Miracle-dz/UniFAR-FTUs huggingface dataset:
Exploring American Parents’ Lived Experiences During the COVID-19 Pandemic: Ramifications for Well-Being

Abstract Objective The objective of this study was to document the direct impact of the COVID-19 pandemic on parents and families in the United States. Methods Parents’ experiences during the pandemic were examined using an online survey (N = 564) collected during May and June 2020. Results Parents reported experiencing a high frequency of COVID-19-related events (e.g., job loss and health concerns) and impact on their lives. Parents’ experiences with COVID-19, as well as self-reported perceived increase in home labor, experiences with assisting children with remote schooling, and work-life conflict were all significantly associated with higher levels of parental role overload. COVID-19-related events and impact, as well as parental role overload, significantly predicted parents’ anxiety and depression, even after controlling for demographic factors. Conclusions The findings suggest the importance of providing support for parents and families through direct services and public policy changes.
GP-delivered medication review of polypharmacy, deprescribing, and patient priorities in older people with multimorbidity in Irish primary care (SPPiRE Study): A cluster randomised controlled trial

Background There is a rising prevalence of multimorbidity, particularly in older patients, and a need for evidence-based medicines management interventions for this population. The Supporting Prescribing in Older Adults with Multimorbidity in Irish Primary Care (SPPiRE) trial aimed to investigate the effect of a general practitioner (GP)-delivered, individualised medication review in reducing polypharmacy and potentially inappropriate prescriptions (PIPs) in community-dwelling older patients with multimorbidity in primary care. Methods and findings We conducted a cluster randomised controlled trial (RCT) set in 51 GP practices throughout the Republic of Ireland. A total of 404 patients, aged ≥65 years with complex multimorbidity, defined as being prescribed ≥15 regular medicines, were recruited from April 2017 and followed up until October 2020. Furthermore, 26 intervention GP practices received access to the SPPiRE website where they completed an educational module and used a template for an individualised patient medication review that identified PIP, opportunities for deprescribing, and patient priorities for care. A total of 25 control GP practices delivered usual care. An independent blinded pharmacist assessed primary outcome measures that were the number of medicines and the proportion of patients with any PIP (from a predefined list of 34 indicators based predominantly on the STOPP/START version 2 criteria). We performed an intention-to-treat analysis using multilevel modelling. Recruited participants had substantial disease and treatment burden at baseline with a mean of 17.37 (standard deviation [SD] 3.50) medicines. At 6-month follow-up, both intervention and control groups had reductions in the numbers of medicines with a small but significantly greater reduction in the intervention group (incidence rate ratio [IRR] 0.95, 95% confidence interval [CI]: 0.899 to 0.999, p = 0.045). There was no significant effect on the odds of having at least 1 PIP in the intervention versus control group (odds ratio [OR] 0.39, 95% CI: 0.140 to 1.064, p = 0.066). Adverse events recorded included mortality, emergency department (ED) presentations, and adverse drug withdrawal events (ADWEs), and there was no evidence of harm. Less than 2% of drug withdrawals in the intervention group led to a reported ADWE. Due to the inability to electronically extract data, primary outcomes were measured at just 2 time points, and this is the main limitation of this work. Conclusions The SPPiRE intervention resulted in a small but significant reduction in the number of medicines but no evidence of a clear effect on PIP. This reduction in significant polypharmacy may have more of an impact at a population rather than individual patient level. Trial registration ISRCTN Registry ISRCTN12752680.
Evaluation of nocturnal vs. morning measures of heart rate indices in young athletes

Purpose The purpose of this study was to compare heart rate (HR) and heart rate variability in young endurance athletes during nocturnal sleep and in the morning; and to assess whether changes in these values are associated with changes in submaximal running (SRT) and counter-movement jump (CMJ) performance. Methods During a three-week period of similar training, eleven athletes (16 ± 1 years) determined daily HR and heart rate variability (RMSSD) during sleep utilizing a ballistocardiographic device (Emfit QS), as well as in the morning with a HR monitor (Polar V800). Aerobic fitness and power production were assessed employing SRT and CMJ test. Results Comparison of the average values for week 1 and week 3 revealed no significant differences with respect to nocturnal RMSSD (6.8%, P = 0.344), morning RMSSD (13.4%, P = 0.151), morning HR (-3.9 bpm, P = 0.063), SRT HR (-0.7 bpm, P = 0.447), SRT blood lactate (4.9%, P = 0.781), CMJ (-4.2%, P = 0.122) or training volume (16%, P = 0.499). There was a strong correlation between morning and nocturnal HRs during week 1 (r = 0.800, P = 0.003) and week 3 (r = 0.815, P = 0.002), as well as between morning and nocturnal RMSSD values (for week 1, r = 0.895, P<0.001 and week 3, r = 0.878, P = 0.001). Conclusion This study concluded that HR and RMSSD obtained during nocturnal sleep and in the morning did not differ significantly. In addition, weekly changes in training and performance were small indicating that fitness was similar throughout the 3-week period of observation. Consequently, daily measurement of HR indices during nocturnal sleep provide a potential tool for long-term monitoring of young endurance athletes.
Galectin-3 inhibits cardiac contractility via a tumor necrosis factor alpha-dependent mechanism in cirrhotic rats

Background/Aims Galectin-3 plays a key pathogenic role in cardiac hypertrophy and heart failure. The present study aimed to investigate the effects of galectin-3 on cardiomyopathy – related factors and cardiac contractility in a rat model of cirrhotic cardiomyopathy. Methods Rats were divided into two sets, one for a functional study, the other for cardiac contractile-related protein evaluation. There were four groups in each set: sham operated and sham plus N-acetyllactosamine (N-Lac, a galectin-3 inhibitor; 5 mg/kg); bile duct ligated (BDL) and BDL plus N-Lac. Four weeks after surgery, ventricular level of galectin-3, collagen I and III ratio, tumor necrosis factor alpha (TNFα), and brain natriuretic peptide (BNP) were measured either by Western blots or immunohistochemistry or enzyme-linked immunosorbent assay. Blood pressure was measured by polygraph recorder. Cardiomyocyte contractility was measured by inverted microscopy. Results Galectin-3 and collagen I/III ratio were significantly increased in cirrhotic hearts. TNFα and BNP were significantly increased in BDL serum and heart compared with sham controls. Galectin-3 inhibitor significantly decreased galectin-3, TNFα, and BNP in cirrhotic hearts but not in sham controls. N-Lac also significantly improved the blood pressure, and systolic and diastolic cardiomyocyte contractility in cirrhotic rats but had no effect on sham controls. Conclusion Increased galectin-3 in the cirrhotic heart significantly inhibited contractility via TNFα. Inhibition of galectin-3 decreased the cardiac content of TNFα and BNP and reversed the decreased blood pressure and depressed contractility in the cirrhotic heart. Galectin-3 appears to play a pathogenic role in cirrhotic cardiomyopathy.
Surgical Issues for Operable Early-Stage Non–Small-Cell Lung Cancer

Surgical care for early stage non–small-cell lung cancer continuously evolves with new procedures, techniques and care pathways. The most obvious recent change was the transition to minimally invasive procedures, but numerous other aspects of care have also been refined to improve safety and tolerability. These care advancements are essential as we move into an era with increased early detection as a result of screening and greater indications for the use of adjuvant and neoadjuvant strategies.
Exposure to PM2.5 during Pregnancy and Fetal Growth in Eastern Massachusetts, USA

Background: Prior studies have examined the association between fine particulate matter [PM ≤2. 5μm in aerodynamic diameter (PM2.5)] and fetal growth with either limited spatial or temporal resolution. Objectives: In this study, we examined the association between PM2.5 exposure during pregnancy and fetal growth measures (ultrasound parameters and birth weight) in a pregnancy cohort using spatiotemporally resolved PM2.5 in Eastern Massachusetts, USA. Methods: We used ultrasound measures of biparietal diameter (BPD), head circumference, femur length, and abdominal circumference (AC), in addition to birth weight, from 9,446 pregnancies that were delivered at the Beth Israel Deaconess Medical Center from 2011–2016. We used linear mixed-effects models to examine the associations of PM2.5 in two exposure windows (the first 16 wk of pregnancy and the cumulative exposure up until the assessment of fetal growth) with anatomic scans (ultrasound measures at<24 wk), growth scans (ultrasound measures at≥24wk), and birth weight. All models were adjusted for sociodemographic characteristics, long-term trends, and temperature. Results: Higher PM2.5 exposure in the first 16 wk was associated with smaller fetal growth measures, where associations were particularly strong for BPD, AC, and birth weight. For example, a 5-μg/m3 increase in PM2.5 was associated with a lower mean BPD z-score of −0.19 (95% CI: −0.31, −0.06) before 24 wk, a lower mean AC z-score of −0.15 (95% CI: −0.28, −0.01) after 24 wk, and a lower mean birth weight z-score of −0.11 (95% CI: −0.20, −0.01). Analyses examining the associations with cumulative PM2.5 exposure up until the assessment of fetal growth produced attenuated associations. Conclusions: Higher gestational exposure to PM2.5 was associated with smaller fetal growth measures at levels below the current national standards. https://doi.org/10.1289/EHP9824
A New Predictor of Mortality in ST-Elevation Myocardial Infarction: The Uric Acid Albumin Ratio

Several studies have shown that high uric acid (UA) and low serum albumin (SA) values increase the risk of cardiovascular disease and mortality in ST-elevation myocardial infarction (STEMI). We determined whether the uric acid/albumin ratio (UAR) is a predictor of mortality in STEMI patients. All patients who presented at our center with a diagnosis of STEMI and underwent percutaneous intervention from 2015 to 2020 were screened consecutively; 4599 patients were included. A Cox proportional hazards model was used to evaluate UAR, and adjusted predictors obtained from laboratory findings and clinical characteristics contributed to mortality. Also, a regression model was presented with a directed acyclic graph (DAG). The median age of the patients was 58 years (IQR [interquartile range]: 50–67); 3581 patients (77.9%) were male. The incidence of mortality in the entire patient group was 11.9%. Median follow-up duration of all groups was 42 months. Multivariate Cox proportional regression (model-1) analysis showed age (increase 50 to 67 years; HR [hazard ratio]: 1.34, 95% CI 1.18–1.52) and UAR (increase 1.15–1.73; HR: 1.33, 95% CI 1.16–1.52) were associated with mortality. UAR may be a prognostic factor for mortality in STEMI patients and an easily accessible parameter to identify high-risk patients.
Obatoclax inhibits SARS-CoV-2 entry by altered endosomal acidification and impaired cathepsin and furin activity in vitro

ABSTRACT Coronavirus disease 2019 (COVID-19) caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has set off a global pandemic. There is an urgent unmet need for safe, affordable, and effective therapeutics against COVID-19. In this regard, drug repurposing is considered as a promising approach. We assessed the compounds that affect the endosomal acidic environment by applying human angiotensin-converting enzyme 2 (hACE2)- expressing cells infected with a SARS-CoV-2 spike (S) protein-pseudotyped HIV reporter virus and identified that obatoclax resulted in the strongest inhibition of S protein-mediated virus entry. The potent antiviral activity of obatoclax at nanomolar concentrations was confirmed in different human lung and intestinal cells infected with the SARS-CoV-2 pseudotype system as well as clinical virus isolates. Furthermore, we uncovered that obatoclax executes a double-strike against SARS-CoV-2. It prevented SARS-CoV-2 entry by blocking endocytosis of virions through diminished endosomal acidification and the corresponding inhibition of the enzymatic activity of the endosomal cysteine protease cathepsin L. Additionally, obatoclax impaired the SARS-CoV-2 S-mediated membrane fusion by targeting the MCL-1 protein and reducing furin protease activity. In accordance with these overarching mechanisms, obatoclax blocked the virus entry mediated by different S proteins derived from several SARS-CoV-2 variants of concern such as, Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2). Taken together, our results identified obatoclax as a novel effective antiviral compound that keeps SARS-CoV-2 at bay by blocking both endocytosis and membrane fusion. Our data suggested that obatoclax should be further explored as a clinical drug for the treatment of COVID-19.
Porphyrin induced structural destabilization of a parallel DNA G‐quadruplex in human MRP1 gene promoter

Porphyrins are among the first ligands that have been tested for their quadruplex binding and stabilization potential. We report the differential interaction of the positional cationic porphyrin isomers TMPyP3 and TMPyP4 with a parallel G‐quadruplex (GQ) formed by 33‐mer (TP) regulatory sequence present in the promoter region of the human multidrug resistance protein 1 (MRP1) transporter gene. This GQ element encompasses the three evolutionary conserved SP1 transcription factor binding sites. Taking into account that SP1 binds to a non‐canonical GQ motif with higher affinity than to a canonical duplex DNA consensus motif, it is suggestive that GQ distortion by cationic porphyrin will have important implications in the regulation of MRP1 expression. Herein, we employed biophysical analysis using circular dichroism, visible absorption, UV‐thermal melting and steady‐state fluorescence spectroscopy, reporting destabilization of MRP1 GQ by cationic porphyrins. Results suggest that TMPyP4 and TMPyP3 interact with GQ with a binding affinity of 106 to 107 M−1. Thermodynamic analysis indicated a significant decrease in melting temperature of GQ (ΔTm of 15.5°C‐23.5°C), in the presence of 2 times excess of porphyrins. This study provides the biophysical evidence indicating the destabilisation of a parallel DNA G‐quadruplex by cationic porphyrins.
Total hip arthroplasty in Cambodia – Our experience of two hundred and fifty six consecutive total hip arthroplasties in a low-income country & the challenge of service delivery in this setting

The Children's Surgical Centre has performed 256 THAs since 2007, We aim to assess the outcome of arthroplasty in a LMIC. Primary outcome: all cause of re-operation, Secondary outcome: any other complication. A retrospective review of all consecutive THA since 2007 was conducted. Electronic and physical case notes were reviewed. Statistical analysis was performed using MedCalc. 256 THA. Mean age: 43, gender M2:1F. Common pathologies include (1) AVN (44%), (2) OA (11%) and (3) DDH (11%). Revision rate 13%. Time to revision was 2.8 years (0–9). Common revision reasons: (1) stem fracture (5.8%), (2) aseptic loosening (4.8%) and (3) infection (2.7%). Complications were identified in 85 patients (33.2%). Common complications included (1) aseptic loosening (10.5%) (2) stem fracture (5.8%) and (3) dislocation (5.8%). Patients at CSC benefit from THA, the complication rates at CSC are declining suggesting the apex of the ‘learning curve’ has passed. Cheap poorly manufactured implants continue to cause catastrophic failure.
Quality of the Situation‐Background‐Assessment‐Recommendation tool during nurse‐physician calls in the ICU: An observational study

Abstract Background Situation‐Background‐Assessment‐Recommendation (SBAR) is a tool for structuring communication between healthcare professionals. SBAR reduces medical errors, however few studies have evaluated its quality in real practice. Aims To describe the quality of SBAR utilization by intensive care unit (ICU) nurses during phone conversations with physicians. To assess the influence of nurses' training, professional experience, and call circumstances on this quality. Study Design This observational study was conducted in the adult ICU of a university hospital in French speaking Switzerland. All consecutive telephone calls from nurses to physicians during a calendar month, were recorded. Those related to a change in patients' clinical status were selected and analysed. The quality of SBAR utilization was assessed using a pre‐defined analysis grid. Scores ranged from 0 (worst quality) to 100% (best quality). Nurses' sociodemographics and training record were collected. Multiple regression was used to assess determinants of SBAR quality including nurses characteristics and level of training. Results We analysed 290 phone calls, made by 99 nurses. The median SBAR quality score was 41% (interquartile range [IQR] 33–48). Quality scores varied across the four items of SBAR: Situation 88% (81–94), Background 17% (6–27), Assessment 17% (0–33), and Recommendation 33% (17–40). Factors independently associated with higher SBAR quality were age (−0.66%, p = .002, 95% CI [−1.07; −0.25]), primary language other than French (−8.40%, p = .017, 95% CI [−15.29; −1.51]), lack of ICU expertise (−9.25%, p = .013, 95% CI [−16.5;1–1.99]), and SBAR training in pre‐graduate nursing education (+11.53%, p = .028, 95% CI [1.27; 22.79]). Conclusions The quality of SBAR utilization remains low in ICU clinical practice. Pre‐ and post‐graduate training seem to improve its quality. Relevance to Clinical Practice Pre‐graduate mandatory training associated with multiple repetitions could improve nurses' SBAR utilization. Training using the SBAR tool should be combined with the development of nursing skills in assessment and clinical judgment.
The interaction of DNMT1 and DNMT3A epigenetic enzymes with phthalates and perfluoroalkyl substances: an in silico approach

Abstract The occurrence of long-lasting adverse effects of the environmental contaminants on human health is a current emerging issue. In particular, phthalates, poly- and perfluoroalkyl substances are proposed to trigger toxic effects as well as persistent changes on human development and metabolism by different mechanisms, including epigenetic modifications, although the specific underlying pathways are still unknown. This study contributes to identify the potential molecular initiating events of epigenetic-mediated adverse effects by an in silico approach, which combines molecular docking and molecular dynamics simulation. The approach probes the potential molecular interaction between several different phthalates and persistent organic pollutants and a specific class of epigenetic modulators, namely the DNA methyltransferases (DNMTs). The dynamics of interaction and the binding free energies of the ligand-DNMTs complexes demonstrated that pollutants can be classified into two main groups, according to the ligand-target complex stability: (1) a larger class of phthalates (DBP, DEHP, MBP and MEHP) acting as inhibitors of the enzymatic activity of the epigenetic targets and (2) a smaller class of phthalates (DMP and MMP) and perfluoroalkyl substances (PFOA and PFOS) which do not interact stably with the human DNMTs. These findings provide the first valuable in silico insights on the ability of these specific environmental pollutants to directly bind and inhibit a key class of epigenetic regulators. Communicated by Ramaswamy H. Sarma
Predictors of FabAV use in copperhead envenomation

Abstract Context Crotaline snake envenomation is a serious medical condition affecting thousands of Americans each year. Variation in the treatment of Crotaline snakebites exists among physicians in the United States. Management of copperhead snakebites is controversial with some experts advocating minimal intervention, rarely necessitating antivenom use and, even more rarely, surgical intervention. This study assessed the use of Crotaline Polyvalent Immune Fab antivenom (Ovine) (FabAV) and explored factors influencing the decision to prescribe antivenom for copperhead envenomation in patients in Northeastern Oklahoma. Methods A retrospective cohort study examining electronic medical records of patients with copperhead snakebites from July 1, 2014 to August 31, 2019. Data collected included: patient demographics, transfer information, snake species, bite site, progression of local tissue effects, additional clinical and lab results, patient comorbidities, and treatment strategy. Associations between patient variables and treatment were evaluated using the chi-square test of independence, median test, and logistic regression analysis. Associations were statistically significant if p < 0.05. Discussion Of the 130 patients bitten by a copperhead, a majority (75%) received FabAV. Symptoms of copperhead envenomation were mostly limited to the progression of tissue damage. Predictors of treatment with FabAV included progression of venom effects across major joints, younger age, comorbidities, and upper extremity bites. Conclusions Patients who have multiple comorbidities, upper extremity bites and progression of venom effects across major joints are more likely to be treated with FabAV. The high usage of FabAV at the study site underscores the need for continued work to optimize the use of antivenom for copperhead envenomations.
Incidence and correlates of insomnia and its impact on health-related quality of life among Chinese pregnant women: a cross-sectional study

ABSTRACT Objective The aims of this study were to examine the incidence and correlates of insomnia and its impact on health-related quality of life among Chinese pregnant women. Method A cross-sectional study was performed from November 2018 to April 2019 in a university-affiliated general hospital in Guangzhou, China. Seven hundred and seventeen pregnant women completed the 36-item Short-Form Health Survey (SF-36), the Self-Rating Anxiety Scale (SAS), the Self-Rating Depression Scale (SDS), and the obstetric and sociodemographic data sheet. Findings 24.3% of the pregnant women suffered from insomnia. Compared with women without insomnia, those with insomnia had a significantly lower health-related quality of life during pregnancy. Maternal age, educational level, occupation, economic status, insurance coverage, gestational age, the woman’s relationship with her mother-in-law and anxiety were significantly associated with insomnia among pregnant women. Conclusion The incidence of insomnia among pregnant women is high, and insomnia is negatively correlated with health-related quality of life. Appropriate measures and practical therapeutic programmes should be provided to prevent the adverse effects of insomnia in pregnant women with advanced maternal age, lower education, lower economic status, unemployment, lack of insurance coverage, unsatisfied with their relationships with their mothers-in-law, and suffering from anxiety symptoms, especially in the third trimester.