Miracle-dz/UniFAR-FTUs huggingface dataset:
c-Myc Represses Transcription of Epstein-Barr Virus Latent Membrane Protein 1 Early after Primary B Cell Infection

ABSTRACT Recent evidence has shown that the Epstein-Barr virus (EBV) oncogene LMP1 is not expressed at high levels early after EBV infection of primary B cells, despite its being essential for the long-term outgrowth of immortalized lymphoblastoid cell lines (LCLs). In this study, we found that expression of LMP1 increased 50-fold between 7 days postinfection and the LCL state. Metabolic labeling of nascent transcribed mRNA indicated that this was primarily a transcription-mediated event. EBNA2, the key viral transcription factor regulating LMP1, and CTCF, an important chromatin insulator, were recruited to the LMP1 locus similarly early and late after infection. However, the activating histone H3K9Ac mark was enriched at the LMP1 promoter in LCLs relative to that in infected B cells early after infection. We found that high c-Myc activity in EBV-infected lymphoma cells as well as overexpression of c-Myc in an LCL model system repressed LMP1 transcription. Finally, we found that chemical inhibition of c-Myc both in LCLs and early after primary B cell infection increased LMP1 expression. These data support a model in which high levels of endogenous c-Myc activity induced early after primary B cell infection directly repress LMP1 transcription. IMPORTANCE EBV is a highly successful pathogen that latently infects more than 90% of adults worldwide and is also causally associated with a number of B cell malignancies. During the latent life cycle, EBV expresses a set of viral oncoproteins and noncoding RNAs with the potential to promote cancer. Critical among these is the viral latent membrane protein LMP1. Prior work suggests that LMP1 is essential for EBV to immortalize B cells, but our recent work indicates that LMP1 is not produced at high levels during the first few weeks after infection. Here we show that transcription of the LMP1 gene can be negatively regulated by a host transcription factor, c-Myc. Ultimately, understanding the regulation of EBV oncogenes will allow us to better treat cancers that rely on these viral products for survival.
Training replicable predictors in multiple studies

This article considers replicability of the performance of predictors across studies. We suggest a general approach to investigating this issue, based on ensembles of prediction models trained on different studies. We quantify how the common practice of training on a single study accounts in part for the observed challenges in replicability of prediction performance. We also investigate whether ensembles of predictors trained on multiple studies can be combined, using unique criteria, to design robust ensemble learners trained upfront to incorporate replicability into different contexts and populations.
The hypoxia-inducible factors HIF1α and HIF2α are dispensable for embryonic muscle development but essential for postnatal muscle regeneration

Muscle satellite cells are myogenic stem cells whose quiescence, activation, self-renewal, and differentiation are influenced by oxygen supply, an environmental regulator of stem cell activity. Accordingly, stem cell-specific oxygen signaling pathways precisely control the balance between muscle growth and regeneration in response to oxygen fluctuations, and hypoxia-inducible factors (HIFs) are central mediators of these cellular responses. However, the in vivo roles of HIFs in quiescent satellite cells and activated satellite cells (myoblasts) are poorly understood. Using transgenic mouse models for cell-specific HIF expression, we show here that HIF1α and HIF2α are preferentially expressed in pre- and post-differentiation myoblasts, respectively. Interestingly, double knockouts of HIF1α and HIF2α (HIF1α/2α dKO) generated with the MyoDCre system in embryonic myoblasts resulted in apparently normal muscle development and growth. However, HIF1α/2α dKO produced with the tamoxifen-inducible, satellite cell-specific Pax7CreER system in postnatal satellite cells delayed injury-induced muscle repair due to a reduced number of myoblasts during regeneration. Analysis of satellite cell dynamics on myofibers confirmed that HIF1α/2α dKO myoblasts exhibit reduced self-renewal but more pronounced differentiation under hypoxic conditions. Mechanistically, the HIF1α/2α dKO blunted hypoxia-induced activation of Notch signaling, a key determinant of satellite cell self-renewal. We conclude that HIF1α and HIF2α are dispensable for muscle stem cell function under normoxia but are required for maintaining satellite cell self-renewal in hypoxic environments. Our insights into a critical mechanism in satellite cell homeostasis during muscle regeneration could help inform research efforts to treat muscle diseases or improve muscle function.
Analytic Model for Area-Constrained OPtimal Repeater Insertion.

We present an analytic formula for repeater insertion in global interconnects with a precise allowance of the total available repeater area. Given this repeater area, the repeater sizes and distances are determined such that there is no other solution using the same (or less) area with a better performance. The analytic model requires only basic technology characterization data that are easily obtained, and shows excellent agreement to SPICE simulations. The results confirm that ultimate performance is expensive in terms of area and that e.g. 70% reduction in area only costs 15% of the performance.
Genetic Diversity and Population Structure in a Legacy Collection of Spring Barley Landraces Adapted to a Wide Range of Climates

Global environmental change and increasing human population emphasize the urgent need for higher yielding and better adapted crop plants. One strategy to achieve this aim is to exploit the wealth of so called landraces of crop species, representing diverse traditional domesticated populations of locally adapted genotypes. In this study, we investigated a comprehensive set of 1485 spring barley landraces (Lrc1485) adapted to a wide range of climates, which were selected from one of the largest genebanks worldwide. The landraces originated from 5° to 62.5° N and 16° to 71° E. The whole collection was genotyped using 42 SSR markers to assess the genetic diversity and population structure. With an average allelic richness of 5.74 and 372 alleles, Lrc1485 harbours considerably more genetic diversity than the most polymorphic current GWAS panel for barley. Ten major clusters defined most of the population structure based on geographical origin, row type of the ear and caryopsis type – and were assigned to specific climate zones. The legacy core reference set Lrc648 established in this study will provide a long-lasting resource and a very valuable tool for the scientific community. Lrc648 is best suited for multi-environmental field testing to identify candidate genes underlying quantitative traits but also for allele mining approaches.
Variations in depressive affects due to differences in gender and residence

The study explores the phenomenon of depression as a function of gender and residence. A total of 40 respondents constituted the sample. The age of the respondents ranged from 40-65 years. A 2×2 factorial design representing two levels of gender (Male/Female) and two levels of residential background (Urban/Rural) was used. Two hypotheses were formulated. The first hypothesis states that female would exhibit more depressive symptoms than the males. The second hypothesis states that respondents with rural residential background would exhibit more depressive symptoms than the respondents with urban residential background. The statistical technique of analysis of variance (ANOVA) was used for the analysis of data. The results provided empirical support to the second hypothesis. It was found that respondents with rural residential background expressed significantly more depressive symptoms than the respondents with urban residential background. Key words: Depressive affect; self-esteem; adolescence; brain chemistry; mental health. DOI: 10.3329/jles.v2i2. 7498 J. Life Earth Sci., Vol. 2(2) 51-55, 2007
Factors Associated with Colostrum Quality and Effects on Serum Gamma Globulin Concentrations of Calves in Swiss Dairy Herds

Background Previous studies have shown a high prevalence of failure of passive transfer of immunity (FPT) in Swiss dairy calves. Objectives To investigate risk factors associated with poor colostrum quality and FPT on Swiss dairy farms. Animals Colostrum and serum samples from 373 dam‐calf pairs at 141 farms. Methods The gamma globulin (Gg) concentrations of the dams’ colostrum and the calves’ serum samples were determined by electrophoresis. Potential risk factors were assessed by logistic regression of questionnaire data. Results Prevalence values of 15.5% (95% confidence interval [CI], 12.0–19.6%) for low‐quality colostrum (<50 g Gg/L) in cows and 43.5% (95% CI, 38.4–48.8%) for FPT (serum Gg < 10 g/L) in calves were estimated. The main factors associated with low colostrum quality included colostrum leakage before or during parturition and a time lag > 6 hours between parturition and first milking. The results confirm that the occurrence of FPT in calves primarily was influenced by the quality of colostrum, the amount of ingested colostrum, and the time between birth and first feeding. Conclusions and Clinical Importance These results confirm a large potential for improvement in colostrum harvesting and colostrum feeding procedures in the study herds. Control for colostrum leaking intra‐partum, early colostrum milking, and ensuring that the calves ingest a sufficient volume of colostrum within the first hours of life are measures that can be readily implemented by farmers to decrease the incidence of FPT without additional workload.
Temperate Mountain Forest Biodiversity under Climate Change: Compensating Negative Effects by Increasing Structural Complexity

Species adapted to cold-climatic mountain environments are expected to face a high risk of range contractions, if not local extinctions under climate change. Yet, the populations of many endothermic species may not be primarily affected by physiological constraints, but indirectly by climate-induced changes of habitat characteristics. In mountain forests, where vertebrate species largely depend on vegetation composition and structure, deteriorating habitat suitability may thus be mitigated or even compensated by habitat management aiming at compositional and structural enhancement. We tested this possibility using four cold-adapted bird species with complementary habitat requirements as model organisms. Based on species data and environmental information collected in 300 1-km2 grid cells distributed across four mountain ranges in central Europe, we investigated (1) how species’ occurrence is explained by climate, landscape, and vegetation, (2) to what extent climate change and climate-induced vegetation changes will affect habitat suitability, and (3) whether these changes could be compensated by adaptive habitat management. Species presence was modelled as a function of climate, landscape and vegetation variables under current climate; moreover, vegetation-climate relationships were assessed. The models were extrapolated to the climatic conditions of 2050, assuming the moderate IPCC-scenario A1B, and changes in species’ occurrence probability were quantified. Finally, we assessed the maximum increase in occurrence probability that could be achieved by modifying one or multiple vegetation variables under altered climate conditions. Climate variables contributed significantly to explaining species occurrence, and expected climatic changes, as well as climate-induced vegetation trends, decreased the occurrence probability of all four species, particularly at the low-altitudinal margins of their distribution. These effects could be partly compensated by modifying single vegetation factors, but full compensation would only be achieved if several factors were changed in concert. The results illustrate the possibilities and limitations of adaptive species conservation management under climate change.
Smartphone Use and Perceptions among Medical Students and Practicing Physicians

Results: A total of 544 surveys were submitted; 347 were completed and analyzed. 93.9% of respondents had smartphones, with no significant difference between students and physicians. Of those with the technology, 82.9% stated they have used it at least once in a clinical setting. Respondents perceived fast access to information to be the greatest benefit to mobile medical technology (96.6%), as well as simplified access (75.5%). Greatest perceived barriers to using this technology were uncertainty about available applications (39.4%) and inexperience (23.4%). There was no significant difference between students and physicians with regard to either category. Concerning patient-centered applications, assistance with lifestyle modification (78.8%) and increased adherence to treatment plans (73.8%) were agreed upon as potential benefits. Greatest perceived barriers to recommending this technology were added cost to the patient (52.6%) and concerns about patient self-diagnosis (47.7%), with no significant difference found between students and physicians.
Understanding ACGME Scholarly Activity Requirements for General Surgery Programs in the Era of Single Accreditation and the Next Accreditation System

Becoming compliant with the Accreditation Council for Graduate Medical Education (ACGME) requirements for scholarly activity and remaining compliant over time requires time and attention to the development of an environment of inquiry, which is reflected in detailed documentation submitted in program applications and annual updates. Since the beginning of the next accreditation system, all ACGME programs have been required to submit evidence of scholarly activity of both residents and faculty on an annual basis. Since 2014, American Osteopathic Association–accredited programs have been able to apply for ACGME accreditation under the Single Graduate Medical Education Accreditation initiative. The Residency Program Director, Chair, Designated Institutional Official, Faculty, and coordinator need to work cohesively to ensure compliance with all program requirements, including scholarly activity in order for American Osteopathic Association–accredited programs to receive Initial ACGME Accreditation and for current ACGME-accredited programs to maintain accreditation. Fortunately, there are many ways to show the type of scholarly activity that is required for the training of surgeons. In this article, we will review the ACGME General Surgery Program Requirements and definitions of scholarly activity. We will also offer suggestions for how programs may show evidence of scholarly activity.
Semiparametric analysis of case series data

Summary. The case series model for estimating the association between an age‐dependent exposure and an outcome event requires information only on cases and implicitly adjusts for all age‐independent multiplicative confounders, while allowing for an age‐dependent base‐line incidence. In the paper the model is presented in greater generality than hitherto, including more general discussion of its derivation, underlying assumptions, applicability, limitations and efficiency. A semiparametric version of the model is developed, in which the age‐specific relative incidence is left unspecified. Modelling covariate effects and testing assumptions are discussed. The small sample performance of this model is studied in simulations. The methods are illustrated with several examples from epidemiology.
Oxidative Role of HIV/AIDS: Antiretroviral Drugs and Medicinal Plants with Anti-HIV Activity

More than three decades after its outbreak, the Acquired Immune Deficiency Syndrome (AIDS) remains a great mystery because there is neither an existing vaccine against its causative agent (the human immune deficiency virus) nor a cure against it. Worst of all is the popular attention that is tuned to the AIDS virus, ignoring oxidative stress which is the major cause of mortality in HIV/AIDS as in many other chronic diseases. Antiretroviral drugs introduced in 1996 have been shown to increase oxidative stress among other drug-related complications. With these backdrops, an antioxidant therapy is necessary to accompany antiretroviral treatment without which its beneficial effects are null. The present review aims to discuss the Oxidative Role of HIV/AIDS and antiretroviral drugs as well as some plants that have recently been revealed to be rich sources of antioxidants.
Multivariate analysis reveals genetic associations of the resting default mode network in psychotic bipolar disorder and schizophrenia

Significance Connectivity within the brain’s resting-state default mode network (DMN) has been shown to be compromised in multiple genetically complex/heritable neuropsychiatric disorders. Uncovering the source of such alterations will help in developing targeted treatments for these disorders. To our knowledge, this study is the first attempt to do so by using a multivariate data-driven fusion approach. We report five major DMN subnodes, all of which were found to be hypo-connected in probands with psychotic illnesses. Further, we found an overrepresentation of genes in major relevant pathways such as NMDA potentiation, PKA/immune response signalling, synaptogenesis, and axon guidance that influenced altered DMN connectivity in psychoses. The study thus identifies several putative genes and pathways related to an important biological marker known to be compromised in psychosis. The brain’s default mode network (DMN) is highly heritable and is compromised in a variety of psychiatric disorders. However, genetic control over the DMN in schizophrenia (SZ) and psychotic bipolar disorder (PBP) is largely unknown. Study subjects (n = 1,305) underwent a resting-state functional MRI scan and were analyzed by a two-stage approach. The initial analysis used independent component analysis (ICA) in 324 healthy controls, 296 SZ probands, 300 PBP probands, 179 unaffected first-degree relatives of SZ probands (SZREL), and 206 unaffected first-degree relatives of PBP probands to identify DMNs and to test their biomarker and/or endophenotype status. A subset of controls and probands (n = 549) then was subjected to a parallel ICA (para-ICA) to identify imaging–genetic relationships. ICA identified three DMNs. Hypo-connectivity was observed in both patient groups in all DMNs. Similar patterns observed in SZREL were restricted to only one network. DMN connectivity also correlated with several symptom measures. Para-ICA identified five sub-DMNs that were significantly associated with five different genetic networks. Several top-ranking SNPs across these networks belonged to previously identified, well-known psychosis/mood disorder genes. Global enrichment analyses revealed processes including NMDA-related long-term potentiation, PKA, immune response signaling, axon guidance, and synaptogenesis that significantly influenced DMN modulation in psychoses. In summary, we observed both unique and shared impairments in functional connectivity across the SZ and PBP cohorts; these impairments were selectively familial only for SZREL. Genes regulating specific neurodevelopment/transmission processes primarily mediated DMN disconnectivity. The study thus identifies biological pathways related to a widely researched quantitative trait that might suggest novel, targeted drug treatments for these diseases.
The Enhanced Care Program: Impact of a Care Transition Program on 30-Day Hospital Readmissions for Patients Discharged From an Acute Care Facility to Skilled Nursing Facilities

BACKGROUND Increased acuity of skilled nursing facility (SNF) patients challenges the current system of care for these patients. OBJECTIVE Evaluate the impact on 30-day readmissions of a program designed to enhance the care of patients discharged from an acute care facility to SNFs. DESIGN An observational, retrospective cohort analysis of 30-day hospital readmissions for patients discharged to 8 SNFs between January 1, 2014, and June 30, 2015. SETTING A collaboration between a large, acute care hospital in an urban setting, an interdisciplinary clinical team, 124 community physicians, and 8 SNFs. PATIENTS All patients discharged from Cedars-Sinai Medical Center to 8 partner SNFs were eligible for participation. INTERVENTION The Enhanced Care Program (ECP) involved the following 3 interventions in addition to standard care: (1) a team of nurse practitioners participating in the care of SNF patients; (2) a pharmacist-driven medication reconciliation at the time of transfer; and (3) educational in-services for SNF nursing staff. MEASUREMENT Thirty-day readmission rate for ECP patients compared to patients not enrolled in ECP. RESULTS The average unadjusted, 30-day readmission rate for ECP patients over the 18-month study period was 17.2% compared to 23.0% among patients not enrolled in ECP (P < .001). After adjustment for sociodemographic and clinical characteristics, ECP patients had 29% lower odds of being readmitted within 30 days (P < .001). These effects were robust to stratified analyses, analyses adjusted for clustering, and balancing of covariates using propensity weighting. CONCLUSIONS A coordinated, interdisciplinary team caring for SNF patients can reduce 30-day hospital readmissions. Journal of Hospital Medicine 2018;13:229-235. Published online first October 4, 2017
The Scoop on Health: How Native American Newspapers Frame and Report Health News

ABSTRACT The health status of Native Americans is known to be lower than that of other Americans. One way to get relevant health information to this population is through Native-produced media. Tribal newspapers are the most popular form of Native media, consumed more often than their mainstream counterparts. As such, these community-based newspapers are meaningful tools for relevant health information gathering. This study content analyzes a census of health-related newspaper articles (N = 644) over a 1-year period from 20 Tribal newspapers across 10 regions designated by the U.S. Bureau of Indian Affairs. Findings profile the nature of health topics reported in Native news publications. Health news stories were shown to use episodic frames significantly more than thematic frames. Inclusion of supplementary information (e.g., causes/symptoms, treatment, and prevention) and inclusion of mobilizing information (i.e., provides readers resources for further action) were both shown to significantly differ by health topic. Results provide an important baseline understanding of how health news is reported in Native news publications.
A single‐session intervention (the Mini‐AFTERc) for fear of cancer recurrence: A feasibility study

One of the most prevalent concerns for cancer survivors is fear of cancer recurrence (FCR), defined as “the fear that cancer may return or progress in the same place or another part of the body. ” Roughly half of all cancer survivors report moderate FCR, and an intensive intervention may be counterproductive for these patients. A short intervention used as part of routine care may be helpful to prevent FCR from increasing. The 6‐session AFTER intervention has been adapted into a single‐session intervention named the Mini‐Adjustment to Fear, Threat and Expectation of Recurrence (“Mini‐AFTERc”). This, 30‐minute, single‐session intervention is designed for patients with moderate FCR and for it to be incorporated into routine cancer care by specialist cancer nurses. The intervention may assist patients with severe FCR; however, the small duration and intensity may be insufficient. For higher FCR levels, a multisession intervention may be recommended. The aim of this study was to conduct a small, feasibility study by using the Mini‐AFTERc intervention with breast cancer patients with moderate FCR. The objectives were to (i) assess the feasibility of incorporating the intervention into routine care, (ii) evaluate the intervention effect, and (iii) assess the fidelity to the intervention manual.