bluuebunny/crossref_metadata_2025 huggingface dataset:
Corticolimbic Modulation via Intermittent Theta Burst Stimulation as a Novel Treatment for Functional Movement Disorder: A Proof-of-Concept Study
Authors: Spagnolo Primavera A. , Parker Jacob , Horovitz Silvina , Hallett Mark
Published: June 2021

Neuroimaging studies suggest that corticolimbic dysfunctions, including increased amygdala reactivity to emotional stimuli and heightened fronto-amygdala coupling, play a central role in the pathophysiology of functional movement disorders (FMD). Transcranial magnetic stimulation (TMS) has the potential to probe and modulate brain networks implicated in neuropsychiatric disorders, including FMD. Therefore, the objective of this proof-of-concept study was to investigate the safety, tolerability and preliminary efficacy of fronto-amygdala neuromodulation via targeted left prefrontal intermittent theta burst stimulation (iTBS) on brain and behavioral manifestations of FMD. Six subjects with a clinically defined diagnosis of FMD received three open-label iTBS sessions per day for two consecutive study visits. Safety and tolerability were assessed throughout the trial. Amygdala reactivity to emotionally valenced stimuli presented during an fMRI task and fronto-amygdala connectivity at rest were evaluated at baseline and after each stimulation visit, together with subjective levels of arousal and valence in response to affective stimuli. The FMD symptom severity was assessed at baseline, during treatment and 24 h after the last iTBS session. Multiple doses of iTBS were well-tolerated by all participants. Intermittent TBS significantly decreased fronto-amygdala connectivity and influenced amygdala reactivity to emotional stimuli. These neurocircuitry changes were associated to a marked reduction in FMD symptom severity. Corticolimbic modulation via iTBS represents a promising treatment for FMD that warrants additional research.
The Role of KRAS Mutations in Cortical Malformation and Epilepsy Surgery: A Novel Report of Nevus Sebaceous Syndrome and Review of the Literature
Authors: Pepi Chiara , de Palma Luca , Trivisano Marina , Pietrafusa Nicola , Lepri Francesca Romana , Diociaiuti Andrea , Camassei Francesca Diomedi , Carfi-Pavia Giusy , De Benedictis Alessandro , Rossi-Espagnet Camilla , Vigevano Federico , Marras Carlo Efisio , Novelli Antonio , Bluemcke Ingmar , Specchio Nicola
Published: June 2021

The rare nevus sebaceous (NS) syndrome (NSS) includes cortical malformations and drug-resistant epilepsy. Somatic RAS-pathway genetic variants are pathogenetic in NS, but not yet described within the brain of patients with NSS. We report on a 5-year-old boy with mild psychomotor delay. A brown-yellow linear skin lesion suggestive of NS in the left temporo-occipital area was evident at birth. Epileptic spasms presented at aged six months. EEG showed continuous left temporo-occipital epileptiform abnormalities. Brain MRI revealed a similarly located diffuse cortical malformation with temporal pole volume reduction and a small hippocampus. We performed a left temporo-occipital resection with histopathological diagnosis of focal cortical dysplasia type Ia in the occipital region and hippocampal sclerosis type 1. Three years after surgery, he is seizure-and drug-free (Engel class Ia) and showed cognitive improvement. Genetic examination of brain and skin specimens revealed the c.35G > T (p.Gly12Val) KRAS somatic missense mutation. Literature review suggests epilepsy surgery in patients with NSS is highly efficacious, with 73% probability of seizure freedom. The few histological analyses reported evidenced disorganized cortex, occasionally with cytomegalic neurons. This is the first reported association of a KRAS genetic variant with cortical malformations associated with epilepsy, and suggests a possible genetic substrate for hippocampal sclerosis.
Pupillary Responses to Faces Are Modulated by Familiarity and Rewarding Context
Authors: Matyjek Magdalena , Bayer Mareike , Dziobek Isabel
Published: June 2021

Observing familiar (known, recognisable) and socially relevant (personally important) faces elicits activation in the brain’s reward circuit. Although smiling faces are often used as social rewards in research, it is firstly unclear whether familiarity and social relevance modulate the processing of faces differently, and secondly whether this processing depends on the feedback context, i.e., if it is different when smiles are delivered depending on performance or in the absence of any action (passive viewing). In this preregistered study, we compared pupillary responses to smiling faces differing in subjective familiarity and social relevance. They were displayed in a passive viewing task and in an active task (a speeded visual short-term memory task). The pupils were affected only in the active task and only by subjective familiarity. Contrary to expectations, smaller dilations were observed in response to more familiar faces. Behavioural ratings supported the superior rewarding context of the active task, with higher reward ratings for the game than the passive task. This study offers two major insights. Firstly, familiarity plays a role in the processing of social rewards, as known and unknown faces influence the autonomic responses differently. Secondly, the feedback context is crucial in reward research as positive stimuli are rewarding when they are dependent on performance.
Let Me See: Correlation between 5-ALA Fluorescence and Molecular Pathways in Glioblastoma: A Single Center Experience
Authors: Specchia Francesco Maria Calamo , Monticelli Matteo , Zeppa Pietro , Bianconi Andrea , Zenga Francesco , Altieri Roberto , Pugliese Beatrice , Di Perna Giuseppe , Cofano Fabio , Tartara Fulvio , Bertero Luca , Cassoni Paola , Melcarne Antonio , Lanotte Michele Maria , Garbossa Diego
Published: June 2021

Background: Despite the aggressiveness of multimodal treatment, glioblastoma (GBM) is still a challenge for neurosurgeons, neurooncologists, and radiotherapists. A surgical approach is still a cornerstone in GBM therapeutic management, as the extent of resection is strongly related both to overall survival and progression-free survival. From this perspective, the use of photodynamic molecules could represent an interesting tool to achieve maximal and safe resection. Being able to trace the lesion’s edges, indeed, could allow to improve the extent of resection and to minimize residual tumor while sparing normal tissue. The use of 5-aminolevulinic acid (5-ALA) as a photodynamic tracer is well established due to its strict correlation both with cellularity and metabolic activity of the GBM cell clones. Objective: Our study aims to define whether a different molecular asset of GBM (especially investigating IDH 1/2 mutation, proliferation index, and MGMT promoter methylation) results in different fluorescence expression, possibly because of differences in metabolic pathways due to different genotypes. Methods: Patients undergoing surgery for GBM removal at our Institute (Dep. Of Neurosurgery, Ospedale Città della Salute e della Scienza, University of Turin, Italy) were retrospectively reviewed. Patients with histological diagnosis confirmation and to whom 5-ALA was given before surgery were included. The whole surgical procedure was recorded and then analyzed by three different people (a medical student, a resident, and a senior surgeon with an interest in neurooncology and experience in using 5-ALA) and a score was assigned to the different degrees of intraoperative fluorescence. The degree of fluorescence was then matched with the genotype. Results: A trend of grade 2 fluorescence (i.e., ”strong”) was observed in the IDH 1/2 wild-type (WT) genotype, suggesting a more intense metabolic activity in this particular subgroup, while, no or weak fluorescence was observed more often in the IDH 1/2 mutated tumors, suggesting a lower metabolic activity. No relations were found between fluorescence grade and MGMT promoter methylation or, interestingly, cellularity. As a secondary analysis, more epileptogenicity of the IDH 1/2 mutated GBM was noticed, similarly to other recent literature. Conclusion: Our results do not support the use of 5-ALA as a diagnostic tool, or a way to substitute the molecular profiling, but confirm 5-ALA as a powerful metabolic tracer, able to easily detect the pathological cells, especially in the IDH WT genotype, and in this perspective, further studies will be necessary to better describe the metabolic activity of GBM cells.
An Integrative Review Considering the Impact of Storytelling and Sharing Interventions in Stroke
Authors: Alawafi Rana , Rosewilliam Sheeba , Soundy Andrew
Published: June 2021

Background: Review-based research is needed which can establish the psychosocial outcomes and mechanisms of “storytelling and sharing” interventions for people with stroke. This information will act to inform the value and development of such interventions. Methods: An integrative review was conducted in three stages: (a) a systematic search strategy was undertaken to focus on articles between 2009 until January 2020 to locate articles the considered storytelling and sharing interventions for people diagnosed with stroke; (b) critical appraisal was undertaken to assess study quality; and (c) synthesis within three stages including data reduction, data display and conclusion. Results: Fourteen articles (including 727 participants) were identified that met the eligibility criteria. Five themes were identified that represented the outcome and mechanisms that appeared to be associated with a stroke intervention. These included introducing the concept of hope and learning to be positive, the enhanced ability to cope, the impact of loneliness and social interaction, impact on emotions, depression and related emotions such as fear. Conclusions: Storytelling interventions appear to impact loneliness, introduce positivity and hope and enable coping through knowledge exchange. The main mechanisms which appeared to influence these outcomes were social comparisons and social control.
DLX Genes: Roles in Development and Cancer
Authors: Tan Yinfei , Testa Joseph R.
Published: June 2021

Homeobox genes control body patterning and cell-fate decisions during development. The homeobox genes consist of many families, only some of which have been investigated regarding a possible role in tumorigenesis. Dysregulation of HOX family genes have been widely implicated in cancer etiology. DLX homeobox genes, which belong to the NK-like family, exert dual roles in development and cancer. The DLX genes are the key transcription factors involved in regulating the development of craniofacial structures in vertebrates. The three DLX bigenes have overlapping expression in the branchial arches. Disruption of DLX function has destructive consequences in organogenesis and is associated with certain congenital disorders in humans. The role of DLX genes in oncogenesis is only beginning to emerge. DLX2 diminishes cellular senescence by regulating p53 function, whereas DLX4 has been associated with metastasis in breast cancer. In human ovarian cancer cells, DLX5 is essential for regulating AKT signaling, thereby promoting cell proliferation and survival. We previously implicated Dlx5 as an oncogene in murine T-cell lymphoma driven by a constitutively active form of Akt2. In this mouse model, overexpression of Dlx5 was caused by a chromosomal rearrangement that juxtaposed the Tcr-beta promoter region near the Dlx5 locus. Moreover, transgenic mice overexpressing Dlx5, specifically in immature T-cells, develop spontaneous thymic lymphomas. Oncogenesis in this mouse model involves binding of Dlx5 to the Notch1 and Notch3 gene loci to activate their transcription. Dlx5 also cooperates with Akt signaling to accelerate lymphomagenesis by activating Wnt signaling. We also discuss the fact that human DLX5 is aberrantly expressed in several human malignancies.
Sensitivity and Specificity of Human Papillomavirus (HPV) 16 Early Antigen Serology for HPV-Driven Oropharyngeal Cancer: A Systematic Literature Review and Meta-Analysis
Authors: Hibbert Julia , Halec Gordana , Baaken Dan , Waterboer Tim , Brenner Nicole
Published: June 2021

Antibodies against HPV16 early proteins have been shown to be promising biomarkers for the identification of HPV-driven oropharyngeal cancer (HPV-OPC) among OPC cases in multiple studies. A systematic literature search was performed to identify original research articles comparing HPV early antigen serology with established reference methods to determine molecular HPV tumor status. Random-effects models were used to calculate summary estimates for sensitivity and specificity of HPV16 E2, E6 and E7 serology for HPV-OPC. Subgroup analyses were performed to explore heterogeneity across studies and describe variables associated with test performance. We identified n = 23 studies meeting all eligibility criteria and included these in the meta-analysis. E6 serology showed the best performance with pooled sensitivity and specificity estimates of 83.1% (95% confidence interval (CI) 72.5–90.2%) and 94.6% (95% CI 89.0–97.4%), respectively, while E2 and E7 serological assays were highly specific (E2: 92.5% (95% CI 79.1–97.6%); E7: 88.5% (95% CI 77.9–94.4%)) but moderately sensitive (E2: 67.8% (95% CI 58.9–75.6%); E7: 67.0% (95% CI 63.2–70.6%)). Subgroup analyses revealed increased pooled sensitivity for bacterially (89.9% (95% CI 84.5–93.6%)) vs. in vitro expressed E6 antigen (55.3% (95% CI 41.0–68.7%)), while both showed high specificity (95.2% (95% CI 93.0–96.7%) and 91.1% (95% CI 46.6–99.2%), respectively). Pooled specificity estimates for HPV16 E2, E6 and E7 serology were significantly lower in studies utilizing HPV DNA PCR as the only molecular reference method compared to those using a combination of any two reference methods (HPV DNA, RNA, in situ hybridization (ISH), p16 immunohistochemistry (IHC)), or histopathological reference methods (ISH or p16 IHC) as stand-alone marker. In conclusion, HPV16 E6 seropositivity is a highly sensitive and specific biomarker for HPV-OPC. However, its performance differs between serological assays and depends on molecular reference methods.
Albumin-Based Nanoparticles for the Delivery of Doxorubicin in Breast Cancer
Authors: Prajapati Rama , Garcia-Garrido Eduardo , Somoza Álvaro
Published: June 2021

Albumin-based nanoparticles are an emerging platform for the delivery of various chemotherapeutics because of their biocompatibility, safety, and ease of surface modification for specific targeting. The most widely used method for the preparation of albumin nanoparticles is by desolvation process using glutaraldehyde (GLU) as a cross-linker. However, limitations of GLU like toxicity and interaction with drugs force the need for alternative cross-linkers. In the present study, several cross-linking systems were evaluated for the preparation of Bovine Serum Albumin (BSA) nanoparticles (ABNs) encapsulating Doxorubicin (Dox). Based on the results obtained from morphological characterization, in vitro release, and therapeutic efficacy in cells, N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP)-modified ABNs (ABN-SPDP) was chosen. Since ABN-SPDP are formed with disulfide linkage, the drug release is facilitated under a highly reducing environment present in the tumor sites. The cytotoxicity studies of those ABN-SPDP were performed in three different breast cell lines, highlighting the mechanism of cell death. The Dox-encapsulated ABN-SPDP showed toxicity in both the breast cancer cells (MCF-7 and MDA-MB-231), but, remarkably, a negligible effect was observed in non-tumoral MCF-10A cells. In addition to the hydrophilic Dox, this system could be used as a carrier for hydrophobic drugs like SN38. The system could be employed for the preparation of nanoparticles based on human serum albumin (HSA), which further enhances the feasibility of this system for clinical use. Hence, the albumin nanoparticles developed herein present an excellent potential for delivering various drugs in cancer therapy.
Research Progress in Enzymatic Synthesis of Vitamin E Ester Derivatives
Authors: Zou Zhiqiang , Dai Lingmei , Liu Dehua , Du Wei
Published: June 2021

Vitamin E is easily oxidized by light, air, oxidizing agents and heat, limiting its application in many ways. Compared to vitamin E, vitamin E ester derivatives exhibit improved stability and a stronger antioxidant capacity, and even gain new biological functions. In recent years, enzymatic synthesis of vitamin E ester derivatives has received increasing attention due to its environmental friendliness, high catalytic efficiency, and inherent selectivity. This paper reviews the related progress of lipase-mediated preparation of vitamin E ester derivatives. The function of different vitamin E ester derivatives, and the main factors influencing the enzymatic acylation process, including enzyme species, acyl donor and acceptor, reaction media and water activity, are summarized in this paper. Finally, the perspective of lipase-catalyzed synthesis of vitamin E ester derivatives is also discussed.
Statistical Approach to Incorporating Experimental Variability into a Mathematical Model of the Voltage-Gated Na+ Channel and Human Atrial Action Potential
Authors: Gratz Daniel , Winkle Alexander J , Weinberg Seth H , Hund Thomas J
Published: June 2021

The voltage-gated Na+ channel Nav1.5 is critical for normal cardiac myocyte excitability. Mathematical models have been widely used to study Nav1.5 function and link to a range of cardiac arrhythmias. There is growing appreciation for the importance of incorporating physiological heterogeneity observed even in a healthy population into mathematical models of the cardiac action potential. Here, we apply methods from Bayesian statistics to capture the variability in experimental measurements on human atrial Nav1.5 across experimental protocols and labs. This variability was used to define a physiological distribution for model parameters in a novel model formulation of Nav1.5, which was then incorporated into an existing human atrial action potential model. Model validation was performed by comparing the simulated distribution of action potential upstroke velocity measurements to experimental measurements from several different sources. Going forward, we hope to apply this approach to other major atrial ion channels to create a comprehensive model of the human atrial AP. We anticipate that such a model will be useful for understanding excitability at the population level, including variable drug response and penetrance of variants linked to inherited cardiac arrhythmia syndromes.
Mapping Surface Charge Distribution of Single-Cell via Charged Nanoparticle
Authors: Ouyang Leixin , Shaik Rubia , Xu Ruiting , Zhang Ge , Zhe Jiang
Published: June 2021

Many bio-functions of cells can be regulated by their surface charge characteristics. Mapping surface charge density in a single cell’s surface is vital to advance the understanding of cell behaviors. This article demonstrates a method of cell surface charge mapping via electrostatic cell–nanoparticle (NP) interactions. Fluorescent nanoparticles (NPs) were used as the marker to investigate single cells’ surface charge distribution. The nanoparticles with opposite charges were electrostatically bonded to the cell surface; a stack of fluorescence distribution on a cell’s surface at a series of vertical distances was imaged and analyzed. By establishing a relationship between fluorescent light intensity and number of nanoparticles, cells’ surface charge distribution was quantified from the fluorescence distribution. Two types of cells, human umbilical vein endothelial cells (HUVECs) and HeLa cells, were tested. From the measured surface charge density of a group of single cells, the average zeta potentials of the two types of cells were obtained, which are in good agreement with the standard electrophoretic light scattering measurement. This method can be used for rapid surface charge mapping of single particles or cells, and can advance cell-surface-charge characterization applications in many biomedical fields.
Cross-Cultural Adaptation of the Brazilian Portuguese-Translated Version of the Mini Sarcopenia Risk Assessment (MSRA) Questionnaire in Cancer Patients
Authors: Ribeiro Lays S. , Souza Bárbarah G. de A. , de Lima Juliana B. , Pimentel Gustavo D.
Published: June 2021

Background and Aims: This study sought (i) to adapt cross-culturally the Brazilian Portuguese-translated version of the MSRA questionnaire, (ii) to estimate the prevalence of risk of sarcopenia, and (iii) to correlate the MSRA Portuguese version with CC in hospitalized cancer patients. Methods: This was a cross-sectional study developed at the hospital in the year 2018. After being translated and adapted to the Portuguese language, the questionnaire was applied and associated with the measurement of calf circumference (CC) to verify its validity. Results: Of the 45 patients, 71.1% presented significant or severe body weight loss, and 55.5% indicated muscle mass loss (CC < 31 cm). From the MSRA of seven and five items, 91.1 and 84.5% of the patients, respectively, presented risk for sarcopenia. Among those at risk for sarcopenia, more than 60% were aged <70 years, >80% were hospitalized in the last year, more than 40% could not walk > 1000 m, >40% did not eat regularly, and >80% lost >2 kg in the last year. CC was correlated with MSRA of five items (r = 0.46, p = 0.001) and seven items (r = 0.53, p = 0.0002). Furthermore, both versions of the MSRA (seven and five items) presented strong agreement and high reliability. Conclusions: The MSRA full and short version was adapted for a Brazilian Portuguese-translated version and showed strong agreement and high reliability to identify the risk for sarcopenia in hospitalized cancer patients. Therefore, this questionnaire can be used as part of nutritional assessment protocols in order to enable early screening of the risk for sarcopenia
MOCVD Growth of GeTe/Sb2Te3 Core–Shell Nanowires
Authors: Kumar Arun , Cecchini Raimondo , Wiemer Claudia , Mussi Valentina , De Simone Sara , Calarco Raffaella , Scuderi Mario , Nicotra Giuseppe , Longo Massimo
Published: June 2021

We report the self-assembly of core–shell GeTe/Sb2Te3 nanowires (NWs) on Si (100), and SiO2/Si substrates by metalorganic chemical vapour deposition, coupled to the vapour–liquid–solid mechanism, catalyzed by Au nanoparticles. Scanning electron microscopy, X-ray diffraction, micro-Raman mapping, high-resolution transmission electron microscopy, and electron energy loss spectroscopy were employed to investigate the morphology, structure, and composition of the obtained core and core–shell NWs. A single crystalline GeTe core and a polycrystalline Sb2Te3 shell formed the NWs, having core and core–shell diameters in the range of 50–130 nm and an average length up to 7 µm.
Effects of Organic Solvent on Curing Behavior and Storage Stability for Waterborne Paint Containing Catalyst Encapsulated in Micelles
Authors: Yomo Shuji
Published: June 2021

In this study, a 2-pack isocyanate curing waterborne paint (without organic solvents) encapsulating dibutyltin dilaurate (hereinafter, DBTL) in nonionic surfactant micelles with an hydrophilic–lipophilic balance of 13–14 in advance releases DBTL when the micelles are collapsed at 80 °C or higher, whereby the curing progresses rapidly. On the other hand, the viscosity levels of the paint before and after being left at 40 °C for 1 h are almost the same. Organic solvents are mandatory for waterborne paints to provide paint and film properties, but they might collapse the micelles when they are formulated in the paint. In this study, we investigate whether the abovementioned paint containing organic solvents can develop switching functionality in terms of maintaining the storage stability at 40 °C and expressing a catalytic function at 80 °C to progress the curing. As a result, we find that if the solubility of the organic solvent in water at 20 °C is at least 10 g/100 mL and the boiling point is ≤200 °C, both curing and storage stability can be achieved.
A Comprehensive Study of Al0.6Ti0.4N Coatings Deposited by Cathodic Arc and HiPIMS PVD Methods in Relation to Their Cutting Performance during the Machining of an Inconel 718 Alloy
Authors: Reolon Luca W. , Aguirre Myriam H. , Yamamoto Kenji , Zhao Qinfu , Zhitomirsky Igor , Fox-Rabinovich German , Veldhuis Stephen Clarence
Published: June 2021

The structural, physical–chemical, and micromechanical characteristics of Al0.6Ti0.4N coatings deposited by different physical vapor deposition (PVD) methods, such as cathodic arc deposition (CAD), as well as advanced HiPIMS techniques were investigated in terms of their cutting performance during the machining of an Inconel 718 alloy. XRD studies had revealed that the HiPIMS coating featured lower residual stresses and more fine-grained structure. Electrochemical characterization with the potentiostat-impendence method shows that the HiPIMS coating has a significantly lower porosity than CAD. SEM and AFM studies of the surface morphology demonstrate that the HiPIMS coating has a smoother surface and an absence of droplet phases, in contrast with CAD. XRD, combined with FIB/TEM studies, shows a difference in the crystal structure of both coatings. The micromechanical characteristics of each coating, such as hardness, elastic modulus, fracture toughness, and adhesion to the substrate, were evaluated. The HiPIMS coating was found to possess a more beneficial combination of micromechanical properties compared to CAD. The beneficial characteristics of the HiPIMS coating alleviated the damage of the coated layer under operation. Combined with grain size refinement, this results in the improved adaptive performance of the HiPIMS coating through the formation of a greater amount of thermal barrier sapphire tribo-films on the friction surface. All of these characteristics contribute to the reduction of flank and crater wear intensity, as well as notching, leading to an improvement of the HiPIMS coating’s tool life.
Molecular Survey of Pathogens in Wild Amazon Parrot Nestlings: Implications for Conservation
Authors: Vaz Frederico Fontanelli , Sipinski Elenise Angelotti Bastos , Seixas Gláucia Helena Fernandes , Prestes Nêmora Pauletti , Martinez Jaime , Raso Tânia Freitas
Published: June 2021

South America presents the greatest Psittacidae diversity in the world, but also has the highest numbers of threatened parrot species. Recently, exotic viruses have been detected in captive native psittacine birds in Brazil, however, their impacts on the health of wild parrots are still unknown. We evaluated the presence of Chlamydia psittaci, Psittacid alphaherpesvirus 1 (PsHV-1), avipoxvirus and beak and feather disease virus (BFDV) in wild Amazona aestiva, A. brasiliensis and A. pretrei nestlings and in wild caught A. aestiva nestlings seized from illegal trade. Samples were collected from 205 wild nestlings and 90 nestlings from illegal trade and pathogen-specific PCR was performed for each sample. Chlamydia DNA prevalence was 4.7% in A. aestiva and 2.5% in A. brasiliensis sampled from the wild. Sequencing revealed that the C. psittaci sample belonged to the genotype A. PsHV-1, avipoxvirus and BFDV DNA was not detected. These results have conservation implications since they suggest that wild parrot populations have a low prevalence of the selected pathogens and, apparently, they were not reached by the exotic BFDV. Stricter health protocols should be established as condition to reintroduction of birds to the wild to guarantee the protection of Neotropical parrots.
The Evaluation of Left Ventricle Ischemic Extent in Patients with Significantly Suspicious Cardiovascular Disease by 99mTc-Sestamibi Dynamic SPECT/CT and Myocardial Perfusion Imaging: A Head-to-Head Comparison
Authors: Chan Hung-Pin , Chang Chin-Chuan , Hu Chin , Wang Wen-Hwa , Peng Nan-Jing , Tyan Yu-Chang , Yang Ming-Hui
Published: June 2021

Heart disease is the second most common cause of mortality in Taiwan, mainly coronary artery disease (CAD).Quantitative coronary blood flow has been collected by dynamic single-photon emission computed tomography (Dynamic SPECT/CT) for CAD diagnosis in previous studies. However, few studies defined the extent of left ventricle (LV) ischemia on Dynamic SPECT/CT for predicting significant coronary artery stenosis. This study evaluates the extent of LV ischemic blockage in patients suspected of CAD who were referred by cardiologists. A total of 181 patients with suspected CAD were enrolled. They underwent 99mTc-Sestamibi (MIBI) Dynamic SPECT/CT survey before cardiac intervention. Dynamic SPECT/CT has better sensitivity (88%), specificity (96%), and accuracy (94%) compared with those of semi-quantitative MIBI MPI (more than 10%). Results indicated that5% of the LV ischemic extent can yield positive PCI results (>70% stenosis in coronary arteries) compared with the moderate abnormal extent of at least 15% of LV. When the percentage of combined moderate abnormal extent and ischemia extent of LV reaches 27.3%, positive PCI results may be indicated. This study revealed Dynamic SPECT/CT has greater sensitivity, specificity, and accuracy as compared with MPI. Thus, the severity of abnormal perfusion extent of LV on Dynamic SPECT/CT might be beneficial to predict positive PCI results in patients with significant suspicion CAD.
Microstructural MRI Correlates of Cognitive Impairment in Multiple Sclerosis: The Role of Deep Gray Matter
Authors: Pitteri Marco , Galazzo Ilaria Boscolo , Brusini Lorenza , Cruciani Federica , Dapor Caterina , Marastoni Damiano , Menegaz Gloria , Calabrese Massimiliano
Published: June 2021

Although cognitive impairment (CI) is frequently observed in people with multiple sclerosis (pwMS), its pathogenesis is still controversial. Conflicting results emerged concerning the role of microstructural gray matter (GM) damage especially when involving the deep GM structures. In this study, we aimed at evaluating whether differences in cortical and deep GM structures between apparently cognitively normal (ACN) and CI pwMS (36 subjects in total) are present, using an extensive set of diffusion MRI (dMRI) indices and conventional morphometry measures. The results revealed increased anisotropy and restriction over several deep GM structures in CI compared with ACN pwMS, while no changes in volume were present in the same areas. Conversely, reduced anisotropy/restriction values were detected in cortical regions, mostly the pericalcarine cortex and precuneus, combined with reduced thickness of the superior frontal gyrus and insula. Most of the dMRI metrics but none of the morphometric indices correlated with the Symbol Digit Modality Test. These results suggest that deep GM microstructural damage can be a strong anatomical substrate of CI in pwMS and might allow identifying pwMS at higher risk of developing CI.
Effects of Topography on Planted Trees in a Headwater Catchment on the Chinese Loess Plateau
Authors: Luo Da , Jin Zhao , Yu Yunlong , Chen Yiping
Published: June 2021

The Chinese Loess Plateau (CLP) is known for its complex topography of hills and gullies, and lots of human land-use management activities have been put into practice to sustain the soil, water and other natural resources. Afforestation has been widely applied on the CLP and it’s important to understand the effects of topography on these planted trees. However, the coarse spatial resolution of remote sensing data makes it insensitive to local topography, and the traditional in-situ measurements would consume vast amounts of time and resources. In this study, a small headwater catchment of the CLP was selected to study the effects of topography on the planted trees. Low altitude unmanned aerial vehicle based light detection and ranging (UAV-based LiDAR) technology was utilized to obtain high-resolution topography and vegetation structure data. Results showed that the middle transition zone (mid-transition, slope > 45°) was an important boundary of topography in the gully area of the CLP. In the forested catchment, the area of the mid-transition zone had the lowest of tree density, canopy coverage and leaf area index due to steep slope gradient. The tall trees ten to twenty meters high were concentrated in the downhill area, which had the highest canopy coverage and leaf area index. Elevation had significant linear relationships with canopy coverage and leaf area index (p < 0.001), which revealed the impact of topography on the forest indexes of the afforestation catchment. We concluded that the high-resolution LiDAR technology facilitated the research of topography and forest interactions in land surface.
New RAD51 Inhibitors to Target Homologous Recombination in Human Cells
Authors: Shkundina Irina S. , Gall Alexander A. , Dick Alexej , Cocklin Simon , Mazin Alexander V.
Published: June 2021

Targeting DNA repair proteins with small-molecule inhibitors became a proven anti-cancer strategy. Previously, we identified an inhibitor of a major protein of homologous recombination (HR) RAD51, named B02. B02 inhibited HR in human cells and sensitized them to chemotherapeutic drugs in vitro and in vivo. Here, using a medicinal chemistry approach, we aimed to improve the potency of B02. We identified the B02 analog, B02-isomer, which inhibits HR in human cells with significantly higher efficiency. We also show that B02-iso sensitizes triple-negative breast cancer MDA-MB-231 cells to the PARP inhibitor (PARPi) olaparib.
Edible Insects and Sustainable Development Goals
Authors: Moruzzo Roberta , Mancini Simone , Guidi Alessandra
Published: June 2021

The insect sector can become an important component of sustainable circular agriculture by closing nutrient and energy cycles, fostering food security, and minimising climate change and biodiversity loss, thereby contributing to SDGs. The high levels of the interaction of the insect sector with the SDGs is clearly illustrated inside the review, analysing all of the SDGs that can have direct and indirect effects on insects. Mapping the interactions between the SDGs goals and insect sector offers a starting point, from which it could be possible to define practical next steps for better insect policy.
Identification of 35 C-Type Lectins in the Oriental Armyworm, Mythimna separata (Walker)
Authors: Li Hao , Liu Fang-Fang , Fu Li-Qing , Liu Ze , Zhang Wen-Ting , Wang Qian , Rao Xiang-Jun
Published: June 2021

Insect C-type lectins (CTLs) play vital roles in modulating humoral and cellular immune responses. The oriental armyworm, Mythimna separata (Walker) (Lepidoptera: Noctuidae) is a migratory pest that causes significant economic loss in agriculture. CTLs have not yet been systematically identified in M. separata. In this study, we first constructed a transcriptome of M. separata larvae, generating a total of 45,888 unigenes with an average length of 910 bp. Unigenes were functionally annotated in six databases: NR, GO, KEGG, Pfam, eggNOG, and Swiss-Prot. Unigenes were enriched in functional pathways, such as those of signal transduction, endocrine system, cellular community, and immune system. Thirty-five unigenes encoding C-type lectins were identified, including CTL-S1~CTL-S6 (single CRD) and IML-1~IML-29 (dual CRD). Phylogenetic analyses showed dramatic lineage-specific expansions of IMLs. Sequence alignment and structural modeling identified potential ligand-interacting residues. Real-time qPCR revealed that CTL-Ss mainly express in eggs and early stage larvae, while IMLs mainly express in mid-late-stage larvae, pupae, and adults. In naïve larvae, hemocytes, fat body, and epidermis are the major tissues that express CTLs. In larvae challenged by Escherichia coli, Staphylococcus aureus, or Beauveria bassiana, the expression of different CTLs was stimulated in hemocytes, fat body and midgut. The present study will help further explore functions of M. separata CTLs.
Comparison of Effectiveness Using Different Dual Bronchodilator Agents in Chronic Obstructive Pulmonary Disease Treatment
Authors: Cheng Shih-Lung
Published: June 2021

The effectiveness and safety of fixed dual long-acting bronchodilators for chronic obstructive pulmonary disease (COPD) patients have been well established; however, there is a paucity of clinical effectiveness comparison in patients with COPD treatment. The aim of the current study was to compare the effectiveness of three once-daily dual bronchodilator agents in patients with COPD. Patients with diagnosed COPD and treated with a long-acting beta-agonist (LABA) + long-acting muscarinic antagonist (LAMA) fixed-dose combination therapy (UME/VIL (umeclidinium and vilanterol inhalation powder), IND/GLY (indacaterol and glycopyrronium), and TIO/OLO (tiotropium and olodaterol)) were enrolled in this retrospective study over a period of 12 months. Effectiveness assessments were evaluated using a COPD assessment test (CAT) and lung function parameters. Besides, times for acute exacerbation were also assessed. The enrolled patients’ number was 177 in IND/GLY, 176 in UME/VIL and 183 in TIO/OLO. Lung function measurements with FEV1 had significantly improved for patients using TIO/OLO (98.7 mL) compared to those of IND/GLY (65.2 mL) and UME/VIL (64.4 mL) (p < 0.001). CAT scores were also significantly decreased in patients treated with TIO/OLO (CAT down 5.6) than those with IND/GLY (3.8) and UME/VIL (3.9) (p = 0.03). Acute exacerbation was also reduced in patients using TIO/OLO (4.9%) compared with those using IND/GLY (10.2%) and UME/VIL (11.9%) (p = 0.01). Significant improvement in pulmonary function, symptoms were demonstrated after 12 months of LABA/LAMA fixed-dose combination therapy with three different treatment options. TIO/OLO demonstrated higher therapeutic effects compared with UME/VIL or IND/GLY. Determining clinical relevance will require a well-designed randomized controlled trial.
The Spectrum of Central Choriocapillaris Abnormalities on Swept-Source Optical Coherence Tomography Angiography in the Fellow Eye of Unilateral Exudative Age-Related Macular Degeneration Patients: From Flow Deficits to Subclinical Non-Exudative Neovascularization
Authors: Khorrami Kashi Alexis , Souied Eric , Fares Selim , Borrelli Enrico , Capuano Vittorio , Jung Camille , Querques Giuseppe , Mouallem Alexandra , Miere Alexandra
Published: June 2021

We evaluated the spectrum of choriocapillaris (CC) abnormalities in the fellow eyes of unilateral exudative age-related macular degeneration (AMD) patients using swept-source optical coherence tomography angiography (SS-OCTA). Fellow eyes of unilateral exudative AMD patients were prospectively included between May 2018 and October 2018. Patients underwent a multimodal imaging including a SS-OCTA. Demographics and clinical findings were analyzed. The estimated prevalence of macular neovascularization (MNV) was computed. Number and size of flow deficits (FDs) and percentage of flow deficits (FD%) were computed on the compensated CC flow images with the Fiji software. We included 97 eyes of 97 patients (mean age was 80 ± 7.66 years, 39 males, 58 females). The prevalence of MNV in the studied eyes was 8.25% (8/97 eyes). In the 89 non-neovascular eyes, FD% averaged 45.84% ± 11.63%, with a corresponding total area of FDs of 4.19 ± 1.12 mm2. There was a higher prevalence of drusenoid pigment epithelial detachment in eyes with subclinical neovascularization (p = 0.021). Fellow eyes with unilateral exudative AMD encompassed a series of CC abnormalities, from FDs of the aging CC to subclinical non-exudative MNV.
Severe COVID-19 in Hospitalized Carriers of Single CFTR Pathogenic Variants
Authors: Baldassarri Margherita , Fava Francesca , Fallerini Chiara , Daga Sergio , Benetti Elisa , Zguro Kristina , Amitrano Sara , Valentino Floriana , Doddato Gabriella , Giliberti Annarita , Di Sarno Laura , Palmieri Maria , Carriero Miriam , Alaverdian Diana , Beligni Giada , Iuso Nicola , Castelli Francesco , Quiros-Roldan Eugenia , Mondelli Mario , Miceli Rosalba , Frullanti Elisa , Furini Simone , Mari Francesca , Renieri Alessandra , Gabbi Chiara ,   on behalf of the GEN-COVID Multicenter Study
Published: June 2021

The clinical presentation of COVID-19 is extremely heterogeneous, ranging from asymptomatic to severely ill patients. Thus, host genetic factors may be involved in determining disease presentation and progression. Given that carriers of single cystic fibrosis (CF)-causing variants of the CFTR gene—CF-carriers—are more susceptible to respiratory tract infections, our aim was to determine their likelihood of undergoing severe COVID-19. We implemented a cohort study of 874 individuals diagnosed with COVID-19, during the first pandemic wave in Italy. Whole exome sequencing was performed and validated CF-causing variants were identified. Forty subjects (16 females and 24 males) were found to be CF-carriers. Among mechanically ventilated patients, CF-carriers were more represented (8.7%) and they were significantly (p < 0.05) younger (mean age 51 years) compared to noncarriers (mean age 61.42 years). Furthermore, in the whole cohort, the age of male CF-carriers was lower, compared to noncarriers (p < 0.05). CF-carriers had a relative risk of presenting an abnormal inflammatory response (CRP ≥ 20 mg/dL) of 1.69 (p < 0.05) and their hazard ratio of death at day 14 was 3.10 (p < 0.05) in a multivariate regression model, adjusted for age, sex and comorbidities. In conclusion, CF-carriers are more susceptible to the severe form of COVID-19, showing also higher risk of 14-day death.
Enhanced Anticancer Activity of Nanoformulation of Dasatinib against Triple-Negative Breast Cancer
Authors: Bahman Fatemah , Pittalà Valeria , Haider Mohamed , Greish Khaled
Published: June 2021

Triple negative breast cancer (TNBC) is the most aggressive breast cancer accounting for around 15% of identified breast cancer cases. TNBC lacks human epidermal growth factor receptor 2 (HER2) amplification, is hormone independent estrogen (ER) and progesterone receptors (PR) negative, and is not reactive to current targeted therapies. Existing treatment relies on chemotherapeutic treatment, but in spite of an initial response to chemotherapy, the inception of resistance and relapse is unfortunately common. Dasatinib is an approved second-generation inhibitor of multiple tyrosine kinases, and literature data strongly support its use in the management of TNBC. However, dasatinib binds to plasma proteins and undergoes extensive metabolism through oxidation and conjugation. To protect dasatinib from fast pharmacokinetic degradation and to prolong its activity, it was encapsulated on poly(styrene-co-maleic acid) (SMA) micelles. The obtained SMA–dasatinib nanoparticles (NPs) were evaluated for their physicochemical properties, in vitro antiproliferative activity in different TNBC cell lines, and in vivo anticancer activity in a syngeneic model of breast cancer. Obtained results showed that SMA–dasatinib is more potent against 4T1 TNBC tumor growth in vivo compared to free drug. This enhanced effect was ascribed to the encapsulation of the drug protecting it from a rapid metabolism. Our finding highlights the often-overlooked value of nanoformulations in protecting its cargo from degradation. Overall, results may provide an alternative therapeutic strategy for TNBC management.
Personalized Genetic Diagnosis of Congenital Heart Defects in Newborns
Authors: Diz Olga María , Toro Rocio , Cesar Sergi , Gomez Olga , Sarquella-Brugada Georgia , Campuzano Oscar
Published: June 2021

Congenital heart disease is a group of pathologies characterized by structural malformations of the heart or great vessels. These alterations occur during the embryonic period and are the most frequently observed severe congenital malformations, the main cause of neonatal mortality due to malformation, and the second most frequent congenital malformations overall after malformations of the central nervous system. The severity of different types of congenital heart disease varies depending on the combination of associated anatomical defects. The causes of these malformations are usually considered multifactorial, but genetic variants play a key role. Currently, use of high-throughput genetic technologies allows identification of pathogenic aneuploidies, deletions/duplications of large segments, as well as rare single nucleotide variants. The high incidence of congenital heart disease as well as the associated complications makes it necessary to establish a diagnosis as early as possible to adopt the most appropriate measures in a personalized approach. In this review, we provide an exhaustive update of the genetic bases of the most frequent congenital heart diseases as well as other syndromes associated with congenital heart defects, and how genetic data can be translated to clinical practice in a personalized approach.
The 6-Minute Walk Test and Anthropometric Characteristics as Assessment Tools in Patients with Obstructive Sleep Apnea Syndrome. A Preliminary Report during the Pandemic
Authors: Stavrou Vasileios T. , Vavougios George D. , Astara Kyriaki , Siachpazidou Dimitra I. , Papayianni Eirini , Gourgoulianis Konstantinos I.
Published: June 2021

Patients with obstructive sleep apnea syndrome (OSAS) exhibit low cardio-fitness impact, attributed to fragmented sleep architecture and associated pathophysiological sequelae. The purpose of our study was to investigate fitness indicators during 6-min walk test (6MWT) and oxidative stress markers in apnea-hypopnea index (AHI) in OSAS patients stratified by severity. A total of 37 newly diagnosed patients, comorbidity-free, were divided into two groups: (Moderate OSAS (n = 12), defined as ≥ 15 AHI < 30 events per hour; Age: 50.7 ± 7.2 years, BMI: 32.5 ± 4.0 kg/m2 vs. Severe OSAS (n = 25), defined as AHΙ ≥ 30 events per hour; Age: 46.3 ± 10.4 years, BMI: 33.3 ± 7.9 kg/m2). Measurements included demographics, anthropometric characteristics, body composition, blood sampling for reactive oxygen metabolites’ levels (d-ROM) and plasma antioxidant capacity (PAT), and followed by a 6MWT. AHI was significantly associated with d-ROMs levels, chest circumference in maximal inhalation and exhalation (Δchest), neck circumference, as well as 6MWT-derived indices. In conclusion, our study determines bidirectional interrelationships between OSAS severity and anthropometrics, body composition, and fitness metrics. These findings indicate that the impact of OSAS should be evaluated well beyond polysomnography-derived parameters.
Geometric Methods for Efficient Planar Swimming of Copepod Nauplii
Authors: Shanbrom Corey , Balisacan Jonas , Wilkens George , Chyba Monique
Published: June 2021

Copepod nauplii are larval crustaceans with important ecological functions. Due to their small size, they experience an environment of low Reynolds number within their aquatic habitat. Here we provide a mathematical model of a swimming copepod nauplius with two legs moving in a plane. This model allows for both rotation and two-dimensional displacement by the periodic deformation of the swimmer’s body. The system is studied from the framework of optimal control theory, with a simple cost function designed to approximate the mechanical energy expended by the copepod. We find that this model is sufficiently realistic to recreate behavior similar to those of observed copepod nauplii, yet much of the mathematical analysis is tractable. In particular, we show that the system is controllable, but there exist singular configurations where the degree of non-holonomy is non-generic. We also partially characterize the abnormal extremals and provide explicit examples of families of abnormal curves. Finally, we numerically simulate normal extremals and observe some interesting and surprising phenomena.