Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of care settings on residents' functional and psychosocial status, physical activity and adverse events.

BACKGROUND Internationally, as the number of older adults increases, different types of care settings are evolving to address the care needs of this growing group of individuals. AIMS AND OBJECTIVES The purpose of this study was to describe and compare clinical outcomes of residents with moderate to severe cognitive impairment living in residential care facilities (RCFs) and nursing homes (NHs). DESIGN This was a secondary data analysis that included data from two studies testing a Function-Focused Care for Cognitively Impaired (FFC-CI) Intervention. METHODS A total of 96 participants were from RCFs and 103 were from NHs. Change scores over a 6-month period in RCF and NH residents were evaluated using a multivariate analysis of variance. RESULTS Residential care facilities residents had more agitation, better function and engaged in approximately twice as much physical activity as those in NH settings at baseline. Controlling for treatment status and baseline differences, over 6 months, RCF residents showed a decrease of -22.77 ± 41.47 kilocalories used in 24 hours while those in NHs increased to a mean of 10.49 ± 33.65 kilocalories used. With regard to function, residents in RCFs declined 10.97 ± 18.35 points on the Barthel Index, while those in NHs increased 10.18 ± 19.56 points. CONCLUSIONS In this sample, NH residents were more likely to be African American, had more comorbidities, less cognitive impairment, engaged in less physical activity, were more impaired functionally and had less agitation than those in RCFs. Controlling for treatment group status and baseline differences in comorbidities, cognitive status and race, residents in RCFs declined more in terms of functional and physical activity over a 6-month period. IMPLICATIONS FOR PRACTICE Ongoing research and clinical work is needed to understand the impact of care settings on clinical outcomes.
Older people in the emergency department: a literature review.

BACKGROUND Emergency departments (EDs) play a unique role in healthcare systems throughout the world by providing acute interventions for older patients with acute/emergency and multiple health problems. The aim of this review was to identify studies that focused on older patients admitted to EDs and to determine the reasons for the visits. DESIGN AND METHODS The literature review was based on a comprehensive search of electronic databases. Inclusion criteria were original research written in English; published 2002-2012; focused on older people; reasons for ED visit; and factors that affect the discharge process and those associated with a repeat ED visit. Other literature reviews and studies unrelated to the ED context, and studies examining patients aged ≥65 years, were excluded. Content analysis was performed. Twenty-five studies were identified and critically evaluated. RESULTS The highest proportion of older people visited the ED because of multiple health conditions. The reasons for the visits were cardiovascular, mental health, musculoskeletal and abdominal conditions; adverse drug reactions; dermatological, neurological and respiratory conditions; poor health status; accidents; and the influence of time factors such as time of day, week or season. Factors that affected the discharge process were unresolved problems, health risk identification, aftercare instructions, medication prescribed at discharge and patient's residence before ED admission. Factors associated with repeat ED visits were sociodemographic characteristics, social problems, health problems, need for systematic health assessment, healthcare service use and inadequacy of care provided. CONCLUSIONS The current review showed that older people are the main population visiting EDs; important factors required for planning and providing nursing care for older people in EDs were identified. More research is needed to determine how EDs support older people and their families. IMPLICATIONS FOR PRACTICE The findings of the current review identified that older people visit ED quite often because of different reasons. Discharge process and repeat visits may be influenced by various factors. To ensure quality nursing care in ED nurses need to be aware why do older people visit the ED, what factors may influence discharge and what factors are associated with repeat ED visits.
Evolutionary dynamism of the primate LRRC37 gene family

Core duplicons in the human genome represent ancestral duplication modules shared by the majority of intrachromosomal duplication blocks within a given chromosome. These cores are associated with the emergence of novel gene families in the hominoid lineage, but their genomic organization and gene characterization among other primates are largely unknown. Here, we investigate the genomic organization and expression of the core duplicon on chromosome 17 that led to the expansion of LRRC37 during primate evolution. A comparison of the LRRC37 gene family organization in human, orangutan, macaque, marmoset, and lemur genomes shows the presence of both orthologous and species-specific gene copies in all primate lineages. Expression profiling in mouse, macaque, and human tissues reveals that the ancestral expression of LRRC37 was restricted to the testis. In the hominid lineage, the pattern of LRRC37 became increasingly ubiquitous, with significantly higher levels of expression in the cerebellum and thymus, and showed a remarkable diversity of alternative splice forms. Transfection studies in HeLa cells indicate that the human FLAG-tagged recombinant LRRC37 protein is secreted after cleavage of a transmembrane precursor and its overexpression can induce filipodia formation.
Genome-wide search for novel human uORFs and N-terminal protein extensions using ribosomal footprinting

So far, the annotation of translation initiation sites (TISs) has been based mostly upon bioinformatics rather than experimental evidence. We adapted ribosomal footprinting to puromycin-treated cells to generate a transcriptome-wide map of TISs in a human monocytic cell line. A neural network was trained on the ribosomal footprints observed at previously annotated AUG translation initiation codons (TICs), and used for the ab initio prediction of TISs in 5062 transcripts with sufficient sequence coverage. Functional interpretation suggested 2994 novel upstream open reading frames (uORFs) in the 5′ UTR, 1406 uORFs overlapping with the coding sequence, and 546 N-terminal protein extensions. The TIS detection method was validated on the basis of previously published alternative TISs and uORFs. Among primates, TICs in newly annotated TISs were significantly more conserved than control codons, both for AUGs and near-cognate codons. The transcriptome-wide map of novel candidate TISs derived as part of the study will shed further light on the way in which human proteome diversity is influenced by alternative translation initiation and regulation.
Genome-wide patterns of natural variation reveal strong selective sweeps and ongoing genomic conflict in Drosophila mauritiana

Although it is well understood that selection shapes the polymorphism pattern in Drosophila, signatures of classic selective sweeps are scarce. Here, we focus on Drosophila mauritiana, an island endemic, which is closely related to Drosophila melanogaster. Based on a new, annotated genome sequence, we characterized the genome-wide polymorphism by sequencing pooled individuals (Pool-seq). We show that the interplay between selection and recombination results in a genome-wide polymorphism pattern characteristic for D. mauritiana. Two large genomic regions (>500 kb) showed the signature of almost complete selective sweeps. We propose that the absence of population structure and limited geographic distribution could explain why such pronounced sweep patterns are restricted to D. mauritiana. Further evidence for strong adaptive evolution was detected for several nucleoporin genes, some of which were not previously identified as genes involved in genomic conflict. Since this adaptive evolution is continuing after the split of D. mauritiana and Drosophila simulans, we conclude that genomic conflict is not restricted to short episodes, but rather an ongoing process in Drosophila.
Epicutaneous sensitization with nematode antigens of fish parasites results in the production of specific IgG and IgE

Abstract Fish consumption plays an important role in the human diet. Hoplias malabaricus, trahira, is a freshwater fish widely appreciated in several Brazilian states and it is frequently infected by Contracaecum multipapillatum third-instar larvae (L3). The aim of the present study was to evaluate the allergenic potential of the C. multipapillatum L3 crude extract (CECM). BALB/c mice were immunized intraperitoneally (ip) with 10 or 50 μg CECM associated with 2 mg of aluminium hydroxide on days 0, 14 and 48. The determination of specific IgG and IgE antibody levels was done after immunization, and the late immunity was evaluated by the intradermal reaction in the ear pavilion. Epicutaneous sensitization was performed in the dorsal region, with antigenic exposure via a Finn-type chamber, containing 100 μg of chicken ovum albumin (OVA) or 100 μg CECM. After the exposures, the specific antibody levels were determined. In the ip immunization, there was a gradual increase in IgG antibody levels, independent of CECM concentration. In relation to IgE production, it was transitory, and immunization with 10 μg was more efficient than that of 50 μg. The same result was observed in the cellular hypersensitivity reaction. In the case of antigen exposure by the epicutaneous route, it was verified that only CECM was able to induce detectable levels of specific IgG and IgE antibodies. In the present study it was demonstrated that both intraperitoneal immunization and epicutaneous contact with C. multipapillatum larval antigens are potentially capable of inducing allergic sensitization in mice.
Nematode assemblages associated with the parthenogenetic lizard Ameivula nativo in six restinga areas along the eastern coast of Brazil

Abstract We surveyed the nematode assemblages associated with populations of the parthenogenetic whiptail lizard Ameivula nativo from six coastal restinga areas in eastern Brazil: Setiba, Comboios and Guriri (State of Espirito Santo) and Guaratiba, Prado and Maraú (State of Bahia). A total of five nematode species (Physaloptera retusa, Physalopteroides venancioi, Skrjabinelazia intermedia, Subulura lacertilia and Parapharyngodon sp.) were recorded from the six different populations of A. nativo. There was considerable variation in overall prevalence of infection (1–42%) among study sites, but geographical distance among areas did not influence similarity in the composition of nematode assemblages. Overall intensity of infection was not affected by lizard body size and did not seem to affect host body condition, based on pooled data of all populations. The studied populations of the unisexual A. nativo had relatively low prevalences and intensities of infection compared to some bisexual congeners and to sympatric lizards from other families for which such data are available. We believe that the low richness of the nematode fauna associated with A. nativo, both locally and regionally, may reflect its narrow geographic distribution and the low diversity of habitats it occupies.
Effects of vedolizumab induction therapy for patients with Crohn's disease in whom tumor necrosis factor antagonist treatment failed.

BACKGROUND & AIMS There is an increasing need for new treatments for patients with Crohn's disease (CD) in whom previous therapy with tumor necrosis factor (TNF) antagonists has failed. We performed a placebo-controlled, phase 3, double-blind trial to evaluate the efficacy and safety of vedolizumab, an antibody against the integrin α4β7, as induction therapy. METHODS Patients with moderately to severely active CD (CD activity index [CDAI] score, 220-400 points) were assigned randomly to groups given vedolizumab (300 mg) or placebo intravenously at weeks 0, 2, and 6. The primary analysis involved 315 patients with previous TNF antagonist failure (ie, an inadequate response to, loss of response to, or intolerance of ≥1 TNF antagonists); we determined the proportion of patients in clinical remission (CDAI, ≤150 points) at week 6. Secondary analyses evaluated outcomes at weeks 6 and 10 in this population and in the overall population (N = 416), which included patients naive to TNF antagonist therapy (n = 101). RESULTS Among patients who had experienced previous TNF antagonist failure, 15.2% of those given vedolizumab and 12.1% of those given placebo were in remission at week 6 (P = .433). At week 10, a higher proportion of this population given vedolizumab was in remission (26.6%) than those given placebo (12.1%) (nominal P = .001; relative risk, 2.2; 95% confidence interval, 1.3-3.6). A higher proportion of patients with previous TNF antagonist failure given vedolizumab also had a CDAI-100 response (≥100-point decrease in CDAI score from baseline) at week 6 than those given placebo (39.2% vs 22.3%; nominal P = .001; relative risk, 1.8; 95% confidence interval, 1.2-2.5). Adverse event results were similar among all groups. CONCLUSIONS Vedolizumab was not more effective than placebo in inducing clinical remission at week 6 among patients with CD in whom previous treatment with TNF antagonists had failed. The therapeutic benefits of vedolizumab in these patients were detectable at week 10. ClinicalTrials.gov number: NCT01224171.
Sympatric chimpanzees and gorillas harbor convergent gut microbial communities

The gut microbial communities within great apes have been shown to reflect the phylogenetic history of their hosts, indicating codiversification between great apes and their gut microbiota over evolutionary timescales. But because the great apes examined to date represent geographically isolated populations whose diets derive from different sources, it is unclear whether this pattern of codiversification has resulted from a long history of coadaptation between microbes and hosts (heritable factors) or from the ecological and geographic separation among host species (environmental factors). To evaluate the relative influences of heritable and environmental factors on the evolution of the great ape gut microbiota, we assayed the gut communities of sympatric and allopatric populations of chimpanzees, bonobos, and gorillas residing throughout equatorial Africa. Comparisons of these populations revealed that the gut communities of different host species can always be distinguished from one another but that the gut communities of sympatric chimpanzees and gorillas have converged in terms of community composition, sharing on average 53% more bacterial phylotypes than the gut communities of allopatric hosts. Host environment, independent of host genetics and evolutionary history, shaped the distribution of bacterial phylotypes across the Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria, the four most common phyla of gut bacteria. Moreover, the specific patterns of phylotype sharing among hosts suggest that chimpanzees living in sympatry with gorillas have acquired bacteria from gorillas. These results indicate that geographic isolation between host species has promoted the evolutionary differentiation of great ape gut bacterial communities.
Investigating Drug-Induced QT and QTc Prolongation in the Clinic: A Review of Statistical Design and Analysis Considerations: Report from the Pharmaceutical Research and Manufacturers of America QT Statistics Expert Team

The dangers inherent to the public via the use of drugs known to prolong the QT and QTc interval such as terfenadine and cisapride call for a careful evaluation of this potential in drug development. Methods in development for this assessment in preclinical and clinical development are reviewed, and statistical issues in the design and analysis of clinical trials used to assess this potential are described. Methods, measurement, and analysis are illustrated using data from clinical trials, and issues in the analysis and interpretation of data are developed. It is recommended that the statistical rigor of the International Conference on Harmonisation guidance currently in development for clinical assessment be enhanced and that further research be conducted in the choice of endpoints, testing of hypotheses, and interpretation of QT and QTc data.
Acceptance of invitations for p53 and BRCA1 predisposition testing: Factors influencing potential utilization of cancer genetic testing

Data on uptake of two cancer predisposition testing programs is presented as the basis for discussion of factors contributing to the acceptance and refusal of genetic testing. Eighty percent (n = 29) of the 36 members of 2 BRCA1 families invited for BRCA1 predisposition testing and counseling accepted, while only 39% (n = 22) of the 57 Li‐Fraumeni syndrome family members invited for p53 predisposition testing and counseling enrolled and 14% (n = 8) postponed enrollment. Factors that may influence utilization of cancer genetic testing programs include programmatic demands, nature and immediacy of cancer risk, demographic factors, perceived lethality of the cancers involved, clarity of surveillance recommendations and perceived efficacy of screening, ego‐strength, and family experience with cancer. Further research is needed to determine the relative weight of these factors and to define how acceptors and decliners of genetic cancer predisposition testing differ. One implication of the hypothesis that individuals seeking testing are psychologically different than those who decline is that more severe psychiatric sequelae of testing might be expected if individuals are tested who have not themselves freely chosen testing. Such subjects might in the future include children whose parents decide about testing or adults tested as a prerequisite to being employed or insured. Further research on decliners and continued psychological evaluation of the impact of cancer predisposition testing is recommended.
Analysis of off-target effects of CRISPR/Cas-derived RNA-guided endonucleases and nickases

RNA-guided endonucleases (RGENs), derived from the prokaryotic adaptive immune system known as CRISPR/Cas, enable targeted genome engineering in cells and organisms. RGENs are ribonucleoproteins that consist of guide RNA and Cas9, a protein component originated from Streptococcus pyogenes. These enzymes cleave chromosomal DNA, whose sequence is complementary, to guide RNA in a targeted manner, producing site-specific DNA double-strand breaks (DSBs), the repair of which gives rise to targeted genome modifications. Despite broad interest in RGEN-mediated genome editing, these nucleases are limited by off-target mutations and unwanted chromosomal translocations associated with off-target DNA cleavages. Here, we show that off-target effects of RGENs can be reduced below the detection limits of deep sequencing by choosing unique target sequences in the genome and modifying both guide RNA and Cas9. We found that both the composition and structure of guide RNA can affect RGEN activities in cells to reduce off-target effects. RGENs efficiently discriminated on-target sites from off-target sites that differ by two bases. Furthermore, exome sequencing analysis showed that no off-target mutations were induced by two RGENs in four clonal populations of mutant cells. In addition, paired Cas9 nickases, composed of D10A Cas9 and guide RNA, which generate two single-strand breaks (SSBs) or nicks on different DNA strands, were highly specific in human cells, avoiding off-target mutations without sacrificing genome-editing efficiency. Interestingly, paired nickases induced chromosomal deletions in a targeted manner without causing unwanted translocations. Our results highlight the importance of choosing unique target sequences and optimizing guide RNA and Cas9 to avoid or reduce RGEN-induced off-target mutations.
Vision impairment and dual sensory problems in middle age

Vision and hearing impairments are known to increase in middle age. In this study we describe the prevalence of vision impairment and dual sensory impairment in UK adults aged 40–69 years in a very large and recently ascertained data set. The associations between vision impairment, age, sex, socioeconomic status, and ethnicity are reported.
ENT cases seen at a local ‘walk-in centre’: a one year review

Abstract Aim and method: This retrospective study reviewed the ENT-related cases seen, and the discharge or transfer outcomes, at both a local ‘walk-in centre’ and the respective emergency department, over one year in Norwich. Results: Of the 7657 ENT cases seen at the walk-in centre, the commonest conditions included tonsillitis or pharyngitis, otalgia, cough, and deafness. In comparison, 1586 patients were seen at the emergency department, and the commonest conditions were epistaxis and throat foreign bodies. Of the ENT cases seen at the walk-in centre, 85.4 per cent were treated and discharged. Of the 14.6 per cent referred to other healthcare providers, 11.1 per cent were to the general practitioner. In comparison, the emergency department discharged 41.2 per cent and referred 58.8 per cent to other healthcare providers. Conclusion: This study indicates that ENT cases may constitute a large proportion of patients seen in walk-in centres, and that the case types seen may differ from those presenting to emergency departments. It also indicates that walk-in centres may potentially be assessing, treating and discharging 85.4 per cent of ENT patients seen.
Signatures of protective memory immune responses during hepatitis C virus reinfection.

BACKGROUND & AIMS Development of a vaccine against hepatitis C virus (HCV) has been hindered by our limited understanding of immune correlates of protection during real-life exposure to the virus. We studied the immune response during HCV reinfection. METHODS We analyzed blood samples from participants in the Montreal Acute Hepatitis C Injection Drug User Cohort Study who were reinfected with HCV from 2009 to 2012. Five patients spontaneously resolved their second infection and 4 developed chronic infections. We monitored the phenotypic and functional dynamics of HCV-specific memory T cell responses in all subjects during natural re-exposure and re-infection. RESULTS Populations of CD4(+) and CD8(+) T cells with HCV-specific polyfunctional memory were expanded in all 5 individuals who resolved 2 successive HCV infections. We detected CD127(hi) HCV-specific memory CD8(+) T cells before reinfection regardless of a subject's ability to clear subsequent infections. Protection against viral persistence was associated with the expansion of a CD127(neg), PD1(lo) effector memory T cells at the peak of the response. We also observed broadening of T-cell response, indicating generation of de novo T-cell responses. The 4 individuals who failed to clear their subsequent infection had limited expansion of HCV-specific CD4(+) and CD8(+) memory T cells and expressed variable levels of the exhaustion marker PD1 on HCV-specific CD8(+) T cells. Dominant epitope regions of HCV strains isolated from patients with persistent reinfection had sequence variations that were not recognized by the pre-existing memory T cells. CONCLUSIONS Protection from persistent HCV reinfection depends on the magnitude, breadth, and quality of the HCV-specific memory T-cell response. Sequence homology among viruses and ability of T cells to recognize multiple strains of HCV are critical determinants of protective memory.