Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of an Automatic Speech Recognition Platform for Dysarthric Speech

Introduction: The use of commercially available automatic speech recognition (ASR) software is challenged when dysarthria accompanies a physical disability. To overcome this issue, a mobile and personal speech assistant (mPASS) platform was developed, using a speaker-dependent ASR software. Objective: The aim of this study was to evaluate the performance of the proposed platform and to compare mPASS recognition accuracy to a commercial speaker-independent ASR software. In addition, secondary aims were to investigate the relationship between severity of dysarthria and accuracy and to explore people with dysarthria perceptions on the proposed platform. Methods: Fifteen individuals with dysarthric speech and 20 individuals with nondysarthric speech recorded 24 words and 5 sentences in a clinical environment. Differences in recognition accuracy between the two systems were evaluated. In addition, mPASS usability was assessed with a technology acceptance model (TAM) questionnaire. Results: In both groups, mean accuracy rates were significantly higher with mPASS compared to the commercial ASR for words and for sentences. mPASS reached good levels of usefulness and ease of use according to the TAM questionnaire. Conclusions: Practical applicability of this technology is realistic: the mPASS platform is accurate, and it could be easily used by individuals with dysarthria.
Priorities for High-quality Care in Rheumatoid Arthritis: Results of Patient, Health Professional, and Policy Maker Perspectives

Objective To elucidate the essential elements of high-quality rheumatoid arthritis (RA) care in order to develop a vision statement and a set of strategic objectives for a national RA quality framework. Methods Focus groups and interviews were conducted by experienced qualitative researchers using a semistructured interview or focus group guide with healthcare professionals, patients, clinic managers, healthcare leaders, and policy makers to obtain their perspectives on elements essential to RA care. Purposive sampling provided representation of stakeholder types and regions. Recorded data was transcribed verbatim. Two teams of 2 coders independently analyzed the deidentified transcripts using thematic analysis. Strategic objectives and the vision statement were drafted based on the overarching themes from the qualitative analysis and finalized by a working group. Results A total of 54 stakeholders from 9 Canadian provinces participated in the project (3 focus groups and 19 interviews). Seven strategic objectives were derived from the qualitative analysis representing the following themes: (1) early access and timeliness of care; (2) evidence-informed, high-quality care for the ongoing management of RA and comorbidities; (3) availability of patient self-management tools and educational materials for shared decision making; (4) multidisciplinary care; (5) patient outcomes; (6) patient experience and satisfaction with care; and (7) equity, the last of which emerged as an overarching theme. The ultimate vision obtained was “ensuring patient-centered, high-quality care for people living with rheumatoid arthritis. ” Conclusion The 7 strategic objectives that were identified highlight priorities for RA quality of care to be used in developing the National RA Quality Measurement Framework.
Overlapping mechanisms of lncRNA and expanded microsatellite RNA

RNA has major regulatory roles in a wide range of biological processes and a surge of RNA research has led to the classification of numerous functional RNA species. One example is long noncoding RNAs (lncRNAs) that are structurally complex transcripts >200 nucleotides (nt) in length and lacking a canonical open reading frame (ORF). Despite a general lack of sequence conservation and low expression levels, many lncRNAs have been shown to have functionality in diverse biological processes as well as in mechanisms of disease. In parallel with the growing understanding of lncRNA functions, there is a growing subset of microsatellite expansion disorders in which the primary mechanism of pathogenesis is an RNA gain of function arising from RNA transcripts from the mutant allele. Microsatellite expansion disorders are caused by an expansion of short (3–10 nt) repeats located within coding genes. Expanded repeat‐containing RNA mediates toxicity through multiple mechanisms, the details of which remain only partially understood. The purpose of this review is to highlight the links between functional mechanisms of lncRNAs and the potential pathogenic mechanisms of expanded microsatellite RNA. These shared mechanisms include protein sequestration, peptide translation, micro‐RNA (miRNA) processing, and miRNA sequestration. Recognizing the parallels between the normal functions of lncRNAs and the negative impact of expanded microsatellite RNA on biological processes can provide reciprocal understanding to the roles of both RNA species.
How potassium came to be the dominant biological cation: of metabolism, chemiosmosis, and cation selectivity since the beginnings of life

In the cytoplasm of practically all living cells, potassium is the major cation while sodium dominates in the media (seawater, extracellular fluids). Both prokaryotes and eukaryotes have elaborate mechanisms and spend significant energy to maintain this asymmetric K+/Na+ distribution. This essay proposes an original line of evidence to explain how bacteria selected potassium at the very beginning of the evolutionary process and why it remains essential for eukaryotes.
Investigating the effect of TRPV4 inhibition on pulmonary-vascular barrier permeability following segmental endotoxin challenge.

BACKGROUND Acute Respiratory Distress Syndrome (ARDS) is associated with increased pulmonary-vascular permeability. In the lung, transient receptor potential vanilloid 4 (TRPV4), a Ca2+-permeable cation channel, is a regulator of endothelial permeability and pulmonary edema. We performed a Phase I, placebo-controlled, double-blind, randomized, parallel group, proof-of-mechanism study to investigate the effects of TRPV4 channel blocker, GSK2798745, on pulmonary-vascular barrier permeability using a model of lipopolysaccharide (LPS)-induced lung inflammation. METHODS Healthy participants were randomized 1:1 to receive 2 single doses of GSK2798745 or placebo, 12 hours apart. Two hours after the first dose, participants underwent bronchoscopy and segmental LPS instillation. Total protein concentration and neutrophil counts were measured in bronchoalveolar lavage (BAL) samples collected before and 24 hours after LPS challenge, as markers of barrier permeability and inflammation, respectively. The primary endpoint was baseline adjusted total protein concentration in BAL at 24 hours after LPS challenge. A Bayesian framework was used to estimate the posterior probability of any percentage reduction (GSK2798745 relative to placebo). Safety endpoints included the incidence of adverse events (AEs), vital signs, 12-lead electrocardiogram, clinical laboratory and haematological evaluations, and spirometry. RESULTS Forty-seven participants were dosed and 45 completed the study (22 on GSK2798745 and 23 on placebo). Overall, GSK2798745 was well tolerated. Small reductions in mean baseline adjusted BAL total protein (∼9%) and neutrophils (∼7%) in the LPS-challenged segment were observed in the GSK2798745 group compared with the placebo group; however, the reductions did not meet pre-specified success criteria of at least a 95% posterior probability that the percentage reduction in the mean 24-hours post LPS BAL total protein level (GSK2798745 relative to placebo) exceeded zero. Median plasma concentrations of GSK2798745 were predicted to inhibit TRPV4 on lung vascular endothelial cells by ∼70-85% during the 24 hours after LPS challenge; median urea-corrected BAL concentrations of GSK2798745 were 3.0- to 8.7-fold higher than those in plasma. CONCLUSIONS GSK2798745 did not affect segmental LPS-induced elevation of BAL total protein or neutrophils, despite blood and lung exposures that were predicted to be efficacious. CLINICALTRIALS. GOV IDENTIFIER NCT03511105.
Participation in activities mediates the effect of Internet use on cognitive functioning in old age

ABSTRACT Research indicates that Internet use positively influences cognitive functioning in later life, but we do not know the behavioral pathways that explain this association. This study explored the role of participation in activities as a potential mediator of the relationship between Internet use and cognitive functioning over a 4-year period. We analyzed representative data from the Survey of Health, Ageing and Retirement in Europe (SHARE). The sample included 8353 European participants between 50 and 97 years of age. We used data from 2013 (T1), 2015 (T2), and 2017 (T3). Participants reported whether they participated in a diverse range of social and leisure activities. In addition, they provided information about their Internet use as well as cognitive functioning measures. Findings from cross-lagged panel analysis indicated a positive association between Internet use and change in cognition over the course of 4 years. This relationship was partly mediated by the number of reported activities. Internet use was positively associated with the change in activities after 2 years, which, in turn, positively predicted cognitive functioning 2 more years later. This is the first study that explores the temporal sequence of Internet use, participation in activities, and cognitive functioning. It sheds light on the mechanisms that account for the positive effects of Internet use on healthy aging.
Expression of Cucumber Mosaic Virus Coat Protein and Its Assembly into Virus Like Particles

Objectives: In this paper, we report the expression and assembly of VLP in cells of E. coli expressing the CMVCP gene. Materials and Methods: In this study, the CMV-CP gene was released from a previously prepared cloning vector. Then, the CMV-CP was ligated into the expression vector. Sequencing was done by Marcrogen, Inc. (South Korea). A recombinant plasmid was transferred to E.coli isolate Rosetta. After inducing by isopropyl thiogalactosides, the molecular weight of the expressed protein was determined by SDS-PAGE. The extraction of proteins was done by NATURE method to see the possible presence of CMV-like particles. Results: CMV-CP was detected by Western blotting by a CMV specific polyclonal antibody and conjugate. The protein extracted from the CP producing clone was studied under a JEOL 100-CXII transmission electron microscope with 100000× magnification at an acceleration voltage of 100 kV. Conclusions: The results showed that the CP gene was expressed in the prokaryotic system successfully and was assembled into the CMVlike particle.
The small regulatory RNA Lpr10 regulates the expression of RpoS in Legionella pneumophila

Legionella pneumophila (Lp) is a waterborne bacterium able to infect human alveolar macrophages, causing Legionnaires’ disease. Lp can survive for several months in water, while searching for host cells to grow in, such as ciliates and amoeba. In Lp, the sigma factor RpoS is essential for survival in water. A previous transcriptomic study showed that RpoS positively regulates the small regulatory RNA Lpr10. In the present study, deletion of lpr10 results in an increased survival of Lp in water. Microarray analysis and RT‐qPCR revealed that Lpr10 negatively regulates the expression of RpoS in the postexponential phase. Electrophoretic mobility shift assay and in‐line probing showed that Lpr10 binds to a region upstream of the previously identified transcription start sites (TSS) of rpoS. A third putative transcription start site was identified by primer extension analysis, upstream of the Lpr10 binding site. In addition, nlpD TSS produces a polycistronic mRNA including the downstream gene rpoS, indicating a fourth TSS for rpoS. Our results suggest that the transcripts from the third and fourth TSS are negatively regulated by the Lpr10 sRNA. Therefore, we propose that Lpr10 is involved in a negative regulatory feedback loop to maintain expression of RpoS to an optimal level.
Chronic Diarrhea as the Presenting Feature of Amyloidosis with Multiple Myeloma: A Case Report Diagnosed by a Myocardial Biopsy

A 73-year-old woman with a history of diarrhea for one year and other various symptoms was admitted to our hospital. Gastrointestinal endoscopy that included enteroscopy with multiple biopsies was performed. However, no significant findings were observed. Electrocardiography showed low voltage in all limb leads, and an echocardiogram showed thickened cardiac walls with granular sparkling pattern. A myocardial biopsy revealed amyloidosis, and a bone marrow biopsy showed multiple myeloma. This case suggests that we should suspect the possibility of amyloidosis in a patient with diarrhea and various symptoms involving multiple organ systems. Additionally, electrocardiograms and echocardiograms should be performed even when gastrointestinal biopsies reveal negative results.
Introducing sexual dysfunction in mental care

ABSTRACT Introduction: People with any psychiatric disorder tend to have difficulties in responding sexually. However,sexual dysfunction (SD) is usually under-recognized, even the tightly hormonal and neuronal common connexions through the brain-sex axis. Multiple sources of resistance to SD assessment and intervention persist. Areas covered: The present review aims to underline the feasibility to introduce SD evaluation in patients with any psychiatric disorders, evaluating the potential mutual benefits of their management. Expert opinion: Women and men living with mental disorders frequently display sexual difficulties; however, some of them consider sexuality as a relevant parameter of their quality of life. In fact, SD as a side effect is a frequent reason for stopping the intake of medication. What is more, a holistic approach integrating sexual function could foster a better understanding of mental pathologies due to a common origin of pathogenesis. This could improve care quality, in keeping with the global tendency toward the development of personalized medicine. Consistently, the integration of SD assessment is highly recommended in mental health, all the more so when a psychotropic drug is prescribed. An expected consequence would be a reconstruction of the healthcare professional’s consideration for the sexuality of people experiencing mental disorders.
Leaving no one behind: using action research to promote male involvement in maternal and child health in Iringa region, Tanzania

Introduction Male involvement has been reported to improve maternal and child health (MCH) outcomes. However, most studies in low-income and middle-income countries have reported low participation of men in MCH-related programmes. While there is a growing interest in the involvement of men in MCH, little is known on how male involvement can be effectively promoted in settings where entrenched unequal gender roles, norms and relations constrain women from effectively inviting men to participate in MCH. Methods and analysis This paper reports participatory action research (PAR) aimed to promote male participation in pregnancy and childbirth in Iringa Region, Tanzania. As part of the Innovating for Maternal and Child Health in Africa project, PAR was conducted in 20 villages in two rural districts in Tanzania. Men and women were engaged separately to identify barriers to male involvement in antenatal care and during delivery; and then they were facilitated to design strategies to promote male participation in their communities. Along with the PAR intervention, researchers undertook a series of research activities. A thematic analysis was used to analyse the data. The common strategies designed were: engaging health facility committees; using male champions and male gatekeepers; and using female champions to sensitise and provide health education to women. These strategies were validated during stakeholders’ meetings, which were convened in each community. Discussion The use of participatory approach not only empowers communities to diagnose barriers to male involvement and develop culturally acceptable strategies but also increases sustainability of the interventions beyond the life span of the project. More lessons will be identified during the implementation of these strategies.
Post translational modifications in tuberculosis: ubiquitination paradox

ABSTRACT Innate immune signaling and xenophagy are crucial innate defense strategies exploited by the host to counteract intracellular pathogens with ubiquitination as a critical regulator of these processes. These pathogens, including Mycobacterium tuberculosis (M. tb), co-opt the host ubiquitin machinery by utilizing secreted or cell surface effectors to dampen innate host defenses. Inversely, the host utilizes ubiquitin ligase-mediated ubiquitination of intracellular pathogens and recruits autophagy receptors to induce xenophagy. In the current article, we discuss the co-option of the ubiquitin pathway by the M. tb virulence effectors. Abbreviations: ANAPC2: anaphase promoting complex subunit 2; IL: interleukin; Lys: lysine (K); MAPK: mitogen-activated protein kinase; MAP3K7/TAK1; mitogen-activated protein kinase kinase kinase 7; M. tb: Mycobacterium tuberculosis; NFKB/NF-κB: nuclear factor kappa B subunit; PtpA: protein tyrosine phosphatase; SQSTM1/p62: sequestosome 1; V-ATPase: vacuolar-type H+-ATPase; UBA: a eukaryotic-like ubiquitin-associated domain
Galaxy formation with L-GALAXIES: Model description

In this supplementary material, we give a full description of the treatment of astrophysical processes in our model of galaxy formation, a variant of the Henriques et al. 2020 public release. The most significant modification of our model with respect to Henriques et al. 2020 is the implementation of a novel gas stripping method. Like its predecessors, our model is built on subhalo merger trees constructed from the Millennium andMillennium-II simulations after scaling to represent the first-year Planck cosmology. A set of coupled differential equations allow us to model the formation and evolution of baryonic matter. In L-Galaxies, baryonic matter bound to each galaxy/subhalo is divided into seven main components: hot gas, cold gas (partitioned into HI and H2), stellar disc, bulge stars, halo stars, the supermassive black hole, and ejected material. There is also diffuse primordial gas associated with dark matter, which is not yet part of any halo. Primordial gas falls with the dark matter onto sufficiently massive haloes, where it is shock-heated. The efficiency of radiative cooling then determines whether it is added directly to the cold gas of the central galaxy, or resides for a while in a hot gas atmosphere. The properties of cold interstellar gas are followed in concentric rings where cold gas is partitioned into HI and H2 and the latter is converted into stars, both quiescently and in merger-induced starbursts which also drive the growth of central supermassive black holes. Stellar evolution is tracked independently in each ring and not only determines the photometric appearance of the final galaxy, but also heats and enriches its gas components, in many cases driving material into the wind reservoir, from which it may later fall back into the galaxy. Accretion of hot gas onto central black holes gives rise to radio mode feedback, regulating condensation of hot gas onto the galaxy. Galaxy mergers affect the gas components of galaxies, as well as the partition of stars between discs, bulges, and the intracluster light (the halo stars), a diffuse component built from tidally disrupted systems. The radial structure of discs and bulge sizes are estimated from simple energy and angular momentum-based arguments. Environmental processes such as tidal and ram-pressure stripping influence the gas content of galaxies and play a key role in quenching star formation of galaxies in dense environments. These processes are implemented based on local background environmentmeasurementsmade directly on the particle data of the underlying dark matter only simulations.
Whole genome sequencing of silver carp (Hypophthalmichthys molitrix) and bighead carp (Hypophthalmichthys nobilis) provide novel insights into their evolution and speciation

The edible silver carp (Hypophthalmichthys molitrix) and bighead carp (H. nobilis), which are two of the “Four Domesticated Fish” of China, are cultivated intensively worldwide. Here, we constructed 837‐ and 845‐Mb draft genome assemblies for the silver carp and the bighead carp, respectively, including 24,571 and 24,229 annotated protein‐coding genes. Genetic maps, anchoring 71.7% and 83.8% of all scaffolds, were obtained for the silver and bighead carp, respectively. Phylogenetic analysis showed that the bighead carp formed a clade with the silver carp, with an estimated divergence time of 3.6 million years ago; the time of divergence between the silver carp and zebrafish was 50.7 million years ago. An East Asian cyprinid genome‐specific chromosome fusion took place ~9.2 million years after this clade diverged from the clade containing the common carp and Sinocyclocheilus. KEGG and GO analyses indicated that the expanded gene families in the silver and bighead carp were associated with diseases, the immune system and environmental adaptations. Genomic regions differentiating the silver and bighead carp populations were detected based on the whole‐genome sequences of 42 individuals. Genes associated with the divergent regions were associated with reproductive system development and the development of primary female sexual characteristics. Thus, our results provided a novel systematic genomic analysis of the East Asian cyprinids, as well as the evolution and speciation of the silver carp and bighead carp.
Establishment and Validation of Nomogram Model Integrated With Inflammation-Based Factors for the Prognosis of Advanced Non-Small Cell Lung Cancer

Objects: Inflammation is one of the hallmarks of cancer. Tumor-associated inflammatory response plays a crucial role in enhancing tumorigenesis. This study aimed to establish an effective predictive nomogram based on inflammation factors in patients with advanced non-small cell lung cancer (NSCLC). Methods: We retrospectively evaluated 887 patients with advanced NSCLC between November 2004 and December 2015 and randomly divided them into primary (n = 520) and validation cohorts (n = 367). Cox regression analysis was used to identify prognostic factors for building the nomogram. The predictive accuracy and discriminative ability of the nomogram were determined using a concordance index (C-index), calibration plot, and decision curve analysis and were compared to the TNM staging system. Results: The nomogram was established using independent risk factors (P < 0.05): age, TNM stage, C reaction protein-to-albumin ratio (CAR), and neutrophils (NEU). The C-index of the model for predicting OS had a superior discrimination power compared to that of the TNM staging system both in the primary [0.711 (95% CI: 0.675-0.747) vs 0.531 (95% CI: 0.488-0.574), P < 0.01] and validation cohorts [0.703, 95% CI: 0.671 -0.735 vs 0.582, 95% CI: 0.545-0.619, P < 0.01]. Decision curves also demonstrated that the nomogram had higher overall net benefits than that of the TNM staging system. Subgroup analyses revealed that the nomogram was a favorable prognostic parameter in advanced NSCLC (P < 0.05). The results were internally validated using the validation cohorts. Conclusions: The proposed nomogram with inflammatory factors resulted in an accurate prognostic prediction in patients with advanced NSCLC.