Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanical stretch promotes tenocyte migration via chromatin remodelling‐mediated nuclear morphology changes

Wound healing and function recovery of injured tendons are still a big challenge for orthopaedic surgery. Evidence in clinic shows that early controlled motion has significant favourable effects on tendon healing; however, the mechanisms involved in are not fully understood. In the present study, it was shown that an appropriate mechanical stretch (10% strain, 0.5 Hz for 1 h) evidently promotes rat tenocyte migration and nuclear morphology changes. The farther research discovered that mechanical stretch had no effect on Lamin A/C expression, but it could promote chromatin decondensation. Moreover, the histone modification plays an important role in mechanical stretch‐mediated chromatin decondensation. Inhibition histone modification could inhibit mechanical stretch‐promoted nuclear morphology changes and tenocyte migration. These results indicating that mechanical stretch may promote tenocyte migration via chromatin remodelling‐mediated nuclear morphology changes, which contribute to a better understanding of the role of mechanical stretch on tenocyte migration and repair of injured tendon.
Household wealth, neighbourhood deprivation and frailty amongst middle-aged and older adults in England: a longitudinal analysis over 15 years (2002–2017)

Abstract Background frailty is a condition of reduced function and health due to ageing processes and is associated with a higher risk of falls, hospitalisation, disability and mortality. Objective to determine the relationship between household wealth and neighbourhood deprivation with frailty status, independently of demographic factors, educational attainment and health behaviours. Design population-based cohort study. Setting communities in England. Subjects in total 17,438 adults aged 50+ from the English Longitudinal Study of Ageing. Methods multilevel mixed-effects ordered logistic regression was used in this study. Frailty was measured using a frailty index. We defined small geographic areas (neighbourhoods) using English Lower layer Super Output Areas. Neighbourhood deprivation was measured by the English Index of Multiple Deprivation, grouped into quintiles. Health behaviours included in this study are smoking and frequency of alcohol consumption. Results the proportion of respondents who were prefrail and frail were 33.8% [95% confidence interval (CI) 33.0–34.6%] and 11.7 (11.1–12.2)%, respectively. Participants in the lowest wealth quintile and living in the most deprived neighbourhood quintile had 1.3 (95% CI = 1.2–1.3) and 2.2 (95% CI = 2.1–2.4) times higher odds of being prefrail and frail, respectively, than the wealthiest participants living in the least deprived neighbourhoods Living in more deprived neighbourhood and poorer wealth was associated with an increased risk of becoming frail. Those inequalities did not change over time. Conclusions in this population-based sample, living in a deprived area or having low wealth was associated with frailty in middle-aged and older adults. This relationship was independent of the effects of individual demographic characteristics and health behaviours.
Associations between ABO non‐identical platelet transfusions and patient outcomes—A multicenter retrospective analysis

Due to platelet availability limitations, platelet units ABO mismatched to recipients are often transfused. However, since platelets express ABO antigens and are collected in plasma which may contain ABO isohemagglutinins, it remains controversial as to whether ABO non‐identical platelet transfusions could potentially pose harm and/or have reduced efficacy.
Adherence and clinical outcomes for twice-daily versus once-daily dosing of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: Is dosing frequency important?

Background Twice-daily dosing of non-vitamin K antagonist oral anticoagulants (NOACs) may reduce drug adherence compared with once-daily dosing of NOACs in patients with atrial fibrillation (AF), thus worsening clinical outcomes. We evaluated adherence to apixaban and dabigatran requiring twice-daily dosing compared with edoxaban or rivaroxaban with a once-daily dosing regimen and the subsequent clinical outcomes in patients with AF. Methods Adherence to each NOAC and outcomes were compared between patients who were diagnosed with AF and initiated NOACs between 2016 and 2017 using Korean claims data. High adherence was defined as the proportion of days covered (PDC) of the index NOAC ≥80%. The clinical outcomes included stroke, acute myocardial infarction, death, and composite outcome. Results A total of 33,515 patients were analyzed (mean follow-up, 1.7 ± 1.3 years). The proportion of patients with high adherence to NOACs was 95%, which did not significantly differ according to the dosing regimen. The mean PDC for NOACs was as high as ~96%, which was the highest for apixaban users, intermediate for edoxaban or rivaroxaban users, and lowest for dabigatran users, regardless of the dosing regimen. Adverse outcomes in low adherence patients for each NOAC were higher than that of high adherence patients, regardless of the dosing frequency. Conclusions Adherence between once- and twice-daily dosing NOACs in patients with AF was high and similar among both dosing regimens. Patients with low NOAC adherence had poorer clinical outcomes, regardless of the dosing frequency.
Associations of HIV and iron status with gut microbiota composition, gut inflammation and gut integrity in South African school‐age children: a two‐way factorial case–control study

Abstract Background Human immunodeficiency virus (HIV) and iron deficiency (ID) affect many African children. Both HIV and iron status interact with gut microbiota composition and related biomarkers. The study's aim was to determine the associations of HIV and iron status with gut microbiota composition, gut inflammation and gut integrity in South African school‐age children. Methods In this two‐way factorial case–control study, 8‐ to 13‐year‐old children were enrolled into four groups based on their HIV and iron status: (1) With HIV (HIV+) and ID (n = 43), (2) HIV+ and iron‐sufficient nonanaemic (n = 41), (3) without HIV (HIV−) and ID (n = 44) and (4) HIV− and iron‐sufficient nonanaemic (n = 38). HIV+ children were virally suppressed (<50 HIV RNA copies/ml) on antiretroviral therapy (ART). Microbial composition of faecal samples (16S rRNA sequencing) and markers of gut inflammation (faecal calprotectin) and gut integrity (plasma intestinal fatty acid–binding protein [I‐FABP]) were assessed. Results Faecal calprotectin was higher in ID versus iron‐sufficient nonanaemic children (p = 0.007). I‐FABP did not significantly differ by HIV or iron status. ART‐treated HIV (redundancy analysis [RDA] R 2 = 0.009, p = 0.029) and age (RDA R 2 = 0.013 p = 0.004) explained the variance in the gut microbiota across the four groups. Probabilistic models showed that the relative abundance of the butyrate‐producing genera Anaerostipes and Anaerotruncus was lower in ID versus iron‐sufficient children. Fusicatenibacter was lower in HIV+ and in ID children versus their respective counterparts. The prevalence of the inflammation‐associated genus Megamonas was 42% higher in children with both HIV and ID versus HIV− and iron‐sufficient nonanaemic counterparts. Conclusions In our sample of 8‐ to 13‐year‐old virally suppressed HIV+ and HIV− children with or without ID, ID was associated with increased gut inflammation and changes in the relative abundance of specific microbiota. Moreover, in HIV+ children, ID had a cumulative effect that further shifted the gut microbiota to an unfavourable composition.
Patients’ Perceptions of Safety and Debriefing in Forensic Mental Health Care in Finland

ABSTRACT Background Safety is of paramount importance to patients and staff in forensic mental health hospitals. Previous research has focused on organizational and nurses’ perceptions of safety and violence in psychiatric wards. However, little is known about how patients view their safety. This study aimed to describe how patient debriefing can improve safety. Methods Qualitative research using thematic analysis was used. Data were collected by semistructured interviews and debriefing forms. Inpatient interviews (n = 45) were conducted between June and July 2018, with debriefing forms (n = 376) collected retrospectively. Results Forensic inpatient responses were divided into two main categories: psychological and physical security. Psychological safety included care culture and patient-related themes. Responses on care culture highlighted weaknesses in nurse–patient communication, whereas patient-related themes related to respondents’ descriptions of the challenges posed by mental illness. Physical safety related to both the environment and patient-related themes, with various restrictions and environmental distractions seen by respondents as negatively affecting patient safety. Conclusions Patients who participated in the study felt that care culture, especially communication with nurses, most significantly impacted their safety. Forensic hospitals should consider patients’ perceptions of their care while systematically gathering information through debriefing, as these practices can contribute to the development of a safer care environment. The next step will be clarifying how changes in nursing practices and the care environment can be used to prevent violence in psychiatric wards.
Predictors of Noninvasive Ventilation Failure in the Post-Extubation Period: A Systematic Review and Meta-Analysis*

Objectives: To identify factors associated with failure of noninvasive ventilation (NIV) in the post-extubation period. Data Sources: We searched Embase Classic +, MEDLINE, and the Cochrane Database of Systematic Reviews from inception to February 28, 2022. Study Selection: We included English language studies that provided predictors of post-extubation NIV failure necessitating reintubation. Data Extraction: Two authors conducted data abstraction and risk-of-bias assessments independently. We used a random-effects model to pool binary and continuous data and summarized estimates of effect using odds ratios (ORs) mean difference (MD), respectively. We used the Quality in Prognosis Studies tool to assess risk of bias and the Grading of Recommendations, Assessment, Development and Evaluations to assess certainty. Data Synthesis: We included 25 studies (n = 2,327). Illness-related factors associated with increased odds of post-extubation NIV failure were higher critical illness severity (OR, 3.56; 95% CI, 1.96–6.45; high certainty) and a diagnosis of pneumonia (OR, 6.16; 95% CI, 2.59–14.66; moderate certainty). Clinical and biochemical factors associated with moderate certainty of increased risk of NIV failure post-extubation include higher respiratory rate (MD, 1.54; 95% CI, 0.61–2.47), higher heart rate (MD, 4.46; 95% CI, 1.67–7.25), lower Pao2:Fio2 (MD, –30.78; 95% CI, –50.02 to –11.54) 1-hour after NIV initiation, and higher rapid shallow breathing index (MD, 15.21; 95% CI, 12.04–18.38) prior to NIV start. Elevated body mass index was the only patient-related factor that may be associated with a protective effect (OR, 0.21; 95% CI, 0.09–0.52; moderate certainty) on post-extubation NIV failure. Conclusions: We identified several prognostic factors before and 1 hour after NIV initiation associated with increased risk of NIV failure in the post-extubation period. Well-designed prospective studies are required to confirm the prognostic importance of these factors to help further guide clinical decision-making.
Association of the practice of contact sports with the development of amyotrophic lateral sclerosis

Abstract Objectives: High-intensity physical activity and sports prone to repetitive injuries of the cervical spine and head (when associated with vigorous practice) have been suggested as possible risk factors for amyotrophic lateral sclerosis (ALS). Our objective was to evaluate the relationship between the practice of contact sports (boxing, hockey, football, rugby) and ALS. Methods: The study included 2247 individuals, 1326 patients and 921 controls from several European countries. Analysis of the effect of contact sports on ALS was conducted in male participants only, as very few women practiced contact sports. Logistic regression models were used with the response variable as the presence or absence of ALS, with α = 0.05 significance level. Results: A relationship between the practice of contact sports and ALS was found, with those practicing contact sports having 76% higher odds of an ALS diagnosis (OR = 1.76, p = 0.001). In addition, univariate analyses for age (higher risk for older people, p < 0.001), smoking status (higher risk for ex-smokers, p = 0.022) and tobacco exposure (higher risk for more exposure, p = 0.038) also indicated that these variables are risk factors for ALS. In multivariate models, in addition to age, the interaction term between practice of contact sports and tobacco exposure was still significant (p = 0.03). Conclusions: This is one of the largest studies on the role of contact sport in ALS development. Our results support the existence of a relationship between the practice of sports with repetitive trauma at the level of the cervical spine and head, and ALS. This risk appears to be enhanced by tobacco exposure.
Structure-based engineering of a novel CD3ε-targeting antibody for reduced polyreactivity

ABSTRACT Bispecific antibodies continue to represent a growth area for antibody therapeutics, with roughly a third of molecules in clinical development being T-cell engagers that use an anti-CD3 binding arm. CD3 antibodies possessing cross-reactivity with cynomolgus monkey typically recognize a highly electronegative linear epitope at the extreme N-terminus of CD3 epsilon (CD3ε). Such antibodies have high isoelectric points and display problematic polyreactivity (correlated with poor pharmacokinetics for monospecific antibodies). Using insights from the crystal structure of anti-Hu/Cy CD3 antibody ADI-26906 in complex with CD3ε and antibody engineering using a yeast-based platform, we have derived high-affinity CD3 antibody variants with very low polyreactivity and significantly improved biophysical developability. Comparison of these variants with CD3 antibodies in the clinic (as part of bi- or multi-specifics) shows that affinity for CD3 is correlated with polyreactivity. Our engineered CD3 antibodies break this correlation, forming a broad affinity range with no to low polyreactivity. Such antibodies will enable bispecifics with improved pharmacokinetic and safety profiles and suggest engineering solutions that will benefit the large and growing sector of T-cell engagers.
The preparation, characterization, and application of porous core–shell composite particles produced with laboratory-scale spray dryer

Abstract Objective To prepare porous core–shell composite particles (PCPs) in order to improve the flowability and compactibility of powder materials for direct compaction (DC), as well as the dissolution of tablets. Significance The results obtained are meaningful to boosting the development and further research of PCPs on DC. Methods: In this study, hydroxypropyl methylcellulose (HPMC E3) and polyvinylpyrrolidone (PVP K30) were selected as shell materials, the Xiao Er Xi Shi formulation powder (XEXS) was used as the core materials, ammonium bicarbonate (NH4HCO3), and sodium bicarbonate (NaHCO3) were employed as pore-forming agent. Using co-spray drying method to prepare composite particles (CPs). Then, the physical properties and comparison between different CPs were characterized comprehensively. Finally, the different CPs were directly compacted as tablets to explore the effect on the dissolution behavior of DC tablets, respectively. Results (i) The XEXS PCPs were prepared successfully by co-spray drying, and the yield of PCPs is almost 80%; (ii) The TS values of PCP-X-P-Na, PCP-X-P-NH4, PCP-X-H-Na and PCP-X-P-Na were 5.70, 7.56, 3.98, and 6.88 times higher than that of raw material (X); (iii) The disintegration time of PCPs tablets decreased 10–25% when compared with CPs tablets; (iv) The values of Carr’s index (CI), Hausner ratio (HR), Caking strength (CS), and Cohesion index (CoI) of PCP-X-H-NH4 were 19.16%, 19.29%, 40.14%, and 6.39% lower than that of X, respectively. Conclusions The PCPs prepared by co-spray drying did improve the flowability and compactibility of powder, as well as the dissolution of tablets.
Tricuspid regurgitation in elderly patients with acute heart failure: insights from the KCHF registry

Several studies demonstrated that tricuspid regurgitation (TR) is associated with poor clinical outcomes. However, data on patients with TR who experienced acute heart failure (AHF) remains scarce. The purpose of this study is to evaluate the association between TR and clinical outcomes in patients admitted with AHF, using a large‐scale Japanese AHF registry.
Insulin resistance and cardiovascular disease

Insulin resistance (IR) and cardiovascular disease (CVD) represent two universal public health hazards, especially in today’s Western societies. A causal-effect relationship has been established that links IR with CVD. The mediating mechanisms are perplexing, under ongoing, rigorous investigation and remain to be fully elucidated. IR is a condition encompassing hyperglycemia and compensatory hyperinsulinemia. It occurs when insulin is not capable of exerting its maximum effects on target tissues, including skeletal muscles, liver and adipose tissue. This alteration of insulin signaling pathways results in the development of cardiometabolic disorders, including obesity, dyslipidemia, low-grade inflammation, endothelial dysfunction and hypertension, all of which are predisposing factors for atherosclerosis and CVD. The management of IR can be achieved through dietary modifications, the inclusion of regular exercise routines in everyday life, pharmacological agents and other interventions tailored to each individual patient’s needs. It is important to underline though that, although various antidiabetic drugs that may improve IR are available, no medications are as yet specifically approved for the treatment of IR. This narrative review will focus on the current scientific and clinical evidence pertaining to IR, the mechanisms connecting IR with CVD, as well as plausible strategies for a holistic, personalized approach for IR management.
Prevalence of Syphilis in Pregnant Women Living With Human Immunodeficiency Virus (HIV) From South Africa Using a Molecular-Based Assay

Background Syphilis is one of the most common sexually transmitted infections (STIs), and it remains a significant public health concern, particularly in low-resource settings including sub-Saharan Africa. There are limited data on the prevalence of syphilis among pregnant women living with HIV in South Africa. This study determined the prevalence of syphilis infection in pregnant women living with HIV by the polymerase chain reaction (PCR). Methods This was a cross-sectional study that included 385 pregnant women living with HIV recruited from the antenatal clinic at the King Edward VIII Hospital in Durban, South Africa between October 2020 and April 2021. Treponema pallidum was detected using the Applied BiosystemsTM TaqMan® Assays from stored DNA samples extracted from vaginal swabs. Results The prevalence of syphilis was 5.2% (20/385). The overall median (Q1–Q3) age of the women was 30.0 years (25.0–36.0). Of the women who tested positive for syphilis, 60.0% had reported STI symptoms (p = 0.030) and of those, 65.0% did not perceive themselves at risk of contracting STIs (p = 0.019). Women who reported having STI symptoms were more likely to test positive for syphilis when compared to women who reported not having any STI symptoms (OR: 2.810; 95% CI 1.119–7.052; p = 0.028). Women who perceived themselves as being at risk of contracting STIs were less likely to test positive for syphilis when compared to women who did not perceive themselves at risk of contracting STIs (OR: 0.328; 95% CI 0.128–0.842; p = 0.020). Conclusion The study has indicated syphilis is prevalent among pregnant women living with HIV in Durban, South Africa however STI risk perception is low. Educational programs on STIs are essential among pregnant women attending antenatal care clinics in Durban.
Influence of affective states on informant impression of neuropsychiatric symptoms in people living with MCI

Abstract Objectives: Alzheimer’s disease (AD) and mild cognitive impairment (MCI) are often accompanied by neuropsychiatric symptoms (NPS; e.g. depression/apathy/irritability) causing challenges for people living with dementia/caregivers and predicting worse disease progression. Accurately assessing NPS is critical to research on AD/MCI. However, there are limitations to both self-reports and clinician evaluations; the field often relies on informants to assess NPS. Informants’ perception of NPS are influenced by disease and caregiver factors that may lead to biased assessments. We aimed to assess the relationship between participants self-reported affective states (valence/arousal) and informant-reported NPS. Methods: Data from a double-blinded intervention design (primarily testing neurostimulation’s effect on NPS) were used to examine the relationship between participant-reported affective states and informant-reported NPS over 1 month. Forty participants (24 females) with MCI and NPS (mean age = 71.7, SD = 7) were enrolled along with informants (primarily spouses/partners) who regularly interact with participants. NPS assessment occurred weekly and at pre- and post-intervention, and participant-reported affective states were assessed at 14 timepoints. Results: Generalized Estimating Equations showed that participant levels of arousal, but not valence, were significantly related to corresponding informant-reported NPS at weekly (arousal: B= −0.59, SE = 0.27, Wald’s χ2 = 4.61, p=.032; valence: B = 0.17, SE = 0.19, Wald’s χ2 = 0.80, p=.37) and pre-/post- (arousal: B= −4.00, SE = 1.58, Wald’s χ2 = 6.42, p=.011; valence: B= −3.34, SE = 1.80, Wald’s χ2 = 3.43, p=.06) assessments. Conclusion: The findings indicate that informant-reported NPS may be more strongly influenced by arousal, and informants may be less attuned to valence in people living with MCI.
Impacts of Free-Tropospheric Temperature and Humidity on Nocturnal Nonprecipitating Marine Stratocumulus

AbstractMarine stratocumulus (MSc) cloud amount can decrease with an increase in the cloud-top instability parameter κ, based on the cloud-top entrainment instability (CTEI) theory. Notice that if boundary layer temperature and humidity remain the same, a given κ can correspond to different combinations of free-tropospheric temperature and humidity. By employing large-eddy simulations coupled with bin microphysics, this study investigates the characteristics of three nocturnal nonprecipitating MSc systems with the same κ but different free-tropospheric conditions. It is found that the spread of liquid water path (LWP) among the three cases is large. The LWPs of these three cases are also compared with the base case where κ is smaller. One of the three cases even has larger LWP than the base case, which is not expected by the CTEI theory. Results indicate that the thermodynamic properties of the free-tropospheric air are important. For the three cases with the same κ, cooler and moister free-tropospheric a.