Miracle-dz/UniFAR-FTUs huggingface dataset:
The Presence of Genotoxic and/or Pro-inflammatory Bacterial Genes in Gut Metagenomic Databases and Their Possible Link With Inflammatory Bowel Diseases

Background: The human gut microbiota is a dynamic community of microorganisms that mediate important biochemical processes. Differences in the gut microbial composition have been associated with inflammatory bowel diseases (IBD) and other intestinal disorders. In this study, we quantified and compared the frequencies of eight genotoxic and/or pro-inflammatory bacterial genes found in metagenomic Whole Genome Sequences (mWGSs) of samples from individuals with IBD vs. a cohort of healthy human subjects. Methods: The eight selected gene sequences were clbN, clbB, cif, cnf-1, usp, tcpC from Escherichia coli, gelE from Enterococcus faecalis and murB from Akkermansia muciniphila. We also included the sequences for the conserved murB genes from E. coli and E. faecalis as markers for the presence of Enterobacteriaceae or Enterococci in the samples. The gene sequences were chosen based on their previously reported ability to disrupt normal cellular processes to either promote inflammation or to cause DNA damage in cultured cells or animal models, which could be linked to a role in IBD. The selected sequences were searched in three different mWGS datasets accessed through the Human Microbiome Project (HMP): a healthy cohort (N = 251), a Crohn’s disease cohort (N = 60) and an ulcerative colitis cohort (N = 17). Results: Firstly, the sequences for the murB housekeeping genes from Enterobacteriaceae and Enterococci were more frequently found in the IBD cohorts (32% E. coli in IBD vs. 12% in healthy; 13% E. faecalis in IBD vs. 3% in healthy) than in the healthy cohort, confirming earlier reports of a higher presence of both of these taxa in IBD. For some of the sequences in our study, especially usp and gelE, their frequency was even more sharply increased in the IBD cohorts than in the healthy cohort, suggesting an association with IBD that is not easily explained by the increased presence of E. coli or E. faecalis in those samples. Conclusion: Our results suggest a significant association between the presence of some of these genotoxic or pro-inflammatory gene sequences and IBDs. In addition, these results illustrate the power and limitations of the HMP database in the detection of possible clinical correlations for individual bacterial genes.
Cellulosic Fibers: Role of Matrix Polysaccharides in Structure and Function

Cellulose, being the major cell wall component and the most abundant organic matter, produced by living organisms, is not uniformly distributed within plant tissues. There are numerous cells, like the parenchyma ones, which even at maturity have thin cell wall. Thick cell walls are characteristic for the tissues with mechanical function. Among those, there are cell walls, which contain several major components, and those, the predominant component of which is cellulose. The most pure natural cellulose is considered to be present in cotton seed hairs (sometimes erroneously called “cotton fibers”) – over 90% of cell wall [1]. Very close to this value is a special group of plant fibers – cellulosic or gelatinous fibers, the proportion of cellulose in which amounts for 85-90% [2,3]. The cell wall thickness in such fibers may reach 15 m, as compared to 0.2 m in cells with thin cell wall. So, the very significant portion of total plant cellulose may be concentrated within the gelatinous fibers, making them the important source for production of biofuels and bio-based products. An additional attractiveness of cellulosic fibers for such applications comes from the fact that gelatinous cell wall layers are devoid of lignin – the major hurdle in using plant biomass [1].
Osteoprotection Through the Deletion of the Transcription Factor Rorβ in Mice

There is a clinical need to identify new molecular targets for the treatment of osteoporosis, particularly those that simultaneously inhibit bone resorption while stimulating bone formation. We have previously shown in overexpression studies that retinoic acid receptor‐related orphan receptor β (Rorβ) suppresses in vitro osteoblast differentiation. In addition, the expression of Rorβ is markedly increased in bone marrow–derived mesenchymal stromal cells with aging in both mice and humans. Here we establish a critical role for Rorβ in regulating bone metabolism using a combination of in vitro and in vivo studies. We used Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 gene editing to demonstrate that loss of Rorβ in osteoblasts enhances Wnt signaling, specifically through increased recruitment of β‐catenin to T‐cell factor/lymphoid enhancer factor (Tcf/Lef) DNA binding sites in the promoters of the Wnt target genes Tcf7 and Opg. This resulted in increased osteogenic gene expression and suppressed osteoclast formation through increased osteoprotegerin (OPG) secretion in Rorβ‐deficient cells. Consistent with our in vitro data, genetic deletion of Rorβ in both female and male mice resulted in preserved bone mass and microarchitecture with advancing age due to increased bone formation with a concomitant decrease in resorption. The improved skeletal phenotype in the Rorβ–/– mice was also associated with increased bone protein levels of TCF7 and OPG. These data demonstrate that loss of Rorβ has beneficial skeletal effects by increasing bone formation and decreasing bone resorption, at least in part through β‐catenin–dependent activation of the Wnt pathway. Thus, inhibition of Rorβ represents a novel approach to potentially prevent or reverse osteoporosis. © 2017 American Society for Bone and Mineral Research.
Surface Properties of Helicobacter pylori Urease Complex Are Essential for Persistence

The enzymatic activity of Helicobacter pylori's urease neutralises stomach acidity, thereby promoting infection by this pathogen. Urease protein has also been found to interact with host cells in vitro, although this property's possible functional importance has not been studied in vivo. To test for a role of the urease surface in the host/pathogen interaction, surface exposed loops that display high thermal mobility were targeted for inframe insertion mutagenesis. H. pylori expressing urease with insertions at four of eight sites tested retained urease activity, which in three cases was at least as stable as was wild-type urease at pH 3. Bacteria expressing one of these four mutant ureases, however, failed to colonise mice for even two weeks, and a second had reduced bacterial titres after longer term (3 to 6 months) colonisation. These results indicate that a discrete surface of the urease complex is important for H. pylori persistence during gastric colonisation. We propose that this surface interacts directly with host components important for the host-pathogen interaction, immune modulation or other actions that underlie H. pylori persistence in its special gastric mucosal niche.
The SPARTACUS Trial: Controversies and Unresolved Issues

Abstract Adrenal vein sampling (AVS) is considered the gold standard for the differential diagnosis in patients with primary aldosteronism (PA). The distinction between unilateral and bilateral disease dictates the targeted therapeutic approach with surgery for aldosterone producing adenomas and medical therapy for patients with bilateral hyperplasia. Thereby, this diagnostic step is crucial in clinical care. As AVS is an invasive, not well standardized procedure that is restricted to few specialized centers, several attempts have been made to simplify diagnostic algorithms. In this clinical scenario, the recently published SPARTACUS trial aimed at answering the question whether AVS in fact is superior for differential diagnosis in comparison to imaging of the adrenal glands. In this multicenter study, patients were randomized to be treated according to AVS results or based on abdominal imaging only. Clinical outcome in both patient groups after one year was reported as not different. While the study results found broad interest, it also stirred considerable controversies. This review provides an overview on the different views regarding the outline of the SPARTACUS trial and the interpretation of its results.
Structural Cost-Optimal Design of Sensor Networks for Distributed Estimation

In this letter, we discuss cost optimization of sensor networks monitoring structurally full-rank systems under distributed observability constraint. Using structured systems theory, the problem is relaxed into two subproblems: first, sensing cost optimization; and second, networking cost optimization. Both problems are reformulated as combinatorial optimization problems. The sensing cost optimization is shown to have a polynomial-order solution. The networking cost optimization is shown to be NP-hard in general, but has a polynomial-order solution under specific conditions. A 2-approximation polynomial-order relaxation is provided for general networking cost optimization, which is applicable in large-scale system monitoring.
Testicular histomorphometrics including Sertoli cell quantitation for evaluating hatchability and fertility issues in commercial breeder‐broiler roosters

&NA; Testicular histomorphometric methods were developed for the investigation of fertility and hatchability problems in commercial broiler‐breeder roosters. Sertoli cell (SC) evaluations were emphasized in view of their role in influencing embryonic testicular organogenesis and spermatogenesis in adults. H&E stained sections prepared from formalized tissues were examined. SC evaluations were mostly made from computer generated images using image analysis software, but were also compared to direct counting with ocular grid reticle. Other measurements were germinal epithelial and total seminiferous tubule widths, quantification of individual spermatozoa and sperm clusters, and determinations of stromal area. Age‐associated changes in SC occurred between 15 to 54 wk of age. A significant reduction in SC concentration occurred at 29 wk of age (P < 0.001) that corresponded with the histologic initiation of spermatogenesis. Expanded morphometric evaluations were performed on 59‐week‐old roosters comparing a flock having good body condition and footpad scores with normal testicular and body weights (optimal profile or OP group) to a second flock demonstrating relatively poor expression of these parameters and decreased fertility (sub‐optimal profile or SOP group). Significant reductions (P < 0.05) in SC concentration, spermatozoa, and tubular widths, but an increased percentage of stroma area occurred in SOP compared to OP flocks. SC results also correlated well with testes weight. A unique finding was a significant relationship between decreasing SC concentration and increasing severity scores for footpad lesions. Differences in all histomorphometric parameters occurred between flocks demonstrating good hatchability compared to flocks exhibiting either low or decreasing hatchability. Significant reductions in SC and other morphometric parameters were observed for the poor relative to good hatchability group. A strong positive association was observed for SC results using computer generated images and direct reticle ocular counting (R = 0.80). Replicate counts on control sections demonstrated generally good reproducibility of methods between experiments. The findings are supportive of the value of testicular histomorphometrics for evaluations of hatchability issues in commercial roosters.
Crystal structures of amyloidogenic segments of human transthyretin

Amyloid diseases are characterized by the deposition of proteins in the form of amyloid fibrils, in organs that eventually fail. The development of effective drug candidates follows from the understanding of the molecular processes that lead to protein aggregation. Here, we study amyloidogenic segments of transthyretin (TTR). TTR is a transporter of thyroxine and retinol in the blood and cerebrospinal fluid. When mutated and/or as a result of aging, TTR aggregates into amyloid fibrils that accumulate in organs such as the heart. Recently, we reported two amyloidogenic segments that drive amyloid aggregation. Here, we report the crystal structure of another six amyloidogenic segments of TTR. We found that the segments from the C‐terminal region of TTR form in‐register steric‐zippers with highly‐interdigitated, wet interfaces, whereas the β‐strand B from the N‐terminal region of TTR forms an out‐of‐register assembly, previously associated with oligomeric formation. Our results contribute fundamental information for understanding the mechanism of aggregation of TTR.
A GRU-Based Encoder-Decoder Approach with Attention for Online Handwritten Mathematical Expression Recognition

In this study, we present a novel end-to-end approach based on the encoder-decoder framework with the attention mechanism for online handwritten mathematical expression recognition (OHMER). First, the input two-dimensional ink trajectory information of handwritten expression is encoded via the gated recurrent unit based recurrent neural network (GRU-RNN). Then the decoder is also implemented by the GRU-RNN with a coverage-based attention model. The proposed approach can simultaneously accomplish the symbol recognition and structural analysis to output a character sequence in LaTeX format. Validated on the CROHME 2014 competition task, our approach significantly outperforms the state-of-the-art with an expression recognition accuracy of 52.43% by only using the official training dataset. Furthermore, the alignments between the input trajectories of handwritten expressions and the output LaTeX sequences are visualized by the attention mechanism to show the effectiveness of the proposed method.
Clinical and Radiographic Predictors of Intracerebral Hemorrhage Outcome

Background: Intracerebral hemorrhage (ICH) represents 10-15% of all stroke cases in the US annually. Fewer than 40% of these patients ever reach long-term functional independence, and mortality rate is roughly 40% at 1 month. Due to the high morbidity and mortality rates after ICH, early detection of high-risk patients would be beneficial in directing the management course and goals of care. This review aims to discuss relevant clinical and radiographic characteristics that can serve as predictors of poor prognosis and examine their efficacy in predicting patient outcomes after ICH. Summary: A literature review was conducted on various clinical and radiographic factors. They were examined for their predictive value in relation to ICH outcome. Studies that focused on each of these factors were included, and their results analyzed for trends with regard to incidence, patient outcome, and mortality rate. Key Message: In this review, we examined clinical and radiographic characteristics that have been found to be significantly associated to a varying degree with poor outcome. Clinical and radiographic predictors of poor patient outcome are invaluable when it comes to identifying high-risk patients and triaging accordingly as well as guiding decision-making.
Clinical Characteristics and Correlation Analysis of Subjects with Chronic Hepatitis B Virus (HBV) Infection and Sustained Low Levels of Hepatitis B Surface Antigen (HBsAg)

Background The aim of this study was to investigate the clinical characteristics of individuals with chronic hepatitis B virus (HBV) infection with persistent low levels of hepatitis B surface antigen (HBsAg) and to undertake a correlation analysis of the clinical characteristics. Material/Methods The study included 1,204 subjects with chronic HBV infection. Serum HBsAg, HBV envelope antigen (HBeAg), and HBV core antigen (HBcAg) levels were measured using the chemiluminescent microparticle immunoassay (CMIA) and the neutralization test. HBV DNA was measured using real-time fluorescence quantitative polymerase chain reaction (RT-FQ-PCR). Results There were 1,023 subjects in the high-level HBsAg group (HBsAg level ≥10 IU/mL) and 181 subjects in the low-level HBsAg group (HBsAg level <10 IU/mL). In the low-level HBsAg group, the main serological pattern (93.37%) was HBsAg and HBeAg and HBcAg-positive (HBV-M2), and the asymptomatic carrier (ASC) status was 98.34%. The low-level HBsAg group had a lower HBV DNA-positive rate compared with the high-level HBsAg group (40.33% vs. 75.07%), with a normal distribution across all age groups (P>0.05). The low-level HBsAg group included an older age group. A low-level of HBsAg was positively correlated with a low level of replication of HBV DNA (r=0.452). Conclusions The findings of this study showed that individuals with chronic HBV infection and sustained low-levels of HBsAg were an older population and had a lower level of replicating HBV DNA when compared with individuals with high levels of HBsAg, and the majority (93.7%) were also HBsAg and HBeAg and HBcAg-positive.
Screening of latent tuberculosis infection among health care workers working in Hajj pilgrimage area in Saudi Arabia, using interferon gamma release assay and tuberculin skin test

BACKGROUND Interferon gamma release assays (IGRA) is highly specific for Mycobacterium tuberculosis and is the preferred test in BCG-vaccinated individuals. The few studies that have screened health care workers (HCWs) in Saudi Arabia for latent tuberculosis infection (LTBI) using IGRA have varied in agreement with the traditional tuberculin skin test (TST). OBJECTIVE Assess the prevalence of LTBI among HCWs working in the Hajj pilgrimage using IGRA and TST and measuring their agreement. DESIGN Cross-sectional prospective. SETTING Multiple non-tertiary care hospitals. PATIENTS AND METHODS HCWs who worked during the Hajj pilgrimage in Saudi Arabia in December 2015. Data was collected by standardized questionnaire. Samples were drawn and analyzed by standard methods. MAIN OUTCOME MEASURES The prevalence of LTBI among HCW and the agreement by kappa statistic between QFT-GIT and TST. SAMPLE SIZE 520 subjects. RESULTS The sample included 30.7% nurses and 19.2% physicians. The majority were BCG vaccinated (98.5%). There were a total of 56 positive by QFT-GIT and the LTBI rate was 10.8%. In 50 QFT positive/476 TST negative the LTBI rate was 10.5% in discordant tests, and in 6 QFT positive/44 TST positive it was 13.6% in concordant tests. The overall agreement between both tests was poor—83% and kappa was 0.02. LTBI prevalence was associated with longer employment (13.1 [9.2] years). The QFT-GIT positive test was significantly higher in physicians (P=.02) and in HCWs working in chest hospitals 16/76 (21.05%) (P=.001). CONCLUSION Agreement between the tests was poor. QFT-GIT detected LTBI when TST was negative in HCWs who had a history of close contact with TB patients. LIMITATIONS A second step TST was not feasible within 2–3 weeks.
Mechanism of grain refining in AZ91 Mg welds by arc oscillation

Grain refining can improve the solidification-cracking resistance and mechanical properties of welds. Mg alloys are increasingly used for vehicle weight reduction, AZ91 Mg being the most widely used Mg casting alloy. The present study was conducted to study grain refining in gas–tungsten arc welding of AZ91 Mg, focusing on identifying the mechanism of grain refining. Significant grain refining was obtained by transverse arc oscillation. Dendrite fragmentation was identified as the grain refining mechanism, instead of heterogeneous nucleation or grain detachment. This was done by using an overlap welding procedure in which the weld made with transverse arc oscillation (test weld) overlapped with another weld made previously without arc oscillation (preweld). It was found that repeated prewelding followed by welding with transverse arc oscillation resulted in very fine grains.
Identifying Maternal Deaths in Texas Using an Enhanced Method, 2012.

OBJECTIVE To more accurately estimate the 2012 maternal mortality ratio for Texas using an enhanced method for identifying maternal deaths. METHODS This population-based descriptive study used both data matching and record review to verify pregnancy or delivery within 42 days for 147 deaths with obstetric cause-of-death codes, and used data matching alone to identify additional maternal deaths within the same timeframe. Crude maternal mortality ratios were calculated for confirmed maternal deaths overall, by race and ethnicity, and by age. These maternal mortality ratios were compared with maternal mortality ratios computed using obstetric cause-of-death codes alone (standard method). RESULTS Fifty-six maternal deaths were confirmed to have occurred during pregnancy or within 42 days postpartum. Using our enhanced method, the 2012 maternal mortality ratio for Texas was 14.6 maternal deaths per 100,000 live births, less than half that obtained using the standard method (n=147). Approximately half (50.3%) of obstetric-coded deaths showed no evidence of pregnancy within 42 days, and a large majority of these incorrectly indicated pregnancy at the time of death. Insufficient information was available to determine pregnancy for 15 obstetric-coded deaths, which were excluded from the 2012 maternal mortality ratio estimate; however, had these deaths been included, the resulting maternal mortality ratio would still be significantly lower than that reported using the standard method. CONCLUSION Relying solely on obstetric codes for identifying maternal deaths appears to be insufficient and can lead to inaccurate maternal mortality ratios. A method enhanced with data matching and record review yields more accurate ratios. Results likely have national implications, because miscoding of obstetric deaths with the standard method may affect the accuracy of other states' maternal mortality ratios.
Sulfidic Anion Concentrations on Early Earth for Surficial Origins-of-Life Chemistry

Abstract A key challenge in origin-of-life studies is understanding the environmental conditions on early Earth under which abiogenesis occurred. While some constraints do exist (e.g., zircon evidence for surface liquid water), relatively few constraints exist on the abundances of trace chemical species, which are relevant to assessing the plausibility and guiding the development of postulated prebiotic chemical pathways which depend on these species. In this work, we combine literature photochemistry models with simple equilibrium chemistry calculations to place constraints on the plausible range of concentrations of sulfidic anions (HS−, HSO3−, SO32−) available in surficial aquatic reservoirs on early Earth due to outgassing of SO2 and H2S and their dissolution into small shallow surface water reservoirs like lakes. We find that this mechanism could have supplied prebiotically relevant levels of SO2-derived anions, but not H2S-derived anions. Radiative transfer modeling suggests UV light would have remained abundant on the planet surface for all but the largest volcanic explosions. We apply our results to the case study of the proposed prebiotic reaction network of Patel et al. (2015) and discuss the implications for improving its prebiotic plausibility. In general, epochs of moderately high volcanism could have been especially conducive to cyanosulfidic prebiotic chemistry. Our work can be similarly applied to assess and improve the prebiotic plausibility of other postulated surficial prebiotic chemistries that are sensitive to sulfidic anions, and our methods adapted to study other atmospherically derived trace species.