Miracle-dz/UniFAR-FTUs huggingface dataset:
COVID-19 and Sepsis Are Associated With Different Abnormalities in Plasma Procoagulant and Fibrinolytic Activity

Supplemental Digital Content is available in the text. Objective: Coronavirus disease 2019 (COVID-19) is associated with derangement in biomarkers of coagulation and endothelial function and has been likened to the coagulopathy of sepsis. However, clinical laboratory metrics suggest key differences in these pathologies. We sought to determine whether plasma coagulation and fibrinolytic potential in patients with COVID-19 differ compared with healthy donors and critically ill patients with sepsis. Approach and Results: We performed comparative studies on plasmas from a single-center, cross-sectional observational study of 99 hospitalized patients (46 with COVID-19 and 53 with sepsis) and 18 healthy donors. We measured biomarkers of endogenous coagulation and fibrinolytic activity by immunoassays, thrombin, and plasmin generation potential by fluorescence and fibrin formation and lysis by turbidity. Compared with healthy donors, patients with COVID-19 or sepsis both had elevated fibrinogen, d-dimer, soluble TM (thrombomodulin), and plasmin-antiplasmin complexes. Patients with COVID-19 had increased thrombin generation potential despite prophylactic anticoagulation, whereas patients with sepsis did not. Plasma from patients with COVID-19 also had increased endogenous plasmin potential, whereas patients with sepsis showed delayed plasmin generation. The collective perturbations in plasma thrombin and plasmin generation permitted enhanced fibrin formation in both COVID-19 and sepsis. Unexpectedly, the lag times to thrombin, plasmin, and fibrin formation were prolonged with increased disease severity in COVID-19, suggesting a loss of coagulation-initiating mechanisms accompanies severe COVID-19. Conclusions: Both COVID-19 and sepsis are associated with endogenous activation of coagulation and fibrinolysis, but these diseases differently impact plasma procoagulant and fibrinolytic potential. Dysregulation of procoagulant and fibrinolytic pathways may uniquely contribute to the pathophysiology of COVID-19 and sepsis.
Machine Learning for Mortality Analysis in Patients with COVID-19

This paper analyzes a sample of patients hospitalized with COVID-19 in the region of Madrid (Spain). Survival analysis, logistic regression, and machine learning techniques (both supervised and unsupervised) are applied to carry out the analysis where the endpoint variable is the reason for hospital discharge (home or deceased). The different methods applied show the importance of variables such as age, O2 saturation at Emergency Rooms (ER), and whether the patient comes from a nursing home. In addition, biclustering is used to globally analyze the patient-drug dataset, extracting segments of patients. We highlight the validity of the classifiers developed to predict the mortality, reaching an appreciable accuracy. Finally, interpretable decision rules for estimating the risk of mortality of patients can be obtained from the decision tree, which can be crucial in the prioritization of medical care and resources.
Detection of Low-Level Fosfomycin-Resistant Variants by Decreasing Glucose-6-Phosphate Concentration in Fosfomycin Susceptibility Determination

Mutations that confer low-level fosfomycin resistance (LLFR) but not clinical resistance in Escherichia coli are increasingly reported. LLFR strains can become clinically resistant under urinary tract physiological conditions or may act as gateways for highly resistant subpopulations by the selection of additional LLFR mutations. Nevertheless, most LLFR strains are impossible to detect under routine fosfomycin susceptibility determinations. Here, we have explored the possibility of detecting LLFR variants by reducing glucose-6-phosphate (G6P) concentration in fosfomycin susceptibility testing for E. coli strains. As a proof of concept, fosfomycin minimal inhibitory concentrations (MICs) and disk diffusion susceptibility tests were performed for E. coli strain BW25113 and 10 isogenic derivatives carrying the most prevalent LLFR chromosomal mutations (∆uhpT, ∆glpT, ∆cyaA, and ∆ptsI) and their double combinations. Whereas standard G6P concentrations detected only ∆uhpT single and double variants, assays with reduced G6P detected all LLFR variants. In addition, G6P levels were determined to be ≤5 µg/mL in urine samples from 30 patients with urinary tract infection (UTI) caused by E. coli and 10 healthy volunteers, suggesting that most bacterial cells in uncomplicated UTIs are facing fosfomycin under low G6P concentration. Reducing G6P allows for the detection of LLFR variants, which may suppose a risk for future resistance development, especially in UTIs.
Accuracy of Heparin-Binding Protein in Diagnosing Sepsis: A Systematic Review and Meta-Analysis

Supplemental Digital Content is available in the text. OBJECTIVES: Existing studies evaluating the accuracy of heparin-binding protein for the diagnosis of sepsis have been inconsistent. We conducted a systematic review and meta-analysis to assess the totality of current evidence regarding the utility of heparin-binding protein to diagnose sepsis in patients with presumed systemic infection. DATA SOURCE: PubMed, Embase, the China National Knowledge infrastructure, and WangFang electronic database were searched from inception to December of 2019. STUDY SELECTION: Two independent reviewers identified eligible studies. Cohort and case-control studies, which measured serum levels of heparin-binding protein among adult patients with suspected sepsis, were eligible for inclusion. DATA EXTRACTION: Two reviewers independently extracted data elements from the selected studies. A bivariate random-effects meta-analysis model was used to synthesize the prognostic accuracy measures. Risk of bias of studies was assessed with Quality Assessment of Diagnostic Accuracy Studies 2 tool. DATA SYNTHESIS: We identified 26 studies with 3,868 patients in the meta-analysis. Heparin-binding protein had a pooled sensitivity of 0.85 (95% CI, 0.79–0.90) and a pooled specificity of 0.91 (95% CI, 0.82–0.96) for the diagnosis of sepsis. There was low heterogeneity between the studies (I2 = 12%), and no evidence of publication bias was detected. Heparin-binding protein had a higher sensitivity and specificity when compared with procalcitonin (0.75 [95% CI, 0.62–0.85] and 0.85 [95% CI, 0.73–0.92]) as well as C-reactive protein (0.75 [95% CI, 0.65–0.84] and 0.71 [95% CI, 0.63–0.77]). Serial measurements of heparin-binding protein also showed that heparin-binding protein levels rose significantly at least 24 hours before a diagnosis of sepsis. CONCLUSIONS: The diagnostic ability of heparin-binding protein is favorable, demonstrating both high sensitivity and specificity in predicting progression to sepsis in critically ill patients. Future studies could assess the incremental value that heparin-binding protein may add to a multimodal sepsis identification and prognostication algorithm for critically ill patients.
Intentions to “Reuse” Medication in the Future Modelled and Measured Using the Theory of Planned Behavior

Background: A range of pro-environmental behaviors are recognized, promoted, and investigated, but urgent action is also needed to tackle the direct and indirect environmental impact of medication waste. One solution is to reissue medicines, returned unused to pharmacies (i.e., reuse medicines). Yet, if medicines reuse is to be formally introduced in the UK, it is imperative also to understand people’s willingness to take part in such a scheme and importantly, the underpinning drivers. This study aimed to develop, validate, and evaluate a Theory of Planned Behavior model aimed at predicting medicines reuse behavioral intentions. Methods: The behavior of interest, medicines reuse, was defined according to its Target, Action, Context, and Time. Then themes from an existing qualitative study were used in order to draft, validate and pilot a Theory of Planned Behavior-based questionnaire before its completion by a representative sample (n = 1003) of participants from across the UK. Results: The majority expressed pro-medicines reuse intentions. The three direct measures accounted for 73.4% of the variance in relation to people’s intention to reuse medicines in the future, which was statistically significant at p < 0.001. People’s specific beliefs about medicines reuse and how they evaluate other people’s expectations of them had a substantial impact on their intentions to reuse medication in the future, mediated in an intricate way via attitudes, subjective norms and perceived behavioral control (PBC). Conclusions: This study shows how people could embrace medicines reuse via practical measures that illustrate the safety and quality assurance of reissued medicines, educational interventions that bolster beliefs about the pro-environmental benefits, and norm-based interventions encouraging doctors and pharmacists to endorse the practice. The findings add to the emerging work on medicines reuse and, significantly, provide a theoretical framework to guide policymakers and other organizations looking to decrease the impact of medication waste through medicines reuse schemes.
Osteogenic Properties of Novel Methylsulfonylmethane-Coated Hydroxyapatite Scaffold

Despite numerous advantages of using porous hydroxyapatite (HAp) scaffolds in bone regeneration, the material is limited in terms of osteoinduction. In this study, the porous scaffold made from nanosized HAp was coated with different concentrations of osteoinductive aqueous methylsulfonylmethane (MSM) solution (2.5, 5, 10, and 20%) and the corresponding MH scaffolds were referred to as MH2.5, MH5, MH10, and MH20, respectively. The results showed that all MH scaffolds resulted in burst release of MSM for up to 7 d. Cellular experiments were conducted using MC3T3-E1 preosteoblast cells, which showed no significant difference between the MH2.5 scaffold and the control with respect to the rate of cell proliferation (p > 0.05). There was no significant difference between each group at day 4 for alkaline phosphatase (ALP) activity, though the MH2.5 group showed higher level of activity than other groups at day 10. Calcium deposition, using alizarin red staining, showed that cell mineralization was significantly higher in the MH2.5 scaffold than that in the HAp scaffold (p < 0.0001). This study indicated that the MH2.5 scaffold has potential for both osteoinduction and osteoconduction in bone regeneration.
Size-Dependent Mechanical Properties of Amorphous SiO2 Nanowires: A Molecular Dynamics Study

Uniaxial tension tests were performed for amorphous SiO2 nanowires using molecular dynamics simulation to probe the size effect on the mechanical properties and plastic deformation by varying the length of nanowires. The simulation results showed that the Young’s modulus of SiO2 nanowires increased with the decrease of nanowires length due to its higher surface stress. The corresponding deformation of SiO2 nanowires during tension exhibited two periods: atomic arrangement at small strain and plastic deformation at large strain. During the atomic arrangement period, the percentage variations of atom number of 2-coordinated silicon and 3-coordinated silicon (PCN2 and PCN3) decreased, while the percentage variations of atom number of 4-coordinated silicon, 5-coordinated silicon (PCN4 and PCN5) and the Si–O bond number (PCB) rose slightly with increasing strain, as the strain was less than 22%. The situation reversed at the plastic deformation period, owing to the numerous breakage of Si–O bonds as the strain grew beyond 22%. The size effect of nanowires radius was considered, finding that the Young’s modulus and fracture stress were higher for the larger nanowire because of fewer dangling bonds and coordinate defeats in the surface area. The elastic deformation occurred at a small strain for the larger nanowire, followed by the massive plastic deformation during tension. A brittle mechanism covers the fracture characteristics, irrespective of the nanowire size.
Flanged fixation: Yamane technique and its application

Purpose of review To review variations of flanged intraocular lens fixation (Yamane technique) and their outcomes. Recent findings Sutureless intrascleral IOL fixation has become popular, and many techniques have been reported. Among them, the Yamane technique has been widely used in recent years, and there are many variations. However, there are no reports that systematically compare them. Summary There are variations of the Yamane technique, such as those used to create a scleral tunnel or to dock needles and haptics. Although few reports have directly compared each technique, small scleral wounds appear to be beneficial for long-term stability of the IOL. A method of fixing a capsule tension segment or iris using a flange has also been reported, demonstrating the diverse range of uses of the flange.
Identification of Patient Characteristics Associated With SARS-CoV-2 Infection and Outcome in Kidney Transplant Patients Using Serological Screening.

BACKGROUND From population studies, solid organ transplant recipients are at increased risk of mortality from RT-PCR confirmed COVID-19 infection. The risk factors associated with infection acquisition and mortality in transplant recipients using serological data has not been reported. METHODS From 1725 maintenance transplant recipients, 855 consecutive patients were screened for SARS-CoV2 antibodies. Serological screening utilized assays to detect both the N protein and Receptor binding domain antibodies. 33/855 (3.9%) of the screened patients had prior infection confirmed with RT-PCR. 21 additional patients from our 1725 maintenance cohort with RT-PCR confirmed infection were included in our analysis. RESULTS 89/855 (10.4%) patients tested positive for SARS-CoV-2 antibodies. 59/89 (66.3%) cases were patients newly identified as exposed, whilst 30/89 (33.7%) seropositive patients had previous infection confirmed by RT-PCR.A diagnosis of SARS-CoV2 (RT-PCR or Ab+) was associated with being from a noncaucasoid background, p=0.015; having a diagnosis of diabetes, p=0.028 and a history of allograft rejection, p<0.01. Compared with the RT-PCR+ cohort, patients with serological proven infection alone, were more likely to be receiving tacrolimus monotherapy, p<0.01 and less likely to have a diagnosis of diabetes, p=0.012. 17/113 (15.0%) of all patients with infection (RT-PCR and/or Ab+) died. Risk factors associated with survival were older age, OR:1.07 (1.00-1.13), p=0.041; receiving prednisolone, OR:5.98 (1.65-21.60), p<0.01 and the absence of diabetes, OR:0.27 (0.07-0.99), p=0.047. CONCLUSIONS This study identifies risk factors and outcome for COVID-19 infection incorporating data on serologically defined infection, and highlights the important contribution of immunosuppression regimen on outcomes.
Clinical Predictors of Transient versus Persistent Neonatal Hyperinsulinism

Introduction: Hyperinsulinism (HI), the most common neonatal cause of persistent hypoglycemia, can be associated with prolonged hospitalizations and risk for long-term neurological sequelae. Rapid identification of transient versus persistent forms of HI is crucial to optimize management. Objectives: The aims of the study were to assess the ability of clinical and biochemical features at presentation to predict transient versus persistent HI, and to evaluate differences in hospital outcomes. Methods: This study is a retrospective review of 79 infants with HI admitted to the Hospital for Sick Children, Toronto, from 2012 to 2017. Patients were classified into 3 groups: transient and the 2 persistent forms, diazoxide responsive and diazoxide unresponsive (DU). Results: Infants with birth weight >90th percentile had an 8-fold increased risk of having a persistent form of HI (OR 8.8, 95% CI 2.5–30) and a 21-fold increased risk of having a DU form of HI (OR 21.1, 95% CI 4.9–91.8). The majority of children with transient HI and a birth weight >90th percentile were born to mothers with gestational diabetes. There were no other useful clinical or biochemical presenting features that differentiated the groups. There were significant differences in outcome measures, with the DU children more likely to require gastrostomy tube insertion and have an extended length of hospital admission. Conclusion: A higher birth weight in the absence of maternal gestational diabetes is highly associated with a persistent form of HI. Given the marked difference in clinical outcomes between groups, expedited genetic testing should be considered in infants with this presentation to inform clinical management.
NAP1-Related Protein 1 (NRP1) has multiple interaction modes for chaperoning histones H2A-H2B

Significance NAP1 family proteins are evolutionarily conserved and important histone chaperones. However, because histone chaperones are very flexible, determination of their crystal structures, especially when complexed with histones, is very difficult. Here we obtained the co-crystal structure of Arabidopsis NAP1-Related Protein 1 (NRP1) and the H2A-H2B heterodimer at 3.0 Å, which led to the discovery of a previously unknown mode of interaction between the NAP1 family and H2A-H2B. Our results provide evidence of multiple interaction modes of a NAP1-family histone chaperone, thereby shedding light on how histone chaperones effectively shield H2A-H2B from nonspecific interaction with DNA. Nucleosome Assembly Protein 1 (NAP1) family proteins are evolutionarily conserved histone chaperones that play important roles in diverse biological processes. In this study, we determined the crystal structure of Arabidopsis NAP1-Related Protein 1 (NRP1) complexed with H2A-H2B and uncovered a previously unknown interaction mechanism in histone chaperoning. Both in vitro binding and in vivo plant rescue assays proved that interaction mediated by the N-terminal α-helix (αN) domain is essential for NRP1 function. In addition, the C-terminal acidic domain (CTAD) of NRP1 binds to H2A-H2B through a conserved mode similar to other histone chaperones. We further extended previous knowledge of the NAP1-conserved earmuff domain by mapping the amino acids of NRP1 involved in association with H2A-H2B. Finally, we showed that H2A-H2B interactions mediated by αN, earmuff, and CTAD domains are all required for the effective chaperone activity of NRP1. Collectively, our results reveal multiple interaction modes of a NAP1 family histone chaperone and shed light on how histone chaperones shield H2A-H2B from nonspecific interaction with DNA.
Trout and Human Plasma Protein Binding of Selected Pharmaceuticals Informs the Fish Plasma Model

Concerns are increasing that pharmaceuticals released into the environment pose a risk to nontarget organism such as fish. The fish plasma model is a read‐across approach that uses human therapeutic blood plasma concentrations for estimating likely effects in fish. However, the fish plasma model neglects differences in plasma protein binding between fish and humans. Because binding data for fish plasma are scarce, the binding of 12 active pharmaceutical ingredients (APIs; acidic, basic, and neutral) to rainbow trout (Oncorhynchus mykiss) and human plasma was measured using solid‐phase microextraction (SPME). The plasma/water distribution ratios (D plasma/w) of neutral and basic APIs were similar for trout and human plasma, differing by no more than a factor of 2.7 for a given API. For the acidic APIs, the D plasma/w values of trout plasma were much lower than for human plasma, by up to a factor of 71 for naproxen. The lower affinity of the acidic APIs to trout plasma compared with human plasma suggests that the bioavailability of these APIs is higher in trout. Read‐across approaches like the fish plasma model should account for differences in plasma protein binding to avoid over‐ or underestimation of effects in fish. For the acidic APIs, the effect ratio of the fish plasma model would increase by a factor of 5 to 60 if the unbound plasma concentrations were used to calculate the effect ratio. Environ Toxicol Chem 2022;41:559–568. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Efficacy of Deep Brain Stimulation on the Improvement of the Bladder Functions in Traumatic Brain Injured Rats

Objective: Traumatic brain injuries (TBIs) are a prime public health challenge with a high incidence of mortality, and also reflect severe economic impacts. One of their severe symptoms is bladder dysfunction. Conventional therapeutic methods are not effective in managing bladder dysfunction. Henceforth, a research endeavor was attempted to explore a new therapeutic approach for bladder dysfunction through deep brain stimulation (DBS) procedures in a TBI animal model. Methods: TBI in this animal model was induced by the weight-drop method. All rats with an induced TBI were housed for 4 weeks to allow severe bladder dysfunction to develop. Subsequently, an initial urodynamic measurement, the simultaneous recording of cystometric (CMG) and external urethral sphincter electromyography (EUS-EMG) activity was conducted to evaluate bladder function. Further, standard DBS procedures with varying electrical stimulation parameters were executed in the target area of the pedunculopontine tegmental nucleus (PPTg). Simultaneously, urodynamic measurements were re-established to compare the effects of DBS interventions on bladder functions. Results: From the variable combinations of electrical stimulation, DBS at 50 Hz and 2.0 V, significantly reverted the voiding efficiency from 39% to 69% in TBI rats. Furthermore, MRI studies revealed the precise localization of the DBS electrode in the target area. Conclusions: The results we obtained showed an insightful understanding of PPTg-DBS and its therapeutic applications in alleviating bladder dysfunction in rats with a TBI. Hence, the present study suggests that PPTg-DBS is an effective therapeutic strategy for treating bladder dysfunction.