Miracle-dz/UniFAR-FTUs huggingface dataset:
Preventive use of beta-blockers for anthracycline-induced cardiotoxicity: A network meta-analysis

Background Anthracyclines are commonly used chemotherapeutic agents to treat malignant tumors. However, cardiotoxicity is a potentially serious adverse effect of anthracyclines. Beta-blockers may be effective in preventing anthracycline-induced cardiotoxicity (AIC). However, the lack of direct comparisons of various beta-blockers interferes with clinical decision-making. Network meta-analysis (NMA) was performed to assess the effectiveness of beta-blockers for AIC. Methods We searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Clinical Trials. The last update was in May 2022. Randomized controlled trials (RCT) of beta-blockers for AIC were included. Four beta-blockers were selected for comparison based on the number of studies. NMA was conducted with STATA 14.0 software. Results A total of 10 RCTs (875 patients) met the selection criteria. NMA results showed that carvedilol was superior to bisoprolol [SMD = −0.50, 95% CI (−0.91, −0.10)] and nebivolol [SMD = −1.46, 95%CI (−2.82, −0.11)] in a delay of LVEF. The results of the cumulative probability ordering are as follows: carvedilol (83.8%) > metoprolol (71.8%) > bisoprolol (43.9%) > placebo (40.9%) > nebivolol (9.5%). Conclusion Based on the available evidence, carvedilol is the best beta-blocker for AIC, followed by metoprolol. However, additional studies with large samples should be conducted to confirm our findings.
Analysis of circulating respiratory syncytial virus A strains in Shanghai, China identified a new and increasingly prevalent lineage within the dominant ON1 genotype

Respiratory syncytial virus A (RSV-A) is one of the commonest pathogens causing acute respiratory tract infections in infants and children globally. The currently dominant circulating genotype of RSV-A, ON1, was first detected in Shanghai, China in 2011, but little data are available regarding its subsequent circulation and clinical impact here. In this work, we analyzed RSV-A infection in a cohort of patients hospitalized for acute respiratory infections in Shanghai Children’s Hospital, and RSV-A was detected in ~10% of these cases. RSV-A G gene sequencing revealed that all successfully sequenced strains belonged to ON1 genotype, but in phylogenetic analysis, the majority of these sequences formed a clade separate from the four previously established lineages within ON1. The new lineage, denoted ON1-5, was supported by phylogenetic analyses using additional G gene sequences from RSV-A strains isolated in Shanghai and elsewhere. ON1-5 first appeared in 2015 in China and the Netherlands, and has since spread to multiple continents and gained dominance in Asia. In our cohort, ON1-5 was not associated with markedly different clinical presentations compared to other ON1 lineages. ON1-5 strains are characterized by four amino acid variations in the two mucin-like regions of G protein, and one variation (N178G) within the highly conserved CCD domain that is involved in receptor binding. These data highlight the continuous evolution of RSV-A, and suggest the possibility of the virus acquiring variations in domains traditionally considered to be conserved for fitness gain.
Differential effects of warming and acidification on chemosensory transmission and detection may strengthen non-consumptive effects of blue crab predators (Callinectes sapidus) on mud crab prey (Panopeus herbstii)

Predators control prey abundance and behavior, both of which strongly influence community dynamics. However, the relative importance of these predator effects may shift with climate change stressors, suggesting understanding the potential effects on these different processes is critical to predicting effects of climate change on community function. We investigated the effects of global warming and ocean acidification on the transmission and detection of chemical cues from blue crab predators (Callinectes sapidus) by mud crab prey (Panopeus herbstii). We measured mud crab feeding rates in the presence of blue crab predator cues, using either predator cues stressed in acidified conditions or mud crabs stressed in warmed and acidified conditions. Mud crabs consumed less food in the presence of predator cues, but acidifying the cues or subjecting mud crabs receiving the cues to acidified environment did not affect this antipredator response. Mud crabs in warmed conditions consumed significantly less food regardless of predator cue, but this effect was reversed in ambient conditions. Therefore, climate change may produce shifts in community regulation as warming potentially compromises consumptive effects of predators by reducing motor function, whereas non-consumptive effects mediated by sensory transmission and detection remain unaffected by acidification. Overall, warming may have stronger effects than acidification on community dynamics in oyster reefs as global temperatures continue to rise.
Forecasting the volatility of European Union allowance futures with time-varying higher moments and time-varying risk aversion

There is increasing evidence that European Union allowance (EUA) futures return distributions exhibit features of time-varying higher moments (skewness and kurtosis), which plays an important role in modeling and forecasting EUA futures volatility. Moreover, a number of studies have shown that time-varying risk aversion (RA) contains useful information for forecasting EUA futures volatility. In light of this, this paper proposes the GARCH-MIDAS with skewness and kurtosis (hereafter GARCH-MIDAS-SK) to empirically investigate the impact and predictive role of RA on EUA futures volatility. Our empirical results show that RA has a significantly negative impact on the long-term volatility of EUA futures. The EUA futures return distributions exhibit obvious features of time-varying higher moments. Incorporating RA and time-varying higher moments improves the in-sample fitting of the model. Furthermore, out-of-sample results suggest that incorporating RA and time-varying higher moments leads to significantly more accurate volatility forecasts. This finding is robust to alternative out-of-sample forecasting windows.
Effectiveness of treating depression with eye movement desensitization and reprocessing among inpatients–A follow-up study over 12 months

Increasing prevalence of depression poses a huge challenge to the healthcare systems, and the success rates of current standard therapies are limited. While 30% of treated patients do not experience a full remission after treatment, more than 75% of patients suffer from recurrent depressive episodes. Eye Movement Desensitization and Reprocessing (EMDR) therapy represents an emerging treatment option of depression, and preliminary studies show promising effects with a probably higher remission rate when compared to control-therapies such as cognitive behavioral therapy. In the present study, 49 patients with severe depression were treated with an integrated systemic treatment approach including EMDR therapy that followed a specific protocol with a treatment algorithm for depression in a naturalistic hospital setting. Following their discharge from the hospital, the patients were followed up by a structured telephone interview after 3 and 12 months. 27 of the 49 (55%) patients fulfilled the Beck’s depression criteria of a full remission when they were discharged. At the follow-up interview, 12 months after discharge, 7 of the 27 patients (26%) reported a relapse, while the remaining 20 patients (74%) had stayed relapse-free. The findings of our observational study confirm reports of earlier studies in patients with depression, showing that EMDR therapy leads to a high rate of remission, and is associated with a decreased number of relapses. Patients with depression receiving EMDR treatment may be more resilient to stressors.
A pilot study about on-farm assessment of health and welfare in rabbits kept in different housing systems

This pilot study tested an on-farm protocol based on resource, management, and animal-based measures to evaluate the on-farm health and welfare of rabbits kept in four different housing systems. In detail, the four housing systems were (1) standard breeding cages for reproducing does (3,300 cm2) with their litters associated with bicellular cages for growing rabbits (1,200 cm2); (2) dual-purpose cages for both reproducing does and growing rabbits (3,655 cm2); (3) enriched cages (4,739 cm2) for both reproducing does and growing rabbits equipped with a wire-mesh elevated platform (1,015 cm2); (4) parks (30,977 cm2) made up of four modules (7,744 cm2 each) joined by removing the wire net walls between them with growing rabbits kept in collective parks and reproducing does individually in the single modules. A total of 12 commercial farms (three farms/four housing systems) were visited during three seasons (summer, autumn, and winter) on two occasions each: (1) a pre-weaning visit for recordings on reproducing does and litters and (2) a pre-slaughtering visit for recordings on growing rabbits. At the pre-weaning visit, the prevalence of health concerns did not differ among does and litters kept in the different housing systems. At the pre-slaughtering visit, a higher prevalence of dermatomycosis was found in farms with dual-purpose cages and parks. Overall, taking into account the limitations due to the small sample size per housing system and the field conditions, the on-farm assessment tested in the present pilot study did not highlight major differences in the welfare and health of reproducing does and their kits as well as of growing rabbits in farms using different housing systems, which need to be confirmed on a large number of farms. The study also outlined the role of several management and environmental factors changing from one farm to another, which stresses the troubles of accounting for on-farm rabbit welfare and health exclusively to the housing system.
Persistent but atypical germinal center reaction among 3rd SARS-CoV-2 vaccination after rituximab exposure

Background Durable vaccine-mediated immunity relies on the generation of long-lived plasma cells and memory B cells (MBCs), differentiating upon germinal center (GC) reactions. SARS-CoV-2 mRNA vaccination induces a strong GC response in healthy volunteers (HC), but limited data is available about response longevity upon rituximab treatment. Methods We evaluated humoral and cellular responses upon 3rd vaccination in seven patients with rheumatoid arthritis (RA) who initially mounted anti-spike SARS-CoV-2 IgG antibodies after primary 2x vaccination and got re-exposed to rituximab (RTX) 1-2 months after the second vaccination. Ten patients with RA on other therapies and ten HC represented the control groups. As control for known long-lived induced immunity, we analyzed humoral and cellular tetanus toxoid (TT) immune responses in steady-state. Results After 3rd vaccination, 5/7 seroconverted RTX patients revealed lower anti-SARS-CoV-2 IgG levels but similar neutralizing capacity compared with HC. Antibody levels after 3rd vaccination correlated with values after 2nd vaccination. Despite significant reduction of circulating total and antigen-specific B cells in RTX re-exposed patients, we observed the induction of IgG+ MBCs upon 3rd vaccination. Notably, only RTX treated patients revealed a high amount of IgA+ MBCs before and IgA+ plasmablasts after 3rd vaccination. IgA+ B cells were not part of the steady state TT+ B cell pool. TNF-secretion and generation of effector memory CD4 spike-specific T cells were significantly boosted upon 3rd vaccination. Summary On the basis of pre-existing affinity matured MBCs within primary immunisation, RTX re-exposed patients revealed a persistent but atypical GC immune response accompanied by boosted spike-specific memory CD4 T cells upon SARS-CoV-2 recall vaccination.
Development and validation of a nomogram to predict the 30-day mortality risk of patients with intracerebral hemorrhage

Background Intracerebral hemorrhage (ICH) is a stroke syndrome with an unfavorable prognosis. Currently, there is no comprehensive clinical indicator for mortality prediction of ICH patients. The purpose of our study was to construct and evaluate a nomogram for predicting the 30-day mortality risk of ICH patients. Methods ICH patients were extracted from the MIMIC-III database according to the ICD-9 code and randomly divided into training and verification cohorts. The least absolute shrinkage and selection operator (LASSO) method and multivariate logistic regression were applied to determine independent risk factors. These risk factors were used to construct a nomogram model for predicting the 30-day mortality risk of ICH patients. The nomogram was verified by the area under the receiver operating characteristic curve (AUC), integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision curve analysis (DCA). Results A total of 890 ICH patients were included in the study. Logistic regression analysis revealed that age (OR = 1.05, P < 0.001), Glasgow Coma Scale score (OR = 0.91, P < 0.001), creatinine (OR = 1.30, P < 0.001), white blood cell count (OR = 1.10, P < 0.001), temperature (OR = 1.73, P < 0.001), glucose (OR = 1.01, P < 0.001), urine output (OR = 1.00, P = 0.020), and bleeding volume (OR = 1.02, P < 0.001) were independent risk factors for 30-day mortality of ICH patients. The calibration curve indicated that the nomogram was well calibrated. When predicting the 30-day mortality risk, the nomogram exhibited good discrimination in the training and validation cohorts (C-index: 0.782 and 0.778, respectively). The AUCs were 0.778, 0.733, and 0.728 for the nomogram, Simplified Acute Physiology Score II (SAPSII), and Oxford Acute Severity of Illness Score (OASIS), respectively, in the validation cohort. The IDI and NRI calculations and DCA analysis revealed that the nomogram model had a greater net benefit than the SAPSII and OASIS scoring systems. Conclusion This study identified independent risk factors for 30-day mortality of ICH patients and constructed a predictive nomogram model, which may help to improve the prognosis of ICH patients.
ANGPTL8 promotes adipogenic differentiation of mesenchymal stem cells: potential role in ectopic lipid deposition

Background Ectopic lipid deposition plays a promoting role in many chronic metabolic diseases. Abnormal adipogenic differentiation of mesenchymal stem cells (MSCs) is an important cause of lipid deposition in organs. Studies have shown that serum angiopoietin-like protein 8 (ANGPTL8) levels are increased in patients with many chronic metabolic diseases (such as type 2 diabetes, obesity, and hepatic steatosis), while the role of ANGPTL8 in ectopic lipid accumulation has not been reported. Methods We used the Gene Expression Omnibus (GEO) database to analyze the expression of ANGPTL8 in subcutaneous adipose tissue of obese patients and qPCR to analyze the expression of ANGPTL8 in the liver of high-fat diet (HFD)-induced obese mice. To explore the potential roles of ANGPTL8 in the progression of ectopic lipid deposition, ANGPTL8 knockout (KO) mice were constructed, and obesity models were induced by diet and ovariectomy (OVX). We analyzed lipid deposition (TG) in the liver, kidney, and heart tissues of different groups of mice by Oil Red O, Sudan black B staining, and the single reagent GPO-PAP method. We isolated and characterized MSCs to analyze the regulatory effect of ANGPTL8 on Wnt/β-Catenin, a key pathway in adipogenic differentiation. Finally, we used the pathway activator LiCl and a GSK3β inhibitor (i.e., CHIR99021) to analyze the regulatory mechanism of this pathway by ANGPTL8. Results ANGPTL8 is highly expressed in the subcutaneous adipose tissue of obese patients and the liver of HFD-induced obese mice. Both normal chow diet (NCD)- and HFD-treated ANGPTL8 KO male mice gained significantly less weight than wild-type (WT) male mice and reduced ectopic lipid deposition in organs. However, the female mice of ANGPTL8 KO, especially the HFD group, did not show differences in body weight or ectopic lipid deposition because HFD could induce estrogen overexpression and then downregulate ANGPTL8 expression, thereby counteracting the reduction in HFD-induced ectopic lipid deposition by ANGPTL8 deletion, and this result was also further proven by the OVX model. Mechanistic studies demonstrated that ANGPTL8 could promote the differentiation of MSCs into adipocytes by inhibiting the Wnt/β-Catenin pathway and upregulating PPARγ and c/EBPα mRNA expression. Conclusions ANGPTL8 promotes the differentiation of MSCs into adipocytes, suggesting that ANGPTL8 may be a new target for the prevention and treatment of ectopic lipid deposition in males.
Clinical implications of central blood pressure measured by radial tonometry and automated office blood pressure measured using automatic devices in cardiovascular diseases

Objective Central aortic systolic blood pressure (CBP) measured by carotid-femoral pulse wave analysis (cfPWA) is a gold standard method to estimate true arterial pressure. However, the impact of the CBP level measured by radial PWA on cardiovascular (CV) risk assessment is unclear. This study aimed to determine the impact on CV outcome assessment and the association between the optimal levels of non-invasively measured CBP and automated office blood pressure (OBP) in clinical practice. Materials and methods A total of 2,115 patients underwent non-invasive semiautomated radial artery applanation tonometry (Omron HEM-9000AI) in the Department of Internal Medicine, St. Vincent’s Hospital, from July 2011 to December 2015. The patients were followed for at least 5 years, and atherosclerotic cardiovascular (ASCVD) outcomes were collected. Results Among 2,115 patients (mean age 58 ± 14 years, 50.4% men) who were followed up, the median follow-up period was 52 months (range: 1–104 months). The total number of patients with ASCVD events was 163 (7.70%). In multivariate Cox regression analysis, a CBP of more than 125 mmHg and an automated OBP of more than 131 mmHg were independently associated with a significant increase in ASCVD outcomes. After adjusting for confounding factors, the hazard ratio for ASCVD events increased by 12.5, 11.7, and 12.7%, for every 10 mmHg increase in automated OBP, CBP, and central pulse pressure (PP), respectively. Conclusion This study demonstrated that the automated OBP measured using the method used in real clinical practice and CBP measured by radial tonometry were associated with an increased risk for adverse ASCVD outcomes.
Synaptic spinules are reliable indicators of excitatory presynaptic bouton size and strength and are ubiquitous components of excitatory synapses in CA1 hippocampus

Synaptic spinules are thin, finger-like projections from one neuron that become embedded within the presynaptic or postsynaptic compartments of another neuron. While spinules are conserved features of synapses across the animal kingdom, their specific function(s) remain unknown. Recent focused ion beam scanning electron microscopy (FIB-SEM) image volume analyses have demonstrated that spinules are embedded within ∼25% of excitatory boutons in primary visual cortex, yet the diversity of spinule sizes, origins, and ultrastructural relationships to their boutons remained unclear. To begin to uncover the function of synaptic spinules, we sought to determine the abundance, origins, and 3D ultrastructure of spinules within excitatory presynaptic spinule-bearing boutons (SBBs) in mammalian CA1 hippocampus and compare them with presynaptic boutons bereft of spinules (non-SBBs). Accordingly, we performed a comprehensive 3D analysis of every excitatory presynaptic bouton, their embedded spinules, and postsynaptic densities, within a 5 nm isotropic FIB-SEM image volume from CA1 hippocampus of an adult male rat. Surprisingly, we found that ∼74% of excitatory presynaptic boutons in this volume contained at least one spinule, suggesting they are fundamental components of excitatory synapses in CA1. In addition, we found that SBBs are 2.5-times larger and have 60% larger postsynaptic densities (PSDs) than non-SBBs. Moreover, synaptic spinules within SBBs are clearly differentiated into two groups: small clathrin-coated spinules, and 29-times larger spinules without clathrin. Together, these findings suggest that the presence of a spinule is a marker for stronger and more stable presynaptic boutons in CA1, and that synaptic spinules serve at least two separable and distinct functions.
Heparin-binding protein-enhanced quick SOFA score improves mortality prediction in sepsis patients

Purpose The Quick Sequential Organ Failure Assessment (qSOFA) score proposed by Sepsis-3 as a sepsis screening tool has shown suboptimal accuracy. Heparin-binding protein (HBP) has been shown to identify early sepsis with high accuracy. Herein, we aim to investigate whether or not HBP improves the model performance of qSOFA. Methods We conducted a multicenter prospective observational study of 794 adult patients who presented to the emergency department (ED) with presumed sepsis between 2018 and 2019. For each participant, serum HBP levels were measured and the hospital course was followed. The qSOFA score was used as the comparator. The data was split into a training dataset (n = 556) and a validation dataset (n = 238). The primary endpoint was 30-day all-cause mortality. Results Compared with survivors, non-survivors had significantly higher serum HBP levels (median: 71.5 ng/mL vs 209.5 ng/mL, p < 0.001). Serum level of HBP weakly correlated with qSOFA class (r2 = 0.240, p < 0.001). Compared with the qSOFA model alone, the addition of admission HBP level to the qSOFA model significantly improved 30-day mortality discrimination (AUC, 0.70 vs. 0.80; P < 0.001), net reclassification improvement [26% (CI, 17–35%); P < 0.001], and integrated discrimination improvement [12% (CI, 9–14%); P < 0.001]. Addition of C-reactive protein (CRP) level or neutrophil-to-lymphocyte ratio (NLR) to qSOFA did not improve its performance. A web-based mortality risk prediction calculator was created to facilitate clinical implementation. Conclusion This study confirms the value of combining qSOFA and HBP in predicting sepsis mortality. The web calculator provides a user-friendly tool for clinical implementation. Further validation in different patient populations is needed before widespread application of this prediction model.