Miracle-dz/UniFAR-FTUs huggingface dataset:
Extracellular Vesicle-Associated Tissue Factor Activity in Prostate Cancer Patients with Disseminated Intravascular Coagulation

Simple Summary Disseminated intravascular coagulation (DIC) may occur in patients with advanced prostate cancer. In the present study, we detected elevated extracellular vesicle (EV)-associated tissue factor (TF) activity in the plasma of prostate cancer patients with DIC compared with matched prostate cancer patients without DIC and healthy individuals. TF-exposing EVs from DIC patients were highly coagulant in a clotting assay. In in vitro co-culture experiments, EV-TF activity was increased by interactions between a TF-exposing prostate cancer cell line (DU145), peripheral blood mononuclear cells (PBMCs), and platelets. Data from this study contribute to the understanding of the pathogenesis of prostate cancer-related DIC. Abstract Patients with advanced prostate cancer may develop fulminant disseminated intravascular coagulation (DIC). Circulating extracellular vesicles (EVs)-exposing tissue factor (TF), the initiator of the coagulation cascade, may play an important role. We included 7 prostate cancer patients with DIC, 10 age- and stage-matched cancer controls without DIC, and 10 age-matched healthy male individuals. EV-TF activity was highly elevated in prostate cancer patients with DIC (11.40 pg/mL; range: 4.34–27.06) compared with prostate cancer patients without DIC (0.09 pg/mL; range: 0.00–0.30, p = 0.001) and healthy controls (0.18 pg/mL; range: 0.09–0.54; p = 0.001). Only EVs from patients with DIC reduced fibrin clot formation time of pooled plasma in a TF-dependent manner. Next, we performed in vitro co-culture experiments including EVs derived from a prostate cancer cell line with high (DU145) and low (LNCaP) TF expression, peripheral blood mononuclear cells (PBMCs), and platelets. Co-incubation of DU145 EVs with PBMCs and platelets significantly increased EV-TF activity in conditioned medium and induced TF activity on monocytes. No such effects were seen in co-culture experiments with LNCaP EVs. In conclusion, the findings indicate that elevated EV-TF activity plays a role in the development of prostate-cancer-related DIC and may result from interactions between tumor-derived EVs, monocytes, and platelets.
The Presence, Trends, and Causes of Security Vulnerabilities in Operating Systems of IoT’s Low-End Devices

Internet of Things Operating Systems (IoT OSs) run, manage and control IoT devices. Therefore, it is important to secure the source code for IoT OSs, especially if they are deployed on devices used for human care and safety. In this paper, we report the results of our investigations of the security status and the presence of security vulnerabilities in the source code of the most popular open source IoT OSs. Through this research, three Static Analysis Tools (Cppcheck, Flawfinder and RATS) were used to examine the code of sixteen different releases of four different C/C++ IoT OSs, with 48 examinations, regarding the presence of vulnerabilities from the Common Weakness Enumeration (CWE). The examination reveals that IoT OS code still suffers from errors that lead to security vulnerabilities and increase the opportunity of security breaches. The total number of errors in IoT OSs is increasing from version to the next, while error density, i.e., errors per 1K of physical Source Lines of Code (SLOC) is decreasing chronologically for all IoT Oss, with few exceptions. The most prevalent vulnerabilities in IoT OS source code were CWE-561, CWE-398 and CWE-563 according to Cppcheck, (CWE-119! /CWE-120), CWE-120 and CWE-126 according to Flawfinder, and CWE-119, CWE-120 and CWE-134 according to RATS. Additionally, the CodeScene tool was used to investigate the development of the evolutionary properties of IoT OSs and the relationship between them and the presence of IoT OS vulnerabilities. CodeScene reveals strong positive correlation between the total number of security errors within IoT OSs and SLOC, as well as strong negative correlation between the total number of security errors and Code Health. CodeScene also indicates strong positive correlation between security error density (errors per 1K SLOC) and the presence of hotspots (frequency of code changes and code complexity), as well as strong negative correlation between security error density and the Qualitative Team Experience, which is a measure of the experience of the IoT OS developers.
Brown meets green: light and nutrients alter detritivore assimilation of microbial nutrients from leaf litter.

In aquatic detrital-based food webs, research suggests that autotroph-heterotroph microbial interactions exert bottom-up controls on energy and nutrient transfer. To address this emerging topic, we investigated microbial responses to nutrient and light treatments during Liriodendron tulipifera litter decomposition and fed litter to the caddisfly larvae Pycnopsyche sp. We measured litter-associated algal, fungal, and bacterial biomass and production. Microbes were also labeled with 14 C and 33 P to trace distinct microbial carbon (C) and phosphorus (P) supporting Pycnopsyche assimilation and incorporation (growth). Litter-associated algal and fungal production rates additively increased with higher nutrient and light availability. Incorporation of microbial P did not differ across diets, except for higher incorporation efficiency of slower-turnover P on low-nutrient, shaded litter. On average, Pycnopsyche assimilated fungal C more efficiently than bacterial or algal C, and Pycnopsyche incorporated bacterial C more efficiently than algal or fungal C. Due to high litter fungal biomass, fungi supported 89.6% to 93.1% of Pycnopsyche C growth, compared to 0.2% to 3.6% supported by bacteria or algae. Overall, Pycnopsyche incorporated the most C in high nutrient and shaded litter. Our findings affirm others' regarding autotroph-heterotroph microbial interactions and extend into the trophic transfer of microbial energy and nutrients through detrital food webs.
Neoadjuvant Chemotherapy in Breast Cancer: Review of the Evidence and Conditions That Facilitated Its Use during the Global Pandemic

Practice and behaviour change in healthcare is complex, and requires a set of critical steps that would be needed to implement and sustain the change. Neoadjuvant chemotherapy for breast cancer is traditionally used for locally advanced disease and is primarily advantageous for surgical downstaging purposes. However, it does also offer patients with certain biologic subtypes such as the triple negative or Her2 positive breast cancers the opportunity to improve survival, even in early stage disease. During the height of the pandemic, an opportunity and motivation for the increased use of neoadjuvant therapy in breast cancer was identified. This paper describes the conditions that have supported this practice change at the provider and institutional levels. We also include our own institutional algorithm based on tumor biology and extent of disease that have guided our decisions on breast cancer management during the pandemic. Our processes can be adapted by other institutions and breast oncology practices in accordance with local conditions and resources, during and beyond the pandemic.
Transference Number Determination in Poor-Dissociated Low Dielectric Constant Lithium and Protonic Electrolytes

Whereas the major potential of the development of lithium-based cells is commonly attributed to the use of solid polymer electrolytes (SPE) to replace liquid ones, the possibilities of the improvement of the applicability of the fuel cell is often attributed to the novel electrolytic materials belonging to various structural families. In both cases, the transport properties of the electrolytes significantly affect the operational parameters of the galvanic and fuel cells incorporating them. Amongst them, the transference number (TN) of the electrochemically active species (usually cations) is, on the one hand, one of the most significant descriptors of the resulting cell operational efficiency while on the other, despite many years of investigation, it remains the worst definable and determinable material parameter. The paper delivers not only an extensive review of the development of the TN determination methodology but as well tries to show the physicochemical nature of the discrepancies observed between the values determined using various approaches for the same systems of interest. The provided critical review is supported by some original experimental data gathered for composite polymeric systems incorporating both inorganic and organic dispersed phases. It as well explains the physical sense of the negative transference number values resulting from some more elaborated approaches for highly associated systems.
Immune response to dermatomyositis-specific autoantigen, transcriptional intermediary factor 1γ can result in experimental myositis

Objectives To investigate whether autoimmunity to transcriptional intermediary factor 1 (TIF1)γ, a ubiquitous nuclear autoantigen for myositis-specific autoantibodies detected in patients with dermatomyositis (DM) is pathogenetic for inflammatory myopathy. Methods Wild-type, β2-microglobulin-null, perforin-null, Igμ‐null and interferon α/β receptor (IFNAR)-null mice were immunised with recombinant human TIF1γ whole protein. A thymidine incorporation assay was performed using lymph node T cells from TIF1γ-immunised mice. Plasma was analysed using immunoprecipitation followed by western blot analysis and enzyme-linked immunosorbent assays. Femoral muscles were histologically and immunohistochemically evaluated. CD8+ or CD4+ T cells isolated from lymph node T cells or IgG purified from plasma were adoptively transferred to naïve mice. TIF1γ-immunised mice were treated with anti-CD8 depleting antibody and a Janus kinase inhibitor, tofacitinib. Results Immunisation with TIF1γ-induced experimental myositis presenting with necrosis/atrophy of muscle fibres accompanied by CD8+ T cell infiltration successfully in wild-type mice, in which TIF1γ-specific T cells and antihuman and murine TIF1γ IgG antibodies were detected. The incidence and severity of myositis were significantly lower in β₂-microglobulin-null, perforin-null, CD8-depleted or IFNAR-null mice, while Igμ‐null mice developed myositis normally. Adoptive transfer of CD8+ T cells induced myositis in recipients, while transfer of CD4+ T cells or IgG did not. Treatment with tofacitinib inhibited TIF1γ-induced myositis. Conclusions Here we show that TIF1γ is immunogenic enough to cause experimental myositis, in which CD8+ T cells and type I interferons, but not CD4+ T cells, B cells or antibodies, are required. This murine model would be a tool for understanding the pathologies of DM.
Attitudes and Knowledge of European Medical Students and Early Graduates about Vaccination and Self-Reported Vaccination Coverage—Multinational Cross-Sectional Survey

Vaccination is one of the most useful preventive interventions in healthcare. The purpose of our study was to gain overview of the opinions, knowledge, and engagement in vaccination practices among medical students (MS) and junior doctors (JD) in Europe. The survey was distributed from March 2016 until August 2016 via the e-mail and social media of the European Medical Students’ Association. In total, 1821 responses from MS and JD from 34 countries in the European region were analysed. The majority of respondents agreed that vaccines are useful (98.7%) and effective (97.2%). Although the necessity of revaccination was supported by 99.2%, only 68.0% of the respondents went through with it. Even though the potential benefit of the flu vaccination seems to be acknowledged by our participants, only 22.1% of MS and JD declared getting the flu shot every or every other season. MS and JD were in favour of specific mandatory vaccination for medical staff (86.0%) and medical students (82.7%). Furthermore, we analysed the self-reported vaccination coverage of our participants regarding 19 vaccines. Of the respondents, 89.5% claimed to provide advice about vaccination to their friends and family. In conclusion, European MS and JD have a very positive attitude towards vaccination. However, their behaviour and knowledge demonstrate certain gaps which should be further addressed in medical education.
Novel HEXA variants in Korean children with Tay–Sachs disease with regression of neurodevelopment from infancy

Tay–Sachs disease (TSD) is a lysosomal storage disease caused by mutations in the HEXA gene that encodes the HexosaminidaseA (HEXA) enzyme. As HEXA normally functions to degrade the protein GM2‐ganglioside in lysosomes, decreased levels of HEXAcauses an accumulation of the protein and leads to neurological toxicity. Typical clinical manifestations of TSD include neurodevelopmental regression, muscle weakness, hypotonia, hyperreflexia, ataxia, seizures, and other neurological symptoms. It is quite rare in Asian populations, wherein only two cases have been reported in Korea to date.
L-Glutaminase Synthesis by Marine Halomonas meridiana Isolated from the Red Sea and Its Efficiency against Colorectal Cancer Cell Lines

L-glutaminase is an important anticancer agent that is used extensively worldwide by depriving cancer cells of L-glutamine. The marine bacterium, Halomonas meridian was isolated from the Red Sea and selected as the more active L-glutaminase-producing bacteria. L-glutaminase fermentation was optimized at 36 h, pH 8.0, 37 °C, and 3.0% NaCl, using glucose at 1.5% and soybean meal at 2%. The purified enzyme showed a specific activity of 36.08 U/mg, and the molecular weight was found to be 57 kDa by the SDS-PAGE analysis. The enzyme was highly active at pH 8.0 and 37 °C. The kinetics’ parameters of Km and Vmax were 12.2 × 10−6 M and 121.95 μmol/mL/min, respectively, which reflects a higher affinity for its substrate. The anticancer efficiency of the enzyme showed significant toxic activity toward colorectal adenocarcinoma cells; LS 174 T (IC50 7.0 μg/mL) and HCT 116 (IC50 13.2 μg/mL). A higher incidence of cell death was observed with early apoptosis in HCT 116 than in LS 174 T, whereas late apoptosis was observed in LS 174 T more than in HCT 116. Also, the L-glutaminase induction nuclear fragmentation in HCT 116 was more than that in the LS 174T cells. This is the first report on Halomonas meridiana as an L-glutaminase producer that is used as an anti-colorectal cancer agent.
The Association between Australian Childcare Centre Healthy Eating Practices and Children’s Healthy Eating Behaviours: A Cross-Sectional Study within Lunchbox Centres

The association between healthy eating practices and child dietary intake in childcare centres where parents pack foods from home has received little attention. This study aimed to: (1) Describe the nutritional content of foods and beverages consumed by children in care; and (2) Assess the association between centre healthy eating practices and child intake of fruit and vegetable servings, added sugar(grams), saturated fat(grams) and sodium(milligrams) in care. A cross-sectional study amongst 448 children attending 22 childcare centres in New South Wales, Australia, was conducted. Child dietary intake was measured via weighed lunchbox measurements, photographs and researcher observation, and centre healthy eating practices were assessed via researcher observation of centre nutrition environments. Children attending lunchbox centres consumed, on average 0.80 servings (standard deviation 0.69) of fruit and 0.27 servings (standard deviation 0.51) of vegetables in care. The availability of foods within children’s lunchboxes was associated with intake of such foods (p < 0.01). Centre provision of intentional healthy eating learning experiences (estimate −0.56; p = 0.01) and the use of feeding practices that support children’s healthy eating (estimate −2.02; p = 0.04) were significantly associated with reduced child intake of saturated fat. Interventions to improve child nutrition in centres should focus on a range of healthy eating practices, including the availability of foods packed within lunchboxes.
X-ray screening identifies active site and allosteric inhibitors of SARS-CoV-2 main protease

A large-scale screen to target SARS-CoV-2 The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome is initially expressed as two large polyproteins. Its main protease, Mpro, is essential to yield functional viral proteins, making it a key drug target. Günther et al. used x-ray crystallography to screen more than 5000 compounds that are either approved drugs or drugs in clinical trials. The screen identified 37 compounds that bind to Mpro. High-resolution structures showed that most compounds bind at the active site but also revealed two allosteric sites where binding of a drug causes conformational changes that affect the active site. In cell-based assays, seven compounds had antiviral activity without toxicity. The most potent, calpeptin, binds covalently in the active site, whereas the second most potent, pelitinib, binds at an allosteric site. Science, this issue p. 642 A repurposed drug-library screen reveals two allosteric drug binding sites of the SARS-CoV-2 main protease. The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous human suffering. To date, no effective drug is available to directly treat the disease. In a search for a drug against COVID-19, we have performed a high-throughput x-ray crystallographic screen of two repurposing drug libraries against the SARS-CoV-2 main protease (Mpro), which is essential for viral replication. In contrast to commonly applied x-ray fragment screening experiments with molecules of low complexity, our screen tested already-approved drugs and drugs in clinical trials. From the three-dimensional protein structures, we identified 37 compounds that bind to Mpro. In subsequent cell-based viral reduction assays, one peptidomimetic and six nonpeptidic compounds showed antiviral activity at nontoxic concentrations. We identified two allosteric binding sites representing attractive targets for drug development against SARS-CoV-2.
Higher Accuracy of Lung Ultrasound over Chest X-ray for Early Diagnosis of COVID-19 Pneumonia

Background: The COVID-19 pandemic rapidly strained healthcare systems worldwide. The reference standard for diagnosis is a positive reverse transcription polymerase chain reaction (RT-PCR) test, but results are not immediate and sensibility is variable. Aim: To evaluate the diagnostic accuracy of lung ultrasound compared to chest X-ray for COVID-19 pneumonia. Design and Setting: A retrospective analysis of symptomatic patients admitted into one primary care centre in Spain between March and September 2020. Method: Patients’ chest X-rays and lung ultrasounds were categorized as normal or pathologic. RT-PCR confirmed COVID-19 infection. Pathologic lung ultrasound images were further categorized as showing either local or diffuse interstitial disease. McNemar and Fisher tests were used to compare diagnostic accuracy. Results: Most of the 212 patients presented fever at admission, either as a standalone symptom (37.74% of patients) or together with others (72.17% of patients). The positive predictive value of the lung ultrasound was 90% for the diffuse interstitial pattern and 46.92% for local pattern. The lung ultrasound had a significantly higher sensitivity (82.75%) (p < 0.001), but lower specificity (71%) than the chest X-ray (54.02% and 86%, respectively) (p = 0.008) for identifying interstitial lung disease. Moreover, sensitivity of the lung ultrasound for severe interstitial disease was 100%, and was significantly higher than the chest X-ray (58.33%) (p = 0.002). Conclusion: The lung ultrasound is more accurate than the chest X-ray for identifying patients with COVID-19 pneumonia and it is especially useful for those presenting diffuse interstitial disease.
Distributive stress: individually variable responses to hypoxia expand trophic niches in fish

Abstract Environmental stress can reshape trophic interactions by excluding predators or rendering prey vulnerable, depending on the relative sensitivity of species to the stressor. Classical models of food web responses to stress predict either complete predator exclusion from stressed areas or complete prey vulnerability if predators are stress tolerant. However, if the consumer response to the stress is individually variable, the result may be a distributive stress model (DSM) whereby predators distribute consumption pressure across a range of prey guilds and their trophic niche is expanded. We test these models in one of the largest hypoxic “Dead Zones” in the world, the northern Gulf of Mexico, by combining geochemical tracers of hypoxia exposure and isotope ratios to assess individual‐level trophic responses. Hypoxia‐exposed fish occupied niche widths that were 14.8% and 400% larger than their normoxic counterparts in two different years, consistent with variable displacement from benthic to pelagic food webs. The degree of isotopic displacement depended on the magnitude of hypoxia exposure. These results are consistent with the DSM and highlight the need to account for individually variable sublethal effects when predicting community responses to environmental stress.
Traditional Societal Practices Can Avert Poor Dietary Habits and Reduce Obesity Risk in Preschool Children of Mothers with Low Socioeconomic Status and Unemployment

Healthy nutritional habits are of vital importance for good health and quality of life for all individuals in all life stages. Nutritional habits shaped in early childhood set the foundation for future dietary practices applied through lifespan, hence informing risk towards chronic diseases. A key contributor to child health is maternal impact. A healthy childhood status translates into increased lifespan, health, and life-quality, as well as better family and social interactions and improved academic performance. These conditions can contribute to a healthier and more vibrant workforce, and thus extend positive impact on the economic and overall development of a country. Evidence related to maternal impact on childhood dietary habits is limited in Turkey, an emerging economy with notable disparities and a significant segment (approximately one third) of its 83 million population under the age of 30. Hence, the aim of this study was to investigate the relationship between the socioeconomic status (SES) of mothers on the dietary habits of their preschool children. A pilot cross-sectional observational study was conducted involving the mothers of 109 preschool children aged 4–6 years. Data on the nutritional status of children were collected through a food frequency questionnaire and a 24-h recall interview, while sociodemographic information was also collected, and statistical analyses conducted. An unexpected finding regarding the lack of association between the socioeconomic and employment status of mothers and the nutritional intakes of their children was observed. Interestingly, it appears that more traditional societal and nutritional practices typically undertaken in the case of lower SES, especially in more traditional settings like the case of Turkey, appear to extend a protective effect as per the nutritional habits and ensuing obesity risk in the case of children of women with lower SES. Another way to interpret our finding is that the difference in education and SES is not adequate to produce a significant effect in terms of children dietary intake. This is an interesting finding that warrants further study. Additionally, such studies serve to increase awareness about the importance of healthy nutritional practices in preschool children and the critical role of the mother on their nutritional status, particularly in the Turkish idiosyncratic setting.