Miracle-dz/UniFAR-FTUs huggingface dataset:
Anticoagulation in COVID-19: current concepts and controversies

Rising incidence of thromboembolism secondary to COVID-19 has become a global concern, with several surveys reporting increased mortality rates. Thrombogenic potential of the SARS-CoV-2 virus has been hypothesised to originate from its ability to produce an exaggerated inflammatory response leading to endothelial dysfunction. Anticoagulants have remained the primary modality of treatment of thromboembolism for decades. However, there is no universal consensus regarding the timing, dosage and duration of anticoagulation in COVID-19 as well as need for postdischarge prophylaxis. This article seeks to review the present guidelines and recommendations as well as the ongoing trials on use of anticoagulants in COVID-19, identify discrepancies between all these, and provide a comprehensive strategy regarding usage of these drugs in the current pandemic.
Influenza vaccination uptake and factors influencing vaccination decision among patients with chronic kidney or liver disease

Introduction Seasonal influenza is a major global health problem causing substantial morbidity and health care costs. Yet, in many countries, the rates of influenza vaccination remain low. Chronic kidney or liver diseases (CKLD) predispose patients to severe influenza infections, but data on vaccination acceptance and status is limited in this risk population. We investigated the influenza vaccination awareness considering sociodemographic factors in CKLD patients. Patients and methods This cross-sectional, questionnaire-based study recruited CKLD patients managed at three Viennese tertiary care centers between July and October 2020. CKLD was defined as chronic kidney- (all stages) or compensated/decompensated liver disease, including kidney/liver transplant recipients. Questionnaires assessed sociodemographic and transplant- associated parameters, patients vaccination status and the individuals self-perceived risks of infection and associated complications. Results In total 516 patients (38.1% female, mean age 56.4 years) were included. 43.9% of patients declared their willingness to be vaccinated in the winter season 2020/2021, compared to 25.4% in 2019/2020 and 27.3% in 2016–2018. Vaccination uptake was associated with the self-perceived risks of infection (OR: 2.8 (95%CI: 1.8–4.5), p<0.001) and associated complications (OR: 3.8 (95%CI: 2.3–6.3), p<0.001) as well as with previously received influenza vaccination (2019/2020: OR 17.1 (95%CI: 9.5–30.7), p<0.001; season 2016–2018: OR 8.9 (95%CI: 5.5–14.5), p<0.001). Most frequent reasons for not planning vaccination were fear of a) graft injury (33.3%), b) complications after vaccination (32.4%) and c) vaccine inefficiency (15.0%). Conclusion While influenza vaccination willingness in patients with CKLD is increasing in the 2020/2021 season, vaccination rates may still remain <50%. Novel co-operations with primary health care, active vaccination surveillance and financial reimbursement may substantially improve vaccination rates in high-risk CKLD patients.
Associations between different measurements of sarcopenic obesity and health outcomes among non-frail community-dwelling older adults in Taiwan

Abstract The most important issue for the clinical application of sarcopenic obesity (SO) is the lack of a consensus definition. The aim of the present study was to determine the best measurement for SO by estimating the association between various definitions and the risk of falls and metabolic syndrome (MS). We studied a community of 765 adults aged 65 years and older in 2015–2017. Sarcopenia obesity was measured by sarcopenia (defined by low muscle mass with either low handgrip strength or low gait speed or both) plus obesity (defined by waist circumference, body fat percentage and BMI). The MS was defined according to the National Cholesterol Education Program ATP III. Logistic regression models were constructed to examine the relationships between sarcopenia obesity and risk of fall and MS. In the analysis of the fall risk with SO defined by waist circumference, the participants with non-sarcopenia/non-obesity were treated as the reference group. The OR to fall in participants with SO was 10·16 (95 % CI 2·71, 38·13) after adjusting for confounding covariates. In the analysis of the risk of the MS between participants with individual components of sarcopenia coupled with obesity defined by waist circumference, the risk was statistically significant for low gait speed (OR: 7·19; 95 % CI 3·61, 14·30) and low grip strength (OR: 9·19; 95 % CI 5·00, 16·91). A combination of low grip strength and abdominal obesity for identifying SO may be a more precise and practical method for predicting target populations with unfavourable health risks, such as falls risk and MS.
Examination of Caregiver Social Factors and Its Influence on Low-Acuity Pediatric Emergency Department Utilization

Supplemental digital content is available in the text. Objectives Social factors, such as adverse childhood experiences (ACEs), often influence health care utilization. Our study explores the association between caregiver social factors and low-acuity pediatric emergency department (ED) utilization, with the hypothesis that caregivers with high ACE exposure may use ED services more frequently for low-acuity complaints. Methods In this case-control study, we performed surveys of caregivers with children aged 1 to 12 years registered for care in our pediatric ED. We defined high utilizers (cases) as those children with ≥3 low-acuity visits in the previous year and low utilizers (controls) as having no prior low-acuity visits, exclusive of the current visit. We compared the proportion of high ACE exposure (≥4 ACEs) between both groups. Results We enrolled 114 cases and 134 controls. We found no association between number of ACEs and odds of being a case or control (ED utilization). Demographics were significantly different between the 2 groups (ie, caregiver age, race, education, and household income); caregiver ACE exposure was high in both groups (20.2% cases vs 29.1% controls with [≥4 ACEs]). Conclusions Although we did not find an association between caregiver ACEs and frequent low-acuity pediatric ED utilization, our data shed light on the overall prevalence of caregiver ACEs in families that seek care in our pediatric ED, even for the first time. Our findings emphasize the risk of conscious bias that can lead to inaccuracy: assuming that it is only high utilizers who experience social stressors. Future work should explore the contribution of structural inequities that influence caretakers' decisions to seek care for their children for low-acuity complaints, and consider types of interventions that could address and mitigate these inequities.
Migrant Women’s Help-Seeking Decisions and Use of Support Resources for Intimate Partner Violence in China

In China, women who domestically relocate from rural or less developed regions to major cities are at a higher risk for intimate partner violence (IPV) than their non-migrant counterparts. Few studies have focused on Chinese domestic migrant women’s help-seeking for IPV and their use of different sources of support. The present study aimed to identify factors that influence migrant women’s help-seeking decisions. In addition, we also examined factors that contribute to migrant women’s use of diverse sources of support for IPV. A sample of 280 migrant women victimized by IPV in the past year at the time of the survey was drawn from a larger cross-sectional study conducted in four major urban cities in China, including Beijing, Shanghai, Guangzhou, and Shenzhen. Using a multinomial logistic regression model and a zero-inflated Poisson model, we found that factors influencing migrant women’s help-seeking decisions and their use of diverse sources of support included socioeconomic factors, IPV type, relationship-related factors, knowledge of China’s first anti-Domestic Violence Law, and perception of the effectiveness of current policies. We discuss implications for future research and interventions.
The Efficacy of LY293558 in Blocking Seizures and Associated Morphological, and Behavioral Alterations Induced by Soman in Immature Male Rats and the Role of the M1 Muscarinic Acetylcholine Receptor in Organophosphate Induced Seizures

Abstract : Poisoning by organophosphorous compounds (OPs) can produce severe symptoms including seizures or status epilepticus (SE), and if left untreated results in long-term brain damage and neuropsychiatric symptoms or death. OPs produce their toxic effects by irreversibly inhibiting the enzyme acetyl cholinesterase (AChE), which subsequently causes a hyper stimulation of the muscarinic acetylcholine receptors (mAChRs) and the nicotinic acetylcholine receptors (nAChRs). The use of OP nerve agents in attacks in Syria recently highlighted the importance of developing treatments for all ages, but specifically, this attack highlighted the importance of developing treatments for seizures induced by OP intoxication for children. We developed an immature rat model appropriate for testing novel anticonvulsants against the nerve agent soman. Using postnatal day 21 male rats (P21), we found them to be highly susceptible to seizure induction and mortality induced by soman exposure. Soman exposure in P21 rats produced profound reduction in the activity of AChE in numerous brain regions but suggested that this reduction must occur specifically in the basolateral amygdala (BLA) to produce seizures as animals that did not experience seizures still retained higher Ache activity within the BLA. Seizures, if treated within 20 min or 60 min post-soma exposure could be arrested with the administration of atropine sulfate (ATS) or theGluK1-subunit containing Kainate (GluK1KR)/-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptor Antagonist LY293558, respectively. We also found an additional GluK1KR antagonist, UBP302 to be efficacious in arresting soman induced seizures when treatment was administered at 60 min post-exposure. Delayed post treatment with LY293558 blocked volumetric reductions in the amygdala and hippocampus induced by soman exposure that was observed 30 or 90 days post-soma exposure in rats that did not receive LY293558 treatment.
Changes in nutrient balance, methane emissions, physiologic biomarkers and production performance in goats fed different forage-to-concentrate ratios during lactation.

The objective was to determine the effect forage to concentrate (F:C) ratio and stage of lactation on methane emissions, digestibility, nutrient balance, lactation performance, and metabolic responses in lactating goats. Twenty Murciano-Granadina dairy goats were used in an experiment divided into three periods: early (30 d), mid (100 d) and late (170 d) lactation. All goats were fed a diet with 35:65 F:C (FCL) during early-lactation. Then, one group (n = 10 goats) remained on FCL through mid and late-lactation while the other group (n = 10 goats) was fed a diet with 50:50 F:C at mid-lactation (FCM) and 65:35 (FCH) at late lactation. A greater proportion of concentrate in the diet was associated with greater overall intake and digestibility (P < 0.05). Energy balance was negative in early-lactation (-77 kJ/kg of BW 0.75, on average) and positive for FCL at mid and late-lactation (13 and 35 kJ/kg of BW 0.75, respectively). Goats fed FCM and FCH maintained negative energy balance throughout lactation. Plasma concentrations of non-esterified fatty acids (NEFA) at mid-lactation were greater for FCM than FCL (680 mEq/L), and at late-lactation concentrations were greater for FCH and FCL (856 mEq/L). A similar response was detected for plasma ß-Hydroxybutyrate (BHB). Methane emission was greater (P < 0.05) for FCM than FCH (1.7 g CH4/d). This study demonstrated that differences in F:C across stages of lactation lead to distinct metabolic responses at the level of the rumen and tissues.
Urodynamic findings in patients with complete and incomplete suprasacral spinal cord injury at different stages after injury.

BACKGROUND Urodynamics is the gold standard for evaluating the function of neurogenic bladder after spinal cord injury (SCI), but there are few studies on urodynamics in patients with complete and incomplete suprasacral SCI in different periods.There is a lack of sufficient evidence for the timing of the first urodynamic examination. METHODS The urodynamic results of 101 patients with complete and incomplete suprasacral SCI at 0-30, 31-60, 61-90, and 91-365 days after injury were included. Urodynamic parameters were compared between 0-90 and 91-365 days, including detrusor overactivity (DO), bladder compliance (BC), bladder-filling sensation, maximum cystometric capacity (MCC), detrusor external sphincter dyssynergia (DESD), maximum urinary flow rate (Qmax), detrusor pressure at a maximum urinary flow rate (PdetQmax). RESULTS There were 45 patients with complete SCI and 56 with incomplete SCI. With the course's prolongation, the proportion of DO increased gradually in patients with complete and incomplete injury within 90 days, while the MCC gradually decreased. The bladder-filling sensation of patients with complete SCI is mostly absent. Significant differences were found between 0-90 and 91-365 days in terms of DO, DESD, MCC, Qmax, and PdetQmax incomplete SCI, and DESD in incomplete SCI, and between complete and incomplete SCI in terms of DO, bladder filling sensation, MCC, Qmax, PdetQmax at 0-90 days after injury, and bladder filling sensation at 91-365 days after injury. CONCLUSIONS Urodynamic examination should be conducted as soon as possible after injury in patients with incomplete suprasacral SCI, while for those with complete injury, the urodynamic examination can be initiated following clinical symptoms within 90 days after injury.
Neurocognitive processing efficiency for discriminating human non-alarm rather than alarm scream calls

Across many species, scream calls signal the affective significance of events to other agents. Scream calls were often thought to be of generic alarming and fearful nature, to signal potential threats, with instantaneous, involuntary, and accurate recognition by perceivers. However, scream calls are more diverse in their affective signaling nature than being limited to fearfully alarming a threat, and thus the broader sociobiological relevance of various scream types is unclear. Here we used 4 different psychoacoustic, perceptual decision-making, and neuroimaging experiments in humans to demonstrate the existence of at least 6 psychoacoustically distinctive types of scream calls of both alarming and non-alarming nature, rather than there being only screams caused by fear or aggression. Second, based on perceptual and processing sensitivity measures for decision-making during scream recognition, we found that alarm screams (with some exceptions) were overall discriminated the worst, were responded to the slowest, and were associated with a lower perceptual sensitivity for their recognition compared with non-alarm screams. Third, the neural processing of alarm compared with non-alarm screams during an implicit processing task elicited only minimal neural signal and connectivity in perceivers, contrary to the frequent assumption of a threat processing bias of the primate neural system. These findings show that scream calls are more diverse in their signaling and communicative nature in humans than previously assumed, and, in contrast to a commonly observed threat processing bias in perceptual discriminations and neural processes, we found that especially non-alarm screams, and positive screams in particular, seem to have higher efficiency in speeded discriminations and the implicit neural processing of various scream types in humans.
Transcutaneous auricular vagal nerve stimulation inhibits hypothalamic P2Y1R expression and attenuates weight gain without decreasing food intake in Zucker diabetic fatty rats

Zucker diabetic fatty (ZDF) rats that harbor a mutation in the leptin receptor innately develop type 2 diabetes (T2D) with obesity. Transcutaneous auricular vagal nerve stimulation (taVNS) has an antidiabetic effect in ZDF rats. However, the underlying mechanisms of the weight-gain attenuating effect in ZDF rats by taVNS is still unclear. This study aimed to assess whether the weight-gain attenuating effect of taVNS in ZDF rats is associated with changes in the central nervous system (CNS) expression of P2Y1 receptors (P2Y1R). Adult male ZDF rats were subjected to taVNS and transcutaneous non-vagal nerve stimulation (tnVNS). Their food intake and body weight were recorded daily and weekly, respectively. P2Y1R expression in the hypothalamus, amygdala, and hippocampus was evaluated by western blotting. Hypothalamic P2Y1R expressing cells were detected using immunohistochemistry. Naïve ZDF rats were much heavier (p < 0.05) than their lean littermates (ZL rats), with elevated hypothalamic P2Y1R expression (p < 0.05). Further, taVNS but not tnVNS attenuated weight gain (p < 0.05) without decreasing food intake (p > 0.05) and suppressed hypothalamic P2Y1R expression in ZDF rats (p < 0.05). Moreover, P2Y1R showed major expression in astrocytes of ZDF rats’ hypothalamus. ZDF rats innately develop obesity associated with elevated hypothalamic P2Y1R expression. taVNS attenuates weight gain in ZDF rats without changes in food intake, suggesting increased energy expenditure. Whether the reduced hypothalamic P2Y1R expression in response to taVNS is mechanistically linked to the increased energy expenditure remains to be determined.
Monoallelic mutations in SLCO2A1 cause autosomal dominant primary hypertrophic osteoarthropathy

Primary hypertrophic osteoarthropathy (PHO) is a rare disease inherited as a recessive or irregular dominant trait and characterized by digital clubbing, pachydermia, and periostosis. Biallelic mutations in HPGD and SLCO2A1, disturbing prostaglandin E2 (PGE2) catabolism and leading to increased circulating PGE2 level, cause PHO autosomal recessive 1 (PHOAR1) and PHO autosomal recessive 2 (PHOAR2), respectively. However, no causative genes have been reported for PHO autosomal dominant (PHOAD). Here, we performed Sanger sequencing and whole‐genome sequencing (WGS) on DNA samples from seven Chinese PHOAD families; after excluding other single‐nucleotide variants (SNVs), structural variations (SVs), and copy number variations (CNVs) in the genomes, we reported six SLCO2A1 monoallelic mutations (c.1660G>A [p.G554R], c.664G>A [p.G222R], c.1106G>A [p.G369D], c.1065dupA [p.Q356TfsX77], c.1293delT [p.S432AfsX48], and c.1807C>T [p.R603X]) in the probands and affected family members. Then, in five other PHO families with probands carrying SLCO2A1 biallelic mutations, we verified that parents with SLCO2A1 monoallelic mutations also displayed PHO manifestations, which further confirmed the pathogenicity of SLCO2A1 monoallelic mutations and illustrated the allelic nature of PHOAD and PHOAR2. Subsequently, through comparison of seven PHOAD probands and 50 PHOAR2 patients, we found onset age in puberty and skewed penetrance rate were similar in both PHO types, but symptoms and signs of PHOAD were milder, including less severe pachydermia (p = .027) and periostosis (p = .005), and less frequent cutis verticis gyrata (p = .011), acne (p = .005), arthralgia (p = .037), and anemia (p = .023). The median urinary PGE2 level in PHOAD probands was almost half that in PHOAR2 patients (PHOAD 277.58 ng/mmoL creatinine, PHOAR2 473.19 ng/mmoL creatinine; p = .038). Moreover, through the 3‐month trial of oral administration of etoricoxib, an effective response similar to that we reported previously in PHOAR2 patients was observed in PHOAD probands. In conclusion, our findings confirm that SLCO2A1 monoallelic mutations are the cause of PHOAD and broaden phenotypic spectrum of PHO. © 2021 American Society for Bone and Mineral Research (ASBMR).
Very Low-Frequency Broadband Electron Paramagnetic Resonance Spectroscopy of Metalloproteins

A previously developed spectrometer for broadband electron paramagnetic resonance (EPR) spectroscopy of dilute randomly oriented systems has been considerably modified to extend the frequency reach down to the hundred MHz range and to boost concentration sensitivity by 1 to 2 orders of magnitude. The instrument is now suitable for the study of biological systems in particular metalloproteins. As a proof of concept, examples from the class of low-spin ferric hemoproteins are studied in terms of frequency-dependent changes in their EPR spectra. Mono-heme cytochrome c EPR is determined by g-strain over a wide frequency range, whereas a combination of unresolved ligand hyperfine interaction and concentration-dependent intermolecular dipolar interaction becomes dominant at very low frequencies. In the four heme containing cytochrome c3, g-strain combines with intramolecular dipolar interaction over the full-studied frequency range of 0.23–12.0 GHz. It is concluded that the point-dipole approach is inappropriate to describe magnetic interactions between low-spin ferric heme systems and that a body of literature on redox interactions in multi-heme proteins will be affected by this conclusion.
Secreted Extracellular Cyclophilin A is a Novel Mediator of Ventilator Induced Lung Injury.

RATIONALE Mechanical ventilation is a mainstay of intensive care but contributes to the mortality of patients through ventilator induced lung injury. Extracellular Cyclophilin A is an emerging inflammatory mediator and metalloproteinase inducer, and the gene responsible for its expression has recently been linked to COVID-19 infection. OBJECTIVES Here we explore the involvement of extracellular Cyclophilin A in the pathophysiology of ventilator-induced lung injury. METHODS Mice were ventilated with low or high tidal volume for up to 3 hours, with or without blockade of extracellular Cyclophilin A signalling, and lung injury and inflammation were evaluated. Human primary alveolar epithelial cells were exposed to in vitro stretch to explore the cellular source of extracellular Cyclophilin A, and Cyclophilin A levels were measured in bronchoalveolar lavage fluid from acute respiratory distress syndrome patients, to evaluate clinical relevance. MEASUREMENTS AND MAIN RESULTS High tidal volume ventilation in mice provoked a rapid increase in soluble Cyclophilin A levels in the alveolar space, but not plasma. In vivo ventilation and in vitro stretch experiments indicated alveolar epithelium as the likely major source. In vivo blockade of extracellular Cyclophilin A signalling substantially attenuated physiological dysfunction, macrophage activation and matrix metalloproteinases. Finally, we found that patients with acute respiratory distress syndrome showed markedly elevated levels of extracellular Cyclophilin A within bronchoalveolar lavage. CONCLUSIONS Cyclophilin A is upregulated within the lungs of injuriously ventilated mice (and critically ill patients), where it plays a significant role in lung injury. Extracellular Cyclophilin A represents an exciting novel target for pharmacological intervention.