Miracle-dz/UniFAR-FTUs huggingface dataset:
Gender differences? Factors related to quality of life among patients with Heart failure

ABSTRACT Heart failure (HF) is a chronic, progressive disease that substantially decreases patients’ quality of life. Few studies have compared quality of life and its related factors across genders in patients with HF. To explore gender differences in quality of life and related factors among adult patients with HF. A comparative study was conducted with 245 HF patients recruited from a medical center and a regional teaching hospital in Taiwan from February 2009 to February 2011. Descriptive and inferential statistics were used, including stepwise multiple regressions. The mean quality of life scores of males were significantly higher than those of females (87.78 ± 13.99 vs. 84.49 ± 11.85). The factors significantly related to quality of life for the male HF patients, in descending order of strength of association were depressive symptoms, physical symptoms, and monthly family income-less than USD 1,000; for the females, the significantly related factors were physical symptoms, depressive symptoms, and monthly family income-less than USD 1,000. The amount variance for which quality of life accounted for male and female HF patients was similar (60% vs. 64%). The results could be used for health professionals to provide more appropriate assessments and care according to gender in the future.
Preoperative alpha-blockers for ureteroscopy for ureteric stones: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION Preoperative alpha-blockers have been proposed to improve intraoperative outcomes and patient stone-free status following ureteroscopy for ureteric stones. MATERIALS AND METHODS We searched 6 databases including Medline, Embase, and Web of Science for randomized controlled trials evaluating alpha-blocker use prior to planned ureteroscopy for the management of ureteric calculi. Meta-analysis was performed using DerSimonian and Laird method with inverse-variance weighting. Quality of evidence was summarized using the GRADE framework. RESULTS Of 3338 records, 26 were screened as full-text and 12 randomized controlled trials were included totaling 1352 patients. Meta-analysis demonstrated a 61% reduction in need for intraoperative ureteral dilatation in patients administered preoperative alpha-blockers (relative risk [RR]: 0.39 [95% CI: 0.31 to 0.48], p<0.00001), as well as increased stone-free status for patients at 4 weeks post-operatively (RR: 1.17 [95% CI: 1.08 to 1.26], p<0.00001) and at final follow-up (RR: 1.18 [95% CI: 1.11 to 1.24], p<0.00001; median final follow-up 4 weeks [range: 2 to 8 weeks]). Urologists were more likely to reach the stone with the ureteroscope in patients administered alpha-blockers (RR: 1.16 [95% CI: 1.10 to 1.23], p<0.00001). A statistically significant reduction in operative time (MD: -6.05 [95% CI: -10.17 to -1.93] minutes, p=0.004) and length of hospital stay (weighted mean difference [MD]: -0.34 [95% CI: -0.55 to -0.13] days, p=0.001) was also demonstrated. Main reported side effects of treatments were abnormal ejaculation, postural hypotension, and dizziness. Outcomes were robust to sensitivity analyses. Results were rated moderate quality evidence using the GRADE framework. CONCLUSIONS Among patients scheduled for semi-rigid ureteroscopy of ureteric stones, use of preoperative alpha-blockers demonstrated a significant reduction in the need for ureteric orifice dilation, increase in patient stone-free status at follow-up, and facilitates higher rate of ureteroscopic access to stones while reducing operative time.
Vestibular Balance Deficits Following Head Injury: Recommendations Concerning Evaluation and Rehabilitation in the Military Setting

Abstract : Vestibular pathology has been documented following barotrauma and/or head acceleration associated with exposure to explosions. The usual symptoms include dizziness and headache, with dizziness and associated imbalance contributing disproportionately to disability. Several agencies have noted the need for better vestibular evaluation and rehabilitation following exposure to improvised explosive devices (IEDs). The authors asked subject matter experts to assist in formulating recommendations for initial assessment and rehabilitation of balance problems following IED exposure, focusing on strategies that are either available or in development. This report summarizes feedback obtained from approximately 50 vestibular researchers, scientific advisors, clinicians, and biomedical engineers working for government agencies, universities, clinics/hospitals, and businesses. Tests appropriate for early (post-injury) functional assessment in the military setting are considered, along with the optimal application of novel tactile balance feedback technologies being developed to augment vestibular rehabilitation.
WALTZ-DB 2.0: an updated database containing structural information of experimentally determined amyloid-forming peptides

Abstract Transition of soluble proteins into insoluble amyloid fibrils is driven by self-propagating short sequence stretches. However, accurate prediction of aggregation determinants remains challenging. Here, we describe WALTZ-DB 2.0, an updated and significantly expanded open-access database providing information on experimentally determined amyloid-forming hexapeptide sequences (http://waltzdb.switchlab.org/). We have updated WALTZ-DB 2.0 with new entries, including: (i) experimental validation of an in-house developed dataset of 229 hexapeptides, using electron microscopy and Thioflavin-T binding assays; (ii) manual curation of 98 amyloid-forming peptides isolated from literature. Furthermore, the content has been expanded by adding novel structural information for peptide entries, including sequences of the previous version. Using a computational methodology developed in the Switch lab, we have generated 3D-models of the putative amyloid fibril cores of WALTZ-DB 2.0 entries. Structural models, coupled with information on the energetic contributions and fibril core stabilities, can be accessed through individual peptide entries. Customized filtering options for subset selections and new modelling graphical features were added to upgrade online accessibility, providing a user-friendly interface for browsing, downloading and updating. WALTZ-DB 2.0 remains the largest open-access repository for amyloid fibril formation determinants and will continue to enhance the development of new approaches focused on accurate prediction of aggregation prone sequences.
Perspective: Guiding Principles for the Implementation of Personalized Nutrition Approaches That Benefit Health and Function

ABSTRACT Personalized nutrition (PN) approaches have been shown to help drive behavior change and positively influence health outcomes. This has led to an increase in the development of commercially available PN programs, which utilize various forms of individual-level information to provide services and products for consumers. The lack of a well-accepted definition of PN or an established set of guiding principles for the implementation of PN creates barriers for establishing credibility and efficacy. To address these points, the North American Branch of the International Life Sciences Institute convened a multidisciplinary panel. In this article, a definition for PN is proposed: "Personalized nutrition uses individual-specific information, founded in evidence-based science, to promote dietary behavior change that may result in measurable health benefits. " In addition, 10 guiding principles for PN approaches are proposed: 1) define potential users and beneficiaries; 2) use validated diagnostic methods and measures; 3) maintain data quality and relevance; 4) derive data-driven recommendations from validated models and algorithms; 5) design PN studies around validated individual health or function needs and outcomes; 6) provide rigorous scientific evidence for an effect on health or function; 7) deliver user-friendly tools; 8) for healthy individuals, align with population-based recommendations; 9) communicate transparently about potential effects; and 10) protect individual data privacy and act responsibly. These principles are intended to establish a basis for responsible approaches to the evidence-based research and practice of PN and serve as an invitation for further public dialog. Several challenges were identified for PN to continue gaining acceptance, including defining the health–disease continuum, identification of biomarkers, changing regulatory landscapes, accessibility, and measuring success. Although PN approaches hold promise for public health in the future, further research is needed on the accuracy of dietary intake measurement, utilization and standardization of systems approaches, and application and communication of evidence.
Dendritic Localization and Exocytosis of NAAG in the Rat Hippocampus

Abstract While a lot is known about classical, anterograde neurotransmission, less is known about the mechanisms and molecules involved in retrograde neurotransmission. Our hypothesis is that N-acetylaspartylglutamate (NAAG), the most abundant dipeptide in the brain, may act as a retrograde transmitter in the brain. NAAG was predominantly localized in dendritic compartments of glutamatergic synapses in the intact hippocampus, where it was present in close proximity to synaptic-like vesicles. In acute hippocampal slices, NAAG was depleted from postsynaptic dendritic elements during neuronal stimulation induced by depolarizing concentrations of potassium or by exposure to glutamate receptor (GluR) agonists. The depletion was completely blocked by botulinum toxin B and strictly dependent on extracellular calcium, indicating exocytotic release. In contrast, there were low levels of NAAG and no effect by depolarization or GluR agonists in presynaptic glutamatergic terminals or GABAergic pre- and postsynaptic elements. Together these data suggest a possible role for NAAG as a retrograde signaling molecule at glutamatergic synapses via exocytotic release.
Diagnosis and clinical outcomes of extrapulmonary tuberculosis in antiretroviral therapy programmes in low‐ and middle‐income countries: a multicohort study

Extrapulmonary tuberculosis (EPTB) is difficult to confirm bacteriologically and requires specific diagnostic capacities. Diagnosis can be especially challenging in under‐resourced settings. We studied diagnostic modalities and clinical outcomes of EPTB compared to pulmonary tuberculosis (PTB) among HIV‐positive adults in antiretroviral therapy (ART) programmes in low‐ and middle‐income countries (LMIC).
NLRP7 is expressed in the ovine ovary and associated with in vitro pre-implantation embryo development

NLRP (NACHT, LRR and PYD domain-containing proteins) family plays pivotal roles in mammalian reproduction. Mutation of NLRP7 is often associated with human recurrent hydatidiform moles. Few studies regarding the functions of NLRP7 have been performed in other mammalian species rather than humans. In the current study, for the first time, the function of NLRP7 has been explored in ovine ovary. NLRP7 protein was mainly located in ovarian follicles and in in vitro pre-implantation embryos. To identify its origin, 763 bp partial CDS of NLRP7 deriving from sheep cumulus oocyte complexes (COCs) was cloned, it showed a great homology with Homo sapiens. The high levels of mRNA and protein of NLRP7 were steadily expressed in oocytes, parthenogenetic embryos or IVF embryos. NLRP7 knockdown by the combination of siRNA and shRNA jeopardized both the parthenogenetic and IVF embryo development. These results strongly suggest that NLRP7 plays an important role in ovine reproduction. The potential mechanisms of NLRP7 will be fully investigated in the future.
Small Molecule Screening in Zebrafish Embryos Identifies Signaling Pathways Regulating Early Thyroid Development

Background Defects in embryonic development of the thyroid gland are a major cause for congenital hypothyroidism in human newborns but the underlying molecular mechanisms are still poorly understood. Organ development relies on a tightly regulated interplay between extrinsic signaling cues and cell intrinsic factors. At present, however, there is limited knowledge about the specific extrinsic signaling cues that regulate foregut endoderm patterning, thyroid cell specification and subsequent morphogenetic processes in thyroid development. Methods To begin to address this problem in a systematic way, we used zebrafish embryos to perform a series of in vivo phenotype-driven chemical genetic screens to identify signaling cues regulating early thyroid development. For this purpose, we treated zebrafish embryos during different developmental periods with a panel of small molecule compounds known to manipulate the activity of major signaling pathways and scored phenotypic deviations in thyroid, endoderm and cardiovascular development using whole mount in situ hybridization and transgenic fluorescent reporter models. Results Systematic assessment of drugged embryos recovered a range of thyroid phenotypes including expansion, reduction or lack of the early thyroid anlage, defective thyroid budding as well as hypoplastic, enlarged or overtly disorganized presentation of the thyroid primordium after budding. Our pharmacological screening identified BMP and FGF signaling as key factors for thyroid specification and early thyroid organogenesis, highlight the importance of low Wnt activities during early development for thyroid specification and implicate drug-induced cardiac and vascular anomalies as likely indirect mechanisms causing various forms of thyroid dysgenesis. Conclusions By integrating the outcome of our screening efforts with previously available information from other model organisms including Xenopus, chicken and mouse, we conclude that signaling cues regulating thyroid development appear broadly conserved across vertebrates. We therefore expect that observations made in zebrafish can inform mammalian models of thyroid organogenesis to further our understanding of the molecular mechanisms of congenital thyroid diseases.
Vascular Plants Are Globally Significant Contributors to Marine Carbon Fluxes and Sinks.

More than two-thirds of global biomass consists of vascular plants. A portion of the detritus they generate is carried into the oceans from land and highly productive blue carbon ecosystems-salt marshes, mangrove forests, and seagrass meadows. This large detrital input receives scant attention in current models of the global carbon cycle, though for blue carbon ecosystems, increasingly well-constrained estimates of biomass, productivity, and carbon fluxes, reviewed in this article, are now available. We show that the fate of this detritus differs markedly from that of strictly marine origin, because the former contains lignocellulose-an energy-rich polymer complex of cellulose, hemicelluloses, and lignin that is resistant to enzymatic breakdown. This complex can be depolymerized for nutritional purposes by specialized marine prokaryotes, fungi, protists, and invertebrates using enzymes such as glycoside hydrolases and lytic polysaccharide monooxygenases to release sugar monomers. The lignin component, however, is less readily depolymerized, and detritus therefore becomes lignin enriched, particularly in anoxic sediments, and forms a major carbon sink in blue carbon ecosystems. Eventual lignin breakdown releases a wide variety of small molecules that may contribute significantly to the oceanic pool of recalcitrant dissolved organic carbon. Marine carbon fluxes and sinks dependent on lignocellulosic detritus are important ecosystem services that are vulnerable to human interventions. These services must be considered when protecting blue carbon ecosystems and planning initiatives aimed at mitigating anthropogenic carbon emissions. Expected final online publication date for the Annual Review of Marine Science, Volume 12 is January 3, 2020. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Historical flaws in bioassays used to generate metabolizable energy values for poultry feed formulation: a critical review

Dietary energy available to animals is key for formulating feed as it is required for all aspects of the animal's life. In poultry, apparent (AME) and true (TME) metabolizable energy (ME) values have been used for feed formulation with (AMEn or TMEn) or without correction for nitrogen balance. For the past 50 yr, the accuracy of ME has been an ongoing debate, and the comparability of data produced using different bioassay systems is often questionable. Overall, the ingredient matric ME values used in feed formulation are not consistent, and to some extent, confusing. This review was to examine ME data published in the past century to elucidate the accuracy of different bioassay systems and examine the values for accuracy and useability. A variety of flaws are identified in the literature, suggesting a thorough re-thinking of feedstuff ME values currently used in feed formulation and in developing prediction equations. Two protocols, namely multiple linear regression and basal diet substitution methods, are proposed as more accurate bioassays for feedstuff ME values. AME aligns more closely with the actual energy levels of feed ingredients likely available to growing birds, which should be used for poultry feed formulations instead of AMEn. It is suggested that nutritionists need to carefully apply any reported AME values and only use those in formulation practice after careful scrutinizing. Any in vitro, NIR or table values must be calibrated or computed based on the values produced from flawless bioassays so as to apply the derived values accurately. Flaws identified in this literature review can be avoided with care to achieve more accurate AME. However, the assumption that the energy of individual ingredients is additive in a complete diet is still untrue at least under some circumstances. This may require efforts from industry and researchers to investigate relations among the main ingredients in a complete diet so that more accurate formulation can be performed based on the outcomes that may fine-tune the additivity assumption.
NKG2D Controls Natural Reactivity of Vγ9Vδ2 T Lymphocytes against Mesenchymal Glioblastoma Cells

Purpose: Cellular immunotherapies are currently being explored to eliminate highly invasive and chemoradioresistant glioblastoma (GBM) cells involved in rapid relapse. We recently showed that concomitant stereotactic injections of nonalloreactive allogeneic Vγ9Vδ2 T lymphocytes eradicate zoledronate-primed human GBM cells. In the present study, we investigated the spontaneous reactivity of allogeneic human Vγ9Vδ2 T lymphocytes toward primary human GBM cells, in vitro and in vivo, in the absence of any prior sensitization. Experimental Design: Through functional and transcriptomic analyses, we extensively characterized the immunoreactivity of human Vγ9Vδ2 T lymphocytes against various primary GBM cultures directly derived from patient tumors. Results: We evidenced that GBM cells displaying a mesenchymal signature are spontaneously eliminated by allogeneic human Vγ9Vδ2 T lymphocytes, a reactivity process being mediated by γδ T-cell receptor (TCR) and tightly regulated by cellular stress–associated NKG2D pathway. This led to the identification of highly reactive Vγ9Vδ2 T lymphocyte populations, independently of a specific TCR repertoire signature. Moreover, we finally provide evidence of immunotherapeutic efficacy in vivo, in the absence of any prior tumor cell sensitization. Conclusions: By identifying pathways implicated in the selective natural recognition of mesenchymal GBM cell subtypes, accounting for 30% of primary diagnosed and 60% of recurrent GBM, our results pave the way for novel targeted cellular immunotherapies.
Organocatalytic Asymmetric Annulation of ortho-Alkynylanilines: Synthesis of Axially Chiral Naphthyl-C2-Indoles.

A chiral Brønsted base-catalyzed asymmetric annulation of ortho-alkynylanilines has been developed to access axially chiral naphthyl-C2-indoles through vinylidene ortho-quinone methides (VQMs) intermediates. This strategy provides a unique organocatalytic atroposelective route to axially chiral aryl-C2-indole skeletons with excellent enantioselectivity and functional group tolerance. This transformation was applicable to the deca-gram preparation (50.0 g) with perfect enantioselectivity through simple recrystallization. Moreover, the utility of this reaction had been demonstrated by a variety of transformations towards the prepared chiral naphthyl-C2-indoles for a series of carbon-heteroatom bonds formation. Furthermore, the prepared axially chiral naphthyl-C2-indoles had been applied as chiral skeleton for organocatalytic aza-Baylis-Hillman reaction and asymmetric formal [4+2] tandem cyclization to give corresponding adducts in high yields with improved enantioselectivities and diastereoselectivities.
Long-term outcomes are poor in intravenous drug users following infective endocarditis, even after surgery.

BACKGROUND Previous studies of outcomes in people who inject drugs (PWID) with infective endocarditis (IE) have often been retrospective, had a small sample size, the duration of follow-up has been short and limited to patients who were operated on. METHODS PWID treated for IE between 01/01/2006 and 31/12/2016 were identified from a prospectively collected database. PWID hospitalised with other infections acted as a novel comparison group. Outcomes were all-cause mortality, cause of death, relapse, recurrence and re-operation. RESULTS There were 105 episodes of IE in 92 PWID and 112 episodes of other infections in 107 PWID in whom IE was suspected but rejected. Survival at 30 days for the IE group was 85% and 30-day survival following surgery was 96%. The most common pathogens were Staphylococcus spp. (60%) and Streptococcus spp. (30%). The surgical intervention rate was 47%. Survival for the IE group at 1, 3, 5 and 10 years was 74%, 63%, 58% and 44%, respectively. This was significantly lower compared with the comparator group of other infections in PWID (p=0.0002). Mortality was higher in patients who required surgery compared to those who did not (HR 1.8, 0.95-3.3). The commonest cause of death was infection (66%), usually a further episode of IE (55%). CONCLUSIONS Whilst early survival was good, long-term life-expectancy was low. This was attributable to ongoing infection risk, rather than other factors known to affect prognosis in PWID. Surgery conferred no long-term survival advantage. More efforts are needed to reduce re-infection risk following an episode of IE in PWID.
SNV identification from single-cell RNA sequencing data.

Integrating single-cell RNA sequencing (scRNA-seq) data with genotypes obtained from DNA sequencing studies facilitates the detection of functional genetic variants underlying cell type specific gene expression variation. Unfortunately, most existing scRNA-seq studies do not come with DNA sequencing data; thus, being able to call single nucleotide variants (SNVs) from scRNA-seq data alone can provide crucial and complementary information, detection of functional SNVs, maximizing the potential of existing scRNA-seq studies. Here, we perform extensive analyses to evaluate the utility of two SNV calling pipelines (GATK and Monovar), originally designed for SNV calling in either bulk or single cell DNA sequencing data. In both pipelines, we examined various parameter settings to determine the accuracy of the final SNV call set and provide practical recommendations for applied analysts. We found that combining all reads from the single cells and following GATK Best Practices resulted in the highest number of SNVs identified with a high concordance. In individual single cells, Monovar resulted in better quality SNVs even though none of the pipelines analysed is capable of calling a reasonable number of SNVs with high accuracy. In addition, we found that SNV calling quality varies across different functional genomic regions. Our results open doors for novel ways to leverage the use of scRNA-seq for the future investigation of SNV function.