Miracle-dz/UniFAR-FTUs huggingface dataset:
The Prospective Association of Patient Hospitalization with Spouse Depressive Symptoms and Self-Reported Heath

Abstract After hospital discharge, patients experience a period of generalized risk for adverse mental and physical health outcomes (post-hospital syndrome [PHS]). Hospital stressors can explain these effects in patients (e.g., sleep disruption, deconditioning). Patients’ partners also experience adverse outcomes following patient hospitalization, but mechanisms of these effects are unknown. The purpose of this study was to test whether greater times and nights of patient hospitalization (proxies for partner exposure to hospital stressors) are prospectively associated with greater increases in partner depression and in partner self-reported poor health. Participants were 7,490 married couples (11,208 individuals) enrolled in the Health and Retirement Study. Outcomes were prospective changes in depressive symptoms and self-reported poor health, and primary predictors were spouse hospitalization over the past two years (yes/no), spouse hospitalized ≥ two times (yes/no), and spouse spent ≥ eight nights in-hospital (yes/no). Covariates included age, gender, race, ethnicity, income, own hospitalization experiences during the past 12 months, and one’s own and spouse comorbidities. Having a spouse who experienced two or more hospitalizations was associated with an increase in one’s own depression over time, as was having a spouse who spent eight or more nights in-hospital. Spouse hospitalization was not associated with prospective changes in self-reported health. Results suggest that PHS mechanisms may account for adverse post-hospitalization outcomes in patients’ partners.
Mutation of the imprinted gene OsEMF2a induces autonomous endosperm development and delayed cellularization in rice

Abstract In angiosperms, endosperm development comprises a series of developmental transitions controlled by genetic and epigenetic mechanisms that are initiated after double fertilization. Polycomb repressive complex 2 (PRC2) is a key component of these mechanisms that mediate histone H3 lysine 27 trimethylation (H3K27me3); the action of PRC2 is well described in Arabidopsis thaliana but remains uncertain in cereals. In this study, we demonstrate that mutation of the rice (Oryza sativa) gene EMBRYONIC FLOWER2a (OsEMF2a), encoding a zinc-finger containing component of PRC2, causes an autonomous endosperm phenotype involving proliferation of the central cell nuclei with separate cytoplasmic domains, even in the absence of fertilization. Detailed cytological and transcriptomic analyses revealed that the autonomous endosperm can produce storage compounds, starch granules, and protein bodies specific to the endosperm. These events have not been reported in Arabidopsis. After fertilization, we observed an abnormally delayed developmental transition in the endosperm. Transcriptome and H3K27me3 ChIP-seq analyses using endosperm from the emf2a mutant identified downstream targets of PRC2. These included >100 transcription factor genes such as type-I MADS-box genes, which are likely required for endosperm development. Our results demonstrate that OsEMF2a-containing PRC2 controls endosperm developmental programs before and after fertilization.
Sequencing at lymphoid neoplasm susceptibility loci maps six myeloma risk genes

Abstract Inherited genetic risk factors play a role in multiple myeloma (MM), yet considerable missing heritability exists. Rare risk variants at genome-wide association study (GWAS) loci are a new avenue to explore. Pleiotropy between lymphoid neoplasms (LNs) has been suggested in family history and genetic studies, but no studies have interrogated sequencing for pleiotropic genes or rare risk variants. Sequencing genetically enriched cases can help discover rarer variants. We analyzed exome sequencing in familial or early-onset MM cases to identify rare, functionally relevant variants near GWAS loci for a range of LNs. A total of 149 distinct and significant LN GWAS loci have been published. We identified six recurrent, rare, potentially deleterious variants within 5 kb of significant GWAS single nucleotide polymorphisms in 75 MM cases. Mutations were observed in BTNL2, EOMES, TNFRSF13B, IRF8, ACOXL and TSPAN32. All six genes replicated in an independent set of 255 early-onset MM or familial MM or precursor cases. Expansion of our analyses to the full length of these six genes resulted in a list of 39 rare and deleterious variants, seven of which segregated in MM families. Three genes also had significant rare variant burden in 733 sporadic MM cases compared with 935 control individuals: IRF8 (P = 1.0 × 10−6), EOMES (P = 6.0 × 10−6) and BTNL2 (P = 2.1 × 10−3). Together, our results implicate six genes in MM risk, provide support for genetic pleiotropy between LN subtypes and demonstrate the utility of sequencing genetically enriched cases to identify functionally relevant variants near GWAS loci.
Replacing dietary antibiotics with 0.20% L-glutamine in swine nursery diets: impact on intestinal physiology and the microbiome following weaning and transport.

Previous research demonstrates that supplementing 0.20% L-glutamine (GLN) in the diets of newly weaned and transported pigs improves growth rate to a similar extent as providing dietary antibiotics (AB). However, research comparing the effects of GLN versus AB on intestinal physiology and the microbiome is limited. Therefore, the study objective was to compare the effects of supplementing nursery diets with GLN, AB, or no dietary antibiotics (NA) on intestinal physiology and the microbiome of pigs in a production environment following weaning and transport. Mixed sex piglets (N=480; 5.62 ± 0.06 kg BW) were weaned (18.4 ± 0.2 d of age) and transported for 12 hr in central Indiana, for two replicates, during the summer of 2016 and the spring of 2017. Pens were blocked by BW and allotted to 1 of 3 dietary treatments [n = 10 pens/dietary treatment/replicate (8 pigs/pen)]; AB [chlortetracycline (441 ppm) + tiamulin (38.6 ppm)], GLN (0.20% as-fed) or NA fed for 14 d. From d 14 to 34, pigs were fed common AB free diets in two phases. On d 33, villus height:crypt depth tended to be increased (P = 0.07; 7.0%) in GLN and AB pigs vs. NA pigs. On d 33, glucagon-like peptide 2 (GLP-2) mRNA abundance was decreased (P = 0.01; 50.3%) in GLN and NA pigs vs. AB pigs. Crypt depth was increased overall on d 33 (P = 0.01; 16.2%) during the spring replicate compared to the summer replicate. Villus height:crypt depth was reduced (P = 0.01; 9.6%) during the spring replicate compared to the summer replicate on d 33. On d 13, tumor necrosis factor alpha and occludin mRNA abundance was increased (P ≤ 0.04; 45.9% and 106.5%, respectively) and zonula occludens 1 mRNA abundance tended to be greater (P = 0.10; 19.2%) in the spring replicate compared to the summer replicate. In addition, AB pigs had increased (P = 0.01; 101.3%) GLP-2 gene expression compared to GLN and NA pigs. Microbiome analysis indicated that on d 13, dietary treatment altered the microbiota community structure (P = 0.03). Specifically, the AB pigs tended to be distinct from both the NA and GLN pigs (P = 0.08), and Lactobacillus was increased nearly 2-fold in AB compared to NA pigs (q = 0.04) and GLN pigs (q = 0.22). In conclusion, GLN supplementation tended to improve some morphological markers of intestinal health similarly to AB pigs while the microbiome composition in GLN pigs was more similar to NA pigs than AB pigs.
Seroprevalence and risk factors for foot‐and‐mouth disease in cattle in Baghlan Province, Afghanistan

Summary A serological study of 376 cattle from 198 herds and a concurrent survey of farmers were undertaken in 53 villages in Khinjan, Doshi and Puli Khumri districts of Baghlan province, Afghanistan to determine the seroprevalence of Foot and Mouth Disease (FMD) and to identify risk factors for seropositive herds. A total of 419 cases of FMD were reported by the farmers in the year preceding the survey. The animal‐level population seroprevalence was estimated at 42.0% (95% CI, 37.0–47.2). The seroprevalence increased with age in the sampled cattle (<2 years ‐ 30.4%, 2–6 years ‐ 40.3% and >6 years ‐ 52.2%). Herds were more likely to be seropositive if the farmers: had purchased cattle in the year prior to the survey (OR = 2.6; 95% CI, 1.37–4.97); purchased ruminants from unknown (potentially risky) sources (OR = 2.13; 95% CI, 1.13–4.03); and sold milk to the market (OR = 1.99; 95% CI, 1.09–3.63). Herds that had been vaccinated had a lower odds of being seropositive (OR = 0.33; 95% CI, 0.68–0.66). This was the first epidemiological study of FMD in Baghlan province and the findings provide valuable direction for disease control on FMD in this and other provinces in Afghanistan.
13 Questions About Using Machine Learning in Causal Research (You Won't Believe the Answer to Number 10!).

Machine learning is gaining prominence in the health sciences, where much of its use has focused on data-driven prediction. However, machine learning can also be embedded within causal analyses, potentially reducing biases arising from model misspecification. Using a question-and-answer format, we provide an introduction and orientation for epidemiologists interested in using machine learning but concerned about potential bias or loss of rigor due to use of 'black box' models. We conclude with sample code that may lower the barrier to entry to using these techniques.
Explaining the association between repetition priming and source memory: No evidence for a contribution of recognition or fluency

In a conjoint memory task (measuring repetition priming, recognition memory, and source memory), items recognised as previously studied and receiving correct source decisions also tend to show a greater magnitude of the repetition priming effect. These associations have been explained as arising from a single memory system or signal, rather than multiple distinct ones. In the present work, we examine whether the association between priming and source memory can alternatively be explained as being driven by recognition or fluency. We first reproduced the basic priming-source association (Experiment 1). In Experiments 2 and 3, we found that the association persisted even when the task was modified so that overt and covert recognition judgements were precluded. In Experiment 4, the association was again present even though fluency (as measured by identification response time) could not influence the source decision, although the association was notably weaker. These findings suggest that the association between priming and source memory is not attributable to a contribution of recognition or fluency; instead, the findings are consistent with a single-system account in which a common memory signal drives responding.
Are Communities Willing to Transition Into Learning Health Care Communities? A Community-Based Participatory Evaluation of Stakeholders’ Receptivity

This article aims to determine receptivity for advancing the Learning Healthcare System (LHS) model to a novel evidence-based health care delivery framework—Learning Health Care Community (LHCC)—in Baltimore, as a model for a national initiative. Using community-based participatory, qualitative approach, we conducted 16 in-depth interviews and 15 focus groups with 94 participants. Two independent coders thematically analyzed the transcripts. Participants included community members (38%), health care professionals (29%), patients (26%), and other stakeholders (7%). The majority considered LHCC to be a viable model for improving the health care experience, outlining certain parameters for success such as the inclusion of home visits, presentation of research evidence, and incorporation of social determinants and patients’ input. Lessons learned and challenges discussed by participants can help health systems and communities explore the LHCC aspiration to align health care delivery with an engaged, empowered, and informed community.
Measuring frailty in younger populations: a rapid review of evidence

Objectives Frailty is typically assessed in older populations. Identifying frailty in adults aged under 60 years may also have value, if it supports the delivery of timely care. We sought to identify how frailty is measured in younger populations, including evidence of the impact on patient outcomes and care. Design A rapid review of primary studies was conducted. Data sources Four databases, three sources of grey literature and reference lists of systematic reviews were searched in March 2020. Eligibility criteria Eligible studies measured frailty in populations aged under 60 years using experimental or observational designs, published after 2000 in English. Data extraction and synthesis Records were screened against review criteria. Study data were extracted with 20% of records checked for accuracy by a second researcher. Data were synthesised using a narrative approach. Results We identified 268 studies that measured frailty in samples that included people aged under 60 years. Of these, 85 studies reported evidence about measure validity. No measures were identified that were designed and validated to identify frailty exclusively in younger groups. However, in populations that included people aged over and under 60 years, cumulative deficit frailty indices, phenotype measures, the FRAIL Scale, the Liver Frailty Index and the Short Physical Performance Battery all demonstrated predictive validity for mortality and/or hospital admission. Evidence of criterion validity was rare. The extent to which measures possess validity across the younger adult age (18–59 years) spectrum was unclear. There was no evidence about the impact of measuring frailty in younger populations on patient outcomes and care. Conclusions Limited evidence suggests that frailty measures have predictive validity in younger populations. Further research is needed to clarify the validity of measures across the adult age spectrum, and explore the utility of measuring frailty in younger groups.
Past physical activity and its influence on female functioning during perimenopause.

OBJECTIVES The objective of the study was to assess correlations between practising sports at an elite level at a young age, and the current physical activity level, selected sociometric features and the severity of menopausal symptoms in women during perimenopause, which will contribute to the knowledge about undertaking sports activity. MATERIAL AND METHODS The study involved a total of 334 females aged 45-65. They were purposefully assigned to both a study and control group. The study group included 148 women - former elite athletes qualified based on the presumed criteria. The control group consisted of 154 women who did not meet the criterion of practising sports activity earlier in life. In order to conduct the study, we applied the method of a diagnostic survey. The outcome measure was a survey questionnaire and contained questions concerning sociometric features, some elements of gynaecological history, and physical activity undertaken in the past. The second part used the International Physical Activity Questionnaire (IPAQ) and Blatt-Kupperman Menopausal Index. RESULTS The groups were homogenous in terms of age and BMI. The former athletes most frequently used to practise athletics, team games and swimming. Both groups displayed no differences regarding the age at menarche, the onset of sexual activity, and the presence and regularity of menstruation. The former athletes had fewer children compared to the controls. They manifested a higher level of physical activity in particular areas and intensity categories. The comparison between the two groups did not show statistically significant differences in the severity of menopausal symptoms. CONCLUSIONS Sports training in the past differentiates selected sociometric features such as economic activity and a numerous pregnancies and births. Sports training in the past has an impact on the current level of physical activity - the females who used to train present its higher level. Sports training in the past does not differentiate the severity of menopausal symptoms.
A cross-neutralizing antibody between HIV-1 and influenza virus

Incessant antigenic evolution enables the persistence and spread of influenza virus in the human population. As the principal target of the immune response, the hemagglutinin (HA) surface antigen on influenza viruses continuously acquires and replaces N-linked glycosylation sites to shield immunogenic protein epitopes using host-derived glycans. Anti-glycan antibodies, such as 2G12, target the HIV-1 envelope protein (Env), which is even more extensively glycosylated and contains under-processed oligomannose-type clusters on its dense glycan shield. Here, we illustrate that 2G12 can also neutralize human seasonal influenza A H3N2 viruses that have evolved to present similar oligomannose-type clusters on their HAs from around 20 years after the 1968 pandemic. Using structural biology and mass spectrometric approaches, we find that two N-glycosylation sites close to the receptor binding site (RBS) on influenza hemagglutinin represent the oligomannose cluster recognized by 2G12. One of these glycan sites is highly conserved in all human H3N2 strains and the other emerged during virus evolution. These two N-glycosylation sites have also become crucial for fitness of recent H3N2 strains. These findings shed light on the evolution of the glycan shield on influenza virus and suggest 2G12-like antibodies can potentially act as broad neutralizers to target human enveloped viruses.
Fusion imaging guided implantation of a Tricento transcatheter heart valve for severe tricuspid regurgitation

We report the case of a 64‐year‐old patient with history of chronic kidney disease on dialysis who was repeatedly hospitalized due to hydropic decompensation. Right heart failure with secondary severe tricuspid regurgitation was diagnosed. An interventional approach was recommended due to the heavy calcification of the sinus venosus and the perioperative risk (EuroScore II 3.2%) and taking into account the explicit request of the patient. After analysis of a full‐cycle computed tomography, the patient was eligible for the implantation of the Tricento transcatheter heart valve. The custom‐made prosthesis was implanted successfully using periprocedural transoesophageal guidance supported by fusion imaging that integrates live co‐registration. After implantation of the valve prosthesis, the primary result was excellent. The patient was discharged without further complications shortly after the procedure and her status is being closely monitored.
Circulating tumour DNA methylation in hepatocellular carcinoma diagnosis using digital droplet PCR

Objective To evaluate the performance of a DNA methylation-based digital droplet polymerase chain reaction (ddPCR) assay to detect aberrant DNA methylation in cell-free DNA (cfDNA) and to determine its application in the detection of hepatocellular carcinoma (HCC). Methods The present study recruited patients with liver-related diseases and healthy control subjects. Blood samples were used for the extraction of cfDNA, which was then bisulfite converted and the extent of DNA methylation quantified using a ddPCR platform. Results A total of 97 patients with HCC, 80 healthy control subjects and 46 patients with chronic hepatitis B/C virus infection were enrolled in the study. The level of cfDNA in the HCC group was significantly higher than that in the healthy control group. For the detection of HCC, based on a cut-off value of 15.7% for the cfDNA methylation ratio, the sensitivity and specificity were 78.57% and 89.38%, respectively. The diagnostic accuracy was 85.27%, the positive predictive value was 81.91% and the negative predictive value was 87.20%. The positive likelihood ratio of 15.7% in HCC diagnosis was 7.40, while the negative likelihood ratio was 0.24. Conclusions A sensitive methylation-based assay might serve as a liquid biopsy test for diagnosing HCC.
A glutaminase isoform switch drives therapeutic resistance and disease progression of prostate cancer

Significance We report that androgen receptor (AR) promotes glutaminase 1 (GLS1) expression and glutamine utilization to support the survival of prostate cancer (PCa) cells. Hormonal therapy inhibits AR and decreases GLS1 expression and glutamine utilization to achieve therapeutic effect. Our results suggest that eventually the tumor cells switch GLS1 expression from the AR-dependent KGA isoform to the androgen-independent and enzymatically more potent GAC isoform, which increases glutamine utilization and can contribute to the development of castration-resistant PCa. Our work has discovered a previously unknown AR function, a metabolic mechanism of hormonal therapy and an important therapeutic target more specific than AR. Targeting GLS1 may achieve similar therapeutic efficacy but without the side effects resulting from inhibiting AR’s other important physiologic functions. Cellular metabolism in cancer is significantly altered to support the uncontrolled tumor growth. How metabolic alterations contribute to hormonal therapy resistance and disease progression in prostate cancer (PCa) remains poorly understood. Here we report a glutaminase isoform switch mechanism that mediates the initial therapeutic effect but eventual failure of hormonal therapy of PCa. Androgen deprivation therapy inhibits the expression of kidney-type glutaminase (KGA), a splicing isoform of glutaminase 1 (GLS1) up-regulated by androgen receptor (AR), to achieve therapeutic effect by suppressing glutaminolysis. Eventually the tumor cells switch to the expression of glutaminase C (GAC), an androgen-independent GLS1 isoform with more potent enzymatic activity, under the androgen-deprived condition. This switch leads to increased glutamine utilization, hyperproliferation, and aggressive behavior of tumor cells. Pharmacological inhibition or RNA interference of GAC shows better treatment effect for castration-resistant PCa than for hormone-sensitive PCa in vitro and in vivo. In summary, we have identified a metabolic function of AR action in PCa and discovered that the GLS1 isoform switch is one of the key mechanisms in therapeutic resistance and disease progression.
High Case-Fatality Rate for Human Anthrax, Northern Ghana, 2005–2016

The human cutaneous anthrax case-fatality rate is ≈1% when treated, 5%–20% when untreated. We report high case-fatality rates (median 35.0%; 95% CI 21.1%–66.7%) during 2005–2016 linked to livestock handling in northern Ghana, where veterinary resources are limited. Livestock vaccination and access to human treatment should be evaluated.
Network‐based analysis using chromosomal microdeletion syndromes as a model

Microdeletion syndromes (MSs) are a heterogeneous group of genetic diseases that can virtually affect all functions and organs in humans. Although systems biology approaches integrating multiomics and database information into biological networks have expanded our knowledge of genetic disorders, cytogenomic network‐based analysis has rarely been applied to study MSs. In this study, we analyzed data of 28 MSs, using network‐based approaches, to investigate the associations between the critical chromosome regions and the respective underlying biological network systems. We identified MSs‐associated proteins that were organized in a network of linked modules within the human interactome. Certain MSs formed highly interlinked self‐contained disease modules. Furthermore, we observed disease modules involving proteins from other disease groups in the MSs interactome. Moreover, analysis of integrated data from 564 genes located in known chromosomal critical regions, including those contributing to topological parameters, shared pathways, and gene–disease associations, indicated that complex biological systems and cellular networks may underlie many genotype to phenotype associations in MSs. In conclusion, we used a network‐based analysis to provide resources that may contribute to better understanding of the molecular pathways involved in MSs.