Miracle-dz/UniFAR-FTUs huggingface dataset:
Weak Middle-Ear-Muscle Reflex in Humans with Noise-Induced Tinnitus and Normal Hearing May Reflect Cochlear Synaptopathy

Abstract Chronic tinnitus is a prevalent hearing disorder, and yet no successful treatments or objective diagnostic tests are currently available. The aim of this study was to investigate the relationship between the presence of tinnitus and the strength of the middle-ear-muscle reflex (MEMR) in humans with normal and near-normal hearing. Clicks were used as test stimuli to obtain a wideband measure of the effect of reflex activation on ear-canal sound pressure. The reflex was elicited using a contralateral broadband noise. The results show that the reflex strength is significantly reduced in individuals with noise-induced continuous tinnitus and normal or near-normal audiometric thresholds compared with no-tinnitus controls. Due to a shallower growth of the reflex strength in the tinnitus group, the difference between the two groups increased with increasing elicitor level. No significant difference in the effect of tinnitus on the strength of the middle-ear muscle reflex was found between males and females. The weaker reflex could not be accounted for by differences in audiometric hearing thresholds between the tinnitus and control groups. Similarity between our findings in humans and the findings of a reduced middle-ear muscle reflex in noise-exposed animals suggests that noise-induced tinnitus in individuals with clinically normal hearing may be a consequence of cochlear synaptopathy, a loss of synaptic connections between inner hair cells (IHCs) in the cochlea and auditory-nerve (AN) fibers that has been termed hidden hearing loss.
Transcriptional Landscape and Regulatory Roles of Small Noncoding RNAs in the Oxidative Stress Response of the Haloarchaeon Haloferax volcanii

ABSTRACT Haloarchaea in their natural environment are exposed to hypersalinity, intense solar radiation, and desiccation, all of which generate high levels of oxidative stress. Previous work has shown that haloarchaea are an order of magnitude more resistant to oxidative stress than most mesophilic organisms. Despite this resistance, the pathways haloarchaea use to respond to oxidative stress damage are similar to those of nonresistant organisms, suggesting that regulatory processes might be key to their robustness. Recently, small regulatory noncoding RNAs (sRNAs) were discovered in Archaea under a variety of environmental conditions. We report here the transcriptional landscape and functional roles of sRNAs in the regulation of the oxidative stress response of the model haloarchaeon Haloferax volcanii. Thousands of sRNAs, both intergenic and antisense, were discovered using strand-specific sRNA sequencing (sRNA-seq), comprising 25 to 30% of the total transcriptome under no-challenge and oxidative stress conditions, respectively. We identified hundreds of differentially expressed sRNAs in response to hydrogen peroxide-induced oxidative stress in H. volcanii. The targets of a group of antisense sRNAs decreased in expression when these sRNAs were upregulated, suggesting that sRNAs are potentially playing a negative regulatory role on mRNA targets at the transcript level. Target enrichment of these antisense sRNAs included mRNAs involved in transposon mobility, chemotaxis signaling, peptidase activity, and transcription factors. IMPORTANCE While a substantial body of experimental work has been done to uncover the functions of small regulatory noncoding RNAs (sRNAs) in gene regulation in Bacteria and Eukarya, the functional roles of sRNAs in Archaea are still poorly understood. This study is the first to establish the regulatory effects of sRNAs on mRNAs during the oxidative stress response in the haloarchaeon Haloferax volcanii. Our work demonstrates that common principles for the response to a major cellular stress exist across the 3 domains of life while uncovering pathways that might be specific to the Archaea. This work also underscores the relevance of sRNAs in adaptation to extreme environmental conditions.
Finding Statistically Significant Repeats in Nucleic Acids and Proteins

DNA repeats have great importance for biological research and a large number of tools for determining repeats have been developed. Herein we define a method for extracting a statistically significant subset of a determined set of repeats. Our aim was to identify a subset of repeats in the input sequences that are not expected to occur with a number of their appearances in a random sequence of the same length. It is expected that results obtained in such manner would reduce the quantity of processed material and could thereby represent a more important biological signal. With DNA, RNA, and protein sequences serving as input material, we also examined the possibility of statistical filtering of repeats in sequences over an arbitrary alphabet. A new method for selecting statistically significant repeats from a set of determined repeats has been defined. The proposed method was tested on a large number of randomly generated sequences. The application of the method on biological sequences revealed that for some viruses, shorter repeats are more statistically significant than longer ones because of their frequent appearance, whereas for bacteria, the majority of identified repeats are statistically significant.
Docosahexaenoic acid (DHA) at the sn-2 position of triacylglycerols increases DHA incorporation in brown, but not in white adipose tissue, of hamsters

Abstract We hypothesised that the incorporation of docosahexaenoic acid (DHA) across adipose tissues will be higher when it is ingested as triacylglycerols (TAG) structured at the sn-2 position. Ten-week old male hamsters were allocated to 4 dietary treatments (n = 10): linseed oil (LSO-control group), fish oil (FO), fish oil ethyl esters (FO-EE) and structured DHA at the sn-2 position of TAG (DHA-SL) during 12 weeks. In opposition to the large variations found for fatty acid composition in retroperitoneal white adipose tissue (WAT), brown adipose tissue (BAT) was less responsive to diets. DHA was not found in subcutaneous and retroperitoneal WAT depots but it was successfully incorporated in BAT reaching the highest percentage in DHA-SL. The PCA on plasma hormones (insulin, leptin, adiponectin) and fatty acids discriminated BAT from WATs pointing towards an individual signature on fatty acid deposition, but did not allow for full discrimination of dietary treatments within each adipose tissue.
Risk of peritoneal metastases in patients who had negative peritoneal staging and received therapy for localized gastric adenocarcinoma

Positive peritoneal cytology (+PCyt) or gross carcinomatosis (GPC) carries a poor prognosis. Laparoscopic staging to detect +PCyt/GPC is recommended for all ≥T1b gastric adenocarcinoma (GAC). The natural history of patients with GAC who have baseline −PCyt and then undergo multimodality therapy is not well documented, particularly for the risk of subsequent GPC.
Plasma 25-Hydroxyvitamin D Concentration and Risk of Islet Autoimmunity

We examined the association between plasma 25-hydroxyvitamin D [25(OH)D] concentration and islet autoimmunity (IA) and whether vitamin D gene polymorphisms modify the effect of 25(OH)D on IA risk. We followed 8,676 children at increased genetic risk of type 1 diabetes at six sites in the U.S. and Europe. We defined IA as positivity for at least one autoantibody (GADA, IAA, or IA-2A) on two or more visits. We conducted a risk set sampled nested case-control study of 376 IA case subjects and up to 3 control subjects per case subject. 25(OH)D concentration was measured on all samples prior to, and including, the first IA positive visit. Nine polymorphisms in VDR, CYP24A, CYP27B1, GC, and RXRA were analyzed as effect modifiers of 25(OH)D. Adjusting for HLA-DR-DQ and ancestry, higher childhood 25(OH)D was associated with lower IA risk (odds ratio = 0.93 for a 5 nmol/L difference; 95% CI 0.89, 0.97). Moreover, this association was modified by VDR rs7975232 (interaction P = 0.0072), where increased childhood 25(OH)D was associated with a decreasing IA risk based upon number of minor alleles: 0 (1.00; 0.93, 1.07), 1 (0.92; 0.89, 0.96), and 2 (0.86; 0.80, 0.92). Vitamin D and VDR may have a combined role in IA development in children at increased genetic risk for type 1 diabetes.
Systems biology analysis of longitudinal functional response of endothelial cells to shear stress

Significance Endothelial responses to shear stress modulate vascular homeostasis. This study offers a comprehensive temporal mechanistic model of shear stress response in cultured human vascular endothelial cells by presenting a systematic time-series RNA-sequencing dataset on endothelial cells exposed to pulsatile and oscillatory shears, consisting of 10 time points across 24 h. The experimental data were used for pathway analysis and construction of transcription factor-to-gene networks. The model highlights (i) dynamic regulation of several key shear-sensitive endothelial functions relevant to atheroprotective vs. atherogenic phenotype, (ii) how these functions may be causally interrelated, and (iii) how they are regulated by common upstream shear-responsive transcription factors. The results provide insights into the dynamics of functional evolution over time. Blood flow and vascular shear stress patterns play a significant role in inducing and modulating physiological responses of endothelial cells (ECs). Pulsatile shear (PS) is associated with an atheroprotective endothelial phenotype, while oscillatory shear (OS) is associated with an atheroprone endothelial phenotype. Although mechanisms of endothelial shear response have been extensively studied, most studies focus on characterization of single molecular pathways, mainly at fixed time points after stress application. Here, we carried out a longitudinal time-series study to measure the transcriptome after the application of PS and OS. We performed systems analyses of transcriptional data of cultured human vascular ECs to elucidate the dynamics of endothelial responses in several functional pathways such as cell cycle, oxidative stress, and inflammation. By combining the temporal data on differentially expressed transcription factors and their targets with existing knowledge on relevant functional pathways, we infer the causal relationships between disparate endothelial functions through common transcriptional regulation mechanisms. Our study presents a comprehensive temporally longitudinal experimental study and mechanistic model of shear stress response. By comparing the relative endothelial expressions of genes between OS and PS, we provide insights and an integrated perspective into EC function in response to differential shear. This study has significant implications for the pathogenesis of vascular diseases.
Probabilistic models of species discovery and biodiversity comparisons

Significance Estimates of species numbers are central to many analyses in fields ranging from conservation biology to macroecology and macroevolution. However, new species continue to be discovered and described at an uneven rate among regions and taxonomic groups, raising questions about the robustness of currently observed biodiversity patterns. We present a statistical approach to the rate of species description that incorporates uncertainty in species numbers across space and among clades. This approach identifies regions or clades where taxonomic knowledge is most complete, and provides estimates of stability in large-scale patterns given continued species discoveries through probabilistic forecasts of diversity levels. Inferring large-scale processes that drive biodiversity hinges on understanding the phylogenetic and spatial pattern of species richness. However, clades and geographic regions are accumulating newly described species at an uneven rate, potentially affecting the stability of currently observed diversity patterns. Here, we present a probabilistic model of species discovery to assess the uncertainty in diversity levels among clades and regions. We use a Bayesian time series regression to estimate the long-term trend in the rate of species description for marine bivalves and find a distinct spatial bias in the accumulation of new species. Despite these biases, probabilistic estimates of future species richness show considerable stability in the currently observed rank order of regional diversity. However, absolute differences in richness are still likely to change, potentially modifying the correlation between species numbers and geographic, environmental, and biological factors thought to promote biodiversity. Applied to scallops and related clades, we find that accumulating knowledge of deep-sea species will likely shift the relative richness of these three families, emphasizing the need to consider the incomplete nature of bivalve taxonomy in quantitative studies of its diversity. Along with estimating expected changes to observed patterns of diversity, the model described in this paper pinpoints geographic areas and clades most urgently requiring additional systematic study—an important practice for building more complete and accurate models of biodiversity dynamics that can inform ecological and evolutionary theory and improve conservation practice.
The giant mycoheterotrophic orchid Erythrorchis altissima is associated mainly with a divergent set of wood‐decaying fungi

The climbing orchid Erythrorchis altissima is the largest mycoheterotroph in the world. Although previous in vitro work suggests that E. altissima has a unique symbiosis with wood‐decaying fungi, little is known about how this giant orchid meets its carbon and nutrient demands exclusively via mycorrhizal fungi. In this study, the mycorrhizal fungi of E. altissima were molecularly identified using root samples from 26 individuals. Furthermore, in vitro symbiotic germination with five fungi and stable isotope compositions in five E. altissima at one site were examined. In total, 37 fungal operational taxonomic units (OTUs) belonging to nine orders in Basidiomycota were identified from the orchid roots. Most of the fungal OTUs were wood‐decaying fungi, but underground roots had ectomycorrhizal Russula. Two fungal isolates from mycorrhizal roots induced seed germination and subsequent seedling development in vitro. Measurement of carbon and nitrogen stable isotope abundances revealed that E. altissima is a full mycoheterotroph whose carbon originates mainly from wood‐decaying fungi. All of the results show that E. altissima is associated with a wide range of wood‐ and soil‐inhabiting fungi, the majority of which are wood‐decaying taxa. This generalist association enables E. altissima to access a large carbon pool in woody debris and has been key to the evolution of such a large mycoheterotroph.
Perspectives of rural health and human service practitioners following suicide prevention training programme in Australia: A thematic analysis

There are well-established training programmes available to support health and human services professionals working with people vulnerable to suicide. However, little is known about involving people with lived experience in the delivery of suicide prevention training with communities with increased rates of suicide. The aim of this paper was to report on a formative dialogical evaluation that explored the views of health and human services workers with regard to a suicide prevention training programme in regional (including rural and remote areas) South Australia which included meaningful involvement of a person with lived experience in the development and delivery of the training. In 2015, eight suicide prevention training workshops were conducted with health and human services workers. All 248 participants lived and worked in South Australian regional communities. We interviewed a subsample of 24 participants across eight sites. A thematic analysis of the interviews identified five themes: Coproduction is key, It is okay to ask the question, Caring for my community, I can make a difference and Learning for future training. The overall meta-theme was "Involvement of a person with lived experience in suicide prevention training supports regional communities to look out for people at risk of suicide. " This paper highlights the need for suicide prevention training and other workforce development programmes to include lived experience participation as a core component in development and delivery.
Interferon regulatory factor 1 is essential for pathogenic CD8+ T cell migration and retention in the brain during experimental cerebral malaria

Host immune response has a key role in controlling the progression of malaria infection. In the well‐established murine model of experimental cerebral malaria (ECM) with Plasmodium berghei ANKA infection, proinflammatory Th1 and CD8+ T cell response are essential for disease development. Interferon regulatory factor 1 (IRF1) is a transcription factor that promotes Th1 responses, and its absence was previously shown to protect from ECM death. Yet the exact mechanism of protection remains unknown. Here we demonstrated that IRF1‐deficient mice (IRF1 knockout) were protected from ECM death despite displaying early neurological signs. Resistance to ECM death was a result of reduced parasite sequestration and pathogenic CD8+ T cells in the brain. Further analysis revealed that IRF1 deficiency suppress interferon‐γ production and delayed CD8+ T cell proliferation. CXCR3 expression was found to be decreased in pathogenic CD8+ T cells, which limited their migration to the brain. In addition, reduced expression of adhesion molecules by brain endothelial cells hampered leucocyte retention in the brain. Taken together, these factors limited sequestration of pathogenic CD8+ T cells and consequently its ability to induce extensive damage to the blood–brain barrier.
User fees exemptions alone are not enough to increase indigent use of healthcare services.

The aim of this study was to assess whether user fees exemptions increased healthcare services use among indigents in the Ouargaye district in Burkina Faso. In this pre-post study, we surveyed 1224 indigents in 2010 about their healthcare services use over the preceding 6 months. Of these, 540 subsequently received a user fees exemption card. A follow-up survey was conducted 1 year later with a 55.3% retention rate. Analyses were performed in accordance with Andersen and Newman's model (Societal and individual determinants of medical care utilization in the United States. Milbank Q 1973;51:95-124) to explain healthcare services use by considering predisposing and facilitating factors and health needs indicators. Logistic regression analyses were performed.Among indigents exempted from user fees, 46.2% increased their healthcare services use in 2011, as opposed to 42.1% among the non-exempted. Being exempted was not associated with increased use of services (odds ratio, OR = 1.1, 95% confidence interval, CI [0.80-1.51]). Regardless of whether they were exempted or not, the indigents most likely to have increased their healthcare services use were older than 69 years of age (OR = 1.66, 95% CI [1.05-2.64]), male (OR = 1.44, 95% CI [0.99-2.08]), in low-income households (OR = 1.71, 95% CI [1.15-2.54]), and had received financial support from their families to obtain healthcare (OR = 1.59, 95% CI [1.1-2.28]). The indigents' increased healthcare services use was not attributable to user fees exemptions. Some contamination of the intervention is conceivable. Interventions combining user fees exemptions with actions targeting other obstacles to healthcare access would probably be more effective in increasing indigents' use of healthcare centres.
Fast Vehicle Detector for Autonomous Driving

This paper presents a fast vehicle detector which can be deployed on NVIDIA DrivePX2 under real-time constraints. The network predicts bounding boxes with different aspect ratio and scale priors from the specifically-designed prediction module given concatenated multi-scale feature map. A new data augmentation strategy is proposed to systematically generate a lot of vehicle training images whose appearance is randomly truncated so our detector could detect occluded vehicles better. Besides, we propose a non-region-based online hard example mining framework which performs fine-tuning by picking (1) hard examples and (2) detection results with insufficient IOU. Compared to other classical object detectors, this work achieves very competitive result in terms of average precision (AP) and computational speed. For the newly-defined vehicle class (car+bus) on VOC2007 test, our detector achieves 85.32 AP and runs at 48 FPS and 30 FPS on NVIDIA Titan X & GP106 (DrivePX2), respectively.
How2Sketch: generating easy-to-follow tutorials for sketching 3D objects

Accurately drawing 3D objects is difficult for untrained individuals, as it requires an understanding of perspective and its effects on geometry and proportions. Step-by-step tutorials break the complex task of sketching an entire object down into easy-to-follow steps that even a novice can follow. However, creating such tutorials requires expert knowledge and is time-consuming. As a result, the availability of tutorials for a given object or viewpoint is limited. How2Sketch (H2S) addresses this problem by automatically generating easy-to-follow tutorials for arbitrary 3D objects. Given a segmented 3D model and a camera viewpoint, H2S computes a sequence of steps for constructing a drawing scaffold comprised of geometric primitives, which helps the user draw the final contours in correct perspective and proportion. To make the drawing scaffold easy to construct, the algorithm solves for an ordering among the scaffolding primitives and explicitly makes small geometric modifications to the size and location of the object parts to simplify relative positioning. Technically, we formulate this scaffold construction as a single selection problem that simultaneously solves for the ordering and geometric changes of the primitives. We generate different tutorials on man-made objects using our method and evaluate how easily the tutorials can be followed with a user study.
The Role of Substance Use Coping in the Relation Between Childhood Sexual Abuse and Depression Among Methamphetamine Users in South Africa

Objective: Childhood sexual abuse (CSA) is a critical global health issue associated with poor psychosocial outcomes. Individuals with CSA histories are at risk for drug use, which is a growing problem in the Western Cape of South Africa. The present study of methamphetamine users in this region examined whether substance use coping, a contextually relevant type of avoidance-based coping, mediates the relation between CSA and depressive symptoms. Method: Participants included 161 men and 108 women seeking treatment for methamphetamine use. Participants completed a computer-assisted survey and a face-to-face interview with clinic staff to evaluate history of CSA, current substance use severity and coping, and current depressive symptoms. Results: Nearly a third of participants reported a history of CSA, and the average methamphetamine use severity score exceeded the threshold of high risk. A history of CSA was significantly associated with higher substance use coping and more depression symptoms. Substance use coping was a significant mediator of the association between CSA and depression symptoms. Conclusions: In this study of high-risk methamphetamine users, substance use coping emerged as a common means of managing stress, especially for those with a history of CSA, which was further linked to depressive symptoms. These findings underscore the potential benefit of integrating coping interventions and mental health treatment into substance abuse treatment programs, particularly for those with a history of childhood abuse and violence.