Miracle-dz/UniFAR-FTUs huggingface dataset:
Endometriosis Is Associated with a Significant Increase in hTERC and Altered Telomere/Telomerase Associated Genes in the Eutopic Endometrium, an Ex-Vivo and In Silico Study

Telomeres protect chromosomal ends and they are maintained by the specialised enzyme, telomerase. Endometriosis is a common gynaecological disease and high telomerase activity and higher hTERT levels associated with longer endometrial telomere lengths are characteristics of eutopic secretory endometrial aberrations of women with endometriosis. Our ex-vivo study examined the levels of hTERC and DKC1 RNA and dyskerin protein levels in the endometrium from healthy women and those with endometriosis (n = 117). The in silico study examined endometriosis-specific telomere- and telomerase-associated gene (TTAG) transcriptional aberrations of secretory phase eutopic endometrium utilising publicly available microarray datasets. Eutopic secretory endometrial hTERC levels were significantly increased in women with endometriosis compared to healthy endometrium, yet dyskerin mRNA and protein levels were unperturbed. Our in silico study identified 10 TTAGs (CDKN2A, PML, ZNHIT2, UBE3A, MCCC2, HSPC159, FGFR2, PIK3C2A, RALGAPA1, and HNRNPA2B1) to be altered in mid-secretory endometrium of women with endometriosis. High levels of hTERC and the identified other TTAGs might be part of the established alteration in the eutopic endometrial telomerase biology in women with endometriosis in the secretory phase of the endometrium and our data informs future research to unravel the fundamental involvement of telomerase in the pathogenesis of endometriosis.
Acquired capability for suicide among Belgian and Australian University students: Psychometric properties of the German capability for suicide questionnaire and a test of the interpersonal theory of suicide.

OBJECTIVE The Interpersonal Theory of Suicide (IPTS) posits fearlessness of death and pain tolerance as two components of suicide capability. The German Capability for Suicide Questionnaire (GCSQ) is the first measure of both these components, but few data are available on its psychometrics. We (a) examined the psychometric properties of the GCSQ and used it to test (b) the latent structure of suicide capability and (c) its associations with suicidal behavior. METHOD As part of the WHO World Mental Health International College Student Initiative, Belgian (N = 3715) and Australian (N = 2828) students completed the GCSQ (Dutch or English versions). RESULTS The factor structure of the GCSQ was well represented by two first-order factors (fearlessness of death, pain tolerance) and a higher-order suicide capability factor. The fearlessness of death scale and pain tolerance scale (minus two reverse-scored items) showed good reliability (α = 0.81- 0.90). Fearlessness of death was associated with suicidal behaviors, but the pain tolerance scale was inversely associated with suicidal behaviors. CONCLUSIONS Consistent with the Interpersonal Theory of Suicide, fearlessness of death and pain tolerance are components of a higher-order suicide capability construct. The GCSQ is a reliable measure of this construct, though its pain tolerance scale requires modification.
Ab initio molecular orbital calculations of DNA radical ions. 5. Scaling of calculated electron affinities and ionization potentials to experimental values

Ab initio molecular orbital calculations of the electron affinities (EAs) and ionization potentials (IPs) of the DNA bases are presented in this work. Comparisons of calculated and experimental values are made for a series of compounds of size and/or structure similar to the DNA bases. Excellent correlations between calculated and experimental values are found for both Koopmans EAs at the 6-31G[sup *] and D95v levels and calculated vertical EAs of the model compounds. Several basis sets are considered: 6-31G[sup *], 6-31+G(d), and D95v. Calculations at 6-31G[sup *] and 6-31+G(d) using both ROHF and ROMP2 theories show a consistent difference between calculated vertical and adiabatic EAs. This allows for a good estimate of DNA base adiabatic EAs. i.e., -0.7, -0.3, 0.2, 0.3, and 0.4 eV; from the vertical EAs -1.23, -0.74, -0.40, -0.32, and -0.19 eV for G, A, C, T, and U respectively. While EAs must be scaled, we find that Koopmans IPs calculated at the simple 3-21G level predict vertical IPs of the DNA bases with only a 0.15 eV average absolute deviation from the experimentally reported values and calculations at MP2/6-31+G(d)//6-31G[sup *] for the adiabatic ionization potentials of the DNA bases are all within 0.1 eV of experiment.more » 41 refs., 2 figs., 5 tabs. « less
Evaluation of POI Recommendation System Beyond Accuracy: Diversity, Explainability and Computation Cost

The Point of Interest (POI) recommendation systems are widely used in many applications. Most researches are devoted to increase accuracy. However, in the real scenario, user s would be more satisfied with the recommendation result if it contains diversified POIs or explanation can be given. Besides, the number of users and check-ins are large and increasing quickly, which requires much computation resource to handle. Thus, the diversity, interpretability and computation cost of POI recommendation system is crucial for the industry field. In this paper, we evaluate several existing POI recommendation systems, such as USG, LFBCA, and MGMPFM, on Yelp dataset in following aspect: (1) diversity: we analyze the diversity of recommendation result list in categorical and geographical aspect; (2) explainability: we evaluate fidelity of each POI recommendation system, which is the ratio of explainable items in recommendation list; (3) computation cost: we measure the execution time and the peak consumed memory when running models. We describe several essential findings from the evaluation, based on which the quality of the POI recommendation system could be improved.
Electron microscopy in renal pathology: overall applications and guidelines for tissue, collection, preparation, and stains

ABSTRACT Electron microscopy is a mainstay in the analysis of renal biopsies, where it is typically employed in a correlative fashion along with light and immunofluorescence microscopy. Despite the development of a growing armamentarium of molecular and biochemical analytic methods as well as new immunostains with a widening panel of immunoreactants, electron microscopy remains crucial to the diagnosis of a number of disorders involving the renal glomerulus, vasculature, and tubulointerstitial compartment. The number of renal biopsies continues to grow and the indications for these biopsies continue expanding together with our understanding of disease processes. Proper collection of biopsies and careful analysis of data emanating from diagnostic modalities, clinical information, imaging, gross and microscopic tissue analysis, including a wide range of ancillary studies, represent the essential paradigm for generating detailed diagnoses with clinical significance. This communication offers a guide to the pre-analytic and analytic process for renal biopsy examination, discusses diagnostic keys and pitfalls for an important category of renal diseases (immune complex disorders), and provides an introduction to a useful adjunct diagnostic method (ultrastructural immunolabeling). Renal pathologists should render expert diagnoses that guide patient management, provide prognostic information and lead to targeted new therapeutic interventions that are currently available.
Geometric Parameters in Nucleic Acids: Sugar and Phosphate Constituents

A statistical survey of the torsion angles, bond angles, and bond lengths in the sugar and phosphate groups of well-refined mononucleoside, mononucleotide, dinucleoside monophosphate, and trinucleoside diphosphate crystal structures contained in the Cambridge Structural Database and the Nucleic Acid Database is reported. The mean values of the geometrical parameters in these structures and their estimated standard deviations are separated according to their chemistry and conformation. These new parameters serve as a basis for a dictionary of standard nucleic acid geometry.
IL-17A–Secreting Memory γδ T Cells Play a Pivotal Role in Sensitization and Development of Hypersensitivity Pneumonitis

Key Points IL-17A is produced mainly by γδ T cells in hypersensitivity pneumonitis (HP). The IL-17A/chemokines/CD11b+ alveolar macrophage axis underlies development of HP. Memory responses of γδ T cells are involved in sensitization and development of HP. Visual Abstract Hypersensitivity pneumonitis (HP) typically presents with interstitial inflammation and granulomas induced by an aberrant immune response to inhaled Ags in sensitized individuals. Although IL-17A is involved in the development of HP, the cellular sources of IL-17A and the mechanisms by which IL-17A contributes to granuloma formation remain unclear. Recent studies report that γδ T cells produce IL-17A and exhibit memory properties in various diseases. Therefore, we focused on IL-17A–secreting memory γδ T cells in the sensitization phase and aimed to elucidate the mechanisms by which IL-17A contributes to granuloma formation in HP. We induced a mouse model of HP using pigeon dropping extract (PDE) in wild-type and IL-17A knockout (IL-17A−/−) mice. IL-17A−/− mice exhibited reduced granulomatous areas, attenuated aggregation of CD11b+ alveolar macrophages, and reduced levels of CCL2, CCL4, and CCL5 in the bronchoalveolar lavage fluid. Among IL-17A+ cells, more γδ T cells than CD4+ cells were detected after intranasal PDE administration. Interestingly, the expansion of IL-17A–secreting Vγ4+ or Vγ1−Vγ4− cells of convalescent mice was enhanced in response to the sensitizing Ag. Additionally, coculture of macrophages with PDE and Vγ4+ cells purified from PDE-exposed convalescent mice produced significantly more IL-17A than coculture with Vγ4+ cells from naive mice. Our findings demonstrate that in the sensitization phase of HP, IL-17A–secreting memory γδ T cells play a pivotal role. Furthermore, we characterized the IL-17A/CCL2, CCL4, CCL5/CD11b+ alveolar macrophage axis, which underlies granuloma formation in HP. These findings may lead to new clinical examinations or therapeutic targets for HP.
Adolescents perception on parent child conflict and its resolution: A qualitative study

Adolescent period is marked by strain in relationship and misunderstanding with parents. Understanding perception of adolescents about this issue is necessary for conflict resolution. The current study is aimed at exploring adolescent perception on nature of parent child conflict and the strategies for resolving such problems. A qualitative study was conducted among 150 (60 females & 90 males) college students in late adolescence period. Three colleges were conveniently selected in Kathmandu. Semi-structured questions were asked to the participant adolescents. They were asked to list on common issues or problems with their parents and type of parental behavior which would facilitate in resolving conflict. Data was analyzed using thematic analysis method. Seven main themes emerged in the sources of conflict in parent adolescent relationship. They are lack of warmth, acceptance and understanding, restriction in personal freedom and imposing control, comparison and discrimination, conflicting messages (double bind communication), unduly focus on adolescents’ negative behavior, over emphasis on studies and unreasonable aggression/ lack of trust. Regarding strategies to mitigate conflict, participants’ suggestion for parents were analyzed into themes of listening and empathic understanding, freedom, flexibility, forgiveness and not discriminating. These themes on sources of conflict and strategies in resolution could be utilized by parents and adolescents in building healthy relationship.
The mRNA-Binding Protein RBM3 Regulates Activity Patterns and Local Synaptic Translation in Cultured Hippocampal Neurons

The activity and the metabolism of the brain change rhythmically during the day/night cycle. Such rhythmicity is also observed in cultured neurons from the suprachiasmatic nucleus, which is a critical center in rhythm maintenance. However, this issue has not been extensively studied in cultures from areas less involved in timekeeping, as the hippocampus. Using neurons cultured from the hippocampi of newborn rats (both male and female), we observed significant time-dependent changes in global activity, in synaptic vesicle dynamics, in synapse size, and in synaptic mRNA amounts. A transcriptome analysis of the neurons, performed at different times over 24 h, revealed significant changes only for RNA-binding motif 3 (Rbm3). RBM3 amounts changed, especially in synapses. RBM3 knockdown altered synaptic vesicle dynamics and changed the neuronal activity patterns. This procedure also altered local translation in synapses, albeit it left the global cellular translation unaffected. We conclude that hippocampal cultured neurons can exhibit strong changes in their activity levels over 24 h, in an RBM3-dependent fashion. SIGNIFICANCE STATEMENT This work is important in several ways. First, the discovery of relatively regular activity patterns in hippocampal cultures implies that future studies using this common model will need to take the time parameter into account, to avoid misinterpretation. Second, our work links these changes in activity strongly to RBM3, in a fashion that is independent of the canonical clock mechanisms, which is a very surprising observation. Third, we describe here probably the first molecule (RBM3) whose manipulation affects translation specifically in synapses, and not at the whole-cell level. This is a key finding for the rapidly growing field of local synaptic translation.
Mosaic Evolution of the Phosphopantothenate Biosynthesis Pathway in Bacteria and Archaea

Abstract Phosphopantothenate is a precursor to synthesis of coenzyme A, a molecule essential to many metabolic pathways. Organisms of the archaeal phyla were shown to utilize a different phosphopantothenate biosynthetic pathway from the eukaryotic and bacterial one. In this study, we report that symbiotic bacteria from the group Candidatus poribacteria present enzymes of the archaeal pathway, namely pantoate kinase and phosphopantothenate synthetase, mirroring what was demonstrated for Picrophilus torridus, an archaea partially utilizing the bacterial pathway. Our results not only support the ancient origin of the coenzyme A pathway in the three domains of life but also highlight its complex and dynamic evolution. Importantly, this study helps to improve protein annotation for this pathway in the C. poribacteria group and other related organisms.
Effects of a community health worker delivered intervention on maternal depressive symptoms in rural Tanzania

Abstract Maternal depression affects one in four women in sub-Saharan Africa, yet evidence on effective and scalable interventions is limited. Our objective was to evaluate the effect of a community health worker (CHW) delivered home visit responsive stimulation, health and nutrition intervention, and conditional cash transfers (CCTs) for antenatal care and child growth monitoring attendance on maternal depressive symptoms. We conducted a cluster-randomized controlled trial in 12 villages in rural Ifakara, Tanzania (September 2017 to May 2019). Study villages were randomly assigned to one of three arms: (1) CHW, (2) CHW + CCT and (3) Control. Pregnant women and mothers with a child <12 months were enrolled. Maternal depressive symptoms were assessed using a Tanzanian-adapted version of the Hopkins Symptoms Checklist-25 (HSCL-25) after 18 months of follow-up. We used linear mixed-effects models to estimate intervention effects on HSCL-25 scores. Results showed that the CHW intervention significantly reduced HSCL-25 scores as compared with control [unadjusted mean difference (MD) −0.31, 95% confidence interval (CI) −0.47, −0.15]. The CHW + CCT intervention also appeared to lower HSCL-25 scores (MD −0.17, 95% CI −0.33, −0.01), but results were not statistically significant. Our findings showed that a low-intensity CHW-delivered home visit responsive stimulation, health and nutrition intervention, which did not explicitly aim to improve mental health, reduced maternal depressive symptoms, though the precise mechanisms of action remain unknown. CCTs for antenatal care and child growth monitoring appeared to provide limited to no additional benefit. Community-based integrated interventions that broadly consider maternal and child health, development and well-being have the potential to promote maternal mental health in rural Tanzania and similar settings.
Dimensions of self-reported listening effort and fatigue on a digits-in-noise task, and association with baseline pupil size and performance accuracy

Abstract Objective Pupillometry is sensitive to cognitive resource allocation and has been used as a potential measure of listening-related effort and fatigue. We investigated associations between peak pupil diameter, pre-stimulus pupil diameter, performance on a listening task, and the dimensionality of self-reported outcomes (task-related listening effort and fatigue). Design Pupillometry was recorded while participants performed a speech-in-noise task. Participants rated their experience of listening effort and fatigue using the NASA-Task Load Index (NASA-TLX) and the Visual Analogue Scale of Fatigue (VAS-F), respectively. The dimensionality of the NASA-TLX and the VAS-F was investigated using factor analysis. Study sample 82 participants with either normal hearing or aided hearing impairment (age range: 55–85 years old, 43 male). Results Hierarchal linear regression analyses suggested that pre-stimulus pupil diameter predicts a dimension of self-reported fatigue, which we interpreted as tiredness/drowsiness, and listening task performance when controlling for hearing level and age: Larger pre-stimulus pupil diameter was associated with less tiredness/drowsiness and better task performance. Conclusion Pre-stimulus pupil diameter is a potential index of listening fatigue associated with speech processing in challenging listening conditions. To our knowledge, this is the first investigation of the associations between pre-stimulus pupil diameter and self-reported ratings of listening effort and fatigue.
Special collection: The Rise of Ticks and Tick-Borne Diseases Discovery and Surveillance of Tick-Borne Pathogens

Within the past 30 yr molecular assays have largely supplanted classical methods for detection of tick-borne agents. Enhancements provided by molecular assays, including speed, throughput, sensitivity, and specificity, have resulted in a rapid increase in the number of newly characterized tick-borne agents. The use of unbiased high throughput sequencing has enabled the prompt identification of new pathogens and the examination of tick microbiomes. These efforts have led to the identification of hundreds of new tick-borne agents in the last decade alone. However, little is currently known about the majority of these agents beyond their phylogenetic classification. Our article outlines the primary methods involved in tick-borne agent discovery and the current status of our understanding of tick-borne agent diversity.
A conserved role for AMP-activated protein kinase in NGLY1 deficiency

Mutations in human N-glycanase 1 (NGLY1) cause the first known congenital disorder of deglycosylation (CDDG). Patients with this rare disease, which is also known as NGLY1 deficiency, exhibit global developmental delay and other phenotypes including neuropathy, movement disorder, and constipation. NGLY1 is known to regulate proteasomal and mitophagy gene expression through activation of a transcription factor called "nuclear factor erythroid 2-like 1" (NFE2L1). Loss of NGLY1 has also been shown to impair energy metabolism, but the molecular basis for this phenotype and its in vivo consequences are not well understood. Using a combination of genetic studies, imaging, and biochemical assays, here we report that loss of NGLY1 in the visceral muscle of the Drosophila larval intestine results in a severe reduction in the level of AMP-activated protein kinase α (AMPKα), leading to energy metabolism defects, impaired gut peristalsis, failure to empty the gut, and animal lethality. Ngly1–/– mouse embryonic fibroblasts and NGLY1 deficiency patient fibroblasts also show reduced AMPKα levels. Moreover, pharmacological activation of AMPK signaling significantly suppressed the energy metabolism defects in these cells. Importantly, the reduced AMPKα level and impaired energy metabolism observed in NGLY1 deficiency models are not caused by the loss of NFE2L1 activity. Taken together, these observations identify reduced AMPK signaling as a conserved mediator of energy metabolism defects in NGLY1 deficiency and suggest AMPK signaling as a therapeutic target in this disease.
Development of a Physiologically Based Pharmacokinetic Model for Prediction of Ethanol Concentration-Time Profile in Different Organs.

AIMS A physiologically based pharmacokinetic (PBPK) modeling approach was used to simulate the concentration-time profile of ethanol (EtOH) in stomach, duodenum, plasma and other tissues upon consumption of beer and whiskey under fasted and fed conditions. METHODS A full PBPK model was developed for EtOH using the advanced dissolution, absorption and metabolism (ADAM) model fully integrated into the Simcyp Simulator® 15 (Simcyp Ltd., Sheffield, UK). The prediction performance of the developed model was verified and the EtOH concentration-time profile in different organs was predicted. RESULTS Simcyp simulation showed ≤ 2-fold difference in values of EtOH area under the concentration-time curve (AUC) in stomach and duodenum as compared to the observed values. Moreover, the simulated EtOH maximum concentration (Cmax), time to reach Cmax (Tmax) and AUC in plasma were comparable to the observed values. We showed that liver is exposed to the highest EtOH concentration, faster than other organs (Cmax = 839.50 mg/L and Tmax = 0.53 h), while brain exposure of EtOH (AUC = 1139.43 mg·h/L) is the highest among all other organs. Sensitivity analyses (SAs) showed direct proportion of EtOH rate and extent of absorption with administered EtOH dose and inverse relationship with gastric emptying time (GE) and steady-state volume of distribution (Vss). CONCLUSIONS The current PBPK model approach might help with designing in vitro experiments in the area of alcohol organ damage or alcohol-drug interaction studies.