Miracle-dz/UniFAR-FTUs huggingface dataset:
Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale: a meta-analysis of genome-wide association studies

Background Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains. Method We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons). Results One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (p discovery = 3.82 × 10−8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (p discovery+replication = 1.10 × 10−6) with evidence of heterogeneity. Conclusions Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.
How Effective is Physical Therapy for Common Low Back Pain Diagnoses?: A Multivariate Analysis of 4597 Patients

Study Design. A retrospective review. Objective. The aim of this study is to evaluate whether the treatment of low back pain with physical therapy results in clinically significant improvements in patient-reported pain and functional outcomes. Summary of Background Data. Low back pain is a major cause of morbidity and disability in health care. Previous studies have found poor efficacy for surgery in the absence of specific indications. A variety of nonoperative treatments are available; however, there is scant evidence to guide the practitioner as to the efficacy of these treatments. Methods. Four thousand five hundred ninety-seven patients who underwent physical therapy for the nonoperative treatment of low back pain were included. The primary outcome measures were pre-and post-treatment scores on the Oswestry Disability Index (ODI), Numeric Pain Rating Scale (NPRS) during activity, and NPRS during rest. Previously published thresholds for minimal clinically important difference (MCID) were used to determine the proportion of patients meeting MCID for each of our outcomes. Patients with starting values below the MCID for each variable were excluded from analysis. Logistic regression analysis was used to determine patient risk factors predictive of treatment failure. Results. About 28.5% of patients met the MCID for improvement in ODI. Presence of night symptoms, obesity, and smoking were predictors of treatment failure for ODI. Fifty-nine percent of patients met the MCID for improvement in resting NPRS, with a history of venous thromboembolism, night symptoms, psychiatric disease, workers’ compensation status, smoking, and obesity predictive of treatment failure. Sixty percent of patients met the MCID for improvement in activity NPRS, with night symptoms, workers’ compensation status, and smoking predictive of treatment failure. Conclusion. We observed that a substantial percentage of the population did not meet MCID for pain and function following treatment of low back pain with physical therapy. Common risk factors for treatment failure included smoking and presence of night symptoms. Level of Evidence: 4
Anaerobic Oxidization of Methane in a Minerotrophic Peatland: Enrichment of Nitrite-Dependent Methane-Oxidizing Bacteria

ABSTRACT The importance of anaerobic oxidation of methane (AOM) as a methane sink in freshwater systems is largely unexplored, particularly in peat ecosystems. Nitrite-dependent anaerobic methane oxidation (n-damo) was recently discovered and reported to be catalyzed by the bacterium “Candidatus Methylomirabilis oxyfera,” which is affiliated with the NC10 phylum. So far, several “Ca. Methylomirabilis oxyfera” enrichment cultures have been obtained using a limited number of freshwater sediments or wastewater treatment sludge as the inoculum. In this study, using stable isotope measurements and porewater profiles, we investigated the potential of n-damo in a minerotrophic peatland in the south of the Netherlands that is infiltrated by nitrate-rich ground water. Methane and nitrate profiles suggested that all methane produced was oxidized before reaching the oxic layer, and NC10 bacteria could be active in the transition zone where countergradients of methane and nitrate occur. Quantitative PCR showed high NC10 bacterial cell numbers at this methane-nitrate transition zone. This soil section was used to enrich the prevalent NC10 bacteria in a continuous culture supplied with methane and nitrite at an in situ pH of 6.2. An enrichment of nitrite-reducing methanotrophic NC10 bacteria was successfully obtained. Phylogenetic analysis of retrieved 16S rRNA and pmoA genes showed that the enriched bacteria were very similar to the ones found in situ and constituted a new branch of NC10 bacteria with an identity of less than 96 and 90% to the 16S rRNA and pmoA genes of “Ca. Methylomirabilis oxyfera,” respectively. The results of this study expand our knowledge of the diversity and distribution of NC10 bacteria in the environment and highlight their potential contribution to nitrogen and methane cycles.
Dendritic small conductance calcium-activated potassium channels activated by action potentials suppress EPSPs and gate spike-timing dependent synaptic plasticity

Small conductance calcium-activated potassium channels (SK channels) are present in spines and can be activated by backpropagating action potentials (APs). This suggests they may play a critical role in spike-timing dependent synaptic plasticity (STDP). Consistent with this idea, EPSPs in both cortical and hippocampal pyramidal neurons were suppressed by preceding APs in an SK-dependent manner. In cortical pyramidal neurons EPSP suppression by preceding APs depended on their precise timing as well as the distance of activated synapses from the soma, was dendritic in origin, and involved SK-dependent suppression of NMDA receptor activation. As a result SK channel activation by backpropagating APs gated STDP induction during low-frequency AP-EPSP pairing, with both LTP and LTD absent under control conditions but present after SK channel block. These findings indicate that activation of SK channels in spines by backpropagating APs plays a key role in regulating both EPSP amplitude and STDP induction.
The Role of Co-chaperones in Synaptic Proteostasis and Neurodegenerative Disease

Synapses must be preserved throughout an organism's lifespan to allow for normal brain function and behavior. Synapse maintenance is challenging given the long distances between the termini and the cell body, reliance on axonal transport for delivery of newly synthesized presynaptic proteins, and high rates of synaptic vesicle exo- and endocytosis. Hence, synapses rely on efficient proteostasis mechanisms to preserve their structure and function. To this end, the synaptic compartment has specific chaperones to support its functions. Without proper synaptic chaperone activity, local proteostasis imbalances lead to neurotransmission deficits, dismantling of synapses, and neurodegeneration. In this review, we address the roles of four synaptic chaperones in the maintenance of the nerve terminal, as well as their genetic links to neurodegenerative disease. Three of these are Hsp40 co-chaperones (DNAJs): Cysteine String Protein alpha (CSPα; DNAJC5), auxilin (DNAJC6), and Receptor-Mediated Endocytosis 8 (RME-8; DNAJC13). These co-chaperones contain a conserved J domain through which they form a complex with heat shock cognate 70 (Hsc70), enhancing the chaperone's ATPase activity. CSPα is a synaptic vesicle protein known to chaperone the t-SNARE SNAP-25 and the endocytic GTPase dynamin-1, thereby regulating synaptic vesicle exocytosis and endocytosis. Auxilin binds assembled clathrin cages, and through its interactions with Hsc70 leads to the uncoating of clathrin-coated vesicles, a process necessary for the regeneration of synaptic vesicles. RME-8 is a co-chaperone on endosomes and may have a role in clathrin-coated vesicle endocytosis on this organelle. These three co-chaperones maintain client function by preserving folding and assembly to prevent client aggregation, but they do not break down aggregates that have already formed. The fourth synaptic chaperone we will discuss is Heat shock protein 110 (Hsp110), which interacts with Hsc70, DNAJAs, and DNAJBs to constitute a disaggregase. Hsp110-related disaggregase activity is present at the synapse and is known to protect against aggregation of proteins such as α-synuclein. Congruent with their importance in the nervous system, mutations of these co-chaperones lead to familial neurodegenerative disease. CSPα mutations cause adult neuronal ceroid lipofuscinosis, while auxilin mutations result in early-onset Parkinson's disease, demonstrating their significance in preservation of the nervous system.
Providing a Foundation for Analysis of Volatile Data Stores

Current threats against typical computer systems demonstrate a need for forensic analysis of memory-resident data in addition to the conventional static analysis common today. Â Certain attacks and types of malware exist solely in memory and leave little or no evidentiary information on nonvolatile stores such as a hard disk drive. Â The desire to preserve system state at the time of response may even warrant memory acquisition independent of perceived threats and the ability to analyze the acquired duplicate. Â Tools capable of duplicating various types of volatile data stores are becoming widely available. Â Once the data store has been duplicated, current forensic procedures have no method for extrapolating further useful information from the duplicate. Â This paper is focused on providing the groundwork for performing forensic investigations on the data that is typically stored in a volatile data store, such as system RAM. It is intended that, when combined with good acquisition techniques, it will be shown that it is possible to obtain more post incident response information along with less impact to potential evidence when compared to typical incident response procedures. Â
Contribution to digital representation of materials subjected to thermomechanical processing

Development of software tools, which allow connection between phenomena occurring in materials in various length scales, is presented in the paper. Multiscale CAFE approach, which combines cellular automata (CA) and finite element (FE) methods, is selected for modeling. In this approach FE method describes material behavior in the macro scale, while CA method simulates micro and mezo scale phenomena. Capability of accounting for these phenomena, which are either stochastic or discontinuous or both, is the main advantage of the cellular automata. The objective of the present work is to improve qualitative and quantitative accuracy of the model. Two phenomena are considered. Micro shear band initiation and propagation is the first and recrystallization is the second. The main emphasis is put on improvement of the transition rules, which describe the state of the material at the grain level. Beyond this, the common features of both models are distinguished to develop better numerical tool, which will allow to combine CA with the FE simulations of real processes. Finally, results of the CAFE modeling of the polycrystalline microstructure deformation and recrystallization are presented.
Association study of folate-related enzymes (MTHFR, MTR, MTRR) genetic variants with non-obstructive male infertility in a Polish population

Spermatogenesis is a process where an important contribution of genes involved in folate-mediated one-carbon metabolism is observed. The aim of the present study was to investigate the association between male infertility and the MTHFR (677C > T; 1298A > C), MTR (2756A > G) and MTRR (66A > G) polymorphisms in a Polish population. No significant differences in genotype or allele frequencies were detected between the groups of 284 infertile men and of 352 fertile controls. These results demonstrate that common polymorphisms in folate pathway genes are not major risk factors for non-obstructive male infertility in the Polish population.
Construction of Multiple Choice Questions Before and After An Educational Intervention.

INTRODUCTION Khesar Gyalpo University of Medical Sciences of Bhutan, established in 2014, has ushered in a new era in medical education in Bhutan. Multiple Choice Questions are a common means of written assessment in medical education. METHODS This was a quasi-experimental study conducted at the Faculty of Postgraduate Medicine, KGUMSB, Thimphu in December 2016. A total of 8 MCQs were prepared by four teaching faculties from different fields who had no prior training on construction of MCQs. It was delivered to a group of 16 randomly selected intern doctors. A 2 hours long workshop on construction of MCQs was conducted. After the workshop, the same MCQs were modified according to standard guidelines on developing MCQs and were tested in the same group of intern doctors. An analysis on the performance, difficulty factor, discrimination index and distractor analysis was done on the two sets of MCQs using Microsoft Excel and SPSS 20.0. RESULTS For the pre- and post-workshop questions respectively, the pass percentage was 69.8% (11) and 81.3% (13), difficulty factor was 0.51 and 0.53, discrimination index was 0.59 and 0.47, distractor effectiveness was 83.3% and 74.9%. CONCLUSIONS The workshop on MCQ development apparently seemed highly valuable and effective in changing the learning and performances of medical educators in the development of MCQs.
Reduced Hip Adduction Is Associated With Improved Function After Movement‐Pattern Training in Young People With Chronic Hip Joint Pain

•STUDY DESIGN: Ancillary analysis, time‐controlled randomized clinical trial. •BACKGROUND: Movement‐pattern training (MPT) has been shown to improve function among patients with chronic hip joint pain (CHJP). •OBJECTIVE: To determine the association among treatment outcomes and mechanical factors associated with CHJP. •METHODS: Twenty‐eight patients with CHJP, 18 to 40 years of age, participated in MPT, either immediately after assessment or after a wait‐list period. Movement‐pattern training included task‐specific training to reduce hip adduction motion during functional tasks and hip muscle strengthening. Hip‐specific function was assessed using the Modified Harris Hip Score (MHHS) and Hip disability and Osteoarthritis Outcome Score (HOOS). Three‐dimensional kinematic data were used to quantify hip adduction motion, dynamometry to quantify abductor strength, and magnetic resonance imaging to measure femoral head sphericity using the alpha angle. Paired t tests assessed change from pretreatment to posttreatment. Spearman correlations assessed associations. •RESULTS: There was significant improvement in MHHS and HOOS scores (P≤.02), adduction motion (P = .045), and abductor strength (P = .01) from pretreatment to posttreatment. Reduction in hip adduction motion (r = ‐0.67, P<.01) and lower body mass index (r = ‐0.38, P = .049) correlated with MHHS improvement. Alpha angle and abductor strength change were not correlated with change in MHHS or HOOS scores. •CONCLUSION: After MPT, patients reported improvements in pain and function that were associated with their ability to reduce hip adduction motion during functional tasks. •LEVEL OF EVIDENCE: Therapy, level 2b.
Lymph node segmentation by dynamic programming and active contours.

PURPOSE Enlarged lymph nodes are indicators of cancer staging, and the change in their size is a reflection of treatment response. Automatic lymph node segmentation is challenging, as the boundary can be unclear and the surrounding structures complex. This work communicates a new three-dimensional algorithm for the segmentation of enlarged lymph nodes. METHODS The algorithm requires a user to draw a region of interest (ROI) enclosing the lymph node. Rays are cast from the center of the ROI, and the intersections of the rays and the boundary of the lymph node form a triangle mesh. The intersection points are determined by dynamic programming. The triangle mesh initializes an active contour which evolves to low-energy boundary. Three radiologists independently delineated the contours of 54 lesions from 48 patients. Dice coefficient was used to evaluate the algorithm's performance. RESULTS The mean Dice coefficient between computer and the majority vote results was 83.2%. The mean Dice coefficients between the three radiologists' manual segmentations were 84.6%, 86.2%, and 88.3%. CONCLUSIONS The performance of this segmentation algorithm suggests its potential clinical value for quantifying enlarged lymph nodes.
Presurgical Biomarker Performance in the Detection of Gleason Upgrading in Prostate Cancer

Background: Gleason Score (GS) upgrading is generally considered a trigger for exit to definitive treatment during active surveillance (AS). Predicting the potential for GS upgrading would be of value in assessing AS eligibility. Methods: We assessed the performance of biomarkers in presurgical specimens of expressed prostatic secretion (EPS) in this setting. Results: Although EPS volume, total recovered RNA, and RNA expression biomarkers (TMPRSS2: ERG, PCA3, PSA) have been successful in both biopsy outcome prediction, and in the prediction of upstaging in active surveillance eligible patients, they were unable to predict upgrading in patients eligible for active surveillance under National Comprehensive Cancer Network guidelines. Conclusions: These biomarkers do not improve the prediction of upgrading over indications from standard clinical parameters. Impact: Additional biomarkers will be needed in this area. Cancer Epidemiol Biomarkers Prev; 25(12); 1643–5. ©2016 AACR.
Identification of sucA, Encoding β-Fructofuranosidase, in Rhizopus microsporus

Rhizopus microsporus NBRC 32995 was found to hydrolyze fructooligosaccharides (FOS), as well as sucrose, almost completely into monosaccharides through the production of sufficient amounts of organic acids, indicating that the complete hydrolysis of FOS was caused by the secretion of β-fructofuranosidase from fungal cells. Thus, the sucA gene, encoding a β-fructofuranosidase, was amplified by degenerate PCR, and its complete nucleotide sequence was determined. The total length of the sucA gene was 1590 bp, and the SucA protein of R. microsporus NBRC 32995 belonged to clade VIa, which also contains Rhizopus delemar and is closely related to Saccharomycotina, a subdivision of the Ascomycota.
Natural Compound Histone Deacetylase Inhibitors (HDACi): Synergy with Inflammatory Signaling Pathway Modulators and Clinical Applications in Cancer

The remarkable complexity of cancer involving multiple mechanisms of action and specific organs led researchers Hanahan and Weinberg to distinguish biological capabilities acquired by cancer cells during the multistep development of human tumors to simplify its understanding. These characteristic hallmarks include the abilities to sustain proliferative signaling, evade growth suppressors, resist cell death, enable replicative immortality, induce angiogenesis, activate invasion and metastasis, avoid immune destruction, and deregulate cellular energetics. Furthermore, two important characteristics of tumor cells that facilitate the acquisition of emerging hallmarks are tumor-promoting inflammation and genome instability. To treat a multifactorial disease such as cancer, a combination treatment strategy seems to be the best approach. Here we focus on natural histone deacetylase inhibitors (HDACi), their clinical uses as well as synergies with modulators of the pro-inflammatory transcription factor signaling pathways.
Experimental validation of the Eclipse AAA algorithm

The present study evaluates the performance of a newly released photon‐beam dose calculation algorithm that is incorporated into an established treatment planning system (TPS). We compared the analytical anisotropic algorithm (AAA) factory‐commissioned with “golden beam data” for Varian linear accelerators with measurements performed at two institutions using 6‐MV and 15‐MV beams. The TG‐53 evaluation regions and criteria were used to evaluate profiles measured in a water phantom for a wide variety of clinically relevant beam geometries. The total scatter factor (TSF) for each of these geometries was also measured and compared against the results from the AAA. At one institute, TLD measurements were performed at several points in the neck and thoracic regions of a Rando phantom; at the other institution, ion chamber measurements were performed in a CIRS inhomogeneous phantom. The phantoms were both imaged using computed tomography (CT), and the dose was calculated using the AAA at corresponding detector locations. Evaluation of measured relative dose profiles revealed that 97%, 99%, 97%, and 100% of points at one institute and 96%, 88%, 89%, and 100% of points at the other institution passed TG‐53 evaluation criteria in the outer beam, penumbra, inner beam, and buildup regions respectively. Poorer results in the inner beam regions at one institute are attributed to the mismatch of the measured profiles at shallow depths with the “golden beam data. ” For validation of monitor unit (MU) calculations, the mean difference between measured and calculated TSFs was less than 0.5%; test cases involving physical wedges had, in general, differences of more than 1%. The mean difference between point measurements performed in inhomogeneous phantoms and Eclipse was 2.1% (5.3% maximum) and all differences were within TG‐53 guidelines of 7%. By intent, the methods and evaluation techniques were similar to those in a previous investigation involving another convolution–superposition photon‐beam dose calculation algorithm in another TPS, so that the current work permitted an independent comparison between the two algorithms for which results have been provided. PACS number: 87.53. Dq