Miracle-dz/UniFAR-FTUs huggingface dataset:
Geographical and ethnic distribution of MTHFR gene polymorphisms and their associations with diseases among Chinese population

Numerous studies have investigated the distribution of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and their associations with diseases in China. In this study we conducted a systematic review and meta‐analysis of these studies (715 eligible studies in total). Results revealed that the frequencies of the MTHFR C677T and A1298C polymorphisms varied markedly in different areas and ethnicities, and even showed geographical gradients. The MTHFR C677T polymorphism was significantly associated with 42 clinical disorders (p < 0.05), mostly relating to the diseases of circulatory system, birth defects and cancers. The association of the A1298C polymorphism with three diseases (coronary heart disease, breast cancer and neural tube defects fathers) was statistically significant (p < 0.05). However, according to the Venice criteria, only the associations of the C677T polymorphism with breast and ovarian cancers were assessed as having strong epidemiological credibility. This is the first study to provide a comprehensive assessment of the current status and gaps in genetic epidemiological study of the two polymorphisms in China, and its findings may be useful for medical and public health practices. Future studies are warranted to focus on the interactions of MTHFR genes with environmental exposure and with other genes, and to improve their methodological quality and reporting of findings.
Proteomic profiling of PrP27‐30‐enriched preparations extracted from the brain of hamsters with experimental scrapie

Transmissible spongiform encephalopathies (TSEs) are neurodegenerative disorders characterized by the accumulation in the CNS of a pathological conformer (PrPTSE) of the host‐encoded cellular prion protein (PrPC). PrPTSE has a central role in the pathogenesis of the disease but other factors are likely involved in the pathological process. In this work we employed a multi‐step proteomic approach for the identification of proteins that co‐purify with the protease‐resistant core of PrPTSE (PrP27‐30) extracted from brains of hamsters with experimental scrapie. We identified ferritin, calcium/calmodulin‐dependent protein kinase α type II, apolipoprotein E, and tubulin as the major components associated with PrP27‐30 but also trace amounts of actin, cofilin, Hsp90α, the γ subunit of the T‐complex protein 1, glyceraldehyde 3‐phosphate dehydrogenase, histones, and keratins. Whereas some of these proteins (tubulin and ferritin) are known to bind PrP, other proteins (calcium/calmodulin‐dependent protein kinase α type II, Hsp90α) may associate with PrPTSE fibrils during disease. Apolipoprotein E and actin have been previously observed in association with PrPTSE, whereas cofilin and actin were shown to form abnormal rods in the brain of patients with Alzheimer disease. The roles of these proteins in the development of brain lesions are still unclear and further work is needed to explain their involvement in the pathogenesis of TSEs.
The Pricing of Investment Grade Credit Risk during the Financial Crisis

This paper uses a structural model to investigate the pricing of investment grade credit risk during the …nancial crisis. Our analysis suggests that the dramatic recent widening of credit spreads is highly consistent with the decline in the equity market, the increase in its long-term volatility, and an improved investor appreciation of the risks embedded in structured products. In contrast to the main argument in favor of using government funds to help purchase structured credit securities, we …nd little evidence that suggests these markets are experiencing …re sales.
Type I IFNs Regulate Effector and Regulatory T Cell Accumulation and Anti-Inflammatory Cytokine Production during T Cell–Mediated Colitis

We explored the function of endogenous type I IFNs (IFN-1) in the colon using the T cell adoptive transfer model of colitis. Colon mononuclear phagocytes (MPs) constitutively produced IFN-1 in a Toll/IL-1R domain–containing adapter-inducing IFN-β–dependent manner. Transfer of CD4+CD45RBhi T cells from wild-type (WT) or IFN-α/β receptor subunit 1 knockout (IFNAR1−/−) mice into RAG−/− hosts resulted in similar onset and severity of colitis. In contrast, RAG−/− × IFNAR1−/− double knockout (DKO) mice developed accelerated severe colitis compared with RAG−/− hosts when transferred with WT CD4+CD45RBhi T cells. IFNAR signaling on host hematopoietic cells was required to delay colitis development. MPs isolated from the colon lamina propria of IFNAR1−/− mice produced less IL-10, IL-1R antagonist, and IL-27 compared with WT MPs. Accelerated colitis development in DKO mice was characterized by early T cell proliferation and accumulation of CD11b+CD103− dendritic cells in the mesenteric lymph nodes, both of which could be reversed by systemic administration of IL-1R antagonist (anakinra). Cotransfer of CD4+CD25+ regulatory T cells (Tregs) from WT or IFNAR1−/− mice prevented disease caused by CD4+CD45RBhi T cells. However, WT CD4+CD25+Foxp3GFP+ Tregs cotransferred with CD4+CD45RBhi T cells into DKO hosts failed to expand or maintain Foxp3 expression and gained effector functions in the colon. To our knowledge, these data are the first to demonstrate an essential role for IFN-1 in the production of anti-inflammatory cytokines by gut MPs and the indirect maintenance of intestinal T cell homeostasis by both limiting effector T cell expansion and promoting Treg stability.
The retention characteristics of Hawley and vacuum-formed retainers with different retention protocols

Background This study aimed to compare the effectiveness of two different protocols of wearing vacuum-formed retainers (VFRs) with the standard protocol of wearing Hawley retainer in maintaining the results of orthodontic treatment. Material and Methods This single-blind randomized clinical trial consisted of 90 patients who finished orthodontic treatment at the Department of Orthodontics of Mashhad Dental School, and required removable retainers. The participants were randomly divided into 3 groups and received the following treatments. Group 1: Hawley retainers (4 months full-time and then night-only); group 2: VFR_4M (4 months full-time and then night-only); group 3: VFR_1W (1 week full-time and then night-only). The study models were prepared after debond and at 4 and 8 months later, and intercanine width, intermolar width, arch length and the Little’s irregularity index were compared between groups. Results No significant differences were found in intercanine and intermolar widths between groups (P<05). Upper arch length was significantly lower in Hawley group than the two VFR groups (p<0.05), but lower arch length values were comparable. Upper irregularity index was significantly lower in two VFR groups compared to Hawley group (p<0.05), whereas in the lower jaw, only VFR_4M group showed significantly lower crowding than Hawley group (p<0.05). Conclusions Both retention regimens of VFRs were more effective than Hawley retainer in maintaining arch length and tooth alignment in the upper arch. For better incisor alignment in the lower jaw, the patients should be advocated to wear VFR 4 months full-time and then at night instead of wearing Hawley retainer. Key words:Essix, Hawley retainer, orthodontic treatment, retention, vacuum-formed retainer.
Ramping single unit activity in the medial prefrontal cortex and ventral striatum reflects the onset of waiting but not imminent impulsive actions

The medial prefrontal cortex (mPFC) and ventral striatum (VS), including the nucleus accumbens, are key forebrain regions involved in regulating behaviour for future rewards. Dysfunction of these regions can result in impulsivity, characterized by actions that are mistimed and executed without due consideration of their consequences. Here we recorded the activity of single neurons in the mPFC and VS of 16 rats during performance on a five‐choice serial reaction time task of sustained visual attention and impulsivity. Impulsive responses were assessed by the number of premature responses made before target stimuli were presented. We found that the majority of cells signalled trial outcome after an action was made (both rewarded and unrewarded). Positive and negative ramping activity was a feature of population activity in the mPFC and VS (49.5 and 50.4% of cells, respectively). This delay‐related activity increased at the same rate and reached the same maximum (or minimum) for trials terminated by either correct or premature responses. However, on premature trials, the ramping activity started earlier and coincided with shorter latencies to begin waiting. For all trial types the pattern of ramping activity was unchanged when the pre‐stimulus delay period was made variable. Thus, premature responses may result from a failure in the timing of the initiation of a waiting process, combined with a reduced reliance on external sensory cues, rather than a primary failure in delay activity. Our findings further show that the neural locus of this aberrant timing signal may emanate from structures outside the mPFC and VS.
GABA Levels Are Decreased After Stroke and GABA Changes During Rehabilitation Correlate With Motor Improvement

Background and Objective. γ-Aminobutyric acid (GABA) is the dominant inhibitory neurotransmitter in the brain and is important in motor learning. We aimed to measure GABA content in primary motor cortex poststroke (using GABA-edited magnetic resonance spectroscopy [MRS]) and in relation to motor recovery during 2 weeks of constraint-induced movement therapy (CIMT). Methods. Twenty-one patients (3-12 months poststroke) and 20 healthy subjects were recruited. Magnetic resonance imaging structural T1 and GABA-edited MRS were performed at baseline and after CIMT, and once in healthy subjects. GABA:creatine (GABA:Cr) ratio was measured by GABA-edited MRS. Motor function was measured using Wolf Motor Function Test (WMFT). Results. Baseline comparison between stroke patients (n = 19) and healthy subjects showed a significantly lower GABA:Cr ratio in stroke patients (P < .001) even after correcting for gray matter content in the voxel (P < .01) and when expressing GABA relative to N-acetylaspartic acid (NAA; P = .03). After 2 weeks of CIMT patients improved significantly on WMFT, but no consistent change across the group was observed for the GABA:Cr ratio (n = 17). However, the extent of improvement on WMFT correlated significantly with the magnitude of GABA:Cr changes (P < .01), with decreases in GABA:Cr ratio being associated with better improvements in motor function. Conclusions. In patients 3 to 12 months poststroke, GABA levels are lower in the primary motor cortex than in healthy subjects. The observed association between GABA and recovery warrants further studies on the potential use of GABA MRS as a biomarker in poststroke recovery.
Variable sigma Gaussian processes: An expectation propagation perspective

Gaussian processes (GPs) provide a probabilistic nonparametric representation of functions in regression, classification, and other problems. Unfortunately, exact learning with GPs is intractable for large datasets. A variety of approximate GP methods have been proposed that essentially map the large dataset into a small set of basis points. The most advanced of these, the variable-sigma GP (VSGP) (Walder et al., 2008), allows each basis point to have its own length scale. However, VSGP was only derived for regression. We describe how VSGP can be applied to classification and other problems, by deriving it as an expectation propagation algorithm. In this view, sparse GP approximations correspond to a KL-projection of the true posterior onto a compact exponential family of GPs. VSGP constitutes one such family, and we show how to enlarge this family to get additional accuracy. In particular, we show that endowing each basis point with its own full covariance matrix provides a significant increase in approximation power.
The Settlement of the United States, 1800 to 2000: The Long Transition Towards Gibrat's Law

This paper studies the long run development of U.S. counties and metro areas from 1800 to 2000. In earlier periods smaller counties converge whereas larger counties diverge. Over time, due to changes in the age composition of locations and net congestion, convergence dissipates and divergence weakens. Gibrat's law emerges gradually without fully attaining it. Our findings suggest that orthogonal growth is a consequence of reaching a steady state population distribution, rather than an explanation of that distribution. A simple one-sector model, with entry of new locations, a growth friction, and decreasing net congestion closely matches these and related dynamics.
Differential PfEMP1 Expression Is Associated with Cerebral Malaria Pathology

Plasmodium falciparum is unique among human malarias in its ability to sequester in post-capillary venules of host organs. The main variant antigens implicated are the P. falciparum erythrocyte membrane protein 1 (PfEMP1), which can be divided into three major groups (A–C). Our study was a unique examination of sequestered populations of parasites for genetic background and expression of PfEMP1 groups. We collected post-mortem tissue from twenty paediatric hosts with pathologically different forms of cerebral malaria (CM1 and CM2) and parasitaemic controls (PC) to directly examine sequestered populations of parasites in the brain, heart and gut. Use of two different techniques to investigate this question produced divergent results. By quantitative PCR, group A var genes were upregulated in all three organs of CM2 and PC cases. In contrast, in CM1 infections displaying high levels of sequestration but negligible vascular pathology, there was high expression of group B var. Cloning and sequencing of var transcript tags from the same samples indicated a uniformly low expression of group A-like var. Generally, within an organ sample, 1–2 sequences were expressed at dominant levels. 23% of var tags were detected in multiple patients despite the P. falciparum infections being genetically distinct, and two tags were observed in up to seven hosts each with high expression in the brains of 3–4 patients. This study is a novel examination of the sequestered parasites responsible for fatal cerebral malaria and describes expression patterns of the major cytoadherence ligand in three organ-derived populations and three pathological states.
School-aged children exhibit domain-specific responses to biological motion

Abstract Prior studies have implicated the superior temporal sulcus region for processing various types of biological motion in children and adults. However, no previous research in children compared this activity to that involved in coherent, meaningful, non-biological motion perception to show specificity for biological motion processing. In this study, we used functional magnetic resonance imaging to explore which brain regions were specific for biological motion in 7- to 10-year-old children. We compared brain activity in response to biological motion by a biological figure (a walking human); biological motion by a non-biological figure (a walking robot); disorganized, non-biological motion by a disjointed mechanical figure; and organized, non-biological motion by a grandfather clock. We identified a network of brain regions that had a greater response evoked by biological than by non-biological motion, including the superior temporal sulcus and mirror neuron regions. Additionally, we found a developmental change suggesting increasing specificity for biological motion with age in the superior temporal sulcus region. We discuss these results in the context of research and theory that has emphasized the important role of biological motion perception in the development of theory-of-mind abilities.
Layer‐specific excitation/inhibition balances during neuronal synchronization in the visual cortex

Understanding the balance between synaptic excitation and inhibition in cortical circuits in the brain, and how this contributes to cortical rhythms, is fundamental to explaining information processing in the cortex. This study used cortical layer‐specific optogenetic activation in mouse cortex to show that excitatory neurons in any cortical layer can drive powerful gamma rhythms, while inhibition balances excitation. The net impact of this is to keep activity within each layer in check, but simultaneously to promote the propagation of activity to downstream layers. The data show that rhythm‐generating circuits exist in all principle layers of the cortex, and provide layer‐specific balances of excitation and inhibition that affect the flow of information across the layers.
Community accountability at peripheral health facilities: a review of the empirical literature and development of a conceptual framework

Public accountability has re-emerged as a top priority for health systems all over the world, and particularly in developing countries where governments have often failed to provide adequate public sector services for their citizens. One approach to strengthening public accountability is through direct involvement of clients, users or the general public in health delivery, here termed ‘community accountability’. The potential benefits of community accountability, both as an end in itself and as a means of improving health services, have led to significant resources being invested by governments and non-governmental organizations. Data are now needed on the implementation and impact of these initiatives on the ground. A search of PubMed using a systematic approach, supplemented by a hand search of key websites, identified 21 papers from low- or middle-income countries describing at least one measure to enhance community accountability that was linked with peripheral facilities. Mechanisms covered included committees and groups (n = 19), public report cards (n = 1) and patients’ rights charters (n = 1). In this paper we summarize the data presented in these papers, including impact, and factors influencing impact, and conclude by commenting on the methods used, and the issues they raise. We highlight that the international interest in community accountability mechanisms linked to peripheral facilities has not been matched by empirical data, and present a conceptual framework and a set of ideas that might contribute to future studies.
Estimating Rates of Carriage Acquisition and Clearance and Competitive Ability for Pneumococcal Serotypes in Kenya With a Markov Transition Model

Background: There are more than 90 serotypes of Streptococcus pneumoniae, with varying biologic and epidemiologic properties. Animal studies suggest that carriage induces an acquired immune response that reduces duration of colonization in a nonserotype-specific fashion. Methods: We studied pneumococcal nasopharyngeal carriage longitudinally in Kenyan children 3–59 months of age, following up positive swabs at days 2, 4, 8, 16, and 32 and then monthly thereafter until 2 swabs were negative for the original serotype. As previously reported, 1868/2840 (66%) of children swabbed at baseline were positive. We estimated acquisition, clearance, and competition parameters for 27 serotypes using a Markov transition model. Results: Point estimates of type-specific acquisition rates ranged from 0.00025/d (type 1) to 0.0031/d (type 19F). Point estimates of time to clearance (inverse of type-specific immune clearance rate) ranged from 28 days (type 20) to 124 days (type 6A). For the serotype most resistant to competition (type 19F), acquisition of other serotypes was 52% less likely (95% confidence interval = 37%–63%) than in an uncolonized host. Fitness components (carriage duration, acquisition rate, lack of susceptibility to competition) were positively correlated with each other and with baseline prevalence, and were associated with biologic properties previously shown to associate with serotype. Duration of carriage declined with age for most serotypes. Conclusions: Common S. pneumoniae serotypes appear superior in many dimensions of fitness. Differences in rate of immune clearance are attenuated as children age and become capable of more rapid clearance of the longest-lived serotypes. These findings provide information for comparison after introduction of pneumococcal conjugate vaccine.
The Meaning of Home and Its Implications on Alternative Tenures: A Malaysian Perspective

Abstract The discourse on the meaning of home is largely centred on the Western experiences and perspectives, producing insights into the economic and psycho-social aspects of home, with less attention on the Eastern context. This paper explores the emotive meaning of home from the perspective of Malaysia, a nation of homeowners. Gurney’s view of home as an emotional “warehouse” framed this inquiry, supporting the notion of feelings associated with the dwelling being created, deposited and drawn by its occupants. This paper represents part of a larger housing study into an alternative housing tenure for Malaysia that argues that the sense of home can be independent of housing tenure. This paper reports the meaning of home as derived from 10 diarists who have been actively involved in creating the “home” and were therefore capable to describe the process of emotional appropriation of their lived space. Findings suggested that the process of assigning meaning to home was dependent on diarists’ feelings, perceptions, attachments and relations regarding their lived space. Diarists mainly associated their emotive construction of home with family-centred activities and space, which took place in both the micro-sense (within the dwelling) and the macro-sense (the neighbourhood).
Impact of acute undernutrition on growth, ileal morphology and nutrient transport in a murine model

Undernutrition represents a major public health challenge for middle- and low-income countries. This study aimed to evaluate whether a multideficient Northeast Brazil regional basic diet (RBD) induces acute morphological and functional changes in the ileum of mice. Swiss mice (∼25 g) were allocated into two groups: i) control mice were fed a standard diet and II) undernourished mice were fed the RBD. After 7 days, mice were killed and the ileum collected for evaluation of electrophysiological parameters (Ussing chambers), transcription (RT-qPCR) and protein expression (western blotting) of intestinal transporters and tight junctions. Body weight gain was significantly decreased in the undernourished group, which also showed decreased crypt depth but no alterations in villus height. Electrophysiology measurements showed a reduced basal short circuit current (I sc) in the undernourished group, with no differences in transepithelial resistance. Specific substrate-evoked I sc related to affinity and efficacy (glutamine and alanyl-glutamine) were not different between groups, except for the maximum I sc (efficacy) induced by glucose. Transcription of Sglt1 and Pept1 was significantly higher in the undernourished group, while SN-2 transcription was decreased. No changes were found in transcription of CAT-1 and CFTR, while claudin-2 and occludin transcriptions were significantly increased in the undernourished group. Despite mRNA changes, SGLT-1, PEPT-1, claudin-2 and occludin protein expression showed no difference between groups. These results demonstrate early effects of the RBD on mice, which include reduced body weight and crypt depth in the absence of significant alterations to villus morphology, intestinal transporters and tight junction expression.
Longitudinal Diffusion Tensor Imaging in Frontotemporal Dementia

Novel biomarkers for monitoring progression in neurodegenerative conditions are needed. Measurement of microstructural changes in white matter (WM) using diffusion tensor imaging (DTI) may be a useful outcome measure. Here we report trajectories of WM change using serial DTI in a cohort with behavioral variant frontotemporal dementia (bvFTD).