bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypothesis and Theory: Characterizing Abnormalities of Energy Metabolism Using a Cellular Platform as a Personalized Medicine Approach for Alzheimer’s Disease
Authors: Ryu Woo-In , Cohen Bruce M. , Sonntag Kai-C.
Published: July 2021

Sporadic or late-onset Alzheimer’s disease (LOAD) is characterized by slowly progressive deterioration and death of CNS neurons. There are currently no substantially disease-modifying therapies. LOAD pathology is closely related to changes with age and include, among others, accumulation of toxic molecules and altered metabolic, microvascular, biochemical and inflammatory processes. In addition, there is growing evidence that cellular energy deficits play a critical role in aging and LOAD pathophysiology. However, the exact mechanisms and causal relationships are largely unknown. In our studies we tested the hypothesis that altered bioenergetic and metabolic cell functions are key elements in LOAD, using a cellular platform consisting of skin fibroblasts derived from LOAD patients and AD-unaffected control individuals and therefrom generated induced pluripotent stem cells that are differentiated to brain-like cells to study LOAD pathogenic processes in context of age, disease, genetic background, cell development, and cell type. This model has revealed that LOAD cells exhibit a multitude of bioenergetic and metabolic alterations, providing evidence for an innate inefficient cellular energy management in LOAD as a prerequisite for the development of neurodegenerative disease with age. We propose that this cellular platform could ultimately be used as a conceptual basis for a personalized medicine tool to predict altered aging and risk for development of dementia, and to test or implement customized therapeutic or disease-preventive intervention strategies.
Functional and Clinical Characteristics of Cell Adhesion Molecule CADM1 in Cancer
Authors: Li Hongxu , Gao Jie , Zhang Shuijun
Published: July 2021

The cell adhesion molecule CADM1, which participates in cell adhesion and signal transduction, has a regulatory effect on the development of tumors. CADM1 is often involved in malignant tumors of multiple organ systems, such as the respiratory and digestive systems. Upregulated CADM1 promotes tumor cell apoptosis and inhibits malignant proliferation. Along with cell cycle-related proteins, it participates in regulating signaling pathways, such as EMT, STAT3, and AKT, and plays an important role in inhibiting invasion and migration. Considering clinical characteristics, low CADM1 expression is associated with aggressive tumors and poor prognosis. In addition, some long non-coding RNAs (lncRNAs) or miRNAs directly or indirectly act on CADM1 to regulate tumor growth and motility. Interestingly, CADM1 function differs in adult T-cell leukemia/lymphoma (ATLL), and NF-κB is thought to be involved in this process. Taken together, CADM1 could be a potential biomarker for early diagnosis and a target for cancer treatment in future clinical practices.
Combination Treatment With Remdesivir and Ivermectin Exerts Highly Synergistic and Potent Antiviral Activity Against Murine Coronavirus Infection
Authors: Tan Yu Ling , Tan Kevin S. W. , Chu Justin Jang Hann , Chow Vincent T.
Published: July 2021

The recent COVID-19 pandemic has highlighted the urgency to develop effective antiviral therapies against the disease. Murine hepatitis virus (MHV) is a coronavirus that infects mice and shares some sequence identity to SARS-CoV-2. Both viruses belong to the Betacoronavirus genus, and MHV thus serves as a useful and safe surrogate model for SARS-CoV-2 infections. Clinical trials have indicated that remdesivir is a potentially promising antiviral drug against COVID-19. Using anin vitromodel of MHV infection of RAW264.7 macrophages, the safety and efficacy of monotherapy of remdesivir, chloroquine, ivermectin, and doxycycline were investigated. Of the four drugs tested, remdesivir monotherapy exerted the strongest inhibition of live virus and viral RNA replication of about 2-log10and 1-log10, respectively (at 6 µM). Ivermectin treatment showed the highest selectivity index. Combination drug therapy was also evaluated using remdesivir (6 µM) together with chloroquine (15 µM), ivermectin (2 µM) or doxycycline (15 µM) – above their IC50 values and at high macrophage cell viability of over 95%. The combination of remdesivir and ivermectin exhibited highly potent synergism by achieving significant reductions of about 7-log10of live virus and 2.5-log10of viral RNA in infected macrophages. This combination also resulted in the lowest cytokine levels of IL-6, TNF-α, and leukemia inhibitory factor. The next best synergistic combination was remdesivir with doxycycline, which decreased levels of live virus by ~3-log10and viral RNA by ~1.5-log10. These results warrant further studies to explore the mechanisms of action of the combination therapy, as well as futurein vivoexperiments and clinical trials for the treatment of SARS-CoV-2 infection.
Bacterial Composition and Metabolomics of Dental Plaque From Adolescents
Authors: Havsed Kristian , Stensson Malin , Jansson Henrik , Carda-Diéguez Miguel , Pedersen Anders , Neilands Jessica , Svensäter Gunnel , Mira Alex
Published: July 2021

Supragingival dental plaque samples were collected from 40 Swedish adolescents, including 20 with caries lesions (CAR) and 20 caries-free (CF). Fresh plaque samples were subjected to an ex vivo acid tolerance (AT) test where the proportion of bacteria resistant to an acid shock was evaluated through confocal microscopy and live/dead staining, and the metabolites produced were quantified by 1H Nuclear Magnetic Resonance (1H NMR). In addition, DNA was extracted and the 16S rRNA gene was sequenced by Illumina sequencing, in order to characterize bacterial composition in the same samples. There were no significant differences in AT scores between CAR and CF individuals. However, 7 out of the 10 individuals with highest AT scores belonged to the CAR group. Regarding bacterial composition, Abiotrophia, Prevotella and Veillonella were found at significantly higher levels in CAR individuals (p=0.0085, 0.026 and 0.04 respectively) and Rothia and Corynebacterium at significantly higher levels in CF individuals (p=0.026 and 0.003). The caries pathogen Streptococcus mutans was found at low frequencies and was absent in 60% of CAR individuals. Random-forest predictive models indicate that at least 4 bacterial species or 9 genera are needed to distinguish CAR from CF adolescents. The metabolomic profile obtained by NMR showed a significant clustering of organic acids with specific bacteria in CAR and/or high AT individuals, being Scardovia wiggsiae the species with strongest associations. A significant clustering of ethanol and isopropanol with health-associated bacteria such as Rothia or Corynebacterium was also found. Accordingly, several relationships involving these compounds like the Ethanol : Lactate or Succinate : Lactate ratios were significantly associated to acid tolerance and could be of predictive value for caries risk. We therefore propose that future caries risk studies would benefit from considering not only the use of multiple organisms as potential microbial biomarkers, but also their functional adaptation and metabolic output.
Household Economic Consequences of Rheumatic Heart Disease in Uganda
Authors: Opara Chinonso C. , Du Yuxian , Kawakatsu Yoshito , Atala Jenifer , Beaton Andrea Z. , Kansiime Rosemary , Nakitto Miriam , Ndagire Emma , Nalubwama Haddy , Okello Emmy , Watkins David A. , Su Yanfang
Published: July 2021

Background: Rheumatic heart disease (RHD) has declined dramatically in wealthier countries in the past three decades, but it remains endemic in many lower-resourced regions and can have significant costs to households. The objective of this study was to quantify the economic burden of RHD among Ugandans affected by RHD.

Methods: This was a cross-sectional cost-of-illness study that randomly sampled 87 participants and their households from the Uganda National RHD registry between December 2018 and February 2020. Using a standardized survey instrument, we asked participants and household members about outpatient and inpatient RHD costs and financial coping mechanisms incurred over the past 12 months. We used descriptive statistics to analyze levels and distributions of costs and the frequency of coping strategies. Multivariate Poisson regression models were used to assess relationships between socioeconomic characteristics and utilization of financial coping mechanisms.

Results: Most participants were young or women, demonstrating a wide variation in socioeconomic status. Outpatient and inpatient costs were primarily driven by transportation, medications, and laboratory tests, with overall RHD direct and indirect costs of $78 per person-year. Between 20 and 35 percent of households experienced catastrophic healthcare expenditure, with participants in the Northern and Western Regions 5–10 times more likely to experience such hardship and utilize financial coping mechanisms than counterparts in the Central Region, a wealthier area. Increases in total RHD costs were positively correlated with increasing use of coping behaviors.

Conclusion: Ugandan households affected by RHD, particularly in lower-income areas, incur out-of-pocket costs that are very high relative to income, exacerbating the poverty trap. Universal health coverage policy reforms in Uganda should include mechanisms to reduce or eliminate out-of-pocket expenditures for RHD and other chronic diseases.
Left Ventricular Global Longitudinal Strain Is Associated With Cardiovascular Outcomes in Patients Who Underwent Permanent Pacemaker Implantation
Authors: Kim Dae-Young , Lkhagvasuren Purevjargal , Seo Jiwon , Cho Iksung , Hong Geu-Ru , Ha Jong-Won , Shim Chi Young
Published: July 2021

Background: Patients who underwent permanent pacemaker (PM) implantation have a potential risk of left ventricular (LV) systolic dysfunction. However, assessment of LV ejection fraction (LVEF) shows a limited role in identifying subclinical LV systolic dysfunction and predicting cardiovascular (CV) outcomes.

Methods: We reviewed 1,103 patients who underwent permanent PM implantation between January 2007 and December 2017. After excluding patients who did not undergo echocardiograms before or after PM implantation and those with LV ejection fraction (LVEF) <50%, significant valve dysfunction, and history of cardiac surgery before PM implantation, 300 (67 ± 13 years, 119 men) were finally analyzed. LV mechanical function was assessed with LV global longitudinal strain (LV-GLS) using 2-dimensional speckle-tracking echocardiography. CV outcomes were defined as a composite of CV death and hospitalization for heart failure.

Results: At 44 ± 28 months after post-PM echocardiogram, 23 patients (7.7%) had experienced CV outcomes. Patients with CV outcomes were older and had more comorbidities and a lower baseline |LV-GLS| than those without CV outcomes. LV mechanical function worsened after PM implantation in patients with CV outcomes. The cut-off value of 11.2% in |LV-GLS| on post-PM echocardiogram had a better predictive value for CV outcomes (AUC; 0.784 vs. 0.647, p = 0.012). CV outcome in patients with |LV-GLS| <11.2% was worse than that in those with |LV-GLS| ≥ 11.2% (log-rank p < 0.001). Multivariate Cox model revealed that reduced |LV-GLS| was independently associated with CV outcomes.

Conclusions: Pacing deteriorates LV mechanical function. Impaired LV-GLS is associated with poor CV outcomes in patients who underwent PM implantation.
Characterization of Surface Runoff Pathways and Erosion Using Hydrological Attributes Under Simulated Rainfall
Authors: Zhang Lichao , Liu Xiaojun , Song Yuejun , Li Jun , Cai Chongfa , Zhao Xiaomin , Li Zhaoxia
Published: July 2021

Conceptualisation of geo-hydrological characteristic of erosive runoff are of particular importance and has been required in recent soil erosion control. This study aimed to explore the feasibility of applying hydrological attributes to characterize surface runoff pathways in the process of hillslope soil erosion due to rainfall. Combined with sub-millimeter high-resolution laser scanning and computer digital image processing method, three hydrological indicators (i.e., sinuosity, gradient and orientation) were used to investigate the changes of the surface runoff pathways on the slope of three typical southern red soils (i.e., shale (HS), and Quaternary red clay soils (HQ1 and HQ2) under simulated rainfall conditions). The results indicated no significant changes of sinuosity with a mean value of 1.19. After the rainfall with the intensity of 1 mm/min and 2 mm/min, the orientation and gradient changed dramatically. The greatest changes appeared at the first rainfall, which showed that the biggest increase of gradient was 26.78% and it tended to be close to the original slope of the test plot, while the orientation dropped by 5.60–31.44%. Compared with HS and HQ1, the runoff pathway characteristics of HQ2 changed more consistent. The rainfall intensities had a significant impact on the correlation between indicators. The determination coefficients sorting with surface roughness were orientation > graient > sinuosity. And they were significantly linearly related to runoff under 1 mm/min rainfall intensity, while had positive correlation with sediment under 2 mm/min rainfall intensity (p < 0.05). In conclusion, there were more remarkable relationships between orientation, gradient and slope erosion under 1 mm/min rainfall intensity. This provided an innovative idea, that is applying the orientation and gradient to the simulation and prediction model of the rainfall erosion process in the sloping farmland in the southern red soil area.
Optimal Investment Decision of Distribution Network With Investment Ability and Project Correlation Constraints
Authors: Yang Jianping , Xiang Yue , Wang Zeqi , Dai Jiakun , Wang Yanliang
Published: July 2021

Power grid enterprises are faced with a serious mismatch between limited investment capacity and numerous investment projects. How to accurately match the weak links with investment projects according to the power system diagnosis is the key to improve investment accuracy. On the basis of an investment-oriented label, a project portfolio optimization framework with coherent diagnosis–evaluation–optimization is proposed in this study. First, a two-layer index system for investment benefit evaluation is established, which considers unit investment efficiency and macroinvestment benefit. Second, by weighing the diagnosis results of power grid and the biased investment environment, the benefit evaluation of the project is implemented as the basis of project portfolio optimization. To meet different investment demands, two combination optimization models of maximizing investment benefit and minimizing investment cost are established considering the coupling benefit relationship and time series relationship between projects. Finally, a case study is conducted for a regional distribution network. The proposed framework has been proven to be able to effectively cope with different investment needs and realize the dynamic adjustment of the scheme in the whole investment cycle.
Money Kills Native Ecosystems: European Crayfish as an Example
Authors: Jussila Japo , Edsman Lennart , Maguire Ivana , Diéguez-Uribeondo Javier , Theissinger Kathrin
Published: July 2021

Native European crayfish conservation was triggered by invasion of crayfish plague disease agent,Aphanomyces astaci, starting 1860s in Northern Italy. Resulting crayfish plague epidemics quickly spread over Continental Europe, then to Finland, Sweden and finally, after running amok around Europe,A. astaciwas discovered also in Iberian Peninsula, Norway, Ireland, and United Kingdom in 1970s and 1980s. By that time significant proportion of native crayfish stocks had been lost, and while crayfish plague epidemics were still recorded, also industrialization and waterways construction were causing damage to remaining native crayfish stocks. While alien crayfish introductions, at leastFaxonius limosus, already gave rise to first wave of crayfish plague epidemics in late 19th century, later in 1960s it was decided that introductions of alienPacifastacus leniusculusshould be initiated to replace native European crayfish populations. Decisions were based on presumed advantages for fishery, suitable habitat requirements and supposed immunity againstA. astaci. Furthermore, conservation of native European crayfish species was sidelined and focus shifted toward alien crayfish stocking routine and consumption. Alien crayfish species introductions resulted in repeated waves of crayfish plague epidemics among remaining native crayfish stocks. It was soon discovered that alien crayfish of North American origin were, as suspected, permanent reservoirs forA. astaci, that some of those alien species were losing their resistance against selected strains ofA. astaciand struggled in European aquatic ecosystems. In this article, we introduce numerous motives behind grand mistake of introducing alien crayfish species to Europe and then promoting their stocks instead of focusing on conservation of native crayfish species. We outline how false economical, biological and ecologic assumptions were used to justify a hasty introduction of alien crayfish, which has further devastated native crayfish and also permanently changed European aquatic ecosystems, both with disastrous consequences. Lesson to be learnt is that science-based warnings about alien species damage to native ecosystems and native crayfish must be taken with utmost caution. Protection of native European crayfish should be core issue, not commercial activities. Finally, we summarize main threats and actions needed to protect remaining native freshwater crayfish fauna in Europe.
Floral Cues of Non-host Plants Attract Oligolectic Chelostoma rapunculi Bees
Authors: Burger Hannah , Joos Nadine , Ayasse Manfred
Published: July 2021

Oligolectic bees are highly dependent on the availability of the host plants to which they are specialized. Nevertheless, females ofChelostoma rapunculihave recently been monitored occasionally to visitMalva moschataandGeranium sanguineumflowers, in addition to their well-knownCampanulaspp. hosts. The questions therefore arise which floral cues promote visits to non-host plants. As host-specific floral cues are key attractants for oligolectic bees, we have studied the attractiveness of olfactory and visual cues of the established hostCampanula tracheliumin comparison to the non-host plantsG. sanguineumandM. moschatain behavioral experiments. Chemical and electrophysiological analyses of the floral scent and spectral measurements of floral colors were used to compare and contrast host and non-host plants. The behavioral experiments showed that foraging-naïve bees, in particular, were attracted by olfactory cues of the non-host plants, and that they did not favor theCampanulahost scent in choice experiments. Many electrophysiologically active floral volatiles were present in common in the studied plants, although each species produced an individual scent profile. Spiroacetals, the key components that enableC. rapunculito recognizeCampanulahosts, were detected in trace amounts inGeraniumbut could not be proved to occur inMalva. The visual floral cues of all species were particularly attractive for foraging-experienced bees. The high attractiveness ofG. sanguineumandM. moschataflowers toC. rapunculibees and the floral traits that are similar to theCampanulahost plants can be a first step to the beginning of a host expansion or change which, however, rarely occurs in oligolectic bees.
Unbiased Screening Identifies Functional Differences in NK Cells After Early Life Psychosocial Stress
Authors: Fernandes Sara B. , Patil Neha D. , Meriaux Sophie , Theresine Maud , Muller Claude. P. , Leenen Fleur A. D. , Elwenspoek Martha M. C. , Zimmer Jacques , Turner Jonathan D.
Published: July 2021

Early Life Adversity (ELA) is closely associated with the risk for developing diseases later in life, such as autoimmune diseases, type-2 diabetes and cardiovascular diseases. In humans, early parental separation, physical and sexual abuse or low social-economic status during childhood are known to have great impact on brain development, in the hormonal system and immune responses. Maternal deprivation (MD) is the closest animal model available to the human situation. This paradigm induces long lasting behavioral effects, causes changes in the HPA axis and affects the immune system. However, the mechanisms underlying changes in the immune response after ELA are still not fully understood. In this study we investigated how ELA changes the immune system, through an unbiased analysis, viSNE, and addressed specially the NK immune cell population and its functionality. We have demonstrated that maternal separation, in both humans and rats, significantly affects the sensitivity of the immune system in adulthood. Particularly, NK cells’ profile and response to target cell lines are significantly changed after ELA. These immune cells in rats are not only less cytotoxic towards YAC-1 cells, but also show a clear increase in the expression of maturation markers after 3h of maternal separation. Similarly, individuals who suffered from ELA display significant changes in the cytotoxic profile of NK cells together with decreased degranulation capacity. These results suggest that one of the key mechanisms by which the immune system becomes impaired after ELA might be due to a shift on the senescent state of the cells, specifically NK cells. Elucidation of such a mechanism highlights the importance of ELA prevention and how NK targeted immunotherapy might help attenuating ELA consequences.
Melioidosis Patient Survival Correlates With Strong IFN-γ Secreting T Cell Responses Against Hcp1 and TssM
Authors: Sengyee Sineenart , Yarasai Atchara , Janon Rachan , Morakot Chumpol , Ottiwet Orawan , Schmidt Lindsey K. , West T. Eoin , Burtnick Mary N. , Chantratita Narisara , Brett Paul J.
Published: July 2021

Melioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, is a serious infectious disease with diverse clinical manifestations. The morbidity and mortality of melioidosis is high in Southeast Asia and no licensed vaccines currently exist. This study was aimed at evaluating human cellular and humoral immune responses in Thai adults against four melioidosis vaccine candidate antigens. Blood samples from 91 melioidosis patients and 100 healthy donors from northeast Thailand were examined for immune responses against B. pseudomallei Hcp1, AhpC, TssM and LolC using a variety of cellular and humoral immune assays including IFN-γ ELISpot assays, flow cytometry and ELISA. PHA and a CPI peptide pool were also used as control stimuli in the ELISpot assays. Hcp1 and TssM stimulated strong IFN-γ secreting T cell responses in acute melioidosis patients which correlated with survival. High IFN-γ secreting CD4+ T cell responses were observed during acute melioidosis. Interestingly, while T cell responses of melioidosis patients against the CPI peptide pool were low at the time of enrollment, the levels increased to the same as in healthy donors by day 28. Although high IgG levels against Hcp1 and AhpC were detected in acute melioidosis patients, no significant differences between survivors and non-survivors were observed. Collectively, these studies help to further our understanding of immunity against disease following natural exposure of humans to B. pseudomallei as well as provide important insights for the selection of candidate antigens for use in the development of safe and effective melioidosis subunit vaccines.
The Promise of Personalized TCR-Based Cellular Immunotherapy for Cancer Patients
Authors: Arnaud Marion , Bobisse Sara , Chiffelle Johanna , Harari Alexandre
Published: July 2021

Mutation-derived neoantigens are now established as attractive targets for cancer immunotherapy. The field of adoptive T cell transfer (ACT) therapy was significantly reshaped by tumor neoantigens and is now moving towards the genetic engineering of T cells with neoantigen-specific T cell receptors (TCRs). Yet, the identification of neoantigen-reactive TCRs remains challenging and the process needs to be adapted to clinical timelines. In addition, the state of recipient T cells for TCR transduction is critical and can affect TCR-ACT efficacy. Here we provide an overview of the main strategies for TCR-engineering, describe the selection and expansion of optimal carrier cells for TCR-ACT and discuss the next-generation methods for rapid identification of relevant TCR candidates for gene transfer therapy.
Increased Expression of Extracellular Vesicles Is Associated With the Procoagulant State in Patients With Established Rheumatoid Arthritis
Authors: Stojanovic Aleksandra , Veselinovic Mirjana , Zong Yanan , Jakovljevic Vladimir , Pruner Iva , Antovic Aleksandra
Published: July 2021

This study sought to identify different subpopulations of extracellular vesicles (EVs) in plasma from female patients with established rheumatoid arthritis (RA) in relation to the activation of coagulation and fibrin formation in these patients. Forty women were included in the study, 20 patients and 20 age-matched healthy controls. The mean disease duration in patients was 13.0 (5.0–25.0) years, with medium to high disease activity despite ongoing treatment with low-dose prednisolone and methotrexate. There were no differences between the investigated groups regarding the presence of traditional cardiovascular risk factors. The concentration of phosphatidylserine-positive (PS+) EVs; platelet (CD42a+), leucocyte (CD45+), monocyte (CD14+), and endothelial (CD144+)-derived EVs; and EVs-expressing tissue factor (CD142+), P-selectin (CD62P+), and E-selectin (CD62E+) were determined by flow cytometry analysis. Overall hemostasis potential (OHP) was assessed to follow the hemostatic disturbances, including the parameters for overall coagulation potential (OCP) and overall fibrinolytic potential (OFP). Fibrin clot turbidity was measured together with clot lysis time, and scanning electron microscopy was performed. Increased concentrations of PS+, CD42a+, CD142+, CD45+, CD14+, and CD62P+ EVs were found in plasma from patients with RA compared to healthy controls, and the concentrations of PS+, CD42a+, CD14+, and CD62P+ EVs were positively correlated with the inflammatory parameters in RA patients. Positive correlations were also found between the levels of PS+ and CD42a+ EVs and OCP as well as between the levels of PS+, CD42a+, and CD62P+EVs and OHP. The levels of PS+, CD42a+, CD14+, CD62P+, and CD62E+ EVs were negatively correlated with OFP. Elevated levels of circulating EVs of different cell origins were found in patients with established RA, in relation to the inflammatory burden and coagulation activation in the disease.
Taxonomy and Molecular Phylogeny of Two New Urostylid Ciliates (Protozoa: Ciliophora) From Chinese Wetlands and Establishment of a New Genus
Authors: Song Wenya , Zhang Tengyue , Dong Jingyi , Luo Xiaotian , Bourland William A. , Wang Yurui
Published: July 2021

Hypotrich ciliates with evolutionary novelties are continually being discovered, challenging the current taxonomic system and attracting increased attention. In the present work, two new urostylid ciliates, Heterobakuella bergeri gen. nov., sp. nov. and Anteholosticha perezuzae sp. nov., isolated from Chinese wetland samples, were identified based on morphology and 18S rRNA gene sequences. Heterobakuella gen. nov. is defined by three frontal cirri, single buccal cirrus, one parabuccal cirrus, midventral complex composed of cirral pairs and one cirral row, one left and two right marginal cirral rows, transverse and pretransverse cirri present, caudal and frontoterminal cirri absent. Heterobakuella can be easily distinguished from the morphologically most similar genus, Apobakuella, mainly by the single buccal cirrus (vs. one buccal cirral row) and one parabuccal cirrus (vs. several parabuccal cirral rows originated from different anlagen). Phylogenetic analyses show that H. bergeri branches within the clade formed by Bergeriella ovata, Monocoronella carnea, Anteholosticha gracilis, and Neourostylopsis spp., rather than the clade represented by Apobakuella. The other species, A. perezuzae, is mainly characterized by a distinctly slender body shape with an average length:width ratio about 7, distinctively shaped biconcave and greenish cortical granules, as well as one or two pretransverse cirri. Phylogenetic analyses indicate the genus Anteholosticha is non-monophyletic.
Pathology Quality Control for Multiplex Immunofluorescence and Image Analysis Assessment in Longitudinal Studies
Authors: Lazcano Rossana , Rojas Frank , Laberiano Caddie , Hernandez Sharia , Parra Edwin Roger
Published: July 2021

Immune profiling of formalin-fixed, paraffin-embedded tissues using multiplex immunofluorescence (mIF) staining and image analysis methodology allows for the study of several biomarkers on a single slide. The pathology quality control (PQC) for tumor tissue immune profiling using digital image analysis of core needle biopsies is an important step in any laboratory to avoid wasting time and materials. Although there are currently no established inclusion and exclusion criteria for samples used in this type of assay, a PQC is necessary to achieve accurate and reproducible data. We retrospectively reviewed PQC data from hematoxylin and eosin (H&E) slides and from mIF image analysis samples obtained during 2019. We reviewed a total of 931 reports from core needle biopsy samples; 123 (13.21%) were excluded during the mIF PQC. The most common causes of exclusion were the absence of malignant cells or fewer than 100 malignant cells in the entire section (n = 42, 34.15%), tissue size smaller than 4 × 1 mm (n = 16, 13.01%), fibrotic tissue without inflammatory cells (n = 12, 9.76%), and necrotic tissue (n = 11, 8.94%). Baseline excluded samples had more fibrosis (90 vs 10%) and less necrosis (5 vs 90%) compared with post-treatment excluded samples. The most common excluded organ site of the biopsy was the liver (n = 19, 15.45%), followed by soft tissue (n = 17, 13.82%) and the abdominal region (n = 15, 12.20%). We showed that the PQC is an important step for image analysis and that the absence of malignant cells is the most limiting sample characteristic for mIF image analysis. We also discuss other challenges that pathologists need to consider to report reliable and reproducible image analysis data.
Gut-Derived Metabolite Phenylacetylglutamine and White Matter Hyperintensities in Patients With Acute Ischemic Stroke
Authors: Yu Fang , Feng Xianjing , Li Xi , Luo Yunfang , Wei Minping , Zhao Tingting , Xia Jian
Published: July 2021

Background: White matter hyperintensity (WMH) burden is associated with a higher risk of ischemic stroke. Phenylacetylglutamine (PAGln) is a gut microbiota-derived metabolite that may induce cardiovascular events by activating platelets and increasing the risk of thrombosis. The relationship between plasma PAGln and WMH burden in patients with ischemic stroke is unknown. This study was designed to investigate the association between plasma PAGln and WMH burden in patients with acute ischemic stroke.

Methods: A total of 595 patients with acute ischemic stroke were enrolled in this study within 14 days of symptom onset. The burden of WMH was evaluated using the Fazekas scale based on the fluid-attenuated inversion recovery sequence. The severity of overall WMH was defined as none–mild WMH (total Fazekas score 0–2) or moderate–severe WMH (total Fazekas score 3–6). Based on the severity of periventricular WMH (P-WMH) and deep WMH (D-WMH), patients were categorized into either a none–mild (Fazekas score 0–1) group or a moderate–severe (Fazekas score 2–3) group. Plasma PAGln levels were quantified using liquid chromatography–mass spectrometry.

Results: We found that patients with moderate–severe overall WMH showed higher plasma PAGln levels than patients with none–mild overall WMH, and similar results were found in the analyses according to P-WMH and D-WMH. The logistic regression analysis showed that the fourth PAGln quartile was independently associated with moderate–severe overall WMH (adjusted 95% CI 1.134–4.018) and P-WMH (adjusted 95% CI 1.174–4.226).

Conclusion: These findings suggest that higher plasma PAGln levels are associated with moderate–severe overall WMH and P-WMH in patients with acute ischemic stroke.
The Effects of Gender, Functional Condition, and ADL on Pressure Pain Threshold in Stroke Patients
Authors: Zhang Yong-Hui , Wang Yu-Chen , Hu Gong-Wei , Ding Xiao-Qin , Shen Xiao-Hua , Yang Hui , Rong Ji-Feng , Wang Xue-Qiang
Published: July 2021

Background

Somatosensory impairments and pain are common symptoms following stroke. However, the condition of perception and pain threshold for pressure stimuli and the factors that can influence this in individuals with stroke are still unclear. This study aimed to investigate the gender differences in pressure pain threshold (PPT) and positive somatosensory signs for pressure stimuli, and explore the effects of joint pain, motor function, and activities of daily living (ADL) on pain threshold in post-stroke patients.

Design

A cross-sectional study.

Methods

A total of 60 participants with stroke were recruited, and their pain condition, motor functions, and ADL were evaluated by the Fugl-Meyer assessment of joint pain scale, motor function scale, and Barthel index, respectively. PPTs in eight tested points at the affected and unaffected sides were assessed.

Results

Significant differences in PPTs were found between male and female patients in all measured muscles (p < 0.05). Positive somatosensory signs for pressure stimuli, including hypoalgesia and hyperalgesia, were frequently found at the affected side, particularly in the extremity muscles, but such signs were not significantly influenced by gender (p > 0.05). More equal PPTs between both sides and relatively lower PPTs at the affected side in the trunk and medial gastrocnemius muscles (p < 0.05) were observed in patients with less pain, better motor functions, and ADL.

Conclusion

Gender differences widely exist in post-stroke survivors either at the affected or unaffected side, which are multifactorial. Sensory loss and central and/or peripheral sensitization, such as hypoalgesia and hyperalgesia for pressure stimuli, caused by a brain lesion are common signs in male and female stroke patients. Moreover, patients who are in a better condition show a more symmetrical pain sensitivity between both sides in the trunk and in female lower extremities, indicating the bidirectional improvement of somatosensory abnormalities caused by a possible neural plasticity.
Fuzzy System Based Medical Image Processing for Brain Disease Prediction
Authors: Hu Mandong , Zhong Yi , Xie Shuxuan , Lv Haibin , Lv Zhihan
Published: July 2021

The present work aims to explore the performance of fuzzy system-based medical image processing for predicting the brain disease. The imaging mechanism of NMR (Nuclear Magnetic Resonance) and the complexity of human brain tissues cause the brain MRI (Magnetic Resonance Imaging) images to present varying degrees of noise, weak boundaries, and artifacts. Hence, improvements are made over the fuzzy clustering algorithm. A brain image processing and brain disease diagnosis prediction model is designed based on improved fuzzy clustering and HPU-Net (Hybrid Pyramid U-Net Model for Brain Tumor Segmentation) to ensure the model safety performance. Brain MRI images collected from a Hospital, are employed in simulation experiments to validate the performance of the proposed algorithm. Moreover, CNN (Convolutional Neural Network), RNN (Recurrent Neural Network), FCM (Fuzzy C-Means), LDCFCM (Local Density Clustering Fuzzy C-Means), and AFCM (Adaptive Fuzzy C-Means) are included in simulation experiments for performance comparison. Results demonstrate that the proposed algorithm has more nodes, lower energy consumption, and more stable changes than other models under the same conditions. Regarding the overall network performance, the proposed algorithm can complete the data transmission tasks the fastest, basically maintaining at about 4.5 s on average, which performs remarkably better than other models. A further prediction performance analysis reveals that the proposed algorithm provides the highest prediction accuracy for the Whole Tumor under DSC (Dice Similarity Coefficient), reaching 0.936. Besides, its Jaccard coefficient is 0.845, proving its superior segmentation accuracy over other models. In a word, the proposed algorithm can provide higher accuracy, a more apparent denoising effect, and the best segmentation and recognition effect than other models while ensuring energy consumption. The results can provide an experimental basis for the feature recognition and predictive diagnosis of brain images.
Inverse Association Between the Mediterranean Diet and COVID-19 Risk in Lebanon: A Case-Control Study
Authors: El Khoury Christine N. , Julien Sofi G.
Published: July 2021

Background: Since 2019, the world is confronting the COVID-19 public health crisis that deeply impacted all aspects of life, from the health sector to economy. Despite the advancement of research targeting pandemic containment measures, more strategies are still needed to alleviate the burden caused by this novel disease. In particular, optimal nutrition was proposed as a possible mitigating factor in the context of COVID-19. Indeed, the light is shed on balanced diets, such as the Mediterranean diet, which present the finest nutritional quality to support the immune system and other physiologic functions. In contrast, less varied diets that lack the needed nutrients and favor inflammation have been correlated with adverse health effects, including a hindered immune response, such as the western diet.

Methods: This observational case control study aimed at exploring the possible associations between the different dietary patterns present among a sample of the Lebanese population and the COVID-19 occurrence and outcomes. An online survey collected information about the sociodemographic characteristics, health status, lifestyle, and dietary habits through the Mediterranean diet questionnaire and a semi-quantitative fod frequency questionnaire, and the COVID-19 infection and its burden. The sample consisted of 399 respondents divided into the case and control groups (37.6 and 62.4%, respectively) on the basis of the presence or absence of a COVID-19 infection history.

Results: The participants in the case and control groups had average adherence to the Mediterranean diet and their dietary intake was closer to the western diet. However, the cases had a lower mean of the MedDiet score (p = 0.009). Food groups consumption analysis showed that this significant difference within the overall similar dietary patterns was due to a higher consumption of poultry and a trend toward decreased consumption of olive oil and increased read meat and alcohol intake among the cases. Additionally, gender influenced the levels of different foods' consumption. Nonetheless, the dietary intake did not impact the COVID-19 burden.

Conclusion: It is recommended to adopt healthy food choices within the different dietary patterns for a better protection against COVID-19. These findings should be validated in larger-scale studies.
CT-Based Pelvic T1-Weighted MR Image Synthesis Using UNet, UNet++ and Cycle-Consistent Generative Adversarial Network (Cycle-GAN)
Authors: Kalantar Reza , Messiou Christina , Winfield Jessica M. , Renn Alexandra , Latifoltojar Arash , Downey Kate , Sohaib Aslam , Lalondrelle Susan , Koh Dow-Mu , Blackledge Matthew D.
Published: July 2021

Background

Computed tomography (CT) and magnetic resonance imaging (MRI) are the mainstay imaging modalities in radiotherapy planning. In MR-Linac treatment, manual annotation of organs-at-risk (OARs) and clinical volumes requires a significant clinician interaction and is a major challenge. Currently, there is a lack of available pre-annotated MRI data for training supervised segmentation algorithms. This study aimed to develop a deep learning (DL)-based framework to synthesize pelvic T1-weighted MRI from a pre-existing repository of clinical planning CTs.

Methods

MRI synthesis was performed using UNet++ and cycle-consistent generative adversarial network (Cycle-GAN), and the predictions were compared qualitatively and quantitatively against a baseline UNet model using pixel-wise and perceptual loss functions. Additionally, the Cycle-GAN predictions were evaluated through qualitative expert testing (4 radiologists), and a pelvic bone segmentation routine based on a UNet architecture was trained on synthetic MRI using CT-propagated contours and subsequently tested on real pelvic T1 weighted MRI scans.

Results

In our experiments, Cycle-GAN generated sharp images for all pelvic slices whilst UNet and UNet++ predictions suffered from poorer spatial resolution within deformable soft-tissues (e.g. bladder, bowel). Qualitative radiologist assessment showed inter-expert variabilities in the test scores; each of the four radiologists correctly identified images as acquired/synthetic with 67%, 100%, 86% and 94% accuracy. Unsupervised segmentation of pelvic bone on T1-weighted images was successful in a number of test cases

Conclusion

Pelvic MRI synthesis is a challenging task due to the absence of soft-tissue contrast on CT. Our study showed the potential of deep learning models for synthesizing realistic MR images from CT, and transferring cross-domain knowledge which may help to expand training datasets for 21 development of MR-only segmentation models.
Mechanisms and Implications of CDK4/6 Inhibitors for the Treatment of NSCLC
Authors: Zhang Jinmeng , Xu Dayu , Zhou Yue , Zhu Zhengfei , Yang Xi
Published: July 2021

Cyclin-dependent kinases (CDKs) are key regulators of cell cycle progression in malignant tumor cells and play an important role through complex molecular interactions. Dysregulation of CDK dependent pathways is often found in non-small cell lung cancer, which indicates its vulnerability and can be used in clinical benefit. CDK4/6 inhibitors can prevent tumor cells from entering the G approved 1 and S phases, which have been studied in a series of explorations and brought great clinical effect to patients and encouragement to both physicians and researchers, thereby showing potential as a new therapeutic agent. A series of preclinical and clinical studies have been carried out on CDK4/6 inhibitors in NSCLC, and have been achieved some results, which may become a new potential treatment in the future. This review focuses on the research progress on CDK4/6 inhibitors in NSCLC, particularly the mechanisms of action, drugs, clinical research progress, and future application.
Colorectal Cancer Screening Prevalence and Adherence for the Cancer Prevention Project of Philadelphia (CAP3) Participants Who Self-Identify as Black
Authors: Blackman Elizabeth L. , Ragin Camille , Jones Resa M.
Published: July 2021

Introduction

Colorectal cancer is the third leading cause of cancer-related deaths among Black men and women. While colorectal cancer screening (CRCS) reduces mortality, research assessing within race CRCS differences is lacking. This study assessed CRCS prevalence and adherence to national screening recommendations and the association of region of birth with CRCS adherence, within a diverse Black population.

Methods

Data from age-eligible adults, 50–75 years, (N = 357) participating in an ongoing, cross-sectional study, was used to measure CRCS prevalence and adherence and region of birth (e.g., Caribbean-, African-, US-born). Prevalence and adherence were based on contemporaneous US Preventive Services Task Force guidelines. Descriptive statistics were calculated and adjusted prevalence and adherence proportions were calculated by region of birth. Adjusted logistic regression models were performed to assess the association between region of birth and overall CRCS and modality-specific adherence.

Results

Respondents were 69.5% female, 43.3% married/living with partner, and 38.4% had <$25,000 annual income. Overall, 78.2% reported past CRCS; however, stool test had the lowest prevalence overall (34.6%). Caribbean (95.0%) and African immigrants (90.2%) had higher prevalence of overall CRCS compared to US-born Blacks (59.2%) (p-value <0.001). African immigrants were five times more likely to be adherent to overall CRCS compared to US-born Blacks (OR = 5.25, 95% CI 1.34–20.6). Immigrants had higher odds of being adherent to colonoscopy (Caribbean OR = 6.84, 95% CI 1.49–31.5; African OR = 7.14, 95% CI 1.27–40.3) compared to US-born Blacks.

Conclusions

While Caribbean and African immigrants have higher prevalence and adherence of CRCS when compared US-born Blacks, CRCS is still sub-optimal in the Black population. Efforts to increase CRCS, specifically stool testing, within the Black population are warranted, with targeted interventions geared towards US-born Blacks.
Standardized Incidence Rate, Risk and Survival Outcomes of Second Primary Malignancy Among Renal Cell Carcinoma Survivors: A Nested Case-Control Study
Authors: Wang Zhixian , Yin Yisheng , Wang Jing , Zhu Yunpeng , Li Xing , Zeng Xiaoyong
Published: July 2021

Purpose

Second primary malignancy (SPM) is challenging for treatment and long-term survival. We sought to investigate the standardized incidence rate (SIR), risk factors, and survival outcomes for SPM after renal cell carcinoma (RCC) treatment.

Method

A nested case-control study was designed, we identified all T1-4N0-1M0 RCC patients diagnosed between 2004 and 2015 in the Surveillance, Epidemiology, and End Results database and followed them for SPM diagnosis for up to 13 years. Patients with SPM diagnosis ≥6 months after treatment of primary T1-4N0-1M0 RCC were identified as the case cohort and SPM-free patients were the control cohort. SIRs and the excess risk were calculated. A competing risks and Cox model were used to evaluate the risk factors of SPM and overall survival (OS).

Results

A cohort of 6,204 RCC patients with SPM were matched with a control group of 31,020 RCC patients without SPM. The median time-to-SPM interval was 54.5 months in RCC patients with SPM diagnosis. Besides, an SPM of T3/4 or/and M1 stage diagnosis was positively associated with a longer time-to-SPM interval. SIR of SPM increased by follow-up time and decreased with age at diagnosis (Pfor all <0.001). SPM in the kidney had the highest SIR (54.6, P <0.001) among all SPMs. Prostate cancer (29.8%) in males and breast cancer (23.5%) in females were the most common SPM. Older age, black ethnicity, male sex, higher family income, papillary RCC, and lower TNM stage were significant risk factors for SPM diagnosis. The proportion of deaths from SPM exceeds that of deaths from RCC 3 years after the first RCC treatment. Patients with SPM and early time-to-SPM interval shortens the OS compared with SPM-free patients. The 5-year OS was 85.9% and 58.9% from the first RCC and the SPM diagnosis, respectively. Besides, patients with low-grade/early-stage SPM could benefit from aggressive surgical treatment for solid tumors.

Conclusions

Collectively, our study described the epidemiological characteristics of SPM among RCC survivors and identified the independent predictors of the SPM diagnosis and its survival outcomes. This study highlights the importance of patient education and follow-up after the surgery for RCC.