Miracle-dz/UniFAR-FTUs huggingface dataset:
Accelerating XPath location steps

This work is a proposal for a database index structure that has been specifically designed to support the evaluation of XPath queries. As such, the index is capable to support all XPath axes (including ancestor, following, preceding-sibling, descendant-or-self, etc.). This feature lets the index stand out among related work on XML indexing structures which had a focus on regular path expressions (which correspond to the XPath axes children and descendant-or-self plus name tests). Its ability to start traversals from arbitrary context nodes in an XML document additionally enables the index to support the evaluation of path traversals embedded in XQuery expressions. Despite its flexibility, the new index can be implemented and queried using purely relational techniques, but it performs especially well if the underlying database host provides support for R-trees. A performance assessment which shows quite promising results completes this proposal.
DeepHMap++: Combined Projection Grouping and Correspondence Learning for Full DoF Pose Estimation

In recent years, estimating the 6D pose of object instances with convolutional neural network (CNN) has received considerable attention. Depending on whether intermediate cues are used, the relevant literature can be roughly divided into two broad categories: direct methods and two-stage pipelines. For the latter, intermediate cues, such as 3D object coordinates, semantic keypoints, or virtual control points instead of pose parameters are regressed by CNN in the first stage. Object pose can then be solved by correspondence constraints constructed with these intermediate cues. In this paper, we focus on the postprocessing of a two-stage pipeline and propose to combine two learning concepts for estimating object pose under challenging scenes: projection grouping on one side, and correspondence learning on the other. We firstly employ a local-patch based method to predict projection heatmaps which denote the confidence distribution of projection of 3D bounding box’s corners. A projection grouping module is then proposed to remove redundant local maxima from each layer of heatmaps. Instead of directly feeding 2D–3D correspondences to the perspective-n-point (PnP) algorithm, multiple correspondence hypotheses are sampled from local maxima and its corresponding neighborhood and ranked by a correspondence–evaluation network. Finally, correspondences with higher confidence are selected to determine object pose. Extensive experiments on three public datasets demonstrate that the proposed framework outperforms several state of the art methods.
Forensic characteristics and phylogenetic analysis of 23 Y-STR loci in the Miao population from Guizhou province, southwest China

Abstract Background: Investigation of haplotype/allele frequency data of Y-STR loci in ethnically diverse populations is essential for forensic reference database construction and genetic application. However, the population genetic characteristics of the Chinese Miao minority from Guizhou Province remain uncharacterised. Aim: To assess forensic characteristics for 23 Y-Chromosomal STR loci in Guizhou Miao and explore population genetic relationships with geographically neighbouring populations. Subjects and methods: Twenty-three Y-Chromosomal STRs were genotyped using the Powerplex® Y23 system in 103 unrelated Chinese Miao males from Guizhou Province, southwest China. Haplotypes and forensic parameters were obtained. Population relationships of Guizhou Miao with others were revealed using AMOVA and an MDS plot. Results: A total of 96 haplotypes were identified with overall haplotype diversity (HD) and discrimination capacity (DC) of 0.9985 and 0.9320, respectively. Genetic differentiation was observed with most of the comparison populations, prominently for Guizhou Shui. Conclusion: The 23 Y-STR loci were highly polymorphic and discriminating in the Guizhou Miao population and could be used for forensic practice and population genetic studies. Population relationship analysis revealed Guizhou Miao had a close genetic relationship with geographically close Guizhou Gelao, as well as Han majorities derived from different regions.
Weevil pgrp-lb prevents endosymbiont TCT dissemination and chronic host systemic immune activation

Significance Permanent infections with beneficial bacteria are widespread in nature and are believed to play a pivotal role in evolution. How hosts’ immune functions are regulated to maintain cooperative bacteria while preventing them from constantly activating the host immune system is a key question in understanding host–bacterial associations’ sustainability. In insects, beneficial bacteria are often confined within specialized host cells, the bacteriocytes, which avoid direct contact between the host’s immune system and bacteria. Here, we report an additional mechanism that prevents bacteria-released immunogenic molecules (i.e., peptidoglycan fragments) from escaping the bacteriocytes. We show that two peptidoglycan-cleaving enzymes are specifically produced in the bacteriocytes, where they cleave bacterial peptidoglycan into nonimmunogenic fragments, thereby preventing continuous and damageable host systemic immune activation. Long-term intracellular symbiosis (or endosymbiosis) is widely distributed across invertebrates and is recognized as a major driving force in evolution. However, the maintenance of immune homeostasis in organisms chronically infected with mutualistic bacteria is a challenging task, and little is known about the molecular processes that limit endosymbiont immunogenicity and host inflammation. Here, we investigated peptidoglycan recognition protein (PGRP)-encoding genes in the cereal weevil Sitophilus zeamais’s association with Sodalis pierantonius endosymbiont. We discovered that weevil pgrp-lb generates three transcripts via alternative splicing and differential regulation. A secreted isoform is expressed in insect tissues under pathogenic conditions through activation of the PGRP-LC receptor of the immune deficiency pathway. In addition, cytosolic and transmembrane isoforms are permanently produced within endosymbiont-bearing organ, the bacteriome, in a PGRP-LC–independent manner. Bacteriome isoforms specifically cleave the tracheal cytotoxin (TCT), a peptidoglycan monomer released by endosymbionts. pgrp-lb silencing by RNAi results in TCT escape from the bacteriome to other insect tissues, where it chronically activates the host systemic immunity through PGRP-LC. While such immune deregulations did not impact endosymbiont load, they did negatively affect host physiology, as attested by a diminished sexual maturation of adult weevils. Whereas pgrp-lb was first described in pathogenic interactions, this work shows that, in an endosymbiosis context, specific bacteriome isoforms have evolved, allowing endosymbiont TCT scavenging and preventing chronic endosymbiont-induced immune responses, thus promoting host homeostasis.
Environmental niche variation and evolutionary diversification of the Brachypodium distachyon grass complex species in their native circum-Mediterranean range.

UNLABELLED • PREMISE OF THE STUDY We conducted environmental niche modeling (ENM) of the Brachypodium distachyon s.l. complex, a model group of two diploid annual grasses (B. distachyon, B. stacei) and their derived allotetraploid (B. hybridum), native to the circum-Mediterranean region. We (1) investigated the ENMs of the three species in their native range based on present and past climate data; (2) identified potential overlapping niches of the diploids and their hybrid across four Quaternary windows; (3) tested whether speciation was associated with niche divergence/conservatism in the complex species; and (4) tested for the potential of the polyploid outperforming the diploids in the native range. • METHODS Geo-referenced data, altitude, and 19 climatic variables were used to construct the ENMs. We used paleoclimate niche models to trace the potential existence of ancestral gene flow among the hybridizing species of the complex. • KEY RESULTS Brachypodium distachyon grows in higher, cooler, and wetter places, B. stacei in lower, warmer, and drier places, and B. hybridum in places with intermediate climatic features. Brachypodium hybridum had the largest niche overlap with its parent niches, but a similar distribution range and niche breadth. • CONCLUSIONS Each species had a unique environmental niche though there were multiple niche overlapping areas for the diploids across time, suggesting the potential existence of several hybrid zones during the Pleistocene and the Holocene. No evidence of niche divergence was found, suggesting that species diversification was not driven by ecological speciation but by evolutionary history, though it could be associated to distinct environmental adaptations.
Sostdc1 Regulates NK Cell Maturation and Cytotoxicity

Key Points Sostdc1 influences tNK to mNK cell differentiation and the Ly49 receptor repertoire. NK cells in Sostdc1−/− mice display impaired ability to kill β2m−/− target cells. Sostdc1 expression in stromal and hematopoietic cells regulates NK cells. NK cells are innate-like lymphocytes that eliminate virally infected and cancerous cells, but the mechanisms that control NK cell development and cytotoxicity are incompletely understood. We identified roles for sclerostin domain–containing-1 (Sostdc1) in NK cell development and function. Sostdc1-knockout (Sostdc1−/−) mice display a progressive accumulation of transitional NK cells (tNKs) (CD27+CD11b+) with age, indicating a partial developmental block. The NK cell Ly49 repertoire in Sostdc1−/− mice is also changed. Lower frequencies of Sostdc1−/− splenic tNKs express inhibitory Ly49G2 receptors, but higher frequencies express activating Ly49H and Ly49D receptors. However, the frequencies of Ly49I+, G2+, H+, and D+ populations were universally decreased at the most mature (CD27−CD11b+) stage. We hypothesized that the Ly49 repertoire in Sostdc1−/− mice would correlate with NK killing ability and observed that Sostdc1−/− NK cells are hyporesponsive against MHC class I–deficient cell targets in vitro and in vivo, despite higher CD107a surface levels and similar IFN-γ expression to controls. Consistent with Sostdc1’s known role in Wnt signaling regulation, Tcf7 and Lef1 levels were higher in Sostdc1−/− NK cells. Expression of the NK development gene Id2 was decreased in Sostdc1−/− immature NK and tNK cells, but Eomes and Tbx21 expression was unaffected. Reciprocal bone marrow transplant experiments showed that Sostdc1 regulates NK cell maturation and expression of Ly49 receptors in a cell-extrinsic fashion from both nonhematopoietic and hematopoietic sources. Taken together, these data support a role for Sostdc1 in the regulation of NK cell maturation and cytotoxicity, and identify potential NK cell niches.
CDKL5 deficiency predisposes neurons to cell death through the deregulation of SMAD3 signaling

CDKL5 deficiency disorder (CDD) is a rare encephalopathy characterized by early onset epilepsy and severe intellectual disability. CDD is caused by mutations in the X‐linked cyclin‐dependent kinase‐like 5 (CDKL5) gene, a member of a highly conserved family of serine‐threonine kinases. Only a few physiological substrates of CDKL5 are currently known, which hampers the discovery of therapeutic strategies for CDD. Here, we show that SMAD3, a primary mediator of TGF‐β action, is a direct phosphorylation target of CDKL5 and that CDKL5‐dependent phosphorylation promotes SMAD3 protein stability. Importantly, we found that restoration of the SMAD3 signaling through TGF‐β1 treatment normalized defective neuronal survival and maturation in Cdkl5 knockout (KO) neurons. Moreover, we demonstrate that Cdkl5 KO neurons are more vulnerable to neurotoxic/excitotoxic stimuli. In vivo treatment with TGF‐β1 prevents increased NMDA‐induced cell death in hippocampal neurons from Cdkl5 KO mice, suggesting an involvement of the SMAD3 signaling deregulation in the neuronal susceptibility to excitotoxic injury of Cdkl5 KO mice. Our finding reveals a new function for CDKL5 in maintaining neuronal survival that could have important implications for susceptibility to neurodegeneration in patients with CDD.
Management practice-related and modifiable factors associated with paediatric emergency return visits.

Objectives We explored practice-related factors associated with preventable unscheduled return visits to an emergency department (RTED). Methods We conducted a retrospective cohort study, using standardized review of health records. We included all visits with at least one RTED within 7 days of the index visit. Cases were reviewed by investigators and clinicians to identify: 1) the proportion of unscheduled RTED, 2) the proportion deemed clinically unnecessary and 3) the contribution of clinical practice pattern and system factors. Results There were 2809 (7.3%) index visits associated with at least one RTED. Of these, 1983 (70.6%) were unscheduled, 784 (39.5%) were considered clinically unnecessary and 739 out of 784 medically unnecessary RTEDs (94.3%) were attributed to a mismatch between parental expectations and natural progression of disease that did not require Emergency Department (ED) reassessment or interventions. Eighty per cent of reviewed written discharge instructions lacked any anticipatory guidance around symptom range and duration and 21.2% contained instructions to return to the ED for signs and symptoms which do not require ED care. An administrative or system challenge was noted as the reason for the unnecessary and unscheduled RTED in 17.5%. In 3.4% of cases, nonemergency consultants were responsible for the disposition decision and discharge process. Conclusions Unscheduled unnecessary return visits to our ED contribute to a significant proportion of our annual volume. Providing discharge instructions that help families distinguish expected range and duration of symptoms from signs requiring ED care was identified as a potential strategy to impact the frequency of unscheduled RTED.
Validity and reliability of the Persian ABILHAND-Kids in a sample of Iranian children with cerebral palsy

Abstract Aim: To develop a Persian version of ABILHAND-Kids and to determine its reliability and validity in Persian-speaking children with cerebral palsy (CP). Method: The ABILHAND-Kids questionnaire was translated into Persian language and cross-culturally adapted following guidelines. The Persian ABILHAND-Kids was administered to 50 parents of CP children. Among the 50 parents of CP children, 30 of them participated in a test–retest reliability phase. Fifty parents of healthy children participated for discriminative validity. Results: The Rasch analysis indicated the unidimensionality, reliability, and global invariance of the Persian ABILHAND-Kids. The internal consistency reliability was high (Cronbach’s alpha = 0.96). Floor and ceiling effects were insignificant (4%). The Intraclass Correlation Coefficients of test–retest reliability were 0.96 and 0.70 for item difficulties and children’s measures, respectively. The standard error of measurement and smallest detectable change for CP measure were 11.21 and 31.07%, respectively. The discriminative validity of the Persian ABILHAND-Kids was demonstrated by statistically significant lower ABILHAND-Kids measures in CP children than in healthy children (p < 0.001). Cross-cultural validity between the Persian and original version was established for 19 out of the 21 ABILHAND-Kids items. Interpretation: The Persian ABILHAND-Kids questionnaire is reliable and valid for assessing manual ability in Persian speaking children with CP. Implications for rehabilitation The Persian version of ABILHAND-Kids is developed and presented as a valid and reliable instrument for use by Persian-speaking clinicians and researchers. It is now possible for the Persian-speaking researchers to participate in international investigations and to compare Persian data with those from other countries.
Differences in Opioid Prescribing Among Generalist Physicians, Nurse Practitioners, and Physician Assistants.

OBJECTIVE To determine if there are differences in opioid prescribing among generalist physicians, nurse practitioners (NPs), and physician assistants (PAs) to Medicare Part D beneficiaries. DESIGN Serial cross-sectional analysis of prescription claims from 2013 to 2016 using publicly available data from the Centers for Medicare and Medicaid Services. SUBJECTS All generalist physicians, NPs, and PAs who provided more than 10 total prescription claims between 2013 and 2016 were included. These prescribers were subsetted as practicing in a primary care, urgent care, or hospital-based setting. METHODS The main outcomes were total opioid claims and opioid claims as a proportion of all claims in patients treated by these prescribers in each of the three settings of interest. Binomial regression was used to generate marginal estimates to allow comparison of the volume of claims by these prescribers with adjustment for practice setting, gender, years of practice, median income of the ZIP code, state fixed effects, and relevant interaction terms. RESULTS There were 36,999 generalist clinicians (physicians, NPs, and PAs) with at least one year of Part D prescription drug claims data between 2013 and 2016. The number of adjusted total opioid claims across these four years for physicians was 660 (95% confidence interval [CI] = 660-661), for NPs was 755 (95% CI = 753-757), and for PAs was 812 (95% CI = 811-814). CONCLUSIONS We find relatively high rates of opioid prescribing among NPs and PAs, especially at the upper margins. This suggests that well-designed interventions to improve the safety of NP and PA opioid prescribing, along with that of their physician colleagues, could be especially beneficial.
Gene Expression Signatures Predictive of Bevacizumab/Erlotinib Therapeutic Benefit in Advanced Nonsquamous Non–Small Cell Lung Cancer Patients (SAKK 19/05 trial)

Purpose: We aimed to identify gene expression signatures associated with angiogenesis and hypoxia pathways with predictive value for treatment response to bevacizumab/erlotinib (BE) of nonsquamous advanced non–small cell lung cancer (NSCLC) patients. Experimental Design: Whole-genome gene expression profiling was performed on 42 biopsy samples (from SAKK 19/05 trial) using Affymetrix exon arrays, and associations with the following endpoints: time-to-progression (TTP) under therapy, tumor-shrinkage (TS), and overall survival (OS) were investigated. Next, we performed gene set enrichment analyses using genes associated with the angiogenic process and hypoxia response to evaluate their predictive value for patients' outcome. Results: Our analysis revealed that both the angiogenic and hypoxia response signatures were enriched within the genes predictive of BE response, TS, and OS. Higher gene expression levels (GEL) of the 10-gene angiogenesis-associated signature and lower levels of the 10-gene hypoxia response signature predicted improved TTP under BE, 7.1 months versus 2.1 months for low versus high-risk patients (P = 0.005), and median TTP 6.9 months versus 2.9 months (P = 0.016), respectively. The hypoxia response signature associated with higher TS at 12 weeks and improved OS (17.8 months vs. 9.9 months for low vs. high-risk patients, P = 0.001). Conclusions: We were able to identify gene expression signatures derived from the angiogenesis and hypoxia response pathways with predictive value for clinical outcome in advanced nonsquamous NSCLC patients. This could lead to the identification of clinically relevant biomarkers, which will allow for selecting the subset of patients who benefit from the treatment and predict drug response. Clin Cancer Res; 21(23); 5253–63. ©2015 AACR. See related commentary by Cascone and Heymach, p. 5188
Estrogen sulfotransferase in the metabolism of estrogenic drugs and in the pathogenesis of diseases

ABSTRACT Introduction: Biotransformation is important in the metabolism of endobiotics and xenobiotics. This process comprises the activity of phase I and phase II enzymes. Estrogen sulfotransferase (SULT1E1 or EST) is a phase II conjugating enzyme that belongs to the family of cytosolic sulfotransferases. The expression of SULT1E1 can be detected in many tissues, including the liver. SULT1E1 catalyzes the transfer of a sulfate group from 3ʹ-phosphoadenosine-5ʹ-phosphosulfate (PAPS) to any available hydroxyl group in estrogenic molecules. The substrates of SULT1E1 include the endogenous and synthetic estrogens. Upon SULT1E1-mediated sulfation, the hydrosolubility of estrogens increases, preventing the binding between the sulfated estrogens and the estrogen receptor (ER). This sulfated state of the estrogens is not irreversible, as the steroid sulfatase (STS) can convert sulfoconjugated estrogens to free estrogens. The expression of SULT1E1 is inducible by several diseases that involve tissue inflammation, such as type 2 diabetes, sepsis, and ischemia-reperfusion injury. Areas covered: This systematic literature review aims to summarize the role of SULT1E1 in the metabolism of estrogenic drugs and xenobiotics, and the role of SULT1E1 in the pathogenesis of several diseases, including cancer, metabolic disease, sepsis, liver injury, and cystic fibrosis. Meanwhile, ablation or pharmacological inhibition of SULT1E1 can affect the outcomes of the aforementioned diseases. Expert opinion: In addition to its role in metabolizing estrogenic drugs, SULT1E1 is unexpectedly being unveiled as a mediator for the disease effect on estrogen metabolism and homeostasis. Meanwhile, because the expression and activity of SULT1E1 can affect the outcome of diseases, the same sulfotransferase and the reversing enzymes STS can be potential therapeutic targets to prevent or manage diseases. Accumulating evidence suggest that the physiological and pathophysiological effects of SULT1E1 can be estrogen-independent and it is necessary to elucidate what other possible substrates may be recognized by the enzyme. Moreover, human studies are paramount to confirm the human relevance of the animal studies.
Gray Matter Volume Covariance Networks, Social Support and Cognition in Older Adults.

OBJECTIVE We examined the neural substrates of social support in older adults. Social support is associated with better outcomes in many facets of aging - including cognitive and functional health - but the underlying neural substrates remain largely unexplored. METHODS Voxel-based morphometry and multivariate statistics were used to identify gray matter volume covariance networks associated with social support in 112 older adults without dementia (M age = 74.6 years, 50% female), using the Medical Outcomes Study Social Support Survey (Sherbourne & Stewart, 1991). RESULTS A gray matter network associated with overall social support was identified and included prefrontal, hippocampal, amygdala, cingulate and thalamic regions. A gray matter network specifically associated with tangible social support (e.g. someone to help you if you were confined to bed) was also identified, included prefrontal, hippocampal, cingulate, insular and thalamic regions, and correlated with memory and executive function. DISCUSSION Gray matter networks associated with overall and tangible social support in this study were composed of regions previously associated with memory, executive function, aging, and dementia. Longitudinal research of the interrelationships between social support, brain structure, and cognition is needed, but strengthening social support may represent a new path toward improving cognition in aging that should be explored.