Miracle-dz/UniFAR-FTUs huggingface dataset:
Associations of Apixaban Dose With Safety and Effectiveness Outcomes in Patients With Atrial Fibrillation and Severe Chronic Kidney Disease

BACKGROUND: Recommendations for apixaban dosing on the basis of kidney function are inconsistent between the US Food and Drug Administration and European Medicines Agency for patients with atrial fibrillation. Optimal apixaban dosing in chronic kidney disease remains unknown. METHODS: With the use of deidentified electronic health record data from the Optum Labs Data Warehouse, patients with atrial fibrillation and chronic kidney disease stage 4/5 initiating apixaban between 2013 and 2021 were identified. Risks of bleeding and stroke/systemic embolism were compared by apixaban dose (5 versus 2.5 mg), adjusted for baseline characteristics by the inverse probability of treatment weighting. The Fine-Gray subdistribution hazard model was used to account for the competing risk of death. Cox regression was used to examine risk of death by apixaban dose. RESULTS: Among 4313 apixaban new users, 1705 (40%) received 5 mg and 2608 (60%) received 2.5 mg. Patients treated with 5 mg apixaban were younger (mean age, 72 versus 80 years), with greater weight (95 versus 80 kg) and higher serum creatinine (2.7 versus 2.5 mg/dL). Mean estimated glomerular filtration rate was not different between the groups (24 versus 24 mL·min–1·1.73 m–2). In inverse probability of treatment weighting analysis, apixaban 5 mg was associated with a higher risk of bleeding (incidence rate 4.9 versus 2.9 events per 100 person-years; incidence rate difference, 2.0 [95% CI, 0.6–3.4] events per 100 person-years; subdistribution hazard ratio, 1.63 [95% CI, 1.04–2.54]). There was no difference between apixaban 5 mg and 2.5 mg groups in the risk of stroke/systemic embolism (3.3 versus 3.0 events per 100 person-years; incidence rate difference, 0.2 [95% CI, –1.0 to 1.4] events per 100 person-years; subdistribution hazard ratio, 1.01 [95% CI, 0.59–1.73]), or death (9.9 versus 9.4 events per 100 person-years; incidence rate difference, 0.5 [95% CI, –1.6 to 2.6] events per 100 person-years; hazard ratio, 1.03 [95% CI, 0.77–1.38]). CONCLUSIONS: Compared with 2.5 mg, use of 5 mg apixaban was associated with a higher risk of bleeding in patients with atrial fibrillation and severe chronic kidney disease, with no difference in the risk of stroke/systemic embolism or death, supporting the apixaban dosing recommendations on the basis of kidney function by the European Medicines Agency, which differ from those issued by the US Food and Drug Administration.
GSDMD gene knockout alleviates hyperoxia-induced hippocampal brain injury in neonatal mice

Background: Neonatal hyperoxia exposure is associated with brain injury and poor neurodevelopment outcomes in preterm infants. Our previous studies in neonatal rodent models have shown that hyperoxia stimulates the brain’s inflammasome pathway, leading to the activation of gasdermin D (GSDMD), a key executor of pyroptotic inflammatory cell death. Moreover, we found inhibition of GSDMD activation attenuates hyperoxia-induced brain injury in neonatal mice. We hypothesized that GSDMD plays a pathogenic role in hyperoxia-induced neonatal brain injury and that GSDMD gene knockout (KO) will alleviate hyperoxia-induced brain injury. Methods: Newborn GSDMD knockout mice and their wildtype (WT) littermates were randomized within 24 h after birth to be exposed to room air or hyperoxia (85% O2) from postnatal day 1 to 14. Hippocampal brain inflammatory injury was assessed in brain sections by immunohistology for allograft inflammatory factor 1 (AIF1), a marker of microglial activation. Cell proliferation was evaluated by Ki-67 staining, and cell death was determined by TUNEL assay. RNA sequencing of the hippocampus was performed to identify the transcriptional effects of hyperoxia and GSDMD-KO, and qRT-PCR was performed to confirm some of the significantly regulated genes. Results: Hyperoxia-exposed WT mice had increased microglia consistent with activation, which was associated with decreased cell proliferation and increased cell death in the hippocampal area. Conversely, hyperoxia-exposed GSDMD-KO mice exhibited considerable resistance to hyperoxia as O2 exposure failed to increase either AIF1+ or TUNEL+ cell numbers, nor decrease cell proliferation. Hyperoxia exposure differentially regulated 258 genes in WT and only 16 in GSDMD-KO mice compared to room air- exposed WT and GSDMD-KO, respectively. Gene set enrichment analysis showed that in the WT brain, hyperoxia differentially regulated genes associated with neuronal and vascular development and differentiation, axonogenesis, glial cell differentiation, and core development pathways hypoxia-induced factor 1, and neuronal growth factor pathways. These changes were prevented by GSDMD-KO. Conclusion: GSDMD-KO alleviates hyperoxia-induced inflammatory injury, cell survival and death, and alterations of transcriptional gene expression of pathways involved in neuronal growth, development, and differentiation in the hippocampus of neonatal mice. This suggests that GSDMD plays a pathogenic role in preterm brain injury, and targeting GSDMD may be beneficial in preventing and treating brain injury and poor neurodevelopmental outcomes in preterm infants.
Interactive association between insomnia symptoms and sleep duration for the risk of dementia—a prospective study in the Swedish National March Cohort

Abstract Objective Given the importance of sleep in maintaining neurocognitive health, both sleep duration and quality might be component causes of dementia. However, the possible role of insomnia symptoms as risk factors for dementia remain uncertain. Methods We prospectively studied 22,078 participants in the Swedish National March Cohort who were free from dementia and stroke at baseline. Occurrence of dementia was documented by national registers during a median follow-up period of 19.2 years. Insomnia symptoms and sleep duration were ascertained by Karolinska Sleep Questionnaire. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results Compared to participants without insomnia at baseline, those who reported any insomnia symptom experienced a greater incidence of dementia during follow-up (HR 1.08, 95% CI: 1.03, 1.35). Difficulty initiating sleep versus non-insomnia (HR 1.24, 95% CI: 1.02, 1.52), but not difficulty maintaining sleep or early morning awakening was associated with an increased risk of dementia. Short sleep duration was associated with increased risk of dementia (6 h vs. 8 h, HR 1.29, 95% CI: 1.11–1.51; 5 h vs. 8 h, HR 1.26, 95% CI: 1.00–1.57). Stratified analyses suggested that insomnia symptoms increased the risk of dementia only amongst participants with ≥7 h sleep (vs. non-insomnia HR 1.24, 95% CI: 1.00–1.54, P = 0.05), but not amongst short sleepers (<7 h). Short sleep duration also did not further inflate the risk of dementia amongst insomniacs. Conclusion Insomnia and short sleep duration increase the risk of dementia amongst middle-aged to older adults.
Preoperative transarterial chemoembolization (TACE) + liver resection versus upfront liver resection for large hepatocellular carcinoma (≥5 cm): a systematic review and meta-analysis

Abstract Background Hepatocellular carcinoma (HCC) accounts for majority of primary liver cancer. Use of preoperative neoadjuvant transarterial chemoembolization (PN-TACE) may result in tumor shrinkage and improve resectability. This study aims to summarize the outcomes of PN-TACE versus upfront liver resection (Up-LR) in large HCC (≥5 cm). Methods PubMed, Embase, The Cochrane Library, and Scopus were systematically searched till September 2022 for studies comparing PN-TACE versus Up-LR. The primary study outcomes were overall survival (OS), disease-free survival (DFS), and recurrence. Our secondary outcomes were postoperative morbidity and mortality. Results There were 12 studies with 15 data sets including 3960 patients (PN-TACE n = 2447, Up-LR n = 1513). Majority (89.5%, n = 1250/1397) of patients had Child’s A liver cirrhosis. Incidence of Child’s B cirrhosis was higher in PN-TACE compared to Up-LR (Odds ratio (OR) 1.69, 95% CI: 1.18, 2.41, p = 0.004). Pooled hazard ratio (HR) for OS showed no significant difference between PN-TACE and Up-LR (HR 0.87, 95% CI: 0.64, 1.18, p = 0.37), but DFS was superior in PN-TACE (HR 0.79, 95% CI: 0.63, 0.99, p = 0.04). Subgroup analysis based on study design failed to show any significant effect in randomized controlled trials (n = 2/15 data sets). However, operating time (mean difference (MD) 31.94 min, 95% CI: 2.42, 61.45, p = 0.03) and blood loss (MD 190.93 ml, 95% CI: 10.22, 317.65, p = 0.04) were higher in PN-TACE. Intrahepatic and extrahepatic recurrence, post-operative morbidity and in-hospital mortality were comparable between PN-TACE and Up-LR. Conclusion In retrospective studies, PN-TACE resulted in superior DFS compared to Up-LR. However, this may be confounded by selection bias.
Perceptions of Acute Care Telemedicine Among Caregivers for Persons Living with Dementia: A Qualitative Study

Persons living with dementia (PLWD) have high emergency department (ED) utilization. Little is known about using telemedicine with PLWD and caregivers as an alternative to ED visits for minor acute health problems. This qualitative interview-based study elicited caregivers’ perspectives about the acceptability of telemedicine for acute complaints. We performed telephone interviews with 28 caregivers of PLWD from two academic EDs, one in the Northeast and another in the South. Using a combined deductive-inductive approach, we coded interview transcripts and elucidated common themes by consensus. All caregivers reported they would need to participate in the telemedicine visit to help overcome communication and digital literacy challenges. People from racial/ethnic minority groups reported lower comfort with the virtual format. In both sites, participants expressed uncertainty about illness severity that could preclude using telemedicine for acute complaints. Overall, respondents deemed acute care telemedicine acceptable, but caregivers describe specific roles as crucial intermediaries to facilitate virtual care.
Mechanism of Simiao Decoction in the treatment of atherosclerosis based on network pharmacology prediction and molecular docking

To explore the molecular mechanism of Simiao Decoction (SMD) intervening atherosclerosis (AS). The main components and potential mechanisms of SMD remain unknown. This study aims to initially clarify the potential mechanism of SMD in the treatment of AS based on network pharmacology and molecular docking techniques. The principal components and corresponding protein targets of SMD were searched on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and the compound-target network was constructed by Cytoscape3.9. 1. AS targets were searched on DrugBank, OMIM, and TTD databases. The intersection of compound target and disease target was obtained and the coincidence target was imported into STRING database to construct a protein–protein interaction network. We further performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis on the targets. The molecular docking method was used to verify the interaction between core components of SMD and targets. We created the active compounds-targets network and the active compounds-AS-targets network based on the network database containing Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, DrugBank, OMIM, and TTD. We discovered that the therapy of AS with SMD involves 3 key substances—quercetin, kaempferol, and luteolin—as well as 5 crucial targets—ALB, AKT1, TNF, IL6, and TP53. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the shared targets involved a number of signaling pathways, including the advanced glycosylation end product-receptor of AGE signaling pathway in diabetic complications, Hepatitis B, Lipid and atherosclerosis, Chemical Carcinogenesis-Receptor Activation, and Pathways in Cancer. The molecular docking demonstrated that the binding energies of quercetin, kaempferol, and luteolin with 5 important targets were favorable. This study reveals the active ingredients and potential molecular mechanism of SMD in the treatment of AS, and provides a reference for subsequent basic research.
Scoping Review of Employer-Led Research Using Employee Health Claims Data

Employers may evaluate employee claims data for various reasons, including assessment of medical insurance and wellness plan efficacy, monitoring employee health trends, and identifying focus areas for wellness measures. The objective of this scoping review (ScR) is to describe the available literature reporting the use, applications, and outcomes of employee health claims data by self-insured employers. The ScR was conducted in a stepwise manner using an established framework: identifying the research question, identifying and selecting relevant studies, charting the data, and collating and reporting results. Literature searches were conducted in PubMed and Embase. Studies of self-insured employee populations that were conducted by the employer/s through May 2022 were identified using predefined criteria. Forty-one studies were included. The majority (90%) were cohort study designs; most employers (51%) were in industries such as aluminum production and health insurance providers. Twenty-four (59%) studies supplemented claims data with other sources such as human resource data to evaluate programs and/or health outcomes. A range of exposures (eg, chronic conditions, wellness program participation) and outcomes (eg, rates or costs of conditions, program effectiveness) were considered. Among the 25 studies that reported on patient confidentiality and privacy, 68% indicated institutional review board approval and 48% reported use of deidentified data. Many self-insured employers have used employee health claims data to gain insights into their employees' needs and health care utilization. These data can be used to identify potential improvements for wellness and other targeted programs to improve employee health and decrease absenteeism.
Association of visceral fat area or BMI with arterial stiffness in ideal cardiovascular health metrics among T2DM patients

Abstract Background “Obesity paradox” occurs in type 2 diabetes mellitus (T2DM) patients when body mass index (BMI) is applied to define obesity. We examined the association of visceral fat area (VFA) as an obesity measurement with arterial stiffness in seven ideal cardiovascular health metrics (ICVHMs). Methods A total of 29 048 patients were included in the analysis from June 2017 to April 2021 in 10 sites of National Metabolic Management Centers. ICVHMs were modified from the recommendations of the American Heart Association. Brachial‐ankle pulse wave velocity (BaPWV) ≥ 1400 cm/s was employed to evaluate increased arterial stiffness. Multivariate regression models were used to compare the different effects of BMI and VFA on arterial stiffness. Results Lower VFA was more strongly associated with low BaPWV than lower BMI when other ICVHMs were included (adjusted odds ratio [OR], 0.85 [95% confidence interval [CI], 0.80–0.90] vs OR 1.08 [95% CI, 1.00–1.17]). Multivariable‐adjusted ORs for arterial stiffness were highest in patients with the VAT area VFA in the range of 150‐200 cm2 (adjusted OR, 1.26 [95% CI 1.12–1.41]). Compared with participants with VAT VFA < 100 cm2, among participants with higher VAT VFA, the OR for arterial stiffness decreased gradually from 1.89 (95% CI, 1.73–2.07) in patients who had ≤1 ICVHM to 0.39 (95% CI, 0.25–0.62) in patients who had ≥5 ICVHMs. Conclusion In patients with T2DM, using VAT for anthropometric measures of obesity, VFA was more relevant to cardiovascular risk than BMI in the seven ICVHMs. For anthropometric measures of obesity in the ICVHMs to describe cardiovascular risk VFA would be more optimal than BMI.
Adaptive spike threshold dynamics associated with sparse spiking of hilar mossy cells are captured by a simple model

Hilar mossy cells (hMCs) in the dentate gyrus (DG) receive inputs from DG granule cells (GCs), CA3 pyramidal cells and inhibitory interneurons, and provide feedback input to GCs. Behavioural and in vivo recording experiments implicate hMCs in pattern separation, navigation and spatial learning. Our experiments link hMC intrinsic excitability to their synaptically evoked in vivo spiking outputs. We performed electrophysiological recordings from DG neurons and found that hMCs displayed an adaptative spike threshold that increased both in proportion to the intensity of injected currents, and in response to spiking itself, returning to baseline over a long time scale, thereby instantaneously limiting their firing rate responses. The hMC activity is additionally limited by a prominent medium after‐hyperpolarizing potential (AHP) generated by small conductance K+ channels. We hypothesize that these intrinsic hMC properties are responsible for their low in vivo firing rates. Our findings extend previous studies that compare hMCs, CA3 pyramidal cells and hilar inhibitory cells and provide novel quantitative data that contrast the intrinsic properties of these cell types. We developed a phenomenological exponential integrate‐and‐fire model that closely reproduces the hMC adaptive threshold nonlinearities with respect to their threshold dependence on input current intensity, evoked spike latency and long‐lasting spike‐induced increase in spike threshold. Our robust and computationally efficient model is amenable to incorporation into large network models of the DG that will deepen our understanding of the neural bases of pattern separation, spatial navigation and learning.
Severity assessment to guide empiric antibiotic therapy for cholangitis in children after Kasai portoenterostomy: a multicenter prospective randomized control trial in China

Background: Cholangitis is common in patients with biliary atresia following Kasai portoenterostomy (KPE). The prompt use of empiric antibiotics is essential due to the lack of identified microorganisms. The authors aimed to validate a severity grading system to guide empiric antibiotic therapy in the management of post-KPE cholangitis. Materials and methods: This multicenter, prospective, randomized, open-label study recruited patients with post-KPE cholangitis and was conducted from January 2018 to December 2019. On admission, patients were categorized into mild, moderate, and severe cholangitis according to the severity grading system. Patients in the mild cholangitis group were randomized to receive cefoperazone sodium tazobactam sodium (CSTS) or meropenem (MEPM). Patients with severe cholangitis were randomized to treatment with MEPM or a combination of MEPM plus immunoglobulin (MEPM+IVIG). Patients with moderate cholangitis received MEPM. Results: The primary endpoint was duration of fever (DOF). Secondary outcomes included blood culture, length of hospital stay, incidence of recurrent cholangitis, jaundice clearance rate, and native liver survival (NLS). For mild cholangitis, DOF, and length of hospital stay were similar between those treated with CSTS or MEPM (all P>0.05). In addition, no significant difference in recurrence rate, jaundice clearance rate, and NLS was observed between patients treated with CSTS and MEPM at 1-month, 3-month, and 6-month follow-up. In patients with moderate cholangitis, the DOF was 36.00 (interquartile range: 24.00–48.00) h. In severe cholangitis, compared with MEPM, MEPM+IVIG decreased DOF and improved liver function by reducing alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and direct bilirubin at 1-month follow-up. However, recurrence rate, jaundice clearance rate, and NLS did not differ significantly between MEPM+IVIG and MEPM at 1-month, 3-month, and 6-month follow-up. Conclusions: In patients with post-KPE cholangitis, MEPM is not superior to CSTS for the treatment of mild cholangitis. However, MEPM+IVIG treatment was associated with better short-term clinical outcomes in patients with severe cholangitis.
Premature termination, satisfaction with care, and shared decision-making during home treatment compared to inpatient treatment: A quasi-experimental trial

Abstract Background Inpatient equivalent home treatment (IEHT), implemented in Germany since 2018, is a specific form of home treatment. Between 2021 and 2022, IEHT was compared to inpatient psychiatric treatment in a 12-months follow-up quasi-experimental study with two propensity score matched cohorts in 10 psychiatric centers in Germany. This article reports results on the treatment during the acute episode and focuses on involvement in decision-making, patient satisfaction, and drop-out rates. Methods A total of 200 service users receiving IEHT were compared with 200 matched statistical “twins” in standard inpatient treatment. Premature termination of treatment as well as reasons for this was assessed using routine data and a questionnaire. In addition, we measured patient satisfaction with care with a specific scale. For the evaluation of patient involvement in treatment decisions, we used the 9-item Shared Decision Making Questionnaire (SDM-Q-9). Results Patients were comparable in both groups with regard to sociodemographic and clinical characteristics. Mean length-of-stay was 37 days for IEHT and 28 days for inpatient treatment. In both groups, a similar proportion of participants stopped treatment prematurely. At the end of the acute episode, patient involvement in decision-making (SDM-Q-9) as well as treatment satisfaction scores were significantly higher for IEHT patients compared to inpatients. Conclusions Compared to inpatient care, IEHT treatment for acute psychiatric episodes was associated with higher treatment satisfaction and more involvement in clinical decisions.
Documenting the microbiome diversity and distribution in selected fleas from South Africa with an emphasis on the cat flea, Ctenocephalides f. felis.

Abstract Abstract The factors that influence parasite associated bacterial microbial diversity and the geographic distributions of bacteria are not fully understood. In an effort to gain a deeper understanding of the relationship between the bacterial diversity of Ctenocephalides fleas and host species and the external environment, we conducted a metagenetic analysis of 107 flea samples collected from 8 distinct sampling sites in South Africa. Pooled DNA samples mostly comprising of 2 or 3 individuals sampled from the same host, and belonging to the same genetic cluster, were sequenced using the Ion PGM™ Hi-Q™ Kit and the Ion 316™ Chip v2. Differences were detected in the microbiome compositions between Ctenocephalides felis, Ctenocephalides canis and Ctenocephalides connatus. Although based on a small sample, C. connatus occurring on wildlife harboured a higher bacterial richness when compared to C. felis on domestic animals. Intraspecific differences in the microbial OTU diversity were detected within C. f. felis that occurred on domestic cats and dogs. Different genetic lineages of C. f. felis were similar in microbial compositions but some differences exist in the presence or absence of rare bacteria. Rickettsia and Bartonella OTU's identified in South African cat fleas differ from those identified in the USA and Australia. Intraspecific microbial compositions also differ across geographic sampling sites. Generalized dissimilarity modelling showed that temperature and humidity are potentially important environmental factors explaining the pattern obtained.