of the families and 33% of the genera detected by amplicon sequencing. Among these isolates, we found several representatives of the most abundant genera: Morganella, Enterococcus, Proteus and Providencia. We also isolated diverse members of the less-abundant phylum Actinobacteria, and a novel genus of the order Clostridiales. We found that 15 of the isolates inhibited at least one of the tested pathogens, suggesting a role in helping to prevent colonization by pathogens in the gut. The resulting culture collection of unique BSFL gut bacteria provides a promising resource for multiple industrial applications.

['Tegtmeier|Dorothee|D|0000-0003-1814-9041', 'Hurka|Sabine|S|0000-0003-2083-5198', 'Mihajlovic|Sanja|S|', 'Bodenschatz|Maren|M|', 'Schlimbach|Stephanie|S|', 'Vilcinskas|Andreas|A|0000-0001-8276-4968']

2021

27363475

Alteration of Phospholipids during the Mitophagic Process in Lung Cancer Cells.

Matrix assisted laser desorption ionization (MALDI)-time of flight/mass spectrometry (TOF/MS) was applied to investigate alterations in phospholipids in mitophagic cancer cells. Several phospholipids, including phosphatidylcholines (PCs), sphingomyelins (SMs), and phosphatidylinositols (PIs), were successfully analyzed in control and mitophagy-induced H460 cells in the positive and negative ion modes. Principal component analysis was applied to differentiate the two groups. The upregulated and downregulated phospholipid species in the mitophagic cells were also represented in a heatmap. In the volcano plot (fold change > 1.3 and p value < 0.01), individual species of seven PCs, two SMs, and three PIs were selected as differentially regulated phospholipids. In particular, almost all the molecular species of PC, SM, and PI were downregulated in the mitophagic cells. Quantification of these lipids indicated that mitophagy induces altered metabolism of phospholipids. Therefore, phospholipid alterations during the mitophagic process of lung cancer cells were well characterized by MALDI-TOF/MS.

['Lee|Jae Won|JW|', 'Cho|Kyung Mi|KM|', 'Jung|Jae Hun|JH|', 'Tran|Quangdon|Q|', 'Jung|Woong|W|', 'Park|Jongsun|J|', 'Kim|Kwang Pyo|KP|']

2016

28735805

Impact of Definition and Timeframe on Capturing Surgery-Related Readmissions After Primary Joint Arthroplasty.

BACKGROUND Readmission rate has emerged as an important metric to measure quality, but varying definitions and timeframes are used. We aimed to evaluate the impact of different readmission definitions (postoperative vs postdischarge) and timeframes (30 vs 90-day) on capturing surgery-related readmissions after primary total joint arthroplasty. METHODS Patients who underwent primary total hip or knee arthroplasty between January 1, 2013 and December 31, 2015 were included. The electronic medical records of readmitted patients were reviewed to determine whether a surgery-related event was most responsible for readmission. The performances of 4 definition-timeframe combinations in capturing surgery-related readmissions were evaluated. RESULTS A total of 2586 patients were included. Using both postoperative and postdischarge definitions, there were no differences in the proportion of readmissions that were surgery-related when comparing 30 and 90-day timeframes (postoperative: 71% vs 60%, P = .118; postdischarge: 68% vs 60%, P = .219). Greater proportion of readmissions between days 0 and 30 were for surgery-related reasons compared with readmissions between days 31 and 90 using both postoperative and postdischarge definitions (postoperative: 71% vs 47%, P = .005; postdischarge: 68% vs 49%, P = .022). Among 104 patients readmitted for surgery-related reasons within 1 year of discharge, 52% were readmitted within 30 days of surgery compared with 79% within 90 days (P < .001). Similarly, 53% and 81% of readmissions were captured by the 30 and 90-day postdischarge definitions, respectively (P < .001). CONCLUSION A 90-day timeframe is superior in capturing surgery-related readmissions after total joint arthroplasty. Important Total hip and knee arthroplasty adverse events may be missed using a 30-day timeframe.

['Chen|Brian P|BP|', 'Dobransky|Johanna|J|', 'Poitras|Stephane|S|', 'Forster|Alan|A|', 'Beaulé|Paul E|PE|']

2017

28605534

Selection on MHC in a Context of Historical Demographic Change in 2 Closely Distributed Species of Tuco-tucos (Ctenomys australis and C. talarum).

Selection necessarily acts within the same current and historical demographic framework as neutral evolutionary processes, and the outcome of the interplay between these forces may vary according to their relative strength. In this study, we compare the variation at a major histocompatibility complex (MHC) locus (DRB exon 2), typically subject to strong diversifying selection, and mitochondrial diversity (D-loop) across populations encompassing the entire distribution of 2 species of South American subterranean rodents: Ctenomys australis and C. talarum (tuco-tucos). Although these species are parapatric along most of their distribution, historically they have followed distinct demographic trajectories associated with sea level changes during the Quaternary. We surveyed 8 populations of C. australis and 15 of C. talarum, from which we analyzed 70 and 212 D-loop haplotypes and 91 and 346 DRB genotypes, respectively. Both species have gone through a recent demographic expansion; however, the signal of this process only encompasses the entire distribution of one of the species: C. australis. While balancing selection on MHC in C. talarum-enhanced DRB diversity at the local level compared to D-loop, although not promoting divergence among populations, in C. australis local diversifying selection may have driven higher population differentiation at DRB than at D-loop. Our findings reinforce the idea that the relative strength of selection acting on MHC genes varies spatially and temporally within and among species, even between species using the same macrohabitat and exposed to similar immune challenges.

['Cutrera|Ana Paula|AP|', 'Mora|Matías Sebastián|MS|']

2017

32593718

Indoxyl sulfate promotes the atherosclerosis through up-regulating the miR-34a expression in endothelial cells and vascular smooth muscle cells in vitro.

Atherosclerosis (AS) is one of the most common cardiovascular events in patients with chronic renal insufficiency (CRI). During the development of CRI, uremic toxins, including indoxyl sulfate (IS), are pivotal risk factors for AS. However, the underlying mechanism between AS and IS has not been fully elucidated. The present study was designed to test our hypothesis that IS promotes the AS by regulating viability, proliferation, migration and apoptosis of endothelial cells and vascular smooth muscle cells. In this present study, our date showed that IS inhibited the cell viability of human umbilical vein endothelial cells (HUVECs) and human aortic vascular smooth muscle cells (HA-VSMCs) in a dose-dependent manner (P < .05). Moreover, IS inhibited the proliferation, migration and induced apoptosis of HUVECs and HA-VSMCs significantly (P < .05). However, inhibition of the miR-34a abolished these effects of IS in vitro, indicating that miR-34a is involved in the development of AS induced by IS. In addition, the luciferase reporter gene assay showed that up-regulating of miR-34a inhibited the Notch1 transcriptional activity remarkably (P < .05). The expression of Notch1 decreased after IS treatment, while miR-34a inhibitor attenuated this effect. Moreover, the expression of miR-34a-related proteins Wnt-1, Jag1, E2F1 and SIRT1 decreased, while the expression of p53 increased in HUVECs and HA-VSMCs after IS treatment. Consistently, blockage of miR-34a abolished the remarkable effects on protein expressions induced by IS. Taken together, this study showed that IS can inhibit the proliferation, migration and promote apoptosis of HUVECs and HA-VSMCs through the Notch1 signal and miR-34a-related proteins by up-regulating miR-34a. These findings may provide new insights into the underlying mechanism of AS in CRI.

['Li|Xiaowei|X|', 'Lu|Zibin|Z|', 'Zhou|Fenghua|F|', 'Jin|Wen|W|', 'Yang|Yaolin|Y|', 'Chen|Sen|S|', 'Xie|Zhiqiu|Z|', 'Zhao|Yiqiao|Y|']

2020

31471175

Predicting Exercise Intentions and Behaviors of Taiwanese Children in a Longitudinal Sample.

PURPOSE The primary purpose of this study was to investigate changes in exercise intentions and behaviors among children across time. Then, we investigated how determinants in the Theory of Planned Behavior (TPB) predicted exercise intentions and behaviors, and explored if demographic predictors contributed to predicting behaviors. DESIGN AND METHODS A three-wave, 12-month longitudinal study was conducted. A proportional stratified random sampling method was adopted, and 1997 children from 11 elementary schools in Taipei City were recruited. Numbers of participants were 1074, 1064, and 995 at times 1, 2, and 3, respectively. RESULTS Children's exercise intentions and behaviors significantly changed (both p < .05) during a 6-month interval. Attitudes, subjective norms, and perceived behavioral control (PBC) at time 1 could respectively explain 51.0% and 17.1% of the variance in time 1 and 2 intentions (F(3, 1068) = 372.20, F(3, 1059) = 73.92, both p < .001). PBC was the strongest predictor of the intention to exercise. Intentions were the immediate determinant of exercise behaviors. PBC not only indirectly affected exercise behaviors through intentions but also directly affected exercise behaviors. Gender and sports club participation directly affected children's exercise behaviors. CONCLUSIONS The findings support the TPB model being suitable for use in longitudinal studies; its core constructs significantly predicted children's exercise intentions and behaviors. PRACTICE IMPLICATIONS This study highlights that clinical practitioners and school nurses working with children can help youth engage in regular exercise by enhancing their intentions and perceived behavioral control, and cultivating positive attitudes and subjective norms when planning exercise intervention programs.

['Lee|Pi-Hsia|PH|', 'Kuo|Shu-Yu|SY|', 'Ou|Tzung-Shiang|TS|', 'Lin|Yen-Kuang|YK|', 'Chi|Mei-Ju|MJ|', 'Chen|Su-Ru|SR|', 'Lin|Pi-Chu|PC|', 'Lai|Hsiang-Ru|HR|']

2020

24685673

Characterization of an avirulent FCV strain with a broad serum cross-neutralization profile and protection against challenge of a highly virulent vs feline calicivirus.

Highly virulent, systemic strains of Feline calicivirus (vs FCV) have been described in recent years. These vs FCV isolates cause severe edema, cutaneous ulcers, lameness and other upper respiratory and oral clinical signs typically associated with FCV infection in cats. Vs FCV isolates can cause high mortality even in cats vaccinated with currently available commercial vaccines. This study reports identification and characterization of an avirulent FCV strain (FCV 21). This strain offers a broader serum cross-neutralization profile in comparison with the commonly used vaccine strain (FCV F9), as tested with two separate viral panels of FCV isolates. The first viral panel consists of 45 FCV strains isolated around 1993. The second viral panel consists of 26 FCV strains with most isolated around 2003. The potential of using this strain as a vaccine, in a 3-way (FCV+FHV+FPV) or 4-way (FCV+FHV+FPV+FCp) format, was tested by using a highly virulent vs FCV strain (FCV-33585) as a challenge virus. The mortality induced by this vs FCV in unvaccinated control cats was 78% (7 out of 9 cats). The mortality decreased to 44% (4 out of 9 cats) in cats vaccinated with a 4-way vaccine containing FCV F9. However, when this novel FCV vaccine strain (FCV 21) was used, either in combination with FCV F9 or by itself, the mortality decreased to 0% (0 out of 10 cats). The 3-way vaccine (FCV+FHV+FPV) that contained both FCV 21 and FCV F9 also had mortality of 0% (0 out of 10 cats). The clinical scores, as calculated taking into consideration the frequency and severity of various clinical signs, correlated with mortality data. The results suggested this FCV vaccine has the potential to be broadly protective against newly emergent FCV isolates, including complete protection against challenge with a highly virulent vs FCV 33585.

['Rong|Sing|S|', 'Lowery|David|D|', 'Floyd-Hawkins|Kim|K|', 'King|Vickie|V|']

2014

34328661

SCU-Net: A deep learning method for segmentation and quantification of breast arterial calcifications on mammograms.

PURPOSE Measurements of breast arterial calcifications (BAC) can offer a personalized, non-invasive approach to risk-stratify women for cardiovascular diseases such as heart attack and stroke. We aim to detect and segment breast arterial calcifications in mammograms accurately and suggest novel measurements to quantify detected BAC for future clinical applications. METHODS To separate BAC in mammograms, we propose a lightweight fine vessel segmentation method Simple Context U-Net (SCU-Net). Due to the large image size of mammograms, we adopt a patch-based way to train SCU-Net and obtain the final whole-image-size results by stitching patchwise results together. To further quantify calcifications, we test five quantitative metrics to inspect the progression of BAC for subjects: sum of mask probability metric ( ), sum of mask area metric ( ), sum of mask intensity metric ( ), sum of mask area with threshold intensity metric , and sum of mask intensity with threshold X metric . Finally, we demonstrate the ability of the metrics to longitudinally measure calcifications in a group of 26 subjects and evaluate our quantification metrics compared with calcified voxels and calcium mass on breast CT for 10 subjects. RESULTS Our segmentation results are compared with state-of-the-art network architectures based on recall, precision, accuracy, F1 score/Dice score, and Jaccard index evaluation metrics and achieve corresponding values of 0.789, 0.708, 0.997, 0.729, and 0.581 for whole-image-size results. The quantification results all show >95% correlation between quantification measures on predicted masks of SCU-Net as compared to the groundtruth and measurement of calcification on breast CT. For the calcification quantification measurement, our calcification volume (voxels) results yield R2 -correlation values of 0.834, 0.843, 0.832, 0.798, and 0.800 for the metrics, respectively; our calcium mass results yield comparable R2 -correlation values of 0.866, 0.873, 0.840, 0.774, and 0.798 for the same metrics. CONCLUSIONS Simple Context U-Net is a simple method to accurately segment arterial calcification retrospectively on routine mammograms. Quantification of the calcifications based on this segmentation in the retrospective cohort study has sufficient sensitivity to detect the normal progression over time and should be useful for future research and clinical applications.

['Guo|Xiaoyuan|X|', "O'Neill|W Charles|WC|", 'Vey|Brianna|B|', 'Yang|Tianen Christopher|TC|', 'Kim|Thomas J|TJ|', 'Ghassemi|Maryzeh|M|', 'Pan|Ian|I|', 'Gichoya|Judy Wawira|JW|', 'Trivedi|Hari|H|', 'Banerjee|Imon|I|']

2021

34842684

Locally Injectable Hydrogels for Tumor Immunotherapy.

Hydrogel-based local delivery systems provide a good delivery platform for cancer immunotherapy. Injectable hydrogels can directly deliver antitumor drugs to the tumor site to reduce systemic toxicity and achieve low-dose amplification immunotherapy. Therefore, it may overcome the problems of low drug utilization rate and the systemic side effects in cancer immunotherapy through systemic immune drugs, and it provides simple operation and little invasion at the same time. This study aimed to review the research progress of injectable hydrogels in tumor immunotherapy in recent years. Moreover, the local delivery of multiple drugs using injectable hydrogels in tumors is introduced to achieve single immunotherapy, combined chemo-immunotherapy, combined radio-immunotherapy, and photo-immunotherapy. Finally, the application of hydrogels in tumor immunotherapy is summarized, and the challenges and prospects for injectable hydrogels in tumor immunotherapy are proposed.

['Zhang|Xinyi|X|', 'Guo|Xiaonan|X|', 'Wu|Yan|Y|', 'Gao|Jie|J|']

2021

31035406

A Novel Method for Classifying Liver and Brain Tumors Using Convolutional Neural Networks, Discrete Wavelet Transform and Long Short-Term Memory Networks.

Rapid classification of tumors that are detected in the medical images is of great importance in the early diagnosis of the disease. In this paper, a new liver and brain tumor classification method is proposed by using the power of convolutional neural network (CNN) in feature extraction, the power of discrete wavelet transform (DWT) in signal processing, and the power of long short-term memory (LSTM) in signal classification. A CNN-DWT-LSTM method is proposed to classify the computed tomography (CT) images of livers with tumors and to classify the magnetic resonance (MR) images of brains with tumors. The proposed method classifies liver tumors images as benign or malignant and then classifies brain tumor images as meningioma, glioma, and pituitary. In the hybrid CNN-DWT-LSTM method, the feature vector of the images is obtained from pre-trained AlexNet CNN architecture. The feature vector is reduced but strengthened by applying the single-level one-dimensional discrete wavelet transform (1-D DWT), and it is classified by training with an LSTM network. Under the scope of the study, images of 56 benign and 56 malignant liver tumors that were obtained from Fırat University Research Hospital were used and a publicly available brain tumor dataset were used. The experimental results show that the proposed method had higher performance than classifiers, such as K-nearest neighbors (KNN) and support vector machine (SVM). By using the CNN-DWT-LSTM hybrid method, an accuracy rate of 99.1% was achieved in the liver tumor classification and accuracy rate of 98.6% was achieved in the brain tumor classification. We used two different datasets to demonstrate the performance of the proposed method. Performance measurements show that the proposed method has a satisfactory accuracy rate at the liver tumor and brain tumor classifying.

['Kutlu|Hüseyin|H|', 'Avcı|Engin|E|']

2019

34648385

Generation of Urine-Derived Induced Pluripotent Stem Cell Line from Patients with Acute Kidney Injury.

Acute kidney injury (AKI) is mainly characterized by rapid decline of renal function. Currently, the strategy of stem cells might be a therapy to treat AKI. The objective of this study was to obtain human urine-derived cells (HUCs) from patients with AKI, followed by establishing induced pluripotent stem (iPS) cell line. We isolated urine cells from patients with AKI and found that the cells could survive long term with epithelioid morphology and maintain a normal karyotype. The cell line had expression of renal-specific markers and renal development-related genes. After induction, the urine cells cotransfecting with TET-ON vectors were converted into iPS cells. The HUC-derived iPS (HUC-iPS) was positive for alkaline phosphatase staining, and had expression of pluripotency markers, consistent with human embryonic fibroblast-derived iPS cell. Notably, HUC-iPS could be induced to undergo directional kidney precursor cells (KPCs) differentiation under defined conditions, and transplantation of KPCs resulted in reducing kidney damage from ischemia-reperfusion injury in mice. Therefore, we successfully established HUC-iPS cell from patients with AKI and provided a novel stem cell resource for cell therapy in AKI.

['Jin|Yong|Y|0000-0003-4567-3762', 'Zhang|Manling|M|', 'Li|Meishuang|M|', 'Zhang|Hao|H|', 'Zhang|Feng|F|', 'Zhang|Hong|H|', 'Yin|Zhibao|Z|', 'Zhou|Meng|M|', 'Wan|Xin|X|', 'Li|Rongfeng|R|', 'Cao|Changchun|C|']

2021

27313229

Influenza evolution and H3N2 vaccine effectiveness, with application to the 2014/2015 season.

Influenza A is a serious disease that causes significant morbidity and mortality, and vaccines against the seasonal influenza disease are of variable effectiveness. In this article, we discuss the use of the pepitope method to predict the dominant influenza strain and the expected vaccine effectiveness in the coming flu season. We illustrate how the effectiveness of the 2014/2015 A/Texas/50/2012 [clade 3C.1] vaccine against the A/California/02/2014 [clade 3C.3a] strain that emerged in the population can be estimated via pepitope In addition, we show by a multidimensional scaling analysis of data collected through 2014, the emergence of a new A/New Mexico/11/2014-like cluster [clade 3C.2a] that is immunologically distinct from the A/California/02/2014-like strains.

['Li|Xi|X|', 'Deem|Michael W|MW|']

2016

28848709

New Treatment Opportunities in Phosphatase and Tensin Homolog (PTEN)-Deficient Tumors: Focus on PTEN/Focal Adhesion Kinase Pathway.

Deep genetic studies revealed that phosphatase and tensin homolog (PTEN) mutations or loss of expression are not early events in cancer development but characterize tumor progression and invasion. Loss of PTEN function causes a full activation of the prosurvival phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway, but the treatment with specific inhibitors of PI3K/AKT/mTOR did not produce the expected results. One of the alternative targets of PTEN is the focal adhesion kinase (FAK) kinase, mainly involved in the control of cancer cell spread. The connection between PTEN and FAK has been demonstrated in different tumor types, with reduced PTEN activity often correlated with increased expression and phosphorylation of FAK. FAK inhibition may thus represent a promising strategy, and some clinical trials are testing FAK inhibitors alone or combined with other agents in a number of solid tumors. However, only few preclinical and clinical data described the effects of the combination of PI3K/AKT/mTOR and FAK inhibitors. Increasing knowledge on the PTEN/FAK connection could confirm PTEN as a good prognostic marker for a combination strategy based on concomitant inhibition of PI3K/AKT and FAK signaling, in advanced metastatic malignancies with altered or reduced PTEN expression.

['Alfieri|Roberta|R|', 'Giovannetti|Elisa|E|', 'Bonelli|Mara|M|', 'Cavazzoni|Andrea|A|']

2017

28540691

Expression of MicroRNAs in Thyroid Carcinoma.

MicroRNA (miRNA) are negative regulators of gene expression and subsequent protein production. This method of action translates into regulatory control over cellular processes, including development, signaling, metabolism, and apoptosis. A broad range of miRNA are shown to have abnormal expressions in thyroid cancers which could explain the pathology of tumor oncogenesis and disease progression. A review is conducted of the current research on miRNA dysregulation in thyroid cancers, including papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), anaplastic thyroid cancer (ATC), and medullary thyroid carcinoma (MTC). Dysregulated miRNA and their associated regulatory pathways are identified and their oncogenic and pathological significance are discussed.

['Zhu|Gaohong|G|', 'Xie|Lijun|L|', 'Miller|Daniel|D|']

2017

34284794

Comparing options for females seeking permanent contraception in high resource countries: a systematic review.

BACKGROUND Multiple options for permanent or long-acting contraception are available, each with adverse effects and benefits. People seeking to end their fertility, and their healthcare providers, need a comprehensive comparison of methods to support their decision-making. Permanent contraceptive methods should be compared with long-acting methods that have similar effectiveness and lower anticipated adverse effects, such as the levonorgestrel-releasing intrauterine contraception (LNG-IUC). We aimed to understand the comparability of options for people seeking to end their fertility, using high-quality studies. We sought studies comparing laparoscopic tubal ligation, hysteroscopic tubal occlusion, bilateral salpingectomy, and insertion of the LNG-IUC, for effectiveness, adverse events, tolerability, patient recovery, non-contraceptive benefits, and healthcare system costs among females in high resource countries seeking to permanently avoid conception. METHODS We followed PRISMA guidelines, searched EMBASE, Pubmed (Medline), Web of Science, and screened retrieved articles to identify additional studies. We extracted data on population, interventions, outcomes, follow-up, health system costs, and study funding source. We used the Newcastle-Ottawa Scale to assess risk of bias and excluded studies with medium-high risk of bias (NOS < 7). Due to considerable heterogeneity, we performed a narrative synthesis. RESULTS Our search identified 6,612 articles. RG, BV, BC independently reviewed titles and abstracts for relevance. We reviewed the full text of 154 studies, yielding 34 studies which met inclusion criteria. We excluded 10 studies with medium-high risk of bias, retaining 24 in our synthesis. Most studies compared hysteroscopic tubal occlusion and/or laparoscopic tubal ligation. Most comparisons reported on effectiveness and adverse events; fewer reported tolerability, patient recovery, non-contraceptive benefits, and/or healthcare system costs. No comparisons reported accessibility, eligibility, or follow-up required. We found inconclusive evidence comparing the effectiveness of hysteroscopic tubal occlusion to laparoscopic tubal ligation. All studies reported adverse events. All forms of tubal interruption reported a protective effect against cancers. Tolerability appeared greater among tubal ligation patients compared to hysteroscopic tubal occlusion patients. No high-quality studies included the LNG-IUC. CONCLUSIONS Studies are needed to directly compare surgical forms of permanent contraception, such as tubal ligation or removal, with alternative options, such as intrauterine contraception to support decision-making. SYSTEMATIC REVIEW REGISTRATION PROSPERO [CRD42016038254].

['Gormley|Rebecca|R|', 'Vickers|Brian|B|', 'Cheng|Brooke|B|', 'Norman|Wendy V|WV|http://orcid.org/0000-0003-4340-7882']

2021

33062605

The Effect of Alpha Mangostin on Epithelial-Mesenchymal Transition on Human Hepatocellular Carcinoma HepG2 Cells Surviving Sorafenib via TGF-β/Smad Pathways.

This study was intended to find out the impact of alpha mangostin administration on the epithelial-mesenchymal transition (EMT) markers and TGF-β/Smad pathways in hepatocellular carcinoma Hep-G2 cells surviving sorafenib. Hepatocellular carcinoma HepG2 cells were treated with sorafenib 10 μM. Cells surviving sorafenib treatment (HepG2surv) were then treated vehicle, sorafenib, alpha mangostin, or combination of sorafenib and alpha mangostin. Afterward, cells were observed for their morphology with an inverted microscope and counted for cell viability. The concentrations of transforming growth factor (TGF)-β1 in a culture medium were examined using ELISA. The mRNA expressions of TGF-β1, TGF-β1-receptor, Smad3, Smad7, E-cadherin, and vimentin were evaluated using quantitative reverse transcriptase-polymerase chain reaction. The protein level of E-cadherin was also determined using western blot analysis. Treatment of alpha mangostin and sorafenib caused a significant decrease in the viability of sorafenib-surviving HepG2 cells versus control (both groups with P <0.05). Our study found that alpha mangostin treatment increased the expressions of vimentin (P <0.001 versus control). In contrast, alpha mangostin treatment tends to decrease the expressions of Smad7 and E-cadherin (both with P >0.05). In line with our findings, the expressions of TGF-β1 and Smad3 are significantly upregulated after alpha mangostin administration (both with P <0.05) versus control. Alpha mangostin reduced cell viability of sorafenib-surviving HepG2 cells; however, it also enhanced epithelial-mesenchymal transition markers by activating TGF-β/Smad pathways.

['Adenina|Syarinta|S|https://orcid.org/0000-0001-9839-1502', 'Louisa|Melva|M|https://orcid.org/0000-0002-9451-0380', 'Soetikno|Vivian|V|', 'Arozal|Wawaimuli|W|', 'Wanandi|Septelia Inawati|SI|']

2020

27765817

Adaptor Protein CD2AP and L-type Lectin LMAN2 Regulate Exosome Cargo Protein Trafficking through the Golgi Complex.

Exosomes, 40-150-nm extracellular vesicles, transport biological macromolecules that mediate intercellular communications. Although exosomes are known to originate from maturation of endosomes into multivesicular endosomes (also known as multivesicular bodies) with subsequent fusion of the multivesicular endosomes with the plasma membrane, it remains unclear how cargos are selected for exosomal release. Using an inducible expression system for the exosome cargo protein GPRC5B and following its trafficking trajectory, we show here that newly synthesized GPRC5B protein accumulates in the Golgi complex prior to its release into exosomes. The L-type lectin LMAN2 (also known as VIP36) appears to be specifically required for the accumulation of GPRC5B in the Golgi complex and restriction of GPRC5B transport along the exosomal pathway. This may occur due to interference with the adaptor protein GGA1-mediated trans Golgi network-to-endosome transport of GPRC5B. The adaptor protein CD2AP-mediated internalization following cell surface delivery appears to contribute to the Golgi accumulation of GPRC5B, possibly in parallel with biosynthetic/secretory trafficking from the endoplasmic reticulum. Our data thus reveal a Golgi-traversing pathway for exosomal release of the cargo protein GPRC5B in which CD2AP facilitates the entry and LMAN2 impedes the exit of the flux, respectively.

['Kwon|Sang-Ho|SH|', 'Oh|Sekyung|S|', 'Nacke|Marisa|M|', 'Mostov|Keith E|KE|', 'Lipschutz|Joshua H|JH|']

2016

32253362

Uncharacteristic Task-Evoked Pupillary Responses Implicate Atypical Locus Ceruleus Activity in Autism.

Autism spectrum disorder (ASD) is characterized partly by atypical attentional engagement, reflected in exaggerated and variable responses to sensory stimuli. Attentional engagement is known to be regulated by the locus ceruleus (LC). Moderate baseline LC activity globally dampens neural responsivity and is associated with adaptive deployment and narrowing of attention to task-relevant stimuli. In contrast, increased baseline LC activity enhances neural responsivity across cortex and widening of attention to environmental stimuli regardless of their task relevance. Given attentional atypicalities in ASD, this study is the first to evaluate whether, under different attentional task demands, individuals with ASD exhibit a different profile of LC activity compared with typically developing controls. Males and females with ASD and age- and gender-matched controls participated in a one-back letter detection test while task-evoked pupillary responses, an established correlate for LC activity, were recorded. Participants completed this task in two conditions, either in the absence or presence of distractor auditory tones. Compared with controls, individuals with ASD evinced atypical pupillary responses in the presence versus absence of distractors. Notably, this atypical pupillary profile was evident despite the fact that both groups exhibited equivalent task performance. Moreover, between-group differences in pupillary responses were observed specifically in response to task-relevant events, providing confirmation that the group differences most likely were specifically associated with distinctions in LC activity. These findings suggest that individuals with ASD show atypical modulation of LC activity with changes in attentional demands, offering a possible mechanistic and neurobiological account for attentional atypicalities in ASD.SIGNIFICANCE STATEMENT Individuals with autism spectrum disorder (ASD) exhibit atypical attentional behaviors, including altered sensory responses and atypical fixedness, but the neural mechanism underlying these behaviors remains elusive. One candidate mechanism is atypical locus ceruleus (LC) activity, as the LC plays a critical role in attentional modulation. Specifically, LC activity is involved in regulating the trade-off between environmental exploration and focused attention. This study shows that, under tightly controlled conditions, task-evoked pupil responses, an LC activity proxy, are lower in individuals with ASD than in controls, but only in the presence of task-irrelevant stimuli. This suggests that individuals with ASD evince atypical modulation of LC activity in accordance with changes in attentional demands, offering a mechanistic account for attentional atypicalities in ASD.

['Granovetter|Michael C|MC|0000-0002-8103-2439', 'Burlingham|Charlie S|CS|0000-0002-9286-2091', 'Blauch|Nicholas M|NM|0000-0002-7843-578X', 'Minshew|Nancy J|NJ|0000-0001-7875-1929', 'Heeger|David J|DJ|0000-0002-3282-9898', 'Behrmann|Marlene|M|0000-0002-3814-1015']

2020

31555294

Glutamine Metabolism in Both the Oxidative and Reductive Directions Is Triggered in Shrimp Immune Cells (Hemocytes) at the WSSV Genome Replication Stage to Benefit Virus Replication.

White spot syndrome virus (WSSV) is the causative agent of a shrimp disease that has caused huge global economic losses. Although its pathogenesis remains poorly understood, it has been reported that in the shrimp immune cells (hemocytes) targeted by WSSV, the virus triggers both the Warburg effect and glutamine metabolism at the WSSV genome replication stage (12 h post infection). Glutamine metabolism follows two pathways: an oxidative pathway mediated by α-KGDH (α-ketoglutarate dehydrogenase) and an alternative reductive pathway mediated by IDH1 and IDH2 (isocitrate dehydrogenase 1 and 2). Here we used isotopically labeled glutamine ([U-13C]glutamine and [1-13C]glutamine) as metabolic tracers to show that, at the replication stage, both the oxidative and reductive glutamine metabolic pathways were activated. We further show that the mRNA expression levels of α-KGDH and IDH1 were increased in WSSV-infected shrimps and that silencing of α-KGDH, IDH1, and IDH2 with their respective dsRNAs led to a decrease in WSSV gene expression and WSSV replication. Taken together, our findings provide new evidence for WSSV-induced metabolic reprogramming in hemocytes and demonstrate its importance in virus replication.

['He|Shu-Ting|ST|', 'Lee|Der-Yen|DY|', 'Tung|Cheng-Yi|CY|', 'Li|Chun-Yuan|CY|', 'Wang|Han-Ching|HC|']

2019

27428810

Investigating locality effects and surprisal in written English syntactic choice phenomena.

We investigate the extent to which syntactic choice in written English is influenced by processing considerations as predicted by Gibson's (2000) Dependency Locality Theory (DLT) and Surprisal Theory (Hale, 2001; Levy, 2008). A long line of previous work attests that languages display a tendency for shorter dependencies, and in a previous corpus study, Temperley (2007) provided evidence that this tendency exerts a strong influence on constituent ordering choices. However, Temperley's study included no frequency-based controls, and subsequent work on sentence comprehension with broad-coverage eye-tracking corpora found weak or negative effects of DLT-based measures when frequency effects were statistically controlled for (Demberg & Keller, 2008; van Schijndel, Nguyen, & Schuler 2013; van Schijndel & Schuler, 2013), calling into question the actual impact of dependency locality on syntactic choice phenomena. Going beyond Temperley's work, we show that DLT integration costs are indeed a significant predictor of syntactic choice in written English even in the presence of competing frequency-based and cognitively motivated control factors, including n-gram probability and PCFG surprisal as well as embedding depth (Wu, Bachrach, Cardenas, & Schuler, 2010; Yngve, 1960). Our study also shows that the predictions of dependency length and surprisal are only moderately correlated, a finding which mirrors Dember & Keller's (2008) results for sentence comprehension. Further, we demonstrate that the efficacy of dependency length in predicting the corpus choice increases with increasing head-dependent distances. At the same time, we find that the tendency towards dependency locality is not always observed, and with pre-verbal adjuncts in particular, non-locality cases are found more often than not. In contrast, surprisal is effective in these cases, and the embedding depth measures further increase prediction accuracy. We discuss the implications of our findings for theories of language comprehension and production, and conclude with a discussion of questions our work raises for future research.

['Rajkumar|Rajakrishnan|R|', 'van Schijndel|Marten|M|', 'White|Michael|M|', 'Schuler|William|W|']

2016

31178260

Recent advances in biorefinery of astaxanthin from Haematococcus pluvialis.

Haematococcus pluvialis is one of the most abundant sources of natural astaxanthin as compared to others microorganism. Therefore, it is important to understand the biorefinery of astaxanthin from H. pluvialis, starting from the cultivation stage to the downstream processing of astaxanthin. The present review begins with an introduction of cellular morphologies and life cycle of H. pluvialis from green vegetative motile stage to red non-motile haematocyst stage. Subsequently, the conventional biorefinery methods (e.g., mechanical disruption, solvent extraction, direct extraction using vegetable oils, and enhanced solvent extraction) and recent advanced biorefinery techniques (e.g., supercritical CO2 extraction, magnetic-assisted extraction, ionic liquids extraction, and supramolecular solvent extraction) were presented and evaluated. Moreover, future prospect and challenges were highlighted to provide a useful guide for future development of biorefinery of astaxanthin from H. pluvialis. The review aims to serve as a present knowledge for researchers dealing with the bioproduction of astaxanthin from H. pluvialis.

['Khoo|Kuan Shiong|KS|', 'Lee|Sze Ying|SY|', 'Ooi|Chien Wei|CW|', 'Fu|Xiaoting|X|', 'Miao|Xiaoling|X|', 'Ling|Tau Chuan|TC|', 'Show|Pau Loke|PL|']

2019

24094641

Determination of catecholamines in plasma and urine.

For more than 20 years, measurement of catecholamines in plasma and urine in clinical chemistry laboratories has been the cornerstone of the diagnosis of neuroendocrine tumors deriving from the neural crest such as pheochromocytoma (PHEO) and neuroblastoma (NB), and is still used to assess sympathetic stress function in man and animals. Although assay of catecholamines in urine are still considered the biochemical standard for the diagnosis of NB, they have been progressively abandoned for excluding/confirming PHEOs to the advantage of metanephrines (MNs). Nevertheless, catecholamine determinations are still of interest to improve the biochemical diagnosis of PHEO in difficult cases that usually require a clonidine-suppression test, or to establish whether a patient with PHEO secretes high concentrations of catecholamines in addition to metanephrines. The aim of this chapter is to provide an update about the catecholamine assays in plasma and urine and to show the most common pre-analytical and analytical pitfalls associated with their determination.

['Grouzmann|Eric|E|', 'Lamine|Faiza|F|']

2013

34572594

The Effects of Fibrinogen's Interactions with Its Neuronal Receptors, Intercellular Adhesion Molecule-1 and Cellular Prion Protein.

Neuroinflammatory diseases, such as Alzheimer's disease (AD) and traumatic brain injury (TBI), are associated with the extravascular deposition of the fibrinogen (Fg) derivative fibrin and are accompanied with memory impairment. We found that during the hyperfibrinogenemia that typically occurs during AD and TBI, extravasated Fg was associated with amyloid beta and astrocytic cellular prion protein (PrPC). These effects coincided with short-term memory (STM) reduction and neurodegeneration. However, the mechanisms of a direct Fg-neuron interaction and its functional role in neurodegeneration are still unclear. Cultured mouse brain neurons were treated with Fg in the presence or absence of function-blockers of its receptors, PrPC or intercellular adhesion molecule-1 (ICAM-1). Associations of Fg with neuronal PrPC and ICAM-1 were characterized. The expression of proinflammatory marker interleukin 6 (IL-6) and the generation of reactive oxygen species (ROS), mitochondrial superoxide, and nitrite in neurons were assessed. Fg-induced neuronal death was also evaluated. A strong association of Fg with neuronal PrPC and ICAM-1, accompanied with overexpression of IL-6 and enhanced generation of ROS, mitochondrial superoxide, and nitrite as well as the resulting neuronal death, was found. These effects were reduced by blocking the function of neuronal PrPC and ICAM-1, suggesting that the direct interaction of Fg with its neuronal receptors can induce overexpression of IL-6 and increase the generation of ROS, nitrite, and mitochondrial superoxide, ultimately leading to neuronal death. These effects can be a mechanism of neurodegeneration and the resultant memory reduction seen during TBI and AD.

['Sulimai|Nurul|N|', 'Brown|Jason|J|', 'Lominadze|David|D|0000-0002-9911-4539']

2021

32914375

Translation and validation of the Korean version of the Sarcopenia Quality of Life (SarQoL-K®) questionnaire and applicability with the SARC-F screening tool.

PURPOSE The purpose of this paper was to translate and validate into the Korea language and setting the Sarcopenia Quality of Life (SarQoL®) questionnaire. METHODS The participants consisted of 450 individuals in Namgaram-2 cohort who were followed up in 2019-2020. The study participants were divided into four groups: (1) SARC-F < 4, (2) SARC-F ≥ 4 and robust grip strength, (3) SARC-F ≥ 4, low grip strength, robust muscle mass, (4) SARC-F ≥ 4, low grip strength, and low muscle mass. To assess construct validity, population with sarcopenia-associated symptoms (SARC-F ≥ 4) apart from the Korean SarQoL (SarQoL-K®) completed the Korean versions of two generic questionnaires, the Short Form-36 and the EuroQoL 5-dimension. To validate the Korean SarQoL®, we assessed its validity (discriminative power, construct validity), reliability (internal consistency, test-retest reliability), and floor/ceiling effects. RESULTS The SarQoL-K® questionnaire was translated without major difficulties. The mean SarQoL-K scores were 72.9 (95%, CI; 71.2-74.6) in SARC-F < 4, 54.6 (95%, CI; 50.7-58.3) in SARC-F ≥ 4 and robust grip strength, 47.0 (95%, CI; 43.8-50.1) in SARC-F ≥ 4, low grip strength, robust muscle mass, 46.6 (95%, CI; 43.0-50.1) in SARC-F ≥ 4, low grip strength, and low muscle mass. The results indicated good discriminative power across each four groups (p < 0.001), high internal consistency (Cronbach's alpha of 0.866), and excellent test-retest reliability (ICC = 0.977, 95% CI 0.975-0.979). No floor- or ceiling-effects were observed. CONCLUSIONS This is the first study to confirm the reliability and validity of the Korean version of the SarQoL®. We demonstrated that the population with sarcopenia-associated symptoms (determined using the SARC-F questionnaire) has a lower quality of life.

['Yoo|Jun-Il|JI|', 'Ha|Yong-Chan|YC|', 'Kim|Miji|M|', 'Seo|Sung-Hyo|SH|', 'Kim|Mi-Ji|MJ|', 'Lee|Gyeong-Ye|GY|', 'Seo|Young-Mi|YM|', 'Sung|Changsu|C|', 'Park|Ki-Soo|KS|http://orcid.org/0000-0001-5571-3639']

2021

31548896

Anaemia and iron dysregulation: untapped therapeutic targets in chronic lung disease?

Hypoxia is common in many chronic lung diseases. Beyond pulmonary considerations, delivery of oxygen (O2) to the tissues and subsequent O2 utilisation is also determined by other factors including red blood cell mass and iron status; consequently, disruption to these mechanisms provides further physiological strains on an already stressed system. O2 availability influences ventilation, regulates pulmonary blood flow and impacts gene expression throughout the body. Deleterious effects of poor tissue oxygenation include decreased exercise tolerance, increased cardiac strain and pulmonary hypertension in addition to pathophysiological involvement of multiple other organs resulting in progressive frailty. Increasing inspired O2 is expensive, disliked by patients and does not normalise tissue oxygenation; thus, other strategies that improve O2 delivery and utilisation may provide novel therapeutic opportunities in patients with lung disease. In this review, we focus on the rationale and possibilities for doing this by increasing haemoglobin availability or improving iron regulation.

['Patel|Mehul S|MS|0000-0003-0435-858X', 'McKie|Elizabeth|E|', 'Steiner|Michael C|MC|0000-0002-0127-0614', 'Pascoe|Steven J|SJ|', 'Polkey|Michael I|MI|']

2019

33286015

Entropy-Based Measures of Hypnopompic Heart Rate Variability Contribute to the Automatic Prediction of Cardiovascular Events.

Surges in sympathetic activity should be a major contributor to the frequent occurrence of cardiovascular events towards the end of nocturnal sleep. We aimed to investigate whether the analysis of hypnopompic heart rate variability (HRV) could assist in the prediction of cardiovascular disease (CVD). 2217 baseline CVD-free subjects were identified and divided into CVD group and non-CVD group, according to the presence of CVD during a follow-up visit. HRV measures derived from time domain analysis, frequency domain analysis and nonlinear analysis were employed to characterize cardiac functioning. Machine learning models for both long-term and short-term CVD prediction were then constructed, based on hypnopompic HRV metrics and other typical CVD risk factors. CVD was associated with significant alterations in hypnopompic HRV. An accuracy of 81.4% was achieved in short-term prediction of CVD, demonstrating a 10.7% increase compared with long-term prediction. There was a decline of more than 6% in the predictive performance of short-term CVD outcomes without HRV metrics. The complexity of hypnopompic HRV, measured by entropy-based indices, contributed considerably to the prediction and achieved greater importance in the proposed models than conventional HRV measures. Our findings suggest that Hypnopompic HRV assists the prediction of CVD outcomes, especially the occurrence of CVD event within two years.

['Yan|Xueya|X|', 'Zhang|Lulu|L|', 'Li|Jinlian|J|', 'Du|Ding|D|', 'Hou|Fengzhen|F|']

2020

27222027

Occurrence of mycotoxins in refrigerated pizza dough and risk assessment of exposure for the Spanish population.

Mycotoxins are toxic metabolites produced by filamentous fungi, as Aspergillus, Penicillium and Fusarium. The first objective of this research was to study the presence of mycotoxins in 60 samples of refrigerated pizza dough, by extraction with methanol and determination by liquid chromatography associated with tandem mass spectrometry (LC-MS/MS). Then, the estimated dietary intakes (EDIs) of these mycotoxins, among the Spanish population, was calculated and the health risk assessment was performed, comparing the EDIs data with the tolerable daily intake values (TDIs). The mycotoxins detected in the analyzed samples were aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1), zearalenone (ZEA), enniatin A (ENA), enniatin A1 (ENA1), enniatin (ENB), enniatin B1 (ENB1) and BEA (beauvericin) with average concentration of the positive samples of 4.09 μg/kg, 0.50 μg/kg, 0.79 μg/kg, 77.78 μg/kg, 14.96 μg/kg, 4.54 μg/kg, 3.37 μg/kg, 1.69 μg/kg and 22.39 μg/kg, respectively. The presence of ZEA, ENA1, ENB and ENB1 was detected in 100% of the samples, AFB2 in 32%, AFB1 in 23%, ENA in 8% and BEA in 3%. Twelve percent of the samples contaminated with AFB1 and 12% of the doughs contaminated with ZEA exceeded the EU legislated maximum limits. The dietary intakes were estimated considering three different age groups of population, and the EDIs calculated for the mycotoxins detected in the samples were all below the established TDI.

['Quiles|Juan Manuel|JM|', 'Saladino|Federica|F|', 'Mañes|Jordi|J|', 'Fernández-Franzón|Mónica|M|', 'Meca|Giuseppe|G|']

2016

29859372

Hepatoprotective effect of lawsone on rifampicin-isoniazid induced hepatotoxicity in in vitro and in vivo models.

The Drug-induced liver injury is one of the common unfavourable impacts, which seriously affects any drug therapy. This study documented the hepatoprotective efficacy of lawsone, the major bioactive naphthoquinone present in Lawsonia inermis L. (Lythraceae) using in vitro and in vivo models. Lawsone was isolated from the leaves of L. inermis and its structure was confirmed using spectroscopic data. In-vitro antioxidant effect of lawsone was evaluated using ABTS assay. Hepatoprotective effect of lawsone was determined with RIF-INH treated HepG2 cells and Wistar rats. Administration of RIF-INH reduced the viability of the HepG2 cells and the treatment with lawsone significantly restored the viability of the cells even at lower concentration (7.5 μM). The other parameters such as the leakage of transaminases and MDA levels were also significantly reduced by the treatment with lawsone. Oral administration of lawsone to the animals did not show any toxicity up to 2 g/kg b.w. concentration. Treatment with lawsone to the RIF-INH administered animals significantly lowered the serum transaminases levels. The ratio of albumin to globulin was improved and the level of bilirubin was lowered. This study indicated the hepatoprotective effect of lawsone; detailed investigations will give deeper understanding of the application of lawsone for hepatoprotection.

['Darvin|S Sylvester|SS|', 'Esakkimuthu|S|S|', 'Toppo|Erenius|E|', 'Balakrishna|K|K|', 'Paulraj|M Gabriel|MG|', 'Pandikumar|P|P|', 'Ignacimuthu|S|S|', 'Al-Dhabi|N A|NA|']

2018

26695639

Early psychiatrics symptoms in familial Alzheimer's disease with presenilin 1 mutation (I83T).

Several clinical phenotypes were associated with presenilin 1 (PSEN1) mutation in early-onset familial Alzheimer's disease (EOFAD). We report the clinical phenotype of two members of a familial dementia kindred who presented with EOFAD and early psychiatric syndrome as behavioral abnormalities. Sequence analysis of the index patient and his brother's PSEN1 transcript revealed a novel T > C transition in exon 4 which was determined as a missense substitution at position 248 of the coding sequence (cDNA. 248T > C).

['Fray|Saloua|S|', 'Ali|Nadia Ben|NB|', 'Rassas|Afef Achouri|AA|', 'Kechaou|Meriem|M|', 'Oudiaa|Nouria|N|', 'Cherif|Aroua|A|', 'Echebbi|Slim|S|', 'Messaoud|Taieb|T|', 'Belal|Samir|S|']

2016

30950241

Prognostic role of cyclin D2/D3 in multiple human malignant neoplasms: A systematic review and meta-analysis.

Cyclin D2/D3 (CCND2/3) are core components of the machinery that drives cell cycle progression and therefore, are associated with tumorigenesis. Currently, there are contradictory evidences on the function of CCND2/3 in tumorigenesis. Thus, we conducted a comprehensive meta-analysis to derive a precise predictive value of CCND2/3 in various tumors. We searched PubMed, EMBASE, Web of Science for eligible studies up to October 8, 2018. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of OS or DFS/PFS/RFS were calculated using Forest plot analysis to demonstrate their associations. A total of 14 studies were ultimately included in this meta-analysis. Our results indicated CCND2/3 played an oncogenic role in all of the cancer patients (CCND2: pooled HR = 2.21, 95% CI: 1.67-2.93; CCND3: pooled HR = 2.29, 95% CI: 1.05-5.03). In tumor subgroup, CCND2 was associated with shorter OS in patients with gastric cancer (HR = 2.20, 95% CI: 1.66-2.92), whereas it might be a tumor suppressor in NSCLC (HR = 0.28, 95% CI: 0.12-0.64). In addition, CCND3 was correlated to reduced OS in breast cancer patients (HR = 1.64, 95% CI: 1.07-2.52) and shorter DFS/PFS/RFS in bladder cancer patients (HR = 4.60, 95% CI: 1.89-12.57). Taken together, CCND2/3 could be the promising biomarkers for predicting the prognosis of patients with malignant neoplasms.

['Ding|Zuo-You|ZY|', 'Li|Ran|R|', 'Zhang|Qi-Jie|QJ|', 'Wang|Yi|Y|', 'Jiang|Yi|Y|', 'Meng|Qing-Yang|QY|', 'Xi|Qiu-Lei|QL|', 'Wu|Guo-Hao|GH|0000-0001-5146-660X']

2019

27994689

Random Assay in Radioimmunoassay: Feasibility and Application Compared with Batch Assay.

PURPOSE The batch assay has been conventionally used for radioimmunoassay (RIA) because of its technical robustness and practical convenience. However, it has limitations in terms of the relative lag of report time due to the necessity of multiple assays in a small number of samples compared with the random assay technique. In this study, we aimed to verify whether the random assay technique can be applied in RIA and is feasible in daily practice. METHODS The coefficients of variation (CVs) of eight standard curves within a single kit were calculated in a CA-125 immunoradiometric assay (IRMA) for the reference of the practically ideal CV of the CA-125 kit. Ten standard curves of 10 kits from 2 prospectively collected lots (pLot) and 85 standard curves of 85 kits from 3 retrospectively collected lots (Lot) were obtained. Additionally, the raw measurement data of both 170 control references and 1123 patients' sera were collected retrospectively between December 2015 and January 2016. A standard curve of the first kit of each lot was used as a master standard curve for a random assay. The CVs of inter-kits were analyzed in each lot, respectively. All raw measurements were normalized by decay and radioactivity. The CA-125 values from control samples and patients' sera were compared using the original batch assay and random assay. RESULTS In standard curve analysis, the CVs of inter-kits in pLots and Lots were comparable to those within a single kit. The CVs from the random assay with normalization were similar to those from the batch assay in the control samples (CVs % of low/high concentration; Lot1 2.71/1.91, Lot2 2.35/1.83, Lot3 2.83/2.08 vs. Lot1 2.05/1.21, Lot2 1.66/1.48, Lot3 2.41/2.14). The ICCs between the batch assay and random assay using patients' sera were satisfactory (Lot1 1.00, Lot2 0.999, Lot3 1.00). CONCLUSION The random assay technique could be successfully applied to the conventional CA-125 IRMA kits. The random assay showed strong agreement with the batch assay. The random assay procedure could increase the flexibility and decrease the turnaround time of the radioimmunoassay technique.

['Lee|Jung Min|JM|', 'Lee|Hwan Hee|HH|', 'Park|Sohyun|S|', 'Kim|Tae Sung|TS|', 'Kim|Seok-Ki|SK|0000-0002-7512-5567']

2016

32976666

Extrahepatic recurrence rates in patients receiving adjuvant hepatic artery infusion and systemic chemotherapy after complete resection of colorectal liver metastases.

BACKGROUND This study investigated the effect of the reduced dose of systemic chemotherapy (SYS) on recurrence patterns in patients receiving adjuvant hepatic artery infusion (HAI) chemotherapy after complete colorectal liver metastases (CRLM) resection. METHODS Patients undergoing complete CRLM resection between 2000 and 2007 were selected from a prospectively maintained database and categorized as receiving SYS or HAI + SYS. Those with pre and/or intraoperative extrahepatic disease, documented death, or recurrence within 30 days of CRLM resection were excluded. Competing risk, Fine and Gray's tests were used to compare SYS versus HAI + SYS for time-to-organ recurrence. RESULTS Of 361 study patients, 153 (42.4%) received SYS and 208 (57.6%) received HAI + SYS. The median follow-up for survivors was 100 (range = 12-185) and 156 months (range = 18-217) for SYS and HAI + SYS, respectively. The 5-year cumulative incidence (CI) of any liver recurrence was greater for those receiving SYS (SYS = 41.9% vs. HAI + SYS = 28.6%, p = .005). The 5-year CI of developing any lung or extrahepatic recurrence for SYS patients was 36.2% and 47.9% compared with 44.5% (p = .242) and 51.7% (p = .551), respectively, in patients receiving HAI + SYS. CONCLUSION Despite the reduced dose of SYS, adjuvant HAI + SYS after CRLM resection is not associated with a significantly increased risk of extrahepatic recurrence.

['Srouji|Rami M|RM|https://orcid.org/0000-0002-1369-8212', 'Narayan|Raja R|RR|', 'Boerner|Thomas|T|', 'Buisman|Florian E|FE|', 'Seier|Kenneth|K|', 'Gonen|Mithat|M|', 'Balachandran|Vinod P|VP|', 'Drebin|Jeffrey A|JA|', 'Jarnagin|William R|WR|', 'Kingham|T Peter|TP|https://orcid.org/0000-0002-3359-3186', 'Wei|Alice|A|', 'Kemeny|Nancy E|NE|', "D'Angelica|Michael I|MI|"]

2020

32014671

Effect of nano-SiO2 packing on postharvest quality and antioxidant capacity of loquat fruit under ambient temperature storage.

Effect of nano-SiO2 packing on postharvest quality and antioxidant capacity of two different loquat cultivars (white-flesh 'Qingzhong' and red-flesh 'Dawuxing') were determined. Results showed that nano-SiO2 packing significantly inhibited internal browning, retarded the decline of total soluble solids, titratable acidity, ascorbic acid content and extractable juice in both cultivars. Decay index of nano-SiO2 packing in 'Dawuxing' and 'Qingzhong' was 53.25% and 42.84% lower than control after the day 12, respectively. Meanwhile, nano-SiO2 packing enhanced the contents of individual phenolic compounds and soluble sugar compounds, induced higher superoxide dismutase and catalase activities, which contributed to improving 1,1-diphenyl-2-picrylhydrazyl and hydroxyl radical scavenging capacity. Furthermore, the contents of total soluble solids, ascorbic acid and soluble sugar were higher in 'Qingzhong' than those in 'Dawuxing', which dedicated to better quality. These results indicated that nano-SiO2 packing was a promising approach in inhibiting decay, maintaining quality and expanding shelf life of loquats.

['Wang|Li|L|', 'Shao|Shuang|S|', 'Madebo|Million Paulos|MP|', 'Hou|Yuanyuan|Y|', 'Zheng|Yonghua|Y|', 'Jin|Peng|P|']

2020

31813895

Analysis Method of the Ion Current-Time Waveform Obtained from Low Aspect Ratio Solid-state Nanopores.

Low aspect ratio nanopores are expected to be applied to the detection of viruses and bacteria because of their high spatial resolution. Multiphysics simulations have revealed that the ion current-time waveform obtained from low aspect ratio nanopores contains information on not only the volume of viruses and bacteria, but also the structure, surface charge, and flow dynamics. Analysis using machine learning extracts information about these analytes from the ion current-time waveform. The combination of low aspect ratio nanopores, multiphysics simulation, and machine learning has made it possible to distinguish different types of viruses and bacteria with high accuracy.

['Taniguchi|Masateru|M|']

2020

29067240

Benign thyroid disease in pregnancy: A state of the art review.

Thyroid dysfunction is the commonest endocrine disorder in pregnancy apart from diabetes. Thyroid hormones are essential for fetal brain development in the embryonic phase. Maternal thyroid dysfunction during pregnancy may have significant adverse maternal and fetal outcomes such as preterm delivery, preeclampsia, miscarriage and low birth weight. In this review we discuss the effect of thyroid disease on pregnancy and the current evidence on the management of different thyroid conditions in pregnancy and postpartum to improve fetal and neonatal outcomes, with special reference to existing guidelines on the topic which we dissect, critique and compare with each other. Overt hypothyroidism and hyperthyroidism should be treated appropriately in pregnancy, aiming to maintain euthyroidism. Subclinical hypothyroidism is often pragmatically treated with levothyroxine, although it has not been definitively proven whether this alters maternal or fetal outcomes. Subclinical hyperthyroidism does not usually require treatment and the possibility of non-thyroidal illness or gestational thyrotoxicosis should be considered. Autoimmune thyroid diseases tend to improve during pregnancy but commonly flare-up or emerge in the post-partum period. Accordingly, thyroid auto-antibodies tend to decrease with pregnancy progression. Postpartum thyroiditis should be managed based on the clinical symptoms rather than abnormal biochemical results.

['Tingi|Efterpi|E|', 'Syed|Akheel A|AA|', 'Kyriacou|Alexis|A|', 'Mastorakos|George|G|', 'Kyriacou|Angelos|A|']

2016

27207585

Fibroproliferative effect of microRNA-21 in hypertrophic scar derived fibroblasts.

Hypertrophic scar (HS) is a fibroproliferative disorder caused by abnormal wound healing, which is characterized by excessive deposition of extracellular matrix (ECM) secreted by fibroblasts. We previous have found that expression of microRNA-21(miR-21) was increased in tissues and fibroblasts of HS. However, the underlying molecular mechanism remains to be further elucidated. In this study, we identified the miR-21 was a marker for the phenotype of HS fibroblasts, as anti-miR-21 reduced expression of fibrosis markers such as Col1A1, Col3A1, Fn and α-SMA in fibroblasts and overexpression of miR-21 promoted fibroproliferative expression in fibroblasts. Furthermore, we also found that miR-21 promoted TGF-β1 induced fibroproliferative expression by repressing Smad7 expression in vitro. In addition, the miR-21 inhibitor inhibited the growth of hypertrophic scar tissue in vivo (nude mice experimental model). These results indicated that miR-21 was a critical regulator for HS formation and TGF- β1/miR-21/Smad7 pathway could be a useful therapeutic target for the treatment of HS.

['Li|Guangzao|G|', 'Zhou|Renpeng|R|', 'Zhang|Qi|Q|', 'Jiang|Banghong|B|', 'Wu|Qingkai|Q|', 'Wang|Chen|C|']

2016

33694116

Prevalence and concentration of fumonisins in cereal-based foods: a global systematic review and meta-analysis study.

Cereal-based foods are utilized as an essential food segment worldwide. Nevertheless, their contamination by mycotoxins, also fumonisins, could pose a critical health risk. The present research provides the first systematic review regarding the prevalence and concentration of fumonisins in cereal-based food with the aid of a meta-analysis. In this regard, some international databases PubMed, Web of Science, Google Scholar, and Scopus were explored during the last 30 years. Among 9729 screened articles, 73 articles (which meet the proposed inclusion criteria), including 11,132 data, were incorporated in the performed meta-analysis. The overall rank order regarding the concentration of fumonisins in cereal-based foods was corn-based foods > wheat-based foods > other cereal foods > barley-based foods > rice-based foods > oat-based foods. Based on the prevalence of fumonisins, the overall rank order was other cereal foods > corn-based foods > rice-based foods > wheat-based foods > oat-based foods > barley-based food. The present meta-analysis results can be a beneficial database for risk assessment model progress, which can help industries and organizations decrease the presence of fumonisins in cereal-based food.

['Farhadi|Ahmad|A|', 'Fakhri|Yadolah|Y|', 'Kachuei|Reza|R|', 'Vasseghian|Yasser|Y|', 'Huseyn|Elcin|E|', 'Mousavi Khaneghah|Amin|A|http://orcid.org/0000-0001-5769-0004']

2021