Miracle-dz/UniFAR-FTUs huggingface dataset:
Copy number variant study of bipolar disorder in Canadian and UK populations implicates synaptic genes

Genome‐wide single nucleotide polymorphism (SNP) data from 936 bipolar disorder (BD) individuals and 940 psychiatrically healthy comparison individuals of North European descent were analyzed for copy number variation (CNV). Using multiple CNV calling algorithms, and validating using in vitro molecular analyses, we identified CNVs implicating several candidate genes that encode synaptic proteins, such as DLG1, DLG2, DPP6, NRXN1, NRXN2, NRXN3, SHANK2, and EPHA5, as well as the neuronal splicing regulator RBFOX1 (A2BP1), and neuronal cell adhesion molecule CHL1. We have also identified recurrent CNVs on 15q13.3 and 16p11.2‐regions previously reported as risk loci for neuropsychiatric disorders. In addition, we performed CNV analysis of individuals from 215 BD trios and identified de novo CNVs involving the NRXN1 and DRD5 genes. Our study provides further evidence of the occasional involvement of genomic mutations in the etiology of BD, however, there is no evidence of an increased burden of CNVs in BD. Further, the identification of CNVs at multiple members of the neurexin gene family in BD individuals, supports the role of synaptic disruption in the etiology of BD. © 2014 Wiley Periodicals, Inc.
The emergence of lobsters: phylogenetic relationships, morphological evolution and divergence time comparisons of an ancient group (decapoda: achelata, astacidea, glypheidea, polychelida).

Lobsters are a ubiquitous and economically important group of decapod crustaceans that include the infraorders Polychelida, Glypheidea, Astacidea and Achelata. They include familiar forms such as the spiny, slipper, clawed lobsters and crayfish and unfamiliar forms such as the deep-sea and "living fossil" species. The high degree of morphological diversity among these infraorders has led to a dynamic classification and conflicting hypotheses of evolutionary relationships. In this study, we estimated phylogenetic relationships among the major groups of all lobster families and 94% of the genera using six genes (mitochondrial and nuclear) and 195 morphological characters across 173 species of lobsters for the most comprehensive sampling to date. Lobsters were recovered as a non-monophyletic assemblage in the combined (molecular + morphology) analysis. All families were monophyletic, with the exception of Cambaridae, and 7 of 79 genera were recovered as poly- or paraphyletic. A rich fossil history coupled with dense taxon coverage allowed us to estimate and compare divergence times and origins of major lineages using two drastically different approaches. Age priors were constructed and/or included based on fossil age information or fossil discovery, age, and extant species count data. Results from the two approaches were largely congruent across deep to shallow taxonomic divergences across major lineages. The origin of the first lobster-like decapod (Polychelida) was estimated in the Devonian (∼409-372 Ma) with all infraorders present in the Carboniferous (∼353-318 Ma). Fossil calibration subsampling studies examined the influence of sampling density (number of fossils) and placement (deep, middle, and shallow) on divergence time estimates. Results from our study suggest including at least 1 fossil per 10 operational taxonomic units (OTUs) in divergence dating analyses. [Dating; decapods; divergence; lobsters; molecular; morphology; phylogenetics. ].
A psychometric evaluation of the Chinese version of the stage of change-readiness and treatment-eagerness scale.

AIMS The present study analysed the psychometric properties of a Chinese version of the stage of change-readiness and treatment-eagerness scale among alcohol-dependent patients and investigated whether a three-factor structure fit the data. BACKGROUND The stage of change-readiness and treatment-eagerness scale is a 19-item instrument designed to measure alcohol-dependent patients' motivation for change. However, this instrument had not been translated and validated for use in Taiwan. DESIGN Survey. METHODS A sample of 161 alcohol-dependent patients receiving alcohol-related treatment in psychiatric hospital outpatient and inpatient units was included. Confirmatory factor analyses were conducted on three-factor measurement models of the stage of change-readiness and treatment-eagerness scale. RESULTS Confirmatory factor analyses supported the presence of a three-factor modified model (ambivalence, recognition and taking steps) among alcohol-dependent patients. Higher internal item consistency was found for the recognition and taking step factors, while the ambivalence factor was shown to have lower internal consistency. Convergent, discriminant and concurrent validity were obtained for the assessment of severity of alcohol dependence. CONCLUSIONS The results indicated that the 11-item, three-factor modified Chinese version of the stage of change readiness and treatment eagerness scale provided best goodness of fit for the data in this study. This study demonstrated that the Chinese version of the stage of change readiness and treatment eagerness scale is a reliable and valid self-report measure for the assessment of changing motivation in alcohol-dependent patients. RELEVANCE TO CLINICAL PRACTICE The Chinese version of stage of change readiness and treatment eagerness scale is applicable for use in clinical treatment and research, predicting motivation for change and evaluating intervention outcomes in Taiwan.
PENGETAHUAN BIDAN MENGENAI IMD

ABSTRAK Pendahuluan. Inisiasi Menyusu Dini merupakan salah satu intervensi dari berbagai intervensi yang dapat dilakukan meningkatkan sistem imunitas pada bayi baru lahir dan meningkatkan praktek menyusui. Pengetahuan dan keterampilan tidak merupakan factor yang berkontribusi terhadap suksesnya menyusui dini. Penelitian ini bertujuan untuk menggambarkan tingkat pengetahuan bidan tentang Inisiasi Menyusu Dini. Metodologi. Metodologi Penelitian ini adalah kualitatif dengan informan adalah anggota Ikatan Bidan Indonesia Cabang Bandung, Bidan yang bekerja di Rumah Sakit, Puskesmas dan klinik pribadi. Hasil. Pengetahuan bidan tentang pengetahuan dasar relatif rendah akan tetapi pengetahuan tentang defenisi dan keuntungan Inisiasi Menyusu Dini sudah baik. Terdapat sedikit perbedaan dalam praktek Inisiasi Menyusu Dini yang harus dikoreksi. Saran. Pengetahuan bidan tentang Inisiasi Menyusu Dini harus ditingkatkan dengan cara meningkatkan sosialisasi dan workshop tentang implementasi Inisiasi Menyusu Dini yang dapat dilakukan oleh organisasi profesi seperti ini. Kata kunci: Inisiasi Menyusu Dini, Bidan, Pengetahuan ABSTRACT Introduction Initiation of breastfeeding is one of many interventions to increase infant’s immune system and breastfeeding practice. Knowledge and skills of the midwife is a contributing factor to the sucseccfull of the intervention. This study aimed to explore midwifes’ knowledge on initiation of breastfeeding. Methodology Quantitatative method was used in this study. The informans in this study were the member of Ikatan Bidan Indonesia in Bandung district. Midwives who work in the hospital, public health center and private clinic were interviewed. The content analysis was used to analyse the results of the interview. Results Midwives’s knowledge on general information of initiation of breastfeeding is relatively low. However, their knowledge about the definition and the benefit of the initiation is already satisfactory. There is still a small difference in the practice of the initiation of breastfeeding among the midwives that must be corrected. Suggestion The midwives’ knowledge on the initiation of breastfeeding should be enhanced by improvement of the socialization and workshop of implementing the intervention. These kinds of activities can be held by the professional organization or the district health office. Keywords: Early Breast-feeding Initiation, knowledge, midwife
Carers' and nurses' appraisals of needs of nursing home placement for frail older in Norway.

AIMS AND OBJECTIVES The aim of this paper was to explore carers' and nurses' appraisals concerning if and when nursing home placement for frail older people awaiting placement was needed and to illuminate ethical issues involved in decisions regarding nursing home placement. BACKGROUND Requesting nursing home placement can be a complicated decision for carers, causing feelings of failure, anxiety and guilt. After the necessity of nursing home care is determined, the names of the older people are put on waiting lists. While waiting, home health care provides support services. Even with this care, many of the older people and their carers face difficult life situations. DESIGN This is a descriptive and comparative cross-sectional study using qualitative methods. METHODS The convenience sample (n = 36) comprised 11 carers of older people on a nursing home placement waiting list in Norway and 11 nurses caring for these older people. Every one willingly participated in interviews that were transcribed and analysed by qualitative content analysis. RESULTS Various similarities and differences between nurses' and carers' appraisals were found. Complex ethical issues of justice, equality, autonomy, beneficence and justifiability in nursing were involved in decision making concerning nursing home placement. Four categories constructed were: 'appraising nursing home to be the level of care needed', 'appraising the older people as able to continue living at home', 'being ambivalent about nursing home placement' and 'being sceptical about use of coercion regarding nursing home placement'. CONCLUSIONS Not all of the older people awaiting nursing home placements could be placed in nursing homes when beds became available. The situations were complex and involved ethical issues. RELEVANCE TO CLINICAL PRACTICE Despite insufficient resources in home health care, providing appropriate support for older people and their carers means that nurses have to consider individual concerns in each situation, cooperate with carers, respect their appraisals of needs and argue for the timely nursing home placement of older people.
Species Delimitation with Gene Flow

&NA; Species are commonly thought to be evolutionarily independent in a way that populations within a species are not. In recent years, studies that seek to identify evolutionarily independent lineages (i.e., to delimit species) using genetic data have typically adopted multispecies coalescent approaches that assume that evolutionary independence is formed by the differential sorting of ancestral alleles due to genetic drift. However, gene flow appears to be common among populations and nascent species, and while this process may inhibit lineage divergence (and thus independence), it is usually not explicitly considered when delimiting species. In this article, we apply Phylogeographic Inference using Approximate Likelihoods (PHRAPL), a recently described method for phylogeographic model selection, to species delimitation. We describe an approach to delimiting species using PHRAPL that attempts to account for both genetic drift and gene flow, and we compare the method's performance to that of a popular delimitation approach (BPP) using both simulated and empirical datasets. PHRAPL generally infers the correct demographic‐delimitation model when the generating model includes gene flow between taxa, given a sufficient amount of data. When the generating model includes only isolation in the recent past, PHRAPL will in some cases fail to differentiate between gene flow and divergence, leading to model misspecification. Nevertheless, the explicit consideration of gene flow by PHRAPL is an important complement to existing delimitation approaches, particularly in systems where gene flow is likely important. [approximate likelihoods; coalescent simulations; genealogical divergence index; Homo sapiens; isolation‐with‐migration; multispecies coalescent; Sarracenia; Scincella. ]
The Mitochondrial Amidoxime-reducing Component (mARC1) Is a Novel Signal-anchored Protein of the Outer Mitochondrial Membrane*

Background: mARC1 is a novel molybdenum enzyme functioning in pro-drug metabolism with unknown subcellular localization. Results: mARC1 localizes to the outer mitochondrial membrane with its catalytic domain facing the cytosol. Import is dependent on two N-terminal motifs (mitochondrial targeting signal, transmembrane domain) resulting in high oligomeric complexes. Conclusion: mARC1 is a novel signal-anchored protein of the outer mitochondrial membrane. Significance: We identify mARC protein maturation. The mitochondrial amidoxime-reducing component (mARC) was recently discovered as the fifth eukaryotic molybdenum cofactor-containing enzyme. The human genome encodes two mARC proteins, mARC1 and mARC2, sharing significant homologies with respect to sequence and function. Whereas mARC2 was identified as a mitochondrial enzyme, the subcellular localization of mARC1 has remained uncharacterized, although the similarity of both proteins suggested identical subcellular localizations. In addition, neither mARC1 nor mARC2 could be attributed unambiguously to one of the four mitochondrial subcompartments. Accordingly, mechanisms triggering the subcellular distribution of both enzymes have been unexplored so far. Here, we shed light on the subcellular localization of mARC1 and demonstrate that it is integrated into the outer mitochondrial membrane. The C-terminal catalytic domain of the protein remains exposed to the cytosol and confers an N(in)-C(out) membrane orientation of mARC1. This localization is triggered by the N terminus of the enzyme, being composed of a weak N-terminal mitochondrial targeting signal and a downstream transmembrane helix. We demonstrate the transmembrane domain of mARC1 to be sufficient for mitochondrial targeting and the N-terminal targeting signal to function as a supportive receptor for the outer mitochondrial membrane. According to its localization and targeting mechanism, we classify mARC1 as a novel signal-anchored mitochondrial protein. During mitochondrial import, mARC1 is not processed, and membrane integration proceeds membrane potential independently but requires external ATP, which finally results in the assembly of mARC1 into high oligomeric protein complexes.
Electrostatic Ratchet in the Protective Antigen Channel Promotes Anthrax Toxin Translocation*

Background: Ratchets are key features in molecular machines that unfold and transport biopolymers. Results: An electrostatic ratchet in the anthrax toxin protein translocase was experimentally identified and modeled. Conclusion: The anthrax toxin translocase harnesses the proton motive force with an electrostatic ratchet. Significance: This report describes an electrostatic ratchet element critical to proton motive force-driven translocation. Central to the power-stroke and Brownian-ratchet mechanisms of protein translocation is the process through which nonequilibrium fluctuations are rectified or ratcheted by the molecular motor to transport substrate proteins along a specific axis. We investigated the ratchet mechanism using anthrax toxin as a model. Anthrax toxin is a tripartite toxin comprised of the protective antigen (PA) component, a homooligomeric transmembrane translocase, which translocates two other enzyme components, lethal factor (LF) and edema factor (EF), into the cytosol of the host cell under the proton motive force (PMF). The PA-binding domains of LF and EF (LFN and EFN) possess identical folds and similar solution stabilities; however, EFN translocates ∼10–200-fold slower than LFN, depending on the electrical potential (Δψ) and chemical potential (ΔpH) compositions of the PMF. From an analysis of LFN/EFN chimera proteins, we identified two 10-residue cassettes comprised of charged sequence that were responsible for the impaired translocation kinetics of EFN. These cassettes have nonspecific electrostatic requirements: one surprisingly prefers acidic residues when driven by either a Δψ or a ΔpH; the second requires basic residues only when driven by a Δψ. Through modeling and experiment, we identified a charged surface in the PA channel responsible for charge selectivity. The charged surface latches the substrate and promotes PMF-driven transport. We propose an electrostatic ratchet in the channel, comprised of opposing rings of charged residues, enforces directionality by interacting with charged cassettes in the substrate, thereby generating forces sufficient to drive unfolding.
RDoC and translational perspectives on the genetics of trauma‐related psychiatric disorders

Individuals with a history of child abuse are at high risk for depression, anxiety disorders, aggressive behavior, and substance use problems. The goal of this paper is to review studies of the genetics of these stress‐related psychiatric disorders. An informative subset of studies that examined candidate gene by environment (GxE) predictors of these psychiatric problems in individuals maltreated as children is reviewed, together with extant genome wide association studies (GWAS). Emerging findings on epigenetic changes associated with adverse early experiences are also reviewed. Meta‐analytic support and replicated findings are evident for several genetic risk factors; however, extant research suggests the effects are pleiotropic. Genetic factors are not associated with distinct psychiatric disorders, but rather diverse clinical phenotypes. Research also suggests adverse early life experiences are associated with changes in gene expression of multiple known candidate genes, genes involved in DNA transcription and translation, and genes necessary for brain circuitry development, with changes in gene expression reported in key brain structures implicated in the pathophysiology of psychiatric and substance use disorders. The finding of pleiotropy highlights the value of using the Research Domain Criteria (RDoC) framework in future studies of the genetics of stress‐related psychiatric disorders, and not trying simply to link genes to multifaceted clinical syndromes, but to more limited phenotypes that map onto distinct neural circuits. Emerging work in the field of epigenetics also suggests that translational studies that integrate numerous unbiased genome‐wide approaches will help to further unravel the genetics of stress‐related psychiatric disorders. © 2015 Wiley Periodicals, Inc.
The economic impact of Alzheimer's disease

With the population aging, Alzheimer's disease will impose an increasingly large economic burden on society. Findings in recent cost studies adjusted to 1990 dollars suggest that the annual cost of formal and informal care for each patient with Alzheimer's disease is as high as $47,000. The overall annual cost associated with all types of dementia patients consists of approximately $20 billion for direct costs and $38 billion for informal care. In their current form, public funding programs leave many gaps in coverage of services for Alzheimer's disease patients, as do private insurance policies. Much-needed changes in funding programs, exercise of private sector funding options, improvement in provision of services, and advances in treatment will each affect the future economic impact of Alzheimer's disease
Millions of Years Behind: Slow Adaptation of Ruminants to Grasslands

Abstract. The Late Cretaceous appearance of grasses, followed by the Cenozoic advancement of grasslands as dominant biomes, has contributed to the evolution of a range of specialized herbivores adapted to new diets, as well as to increasingly open and arid habitats. Many mammals including ruminants, the most diversified ungulate suborder, evolved high‐crowned (hypsodont) teeth as an adaptation to tooth‐wearing diets and habitats. The impact of different causes of tooth wear is still a matter of debate, and the temporal pattern of hypsodonty evolution in relation to the evolution of grasslands remains unclear. We present an improved time‐calibrated molecular phylogeny of Cetartiodactyla, with phylogenetic reconstruction of ancestral ruminant diets and habitats, based on characteristics of extant taxa. Using this timeline, as well as the fossil record of grasslands, we conduct phylogenetic comparative analyses showing that hypsodonty in ruminants evolved as an adaptation to both diet and habitat. Our results demonstrate a slow, perhaps constrained, evolution of hypsodonty toward estimated optimal states, excluding the possibility of immediate adaptation. This augments recent findings that slow adaptation is not uncommon on million‐year time scales.
Review of non-invasive ventilation in the emergency department: clinical considerations and management priorities.

AIMS AND OBJECTIVES We aimed to synthesise evidence from published literature on non-invasive ventilation to inform nurses involved in the clinical management of non-invasive ventilation in the emergency department. BACKGROUND Non-invasive ventilation is a form of ventilatory support that does not require endotracheal intubation and is used in the early management of acute respiratory failure in emergency departments. Safe delivery of this intervention requires a skilled team, educated and experienced in appropriate patient selection, available devices and monitoring priorities. DESIGN Systematic review. METHOD A multi-database search was performed to identify works published in the English language between 1998-2008. Search terms included: non-invasive ventilation, continuous positive airway pressure and emergency department. Inclusion and exclusion criteria for the review were identified and systematically applied. RESULTS Terminology used to describe aspects of non-invasive ventilation is ambiguous. Two international guidelines inform the delivery of this intervention, however, much research has been undertaken since these publications. Strong evidence exists for non-invasive ventilation for patients with acute exacerbation of congestive heart failure and chronic obstructive pulmonary disease. Non-invasive ventilation may be delivered with various interfaces and modes; little evidence is available for the superiority of individual interfaces or modes. CONCLUSIONS Early use of non-invasive ventilation for the management of acute respiratory failure may reduce mortality and morbidity. Though international guidelines exist, specific recommendations to guide the selection of modes, settings or interfaces for various aetiologies are lacking due to the absence of empirical evidence. RELEVANCE TO CLINICAL PRACTICE Monitoring of non-invasive ventilation should focus on assessment of response to treatment, respiratory and haemodynamic stability, patient comfort and presence of air leaks. Complications are related to mask-fit and high air flows; serious complications are few and occur infrequently. The use of non-invasive ventilation has resource implications that must be considered to provide effective and safe management in the emergency department.