Miracle-dz/UniFAR-FTUs huggingface dataset:
Growing Up on an Appalachian Farm

Background Research on centenarians to date has focused on areas with a high population of centenarians. However, there is limited literature on centenarians’ perspectives about growing up on farms from the heartland of Appalachia in Eastern Tennessee. Purpose This qualitative descriptive study was designed to characterize the role of a farming childhood by exploring the viewpoints of community-dwelling centenarians who grew up on farms in south central Appalachia. Methods A qualitative descriptive design was used with a convenience sample (n = 16). Cognitive status was determined with the Short Portable Mental Status Questionnaire. Demographic data were collected. Interviews were transcribed and analyzed with the Neuendorf method of content analysis. Results Main emerging themes were the farm, the family, and the environment. Conclusion The farm was at the center of these centenarians’ childhood, influencing their family, community relations, and social interactions, which provided lessons that they utilized throughout their long lives.
Methicillin-resistant Staphylococcus aureus nasal cariage among hospitalized patients and healthcare workers in the Clinical center of Serbia

The aim of the present study was to provide the first comprehensive analysis of methicillin-resistant Staphylococ - cus aureus (MrSA) carriage among patients and healthcare workers (HCWs) in the largest healthcare facility in Serbia. Specimens from anterior nares obtained from 195 hospitalized patients and 105 HCWs were inoculated after broth enrich- ment onto chromogenic MrSA-ID medium. In total, 21 of 300 specimens yielded MrSA. Among hospitalized patients, 7.7% were colonized with MrSA, and 5.7% HCWs were colonized with MrSA. Five out of 21 (23.8%) tested MrSA strains were classified as community-associated MrSA (CA-MrSA), and four of them were isolated from HCWs. The remaining 16 MrSA strains had characteristics of healthcare-associated MrSA (HA-MrSA), and two of them were isolated from HCWs. The HA-MrSA strains isolated from HCWs were indistinguishable from HA-MrSA of the same cluster isolated from patients. This finding reveals the circulation of HA-MrSA strains between patients and HCWs in the Clinical Center of Serbia.
No Effect of Insecticide Treated Curtain Deployment on Aedes Infestation in a Cluster Randomized Trial in a Setting of Low Dengue Transmission in Guantanamo, Cuba

Objective & Methodology The current study evaluated the effectiveness and cost-effectiveness of Insecticide Treated Curtain (ITC) deployment for reducing dengue vector infestation levels in the Cuban context with intensive routine control activities. A cluster randomized controlled trial took place in Guantanamo city, east Cuba. Twelve neighborhoods (about 500 households each) were selected among the ones with the highest Aedes infestation levels in the previous two years, and were randomly allocated to the intervention and control arms. Long lasting ITC (PermaNet) were distributed in the intervention clusters in March 2009. Routine control activities were continued in the whole study area. In both study arms, we monitored monthly pre- and post-intervention House Index (HI, number of houses with at least 1 container with Aedes immature stages/100 houses inspected), during 12 and 18 months respectively. We evaluated the effect of ITC deployment on HI by fitting a generalized linear regression model with a negative binomial link function to these data. Principal Findings At distribution, the ITC coverage (% of households using ≥1 ITC) reached 98.4%, with a median of 3 ITC distributed/household. After 18 months, the coverage remained 97.4%. The local Aedes species was susceptible to deltamethrin (mosquito mortality rate of 99.7%) and the residual deltamethrin activity in the ITC was within acceptable levels (mosquito mortality rate of 73.1%) after one year of curtain use. Over the 18 month observation period after ITC distribution, the adjusted HI rate ratio, intervention versus control clusters, was 1.15 (95% CI 0.57 to 2.34). The annualized cost per household of ITC implementation was 3.8 USD, against 16.8 USD for all routine ACP activities. Conclusion Deployment of ITC in a setting with already intensive routine Aedes control actions does not lead to reductions in Aedes infestation levels.
A Long-term Prospective Study of Type-Specific Human Papillomavirus Infection and Risk of Cervical Neoplasia Among 20,000 Women in the Portland Kaiser Cohort Study

Background: Human papillomavirus (HPV) DNA testing is more sensitive than cytology for detection of cervical intraepithelial neoplasia grade 3 and cancer (≥CIN3). Adding HPV testing to cytology is recommended for women ≥30 but long-term prospective studies of HPV testing are rare. Methods: Beginning in 1989–1990, ∼20,000 women in a prepaid health maintenance organization (median age = 34) were followed passively by recommended annual cytology. We tested archived cervicovaginal lavage specimens collected at enrollment, primarily by MY09-MY11 PCR-based methods, for carcinogenic HPV types. We calculated positive and negative predictive values for the entire study period, and Kaplan–Meier estimates of cumulative probability for ≥CIN3, up to 18 years of follow-up. Results: We observed 15 cases of invasive cervical cancer during the study period, and 189 cases of CIN3. Predictive values and Kaplan–Meier analyses yielded the same conclusions. In women 30 and older, the reassurance against ≥CIN3 following a single negative HPV test was long-lasting (cumulative probability = 0.7% during follow-up). In this age group, a single HPV test (positive vs. negative, hazard ratio of 8.5, 95% CI = 4.8–15.1) provided greater long-term risk stratification than a single cytologic result (abnormal vs. normal, HR = 2.9, 95% CI = 1.2–6.6). The risk for ≥CIN3 was higher for HPV16 than for the average of the other carcinogenic types (hazard ratio = 2.7). Conclusion and Impact: The data from this cohort study show the long-term predictive value of HPV testing, particularly in women ≥30, and a possible role for distinguishing particularly carcinogenic types like HPV16. Cancer Epidemiol Biomarkers Prev; 20(7); 1398–409. ©2011 AACR.
Examining transitions from youth to adult services for young persons with autism

ABSTRACT Autism Spectrum Disorder (ASD) presents pervasive challenges for individuals throughout their lifetime. Although some financial, community, and individual supports are available for children, there are fewer resources available for adults with ASD, their families, and/or caregivers. It is important to understand the multidimensional shifts associated with the transition from adolescence to adulthood for individuals with ASD. To better understand the transitional process, a qualitative study comprised 11 semi-structured interviews with individuals with ASD and their families. Interviews elicited the experiences of individuals and families impacted by ASD as they transition to adulthood and adult systems of care. This study found that individuals with ASD and their family are exposed to a “lifetime of difficult transitions” due to a limited number of service providers and resources including stringent and restrictive program and funding criteria. As a result, individuals with ASD and their families were concerned about the ability of some individuals with ASD to establish meaningful lives in adulthood. These findings challenge existing barriers and broader societal values and stigma that impede emerging adults with developmental disabilities.
Simulation of multiphase systems utilizing independent force fields to control intraphase and interphase behavior

Fixed‐charge empirical force fields have been developed and widely used over the past three decades for all‐atom molecular simulations. Most simulation programs providing these methods enable only one set of force field parameters to be used for the entire system. Whereas this is generally suitable for single‐phase systems, the molecular environment at the interface between two phases may be sufficiently different from the individual phases to require a different set of parameters to be used to accurately represent the system. Recently published simulations of peptide adsorption to material surfaces using the CHARMM force field have clearly demonstrated this issue by revealing that calculated values of adsorption free energy substantially differ from experimental results. Whereas nonbonded parameters could be adjusted to correct this problem, this cannot be done without also altering the conformational behavior of the peptide in solution, for which CHARMM has been carefully tuned. We have developed a dual‐force‐field approach (Dual‐FF) to address this problem and implemented it in the CHARMM simulation package. This Dual‐FF method provides the capability to use two separate sets of nonbonded force field parameters within the same simulation: one set to represent intraphase interactions and a separate set to represent interphase interactions. Using this approach, we show that interfacial parameters can be adjusted to correct errors in peptide adsorption free energy without altering peptide conformational behavior in solution. This program thus provides the capability to enable both intraphase and interphase molecular behavior to be accurately and efficiently modeled in the same simulation. © 2012 Wiley Periodicals, Inc.
Platelets Contribute to the Pathogenesis of Experimental Autoimmune Encephalomyelitis

Rationale: Multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis (EAE), are inflammatory disorders of the central nervous system (CNS). The function of platelets in inflammatory and autoimmune pathologies is thus far poorly defined. Objective: We addressed the role of platelets in mediating CNS inflammation in EAE. Methods and Results: We found that platelets were present in human MS lesions as well as in the CNS of mice subjected to EAE but not in the CNS from control nondiseased mice. Platelet depletion at the effector-inflammatory phase of EAE in mice resulted in significantly ameliorated disease development and progression. EAE suppression on platelet depletion was associated with reduced recruitment of leukocytes to the inflamed CNS, as assessed by intravital microscopy, and with a blunted inflammatory response. The platelet-specific receptor glycoprotein Ib&agr; (GPIb&agr;) promotes both platelet adhesion and inflammatory actions of platelets and targeting of GPIb&agr; attenuated EAE in mice. Moreover, targeting another platelet adhesion receptor, glycoprotein IIb/IIIa (GPIIb/IIIa), also reduced EAE severity in mice. Conclusions: Platelets contribute to the pathogenesis of EAE by promoting CNS inflammation. Targeting platelets may therefore represent an important new therapeutic approach for MS treatment.
SLCO1B1 Polymorphism Is a Drug Response Predictive Marker for Advanced Pancreatic Cancer Patients Treated With Gemcitabine, S-1, or Gemcitabine Plus S-1.

OBJECTIVES The aim of this study was to evaluate the effects of single-nucleotide polymorphisms (SNPs) on advanced pancreatic cancer risk and overall survival (OS) in a candidate-gene approach. METHODS Overall, 5438 SNPs in 219 candidate genes encoding several drug-metabolizing enzymes or transporters were analyzed. In the screening study, 3 SNPs were found associated with OS (P ≤ 0.0005). We validated these SNPs as part of the randomized phase 3 study (GEST study). The associations between OS and SNPs were investigated using log-rank test and Cox proportional hazards model. RESULTS From the GEST study, the SNP rs4149086 in the 3' UTR of the solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene showed significant interaction with treatment (P = 0.02). In the gemcitabine group, the SNP was associated with short OS (hazard ratio [HR], 3.75; 95% confidence interval [CI], 1.30-10.8; P = 0.008) even after multiple-comparisons adjustment. In contrast, the SNP was not associated with OS in S-1 (HR, 0.77; 95% CI, 0.33-1.81; P = 0.55) or gemcitabine plus S-1 groups (HR, 1.18; 95% CI, 0.46-3.00; P = 0.72). CONCLUSIONS Patients with advanced pancreatic cancer with the rs4149086 AG or GG genotype may obtain good clinical results when treated with S-1-containing regimens.
Identification of Four Oxidative Stress-Responsive MicroRNAs, miR-34a-5p, miR-1915-3p, miR-638, and miR-150-3p, in Hepatocellular Carcinoma

Increasing evidence suggests that oxidative stress plays an essential role during carcinogenesis. However, the underlying mechanism between oxidative stress and carcinogenesis remains unknown. Recently, microRNAs (miRNAs) are revealed to be involved in oxidative stress response and carcinogenesis. This study aims to identify miRNAs in hepatocellular carcinoma (HCC) cells which might involve in oxidative stress response. An integrated analysis of miRNA expression signature was performed by employing robust rank aggregation (RRA) method, and four miRNAs (miR-34a-5p, miR-1915-3p, miR-638, and miR-150-3p) were identified as the oxidative stress-responsive miRNAs. Pathway enrichment analysis suggested that these four miRNAs played an important role in antiapoptosis process. Our data also revealed miR-34a-5p and miR-1915-3p, but not miR-150-3p and miR-638, were regulated by p53 in HCC cell lines under oxidative stress. In addition, clinical investigation revealed that these four miRNAs might be involved in oxidative stress response by targeting oxidative stress-related genes in HCC tissues. Kaplan-Meier analysis showed that these four miRNAs were associated with patients' overall survival. In conclusion, we identified four oxidative stress-responsive miRNAs, which were regulated by p53-dependent (miR-34a-5p and miR-1915-3p) and p53-independent pathway (miR-150-3p and miR-638). These four miRNAs may offer new strategy for HCC diagnosis and prognosis.
A demonstration of the H3 trimethylation ChIP-seq analysis of galline follicular mesenchymal cells and male germ cells

Objective Trimethylation of histone 3 (H3) at 4th lysine N-termini (H3K4me3) in gene promoter region was the universal marker of active genes specific to cell lineage. On the contrary, coexistence of trimethylation at 27th lysine (H3K27me3) in the same loci—the bivalent H3K4m3/H3K27me3 was known to suspend the gene transcription in germ cells, and could also be inherited to the developed stem cell. In galline species, throughout example of H3K4m3 and H3K27me3 ChIP-seq analysis was still not provided. We therefore designed and demonstrated such procedures using ChIP-seq and mRNA-seq data of chicken follicular mesenchymal cells and male germ cells. Methods Analytical workflow was designed and provided in this study. ChIP-seq and RNA-seq datasets of follicular mesenchymal cells and male germ cells were acquired and properly preprocessed. Peak calling by Model-based analysis of ChIP-seq 2 was performed to identify H3K4m3 or H3K27me3 enriched regions (Fold-change≥2, FDR≤0.01) in gene promoter regions. Integrative genomics viewer was utilized for cellular retinoic acid binding protein 1 (CRABP1), growth differentiation factor 10 (GDF10), and gremlin 1 (GREM1) gene explorations. Results The acquired results indicated that follicular mesenchymal cells and germ cells shared several unique gene promoter regions enriched with H3K4me3 (5,704 peaks) and also unique regions of bivalent H3K4m3/H3K27me3 shared between all cell types and germ cells (1,909 peaks). Subsequent observation of follicular mesenchyme-specific genes—CRABP1, GDF10, and GREM1 correctly revealed vigorous transcriptions of these genes in follicular mesenchymal cells. As expected, bivalent H3K4m3/H3K27me3 pattern was manifested in gene promoter regions of germ cells, and thus suspended their transcriptions. Conclusion According the results, an example of chicken H3K4m3/H3K27me3 ChIP-seq data analysis was successfully demonstrated in this study. Hopefully, the provided methodology should hereby be useful for galline ChIP-seq data analysis in the future.
Preparing teachers for competency-based medical education: Fundamental teaching activities

Abstract Introduction: The move to competency-based medical education has created new challenges for medical teachers, including the need to reflect on and further develop their own competencies as teachers. Guidance is needed to ensure comprehensive and coherent programs of faculty development to meet the needs of teachers. Methods: The Working Group on Faculty Development of the College of Family Physicians of Canada developed a new concept, Fundamental Teaching Activities (FTAs), to describe the day-to-day work of teachers. These activities are intended to guide teacher professional development. Using task analysis and iterative reviews with teachers and educational leaders, these FTAs were organized into a framework for teachers to identify the actions involved in various teaching tasks, and to reflect on their teaching performance and next steps in personal development. Results: In addition to use by teachers for personal development, the framework is being employed to guide the development of comprehensive faculty development offerings and curriculum, and to organize the beginnings of a national repository of teaching tools. Conclusions: Designed to support and aid teachers and those charged with faculty development, the Fundamental Teaching Activities Framework holds promise for all teachers in health sciences education.
Elevated fear conditioning to socially relevant unconditioned stimuli in social anxiety disorder.

OBJECTIVE Though conditioned fear has long been acknowledged as an important etiologic mechanism in social anxiety disorder, past psychophysiological experiments have found no differences in general conditionability among social anxiety patients using generally aversive but socially nonspecific unconditioned stimuli (e.g., unpleasant odors and painful pressure). The authors applied a novel fear conditioning paradigm consisting of socially relevant unconditioned stimuli of critical facial expressions and verbal feedback. This study represents the first effort to assess the conditioning correlates of social anxiety disorder within an ecologically enhanced paradigm. METHOD Subjects with social anxiety disorder and age- and gender-matched healthy comparison subjects underwent differential classical conditioning. Conditioned stimuli included images of three neutral facial expressions, each of which was paired with one of three audiovisual unconditioned stimuli: negative insults with critical faces (US(neg)), positive compliments with happy faces (US(pos)), or neutral comments with neutral faces (US(neu)). The conditioned response was measured as the fear-potentiation of the startle-blink reflex elicited during presentation of the conditioned stimuli. RESULTS Only social anxiety subjects demonstrated fear conditioning in response to facial expressions, as the startle-blink reflex was potentiated by the CS(neg) versus both CS(neu) and CS(pos) among those with the disorder, while healthy comparison subjects displayed no evidence of conditioned startle-potentiation. Such group differences in conditioning were independent of levels of anxiety to the unconditioned stimulus, implicating associative processes rather than increased unconditioned stimulus reactivity as the active mechanism underlying enhanced conditioned startle-potentiation among social anxiety subjects. CONCLUSIONS Results support a conditioning contribution to social anxiety disorder and underscore the importance of disorder-relevant unconditioned stimuli when studying the conditioning correlates of pathologic anxiety.
Evaluation of cytarabine against Ewing sarcoma xenografts by the pediatric preclinical testing program

Treatment with the nucleoside analog cytarabine has been shown to mimic changes in gene expression associated with downregulation of the EWS‐FLI1 oncogene in Ewing sarcoma cell lines, selectively inhibit their growth in vitro, and cause tumor regression in athymic nude mice. For this report cytarabine was studied in vitro against a panel of 23 pediatric cancer cell lines and in vivo against 6 Ewing sarcoma xenografts. Acute lymphoblastic leukemia cell lines were the most sensitive to cytarabine in vitro (median IC50 9 nM), while Ewing sarcoma cell lines showed intermediate sensitivity (median IC50 232 nM). Cytarabine at a dose of 150 mg/kg administered daily 5× failed to significantly inhibit growth of five xenograft models, but reduced growth rate of the A673 xenograft by 50%. Cytarabine shows no differential in vitro activity against Ewing sarcoma cell lines and is ineffective in vivo against Ewing sarcoma xenografts at the dose and schedule studied. Pediatr Blood Cancer. 2010;55:1224–1226. © 2010 Wiley‐Liss, Inc.
Reflections of health care professionals on e-learning resources for patient safety

ABSTRACT There is a paucity of evidence on how health care professionals view e-learning as a means of education to achieve safer health care. To address this gap, the reflections of health care professionals who used the resources on BMJ Learning were captured and analyzed. Key themes emerged from the analysis. Health care professionals are keen to put their e-learning into action to achieve safer health care and to learn how to follow guidelines that will help them achieve safer health care. Learners wanted their learning to remain grounded in reality. Finally, many commented that it was difficult for their individual learning to have a real impact when the culture of the organization did not change.
The Upregulation of α2δ-1 Subunit Modulates Activity-Dependent Ca2+ Signals in Sensory Neurons

As auxiliary subunits of voltage-gated Ca2+ channels, the α2δ proteins modulate membrane trafficking of the channels and their localization to specific presynaptic sites. Following nerve injury, upregulation of the α2δ-1 subunit in sensory dorsal root ganglion neurons contributes to the generation of chronic pain states; however, very little is known about the underlying molecular mechanisms. Here we show that the increased expression of α2δ-1 in rat sensory neurons leads to prolonged Ca2+ responses evoked by membrane depolarization. This mechanism is coupled to CaV2.2 channel-mediated responses, as it is blocked by a ω-conotoxin GVIA application. Once initiated, the prolonged Ca2+ transients are not dependent on extracellular Ca2+ and do not require Ca2+ release from the endoplasmic reticulum. The selective inhibition of mitochondrial Ca2+ uptake demonstrates that α2δ-1-mediated prolonged Ca2+ signals are buffered by mitochondria, preferentially activated by Ca2+ influx through CaV2.2 channels. Thus, by controlling channel abundance at the plasma membrane, the α2δ-1 subunit has a major impact on the organization of depolarization-induced intracellular Ca2+ signaling in dorsal root ganglion neurons.
Acute intermittent hypoxia enhances corticospinal synaptic plasticity in humans

Acute intermittent hypoxia (AIH) enhances voluntary motor output in humans with central nervous system damage. The neural mechanisms contributing to these beneficial effects are unknown. We examined corticospinal function by evaluating motor evoked potentials (MEPs) elicited by cortical and subcortical stimulation of corticospinal axons and the activity in intracortical circuits in a finger muscle before and after 30 min of AIH or sham AIH. We found that the amplitude of cortically and subcortically elicited MEPs increased for 75 min after AIH but not sham AIH while intracortical activity remained unchanged. To examine further these subcortical effects, we assessed spike-timing dependent plasticity (STDP) targeting spinal synapses and the excitability of spinal motoneurons. Notably, AIH increased STDP outcomes while spinal motoneuron excitability remained unchanged. Our results provide the first evidence that AIH changes corticospinal function in humans, likely by altering corticospinal-motoneuronal synaptic transmission. AIH may represent a novel noninvasive approach for inducing spinal plasticity in humans.