Takshan/R1 huggingface dataset:
Comparative evaluation of MRSA nasal colonization epidemiology in the urban and rural secondary school community of Kurdistan, Iraq.

BACKGROUND: To study the nasal carriage rate of Staphylococcus aureus (S. aureus) (including methicillin-resistant strains) in secondary school community of the urban and rural districts of the Kurdistan region of Iraq, a cross-sectional population based survey was carried out in the city Duhok and rural areas of Amedya, Akre and Zakho. METHODS: Nasal swabs were obtained from nostrils of 509 students aged 14-23 years. Resistance to methicillin was assessed by Kirby-Bauer disk diffusion and agar dilution assay. Vancomycin sensitivity was also tested on Muller-Hinton agar. RESULTS: It was found that the frequency of overall S. aureus nasal carriage (SANC) was 17.75% (90/509, CI95, 14.58-21.42%). In urban areas, the carriage rate was 20.59% (49/239, CI95, 15.64-26.29%), whereas it was 15.24% (41/270, CI95, 11.17-20.10%) in rural districts. The frequency of methicillin-resistant S. aureus (MRSA) among the isolated strains was found to be 2.04% (1/49) and 21.95% (9/41) in urban and rural areas respectively. It was found that in urban residents, the odd ratio (OR) of acquiring SANC was 1.44 (CI95, 0.91-2.27%) and risk ratio (RR) was at least 1.35 (CI95, 0.92-1.96%) while OR decreased to 0.12 (CI95, 0.01-0.96%) for MRSA carriage. Hence, the S. aureus carriage rate was higher in urban districts compared to rural areas while more MRSA were found in rural areas compared to urban districts. All studied strains were sensitive to vancomycin. CONCLUSION: This study provided baseline information for S. aureus nasal colonization in the region. Also, it showed that living in rural areas increased the odds of MRSA colonization. More attention should be paid to control MRSA colonization in rural communities.
Imaging of glia activation in people with primary lateral sclerosis.

Background: Glia activation is thought to contribute to neuronal damage in several neurodegenerative diseases based on preclinical and human post-mortem studies, but its role in primary lateral sclerosis (PLS) is unknown. Objectives: To localize and measure glia activation in people with PLS compared to healthy controls (HC). Methods: Ten participants with PLS and ten age-matched HCs underwent simultaneous magnetic resonance (MR) and proton emission tomography (PET). The radiotracer [11C]-PBR28 was used to obtain PET-based measures of 18 kDa translocator protein (TSPO) expression, a marker of activated glial cells. MR techniques included a structural sequence to measure cortical thickness and diffusion tensor imaging (DTI) to assess white matter integrity. Results: PET data showed increased [11C]-PBR28 uptake in anatomically-relevant motor regions which co-localized with areas of regional gray matter atrophy and decreased subcortical fractional anisotropy. Conclusions: This study supports a link between glia activation and neuronal degeneration in PLS, and suggests that these disease mechanisms can be measured in vivo in PLS. Future studies are needed to determine the longitudinal changes of these imaging measures and to clarify if MR-PET with [11C]-PBR28 can be used as a biomarker for drug development in the context of clinical trials for PLS.
The T-cell leukemia associated ribosomal RPL10 R98S mutation enhances JAK-STAT signaling.

Several somatic ribosome defects have recently been discovered in cancer, yet their oncogenic mechanisms remain poorly understood. Here we investigated the pathogenic role of the recurrent R98S mutation in ribosomal protein L10 (RPL10-R98S) found in T-ALL. The JAK-STAT signaling pathway is a critical controller of cellular proliferation and survival. A proteome screen revealed overexpression of several Jak-Stat signaling proteins in engineered RPL10-R98S mouse lymphoid cells, which we confirmed in hematopoietic cells from transgenic Rpl10-R98S mice and T-ALL xenograft samples. RPL10-R98S expressing cells displayed JAK-STAT pathway hyper-activation upon cytokine stimulation, as well as increased sensitivity to clinically used JAK-STAT inhibitors like pimozide. A mutually exclusive mutation pattern between RPL10-R98S and JAK-STAT mutations in T-ALL patients further suggests that RPL10-R98S functionally mimics JAK-STAT activation. Mechanistically, besides transcriptional changes, RPL10-R98S caused reduction of apparent programmed ribosomal frameshifting at several ribosomal frameshift signals in mouse and human Jak-Stat genes, as well as decreased Jak1 degradation. Of further medical interest, RPL10-R98S cells showed reduced proteasome activity and enhanced sensitivity to clinical proteasome inhibitors. Collectively, we describe modulation of the JAK-STAT cascade as a novel cancer-promoting activity of a ribosomal mutation, and expand the relevance of this cascade in leukemia. Leukemia accepted article preview online, 24 July 2017. doi:10.1038/leu.2017.225.
Efficient initial volume determination from electron microscopy images of single particles.

MOTIVATION: Structural information of macromolecular complexes provides key insights into the way they carry out their biological functions. The reconstruction process leading to the final 3D map requires an approximate initial model. Generation of an initial model is still an open and challenging problem in single-particle analysis. RESULTS: We present a fast and efficient approach to obtain a reliable, low-resolution estimation of the 3D structure of a macromolecule, without any a priori knowledge, addressing the well-known issue of initial volume estimation in the field of single-particle analysis. The input of the algorithm is a set of class average images obtained from individual projections of a biological object at random and unknown orientations by transmission electron microscopy micrographs. The proposed method is based on an initial non-lineal dimensionality reduction approach, which allows to automatically selecting representative small sets of class average images capturing the most of the structural information of the particle under study. These reduced sets are then used to generate volumes from random orientation assignments. The best volume is determined from these guesses using a random sample consensus (RANSAC) approach. We have tested our proposed algorithm, which we will term 3D-RANSAC, with simulated and experimental data, obtaining satisfactory results under the low signal-to-noise conditions typical of cryo-electron microscopy. AVAILABILITY: The algorithm is freely available as part of the Xmipp 3.1 package [http://xmipp.cnb.csic.es]. CONTACT: jvargas@cnb.csic.es SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Cwp2 from Clostridium difficile exhibits an extended three domain fold and cell adhesion in vitro.

Colonization of the gut by Clostridium difficile requires the adhesion of the bacterium to host cells. A range of cell surface located factors have been linked to adhesion including the S-layer protein LMW SLP and the related protein Cwp66. As well as these proteins, the S-layer of C. difficile may contain many others. One such protein is Cwp2. Here, we demonstrate the production of a C. difficile strain 630 cwp2 knockout mutant and assess the effect on the bacterium. The mutant results in increased TcdA (toxin A) release and impaired cellular adherence in vitro. We also present the extended three domain structure of the 'functional' region of Cwp2, consisting of residues 29-318 at 1.9 Å, which is compared to that of LMW SLP and Cwp8. The adhesive properties of Cwp2 and LMW SLP, which are likely to be shared by Cwp8, are predicted to be mediated by the variable loop regions in domain 2. DATABASES: Structural data are available in the PDB under the accession number 5NJL.
The molecular structure of the glycoside hydrolase domain of Cwp19 from Clostridium difficile.

Clostridium difficile is a burden to healthcare systems around the world, causing tens of thousands of deaths annually. The S-layer of the bacterium, a layer of protein found of the surface of cells, has received a significant amount of attention over the past two decades as a potential target to combat the growing threat presented by C. difficile infections. The S-layer contains a wide range of proteins, each of which possesses three cell wall-binding domains, while many also possess a "functional" region. Here, we present the high resolution structure of the functional region of one such protein, Cwp19 along with preliminary functional characterisation of the predicted glycoside hydrolase. Cwp19 has a TIM barrel fold and appears to possess a high degree of substrate selectivity. The protein also exhibits peptidoglycan hydrolase activity, an order of magnitude slower than that of lysozyme and is the first member of glycoside hydrolase-like family 10 to be characterised. This research goes some way to understanding the role of Cwp19 in the S-layer of C. difficile. DATABASE: Structural data are available in the PDB under the accession numbers 5OQ2 and 5OQ3.
The NF1 somatic mutational landscape in sporadic human cancers.

BACKGROUND: Neurofibromatosis type 1 (NF1: Online Mendelian Inheritance in Man (OMIM) #162200) is an autosomal dominantly inherited tumour predisposition syndrome. Heritable constitutional mutations in the NF1 gene result in dysregulation of the RAS/MAPK pathway and are causative of NF1. The major known function of the NF1 gene product neurofibromin is to downregulate RAS. NF1 exhibits variable clinical expression and is characterized by benign cutaneous lesions including neurofibromas and café-au-lait macules, as well as a predisposition to various types of malignancy, such as breast cancer and leukaemia. However, acquired somatic mutations in NF1 are also found in a wide variety of malignant neoplasms that are not associated with NF1. MAIN BODY: Capitalizing upon the availability of next-generation sequencing data from cancer genomes and exomes, we review current knowledge of somatic NF1 mutations in a wide variety of tumours occurring at a number of different sites: breast, colorectum, urothelium, lung, ovary, skin, brain and neuroendocrine tissues, as well as leukaemias, in an attempt to understand their broader role and significance, and with a view ultimately to exploiting this in a diagnostic and therapeutic context. CONCLUSION: As neurofibromin activity is a key to regulating the RAS/MAPK pathway, NF1 mutations are important in the acquisition of drug resistance, to BRAF, EGFR inhibitors, tamoxifen and retinoic acid in melanoma, lung and breast cancers and neuroblastoma. Other curiosities are observed, such as a high rate of somatic NF1 mutation in cutaneous melanoma, lung cancer, ovarian carcinoma and glioblastoma which are not usually associated with neurofibromatosis type 1. Somatic NF1 mutations may be critical drivers in multiple cancers. The mutational landscape of somatic NF1 mutations should provide novel insights into our understanding of the pathophysiology of cancer. The identification of high frequency of somatic NF1 mutations in sporadic tumours indicates that neurofibromin is likely to play a critical role in development, far beyond that evident in the tumour predisposition syndrome NF1.
Gray matter atrophy patterns in multiple sclerosis: A 10-year source-based morphometry study.

Objectives: To investigate spatial patterns of gray matter (GM) atrophy and their association with disability progression in patients with early relapsing-remitting multiple sclerosis (MS) in a longitudinal setting. Methods: Brain MRI and clinical neurological assessments were obtained in 152 MS patients at baseline and after 10 years of follow-up. Patients were classified into those with confirmed disability progression (CDP) (n = 85) and those without CDP (n = 67) at the end of the study. An optimized, longitudinal source-based morphometry (SBM) pipeline, which utilizes independent component analysis, was used to identify eight spatial patterns of common GM volume co-variation in a data-driven manner. GM volume at baseline and rates of change were compared between patients with CDP and those without CDP. Results: The identified patterns generally included structurally or functionally related GM regions. No significant differences were detected at baseline GM volume between the sub-groups. Over the follow-up, patients with CDP experienced a significantly greater rate of GM atrophy within two of the eight patterns, after correction for multiple comparisons (corrected p-values of 0.001 and 0.007). The patterns of GM atrophy associated with the development of CDP included areas involved in motor functioning and cognitive domains such as learning and memory. Conclusion: SBM analysis offers a novel way to study the temporal evolution of regional GM atrophy. Over 10 years of follow-up, disability progression in MS is related to GM atrophy in areas associated with motor and cognitive functioning.
Effects of motor rehabilitation on mobility and brain plasticity in multiple sclerosis: a structural and functional MRI study.

BACKGROUND: Rehabilitation seems to promote brain plasticity, but objective measures of efficacy are lacking and there is a limited understanding of the mechanisms underlying functional recovery. OBJECTIVE: To study functional and structural brain changes induced by gait rehabilitation. METHODS: We enrolled MS inpatients (EDSS 4.5-6.5) undergoing a 4-week neurorehabilitation. Several clinical measures were obtained, including: 2-min walk test (2MWT), dynamic gait index (DGI), Berg balance scale (BBS). Furthermore, motor-task functional MRI (fMRI) of plantar dorsiflexion, resting state fMRI, and regional diffusion tensor imaging (DTI) metrics were obtained. All the assessments were performed at baseline (T0), after the end of the rehabilitation period (T1) and 3 months later (T2). RESULTS: Twenty-nine patients were enrolled at T0, 26 at T1, and 16 completed all timepoints. At T1, there was a significant improvement of 2MWT, DGI, and BBS scores, along with a reduced extent of the widespread activation related to the motor task at the fMRI and an increased functional connectivity in the precentral and post-central gyrus, bilaterally. None of these changes were maintained at T2. CONCLUSIONS: Our findings show a short-term beneficial effect of motor rehabilitation on gait performances in MS, accompanied by brain functional reorganization in the sensory-motor network.
Genome-wide distribution comparative and composition analysis of the SSRs in Poaceae.

BACKGROUND: The Poaceae family is of great importance to human beings since it comprises the cereal grasses which are the main sources for human food and animal feed. With the rapid growth of genomic data from Poaceae members, comparative genomics becomes a convinent method to study genetics of diffierent species. The SSRs (Simple Sequence Repeats) are widely used markers in the studies of Poaceae for their high abundance and stability. RESULTS: In this study, using the genomic sequences of 9 Poaceae species, we detected 11,993,943 SSR loci and developed 6,799,910 SSR primer pairs. The results show that SSRs are distributed on all the genomic elements in grass. Hexamer is the most frequent motif and AT/TA is the most frequent motif in dimer. The abundance of the SSRs has a positive linear relationship with the recombination rate. SSR sequences in the coding regions involve a higher GC content in the Poaceae than that in the other species. SSRs of 70-80 bp in length showed the highest AT/GC base ratio among all of these loci. The result shows the highest polymorphism rate belongs to the SSRs ranged from 30 bp to 40 bp. Using all the SSR primers of Japonica, nineteen universal primers were selected and located on the genome of the grass family. The information of SSR loci, the SSR primers and the tools of mining and analyzing SSR are provided in the PSSRD (Poaceae SSR Database, http://biodb.sdau.edu.cn/pssrd/). CONCLUSIONS: Our study and the PSSRD database provide a foundation for the comparative study in the Poaceae and it will accelerate the study on markers application, gene mapping and molecular breeding.
Sex differences in white matter alterations following repetitive subconcussive head impacts in collegiate ice hockey players.

Objective: Repetitive subconcussive head impacts (RSHI) may lead to structural, functional, and metabolic alterations of the brain. While differences between males and females have already been suggested following a concussion, whether there are sex differences following exposure to RSHI remains unknown. The aim of this study was to identify and to characterize sex differences following exposure to RSHI. Methods: Twenty-five collegiate ice hockey players (14 males and 11 females, 20.6 ± 2.0 years), all part of the Hockey Concussion Education Project (HCEP), underwent diffusion-weighted magnetic resonance imaging (dMRI) before and after the Canadian Interuniversity Sports (CIS) ice hockey season 2011-2012 and did not experience a concussion during the season. Whole-brain tract-based spatial statistics (TBSS) were used to compare pre- and postseason imaging in both sexes for fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Pre- and postseason neurocognitive performance were assessed by the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT). Results: Significant differences between the sexes were primarily located within the superior longitudinal fasciculus (SLF), the internal capsule (IC), and the corona radiata (CR) of the right hemisphere (RH). In significant voxel clusters (p < 0.05), decreases in FA (absolute difference pre- vs. postseason: 0.0268) and increases in MD (0.0002), AD (0.00008), and RD (0.00005) were observed in females whereas males showed no significant changes. There was no significant correlation between the change in diffusion scalar measures over the course of the season and neurocognitive performance as evidenced from postseason ImPACT scores. Conclusions: The results of this study suggest sex differences in structural alterations following exposure to RSHI. Future studies need to investigate further the underlying mechanisms and association with exposure and clinical outcomes.
Using simultaneous PET/MRI to compare the accuracy of diagnosing frontotemporal dementia by arterial spin labelling MRI and FDG-PET.

Purpose: The clinical utility of FDG-PET in diagnosing frontotemporal dementia (FTD) has been well demonstrated over the past decades. On the contrary, the diagnostic value of arterial spin labelling (ASL) MRI - a relatively new technique - in clinical diagnosis of FTD has yet to be confirmed. Using simultaneous PET/MRI, we evaluated the diagnostic performance of ASL in identifying pathological abnormalities in FTD (FTD) to determine whether ASL can provide similar diagnostic value as FDG-PET. Methods: ASL and FDG-PET images were compared in 10 patients with FTD and 10 healthy older adults. Qualitative and quantitative measures of diagnostic equivalency were used to determine the diagnostic utility of ASL compared to FDG-PET. Sensitivity, specificity, and inter-rater reliability were calculated for each modality from scores of subjective visual ratings and from analysis of regional mean values in thirteen a priori regions of interest (ROI). To determine the extent of concordance between modalities in each patient, individual statistical maps generated from comparison of each patient to controls were compared between modalities using the Jaccard similarity index (JI). Results: Visual assessments revealed lower sensitivity, specificity and inter-rater reliability for ASL (66.67%/62.12%/0.2) compared to FDG-PET (88.43%/90.91%/0.61). Across all regions, ASL performed lower than FDG-PET in discriminating patients from controls (areas under the receiver operating curve: ASL = 0.75 and FDG-PET = 0.87). In all patients, ASL identified patterns of reduced perfusion consistent with FTD, but areas of hypometabolism exceeded hypoperfused areas (group-mean JI = 0.30 ± 0.22). Conclusion: This pilot study demonstrated that ASL can detect similar spatial patterns of abnormalities in individual FTD patients compared to FDG-PET, but its sensitivity and specificity for discriminant diagnosis of a patient from healthy individuals remained unmatched to FDG-PET. Further studies at the individual level are required to confirm the clinical role of ASL in FTD management.
Development and validation of a prognostic model incorporating texture analysis derived from standardised segmentation of PET in patients with oesophageal cancer.

OBJECTIVES: This retrospective cohort study developed a prognostic model incorporating PET texture analysis in patients with oesophageal cancer (OC). Internal validation of the model was performed. METHODS: Consecutive OC patients (n = 403) were chronologically separated into development (n = 302, September 2010-September 2014, median age = 67.0, males = 227, adenocarcinomas = 237) and validation cohorts (n = 101, September 2014-July 2015, median age = 69.0, males = 78, adenocarcinomas = 79). Texture metrics were obtained using a machine-learning algorithm for automatic PET segmentation. A Cox regression model including age, radiological stage, treatment and 16 texture metrics was developed. Patients were stratified into quartiles according to a prognostic score derived from the model. A p-value < 0.05 was considered statistically significant. Primary outcome was overall survival (OS). RESULTS: Six variables were significantly and independently associated with OS: age [HR =1.02 (95% CI 1.01-1.04), p < 0.001], radiological stage [1.49 (1.20-1.84), p < 0.001], treatment [0.34 (0.24-0.47), p < 0.001], log(TLG) [5.74 (1.44-22.83), p = 0.013], log(Histogram Energy) [0.27 (0.10-0.74), p = 0.011] and Histogram Kurtosis [1.22 (1.04-1.44), p = 0.017]. The prognostic score demonstrated significant differences in OS between quartiles in both the development (X(2) 143.14, df 3, p < 0.001) and validation cohorts (X(2) 20.621, df 3, p < 0.001). CONCLUSIONS: This prognostic model can risk stratify patients and demonstrates the additional benefit of PET texture analysis in OC staging. KEY POINTS: • PET texture analysis adds prognostic value to oesophageal cancer staging. • Texture metrics are independently and significantly associated with overall survival. • A prognostic model including texture analysis can help risk stratify patients.
Spectral clustering based on learning similarity matrix.

Motivation: Single-cell RNA-sequencing (scRNA-seq) technology can generate genome-wide expression data at the single-cell levels. One important objective in scRNA-seq analysis is to cluster cells where each cluster consists of cells belonging to the same cell type based on gene expression patterns. Results: We introduce a novel spectral clustering framework that imposes sparse structures on a target matrix. Specifically, we utilize multiple doubly stochastic similarity matrices to learn a similarity matrix, motivated by the observation that each similarity matrix can be a different informative representation of the data. We impose a sparse structure on the target matrix followed by shrinking pairwise differences of the rows in the target matrix, motivated by the fact that the target matrix should have these structures in the ideal case. We solve the proposed non-convex problem iteratively using the ADMM algorithm and show the convergence of the algorithm. We evaluate the performance of the proposed clustering method on various simulated as well as real scRNA-seq data, and show that it can identify clusters accurately and robustly. Availability and implementation: The algorithm is implemented in MATLAB. The source code can be downloaded at https://github.com/ishspsy/project/tree/master/MPSSC. Supplementary information: Supplementary data are available at Bioinformatics online.