Miracle-dz/UniFAR-FTUs huggingface dataset:
Toxins of the Helicobacter Genus and Their Roles in Pathogenesis

In the 20 years since the discovery of Helicobacter pylori the number of formally described Helicobacter spp. has increased dramatically. The majority of species in the genus have been associated with some form of pathology. Similar to other Gram‐negative bacteria, all helicobacters have lipopolysaccharides or endotoxins in the outer leaflet of their outer membrane which is an important modulator of the immune system. H. pylori endotoxin has a number of roles in the pathogenesis of the bacterium. Its relatively low biological and immunological activity and molecular mimicry may contribute to the chronic nature of infection through avoidance of host defence mechanisms and adhesion. In addition to endotoxins, various helicobacters also secrete distinct exotoxins capable of host cell damage. H. pylori has been shown to possess a cytotoxin capable of inducing vacuoles in epithelial cells termed vacuolating cytotoxin or VacA. Although VacA has a number of roles in the pathogenesis of H. pylori its use as a predictor of clinical outcome has yet to be established. In addition, similar to the closely related Campylobacter jejuni, a number of enterohepatic helicobacters express a cytolethal distending toxin capable of inducing severe cell damage in vivo and in vitro. Both endotoxins and exotoxins may play a combined role in the pathogenesis of Helicobacter spp. Both toxin types have been identified as being present on outer membrane vesicles shed by H. pylori which may act as antigen delivery vehicles and contribute to pathogenesis.
Weed Management in Mechanized-Sown, Zero-Till Dry-Seeded Rice

Abstract Weeds are the main constraint in the adoption of zero-till, dry-seeded rice systems because weeds and rice emerge simultaneously in these systems, and there is no standing water at crop establishment to suppress weeds. A study was conducted during the wet season of 2011 and the dry season of 2012 at the International Rice Research Institute to evaluate the performance of different herbicides in mechanized-sown, zero-till dry-seeded rice. Among the treatments evaluated, oxadiazon followed by penoxsulam + cyhalofop followed by one hand-weeding at 42 d after sowing, provided 23 to 35% higher yield than the nontreated control. The yields in the oxadiazon-treated plots were similar to those in the weed-free plots. Some weed species, including eclipta and doveweed, were not controlled by the evaluated herbicides. Therefore, there is a need to evaluate additional herbicides and to integrate them with cultural weed management strategies to manage such problematic weeds. Nomenclature: Cyhalofop; oxadiazon; penoxsulam; doveweed; Murdannia nudiflora (L.) Brenan MUDNU; eclipta; Eclipta prostrata (L.) L. ECLAL; rice; Oryza sativa L. ORYSA Resumen Las malezas son la principal limitante para la adopción de la labranza cero en sistemas de arroz sembrado en secano porque en estos sistemas las malezas y el arroz emergen simultáneamente y no hay una lámina de agua presente que suprima las malezas al momento del establecimiento del cultivo. Se realizó un estudio durante la época lluviosa de 2011 y la época seca de 2012 en el Instituto Internacional de Investigaciones sobre el Arroz para evaluar el desempeño de diferentes herbicidas en siembra mecanizada, labranza cero y siembra de arroz de secano. Entre los tratamientos evaluados, oxadiazon seguido de penoxsulam + cyhalofop seguido por una deshierba manual a 42 d después de la siembra, resultó en un rendimiento 23 a 35% mayor que el testigo no-tratado. Los rendimientos en las parcelas tratadas con oxadiazon fueron similares a los de las parcelas libres de malezas. Algunas especies de malezas, incluyendo Eclipta prostrata y Murdannia nudiflora, no fueron controladas por los herbicidas evaluados. Por esta razón, existe la necesidad de evaluar herbicidas adicionales y su integración con estrategias de manejo cultural para el manejo de estas malezas problemáticas.
Natural Fermentation of Cowpea (Vigna unguiculata) Flour Improves the Nutritive Utilization of Indispensable Amino Acids and Phosphorus by Growing Rats

Cowpea (Vigna unguiculata) is among the most cultivated legumes, with interesting agronomic and environmental properties, and great potential as a nutritious food. The nutritional value of cowpea can be improved by technological processing. In this study, we showed that natural fermentation improved bioavailability of protein, amino acids, and dietary essential minerals from cowpea in growing rats, thus strengthening its potential value as functional food or food supplement. Forty Wistar albino rats (48 ± 1.8 g), were fed one of four experimental diets (n = 10 rats per diet): casein, raw cowpea, fermented cowpea or fermented and autoclaved cowpea. Despite lower growth indices of raw and fermented cowpea protein (PER, FTI) than casein, fermentation enhanced apparent digestibility of arginine, leucine, lysine, methionine, phenylalanine, tyrosine, and valine, and true digestibility of essential amino acids, except for tyrosine and valine, compared to raw cowpea. On the other hand, autoclaving of fermented cowpea flour decreased apparent, as did true digestibility of sulfur amino acids. Regarding the nutritive utilization of dietary essential minerals, Vigna unguiculata was a good source of available P, Mg, and K, while fermentation significantly improved the availability of P. Overall, cowpea was a good source of digestible essential amino acids and minerals and fermentation significantly improved its nutritional value that was not further enhanced by autoclaving.
Psychiatric Aspects of Obesity: A Narrative Review of Pathophysiology and Psychopathology

In the last decades, obesity has become a major concern for clinical and public health. Despite the variety of available treatments, the outcomes remain—by and large—still unsatisfactory, owing to high rates of nonresponse and relapse. Interestingly, obesity is being associated with a growing surge of neuropsychiatric problems, certainly related to the pathogenesis of this condition, and likely to be of great consequence as for its treatment and prognosis. In a neurobiologic direction, a sturdy body of evidence has recently shown that the immune–metabolic–endocrine dyscrasias, notoriously attached to excess body weight/adiposity, affect and impair the morpho-functional integrity of the brain, thus possibly contributing to neuroprogressive/degenerative processes and behavioral deviances. Likewise, in a neuropsychiatric perspective, obesity displays complex associations with mood disorders and affective temperamental dimensions (namely cyclothymia), eating disorders characterized by overeating/binge-eating behaviors, ADHD-related executive dysfunctions, emotional dysregulation and motivational–addictive disturbances. With this review, we attempt to provide the clinician a synoptic, yet exhaustive, tool for a more conscious approach to that subset of this condition, which could be reasonably termed “psychiatric” obesity.
Organizational Support in Healthcare Redesign Education: A Mixed-Methods Exploratory Study of Expert Coach and Executive Sponsor Experiences

Healthcare organizations must continue to improve services to meet the rising demand and patient expectations. For this to occur, the health workforce needs to have knowledge and skills to design, implement, and evaluate service improvement interventions. Studies have shown that effective training in health service improvement and redesign combines didactic education with experiential project-based learning and on-the-ground coaching. Project-based learning requires organizational support and oversight, generally through executive sponsorship. A mixed-methods approach, comprising online surveys and semi-structured interviews, was used to explore the experiences of expert coaches and executive sponsors as key facilitators of workplace-based projects undertaken during an Australian postgraduate healthcare redesign course. Fifteen (54%) expert coaches and 37 (20%) executive sponsors completed the online survey. Ten expert coaches and six executive sponsors participated in interviews. The survey data revealed overall positive experiences for coaches and mixed experiences for sponsors. Interview participants expressed a sense of fulfillment that came from working with project teams to deliver a successful project and educational outcomes. However, concerns were raised about adequate resourcing, organizational recognition, competing priorities, and the skills required to effectively coach and sponsor. Expert coaches and executive sponsors sometimes felt under-valued and may benefit from cohort-tailored and evidence-based professional development.
Conversion of T Follicular Helper Cells to T Follicular Regulatory Cells by Interleukin‐2 Through Transcriptional Regulation in Systemic Lupus Erythematosus

This study was undertaken to identify characteristics of follicular regulatory T (Tfr) cells and elucidate the mechanisms by which follicular helper T (Tfh) cells convert to Tfr cells. We probed the phenotype of T helper cells in patients with systemic lupus erythematosus (SLE) and underlying transcriptional regulation using cytokine‐induced STAT family factors.
Flow-accelerated platelet biogenesis is due to an elasto-hydrodynamic instability

Significance To maintain the high number of blood platelets in mammalian blood, an exceptionally efficient process for platelet biogenesis is required. While recent in vitro experiments demonstrate blood flow as a key factor accelerating biogenesis, the biophysical mechanism behind this acceleration remains unclear. Here we use computer simulations to show how fluid flow can indeed strongly increase biogenesis. The key aspect of our work is that we introduce a physical mechanism, akin to the well-known Rayleigh–Plateau instability of a liquid jet, as the likely origin of accelerated platelet production. Our findings can lead to a more efficient design of microfluidic bioreactors for platelet production, but also explain the exceptionally strong coupling of fluid flow and platelet biogenesis in vivo. Blood platelets are formed by fragmentation of long membrane extensions from bone marrow megakaryocytes in the blood flow. Using lattice-Boltzmann/immersed boundary simulations we propose a biological Rayleigh–Plateau instability as the biophysical mechanism behind this fragmentation process. This instability is akin to the surface tension-induced breakup of a liquid jet but is driven by active cortical processes including actomyosin contractility and microtubule sliding. Our fully three-dimensional simulations highlight the crucial role of actomyosin contractility, which is required to trigger the instability, and illustrate how the wavelength of the instability determines the size of the final platelets. The elasto-hydrodynamic origin of the fragmentation explains the strong acceleration of platelet biogenesis in the presence of an external flow, which we observe in agreement with experiments. Our simulations then allow us to disentangle the influence of specific flow conditions: While a homogeneous flow with uniform velocity leads to the strongest acceleration, a shear flow with a linear velocity gradient can cause fusion events of two developing platelet-sized swellings during fragmentation. A fusion event may lead to the release of larger structures which are observable as preplatelets in experiments. Together, our findings strongly indicate a mainly physical origin of fragmentation and regulation of platelet size in flow-accelerated platelet biogenesis.
Environment versus dispersal in the assembly of western Amazonian palm communities

Aim It is a central issue in ecology and biogeography to understand what governs community assembly and the maintenance of biodiversity in tropical rain forest ecosystems. A key question is the relative importance of environmental species sorting (niche assembly) and dispersal limitation (dispersal assembly), which we investigate using a large dataset from diverse palm communities.
Rapid Increase of CTX-M-Producing Shigella sonnei Isolates in Switzerland Due to Spread of Common Plasmids and International Clones

The Swiss Centre for Antibiotic Resistance (ANRESIS) has recently noted an increase of extended-spectrum cephalosporin-resistant (ESC-R) Shigella sonnei isolates nationwide (3.8% in 2016 versus 37.5% in 2019). To understand this phenomenon, we analyzed 25 representative isolates (of which 14 were ESC-R) collected in Switzerland during 2016 to 2019. Whole-genome sequencing was achieved using both the Illumina and the Nanopore platforms. Both ESC-R and extended-spectrum cephalosporin-susceptible isolates belonged to sequence type 152 (ST152). ABSTRACT The Swiss Centre for Antibiotic Resistance (ANRESIS) has recently noted an increase of extended-spectrum cephalosporin-resistant (ESC-R) Shigella sonnei isolates nationwide (3.8% in 2016 versus 37.5% in 2019). To understand this phenomenon, we analyzed 25 representative isolates (of which 14 were ESC-R) collected in Switzerland during 2016 to 2019. Whole-genome sequencing was achieved using both the Illumina and the Nanopore platforms. Both ESC-R and extended-spectrum cephalosporin-susceptible isolates belonged to sequence type 152 (ST152). The ESC-R isolates carried blaCTX-M-3 in IncI1-pST57 (n = 5), blaCTX-M-15 in IncFII (F2:A-:B-) (n = 5), blaCTX-M-15 in IncI1-pST16, and blaCTX-M-27, blaCTX-M-55, or blaCTX-M-134 in other IncFII plasmids (n = 1 each). Plasmids having the same bla and Inc group exhibited high degrees of genetic identity to each other but also to plasmids previously reported in other Enterobacterales. Core-genome analysis showed that there were 4 main clusters, each of which included strains that differed by <58 single nucleotide variants (SNVs) and that consisted of both blaCTX-M-positive and blaCTX-M-negative isolates. Moreover, most isolates belonging to the same cluster shared an identical core-genome sequence type (cgST). For instance, cluster 1 included 4 isolates of cgST113036, of which only 3 harbored the IncI1-pST57 blaCTX-M-3-positive plasmid. The 25 S. sonnei isolates were also subjected to phylogenetic comparison with deposited international strains. As a result, matching isolates (isolates that had the same cgST and that differed by <8 SNVs) have been reported in the United Kingdom, the United States, France, and the Netherlands. Overall, our results suggest that some common S. sonnei clusters can spread between continents and can be imported into other nations after international trips. Such clusters include, in part, isolates that do not possess blaESBL-harboring plasmids, indicating their tendency to acquire them from other Enterobacterales.
Antimicrobial Activities of Highly Bioavailable Organic Salts and Ionic Liquids from Fluoroquinolones

As the development of novel antibiotics has been at a halt for several decades, chemically enhancing existing drugs is a very promising approach to drug development. Herein, we report the preparation of twelve organic salts and ionic liquids (OSILs) from ciprofloxacin and norfloxacin as anions with enhanced antimicrobial activity. Each one of the fluoroquinolones (FQs) was combined with six different organic hydroxide cations in 93–100% yield through a buffer-assisted neutralization methodology. Six of those were isomorphous salts while the remaining six were ionic liquids, with four of them being room temperature ionic liquids. The prepared compounds were not toxic to healthy cell lines and displayed between 47- and 1416-fold more solubility in water at 25 and 37 °C than the original drugs, with the exception of the ones containing the cetylpyridinium cation. In general, the antimicrobial activity against Klebsiella pneumoniae was particularly enhanced for the ciprofloxacin-based OSILs, with up to ca. 20-fold decreases of the inhibitory concentrations in relation to the parent drug, while activity against Staphylococcus aureus and the commensal Bacillus subtilis strain was often reduced. Depending on the cation–drug combination, broad-spectrum or strain-specific antibiotic salts were achieved, potentially leading to the future development of highly bioavailable and safe antimicrobial ionic formulations.
Concussion Epidemiology in Youth Sports: Sports Study of a Statewide High School Sports Program

Background: Current research on concussion incidence in youth athletes (age <18 years) is small and limited by variability in injury reporting and diagnostic methodology. Hypothesis: Concussion injuries commonly occur in high school sports programs. The likelihood of concussion among student-athletes (aged 13-18 years) depends on the sport they are participating in as well as the sex of the athlete. Study Design: Descriptive epidemiology study. Level of Evidence: Level 4. Methods: A retrospective analysis of all Hawaii high school athletes aged 13 to 18 years participating in 14 sports from 2011 through 2017 was performed as part of a statewide standardized concussion assessment and management program. Results: A total of 5993 concussions were identified among 92,966 athletes. The overall concussion rate was 0.96 (95% CI, 0.94-0.99). Girls’ judo had the highest concussion rate (1.92; 95% CI, 1.68-2.17) followed by football (1.60; 95% CI, 1.53-1.66). The concussion rate for boys (1.0; 95% CI, 0.97-1.03) was higher than that for girls (0.91; 95% CI, 0.87-0.95); however, in 4 of the 5 sports in which both girls and boys participated, girls had a higher rate of concussion injury. Conclusion: The likelihood of concussion among student-athletes aged 13 to 18 years may be higher than previously thought and varies depending on sport and sex. Clinical Relevance: Epidemiologic data on concussion injury in children and adolescents are useful in accurately determining the relative risks of high school sports participation and may be valuable in determining the appropriate allocation of health care and scholastic resources for student-athletes, as well as the impact of rule and training modifications designed to improve participant safety.
Gene expression profiling of hypertrophic cardiomyocytes identifies new players in pathological remodelling

Abstract Aims Pathological cardiac remodelling is characterized by cardiomyocyte (CM) hypertrophy and fibroblast activation, which can ultimately lead to maladaptive hypertrophy and heart failure (HF). Genome-wide expression analysis on heart tissue has been instrumental for the identification of molecular mechanisms at play. However, these data were based on signals derived from all cardiac cell types. Here, we aimed for a more detailed view on molecular changes driving maladaptive CM hypertrophy to aid in the development of therapies to reverse pathological remodelling. Methods and results Utilizing CM-specific reporter mice exposed to pressure overload by transverse aortic banding and CM isolation by flow cytometry, we obtained gene expression profiles of hypertrophic CMs in the more immediate phase after stress, and CMs showing pathological hypertrophy. We identified subsets of genes differentially regulated and specific for either stage. Among the genes specifically up-regulated in the CMs during the maladaptive phase we found known stress markers, such as Nppb and Myh7, but additionally identified a set of genes with unknown roles in pathological hypertrophy, including the platelet isoform of phosphofructokinase (PFKP). Norepinephrine-angiotensin II treatment of cultured human CMs induced the secretion of N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) and recapitulated the up-regulation of these genes, indicating conservation of the up-regulation in failing CMs. Moreover, several genes induced during pathological hypertrophy were also found to be increased in human HF, with their expression positively correlating to the known stress markers NPPB and MYH7. Mechanistically, suppression of Pfkp in primary CMs attenuated stress-induced gene expression and hypertrophy, indicating that Pfkp is an important novel player in pathological remodelling of CMs. Conclusion Using CM-specific transcriptomic analysis, we identified novel genes induced during pathological hypertrophy that are relevant for human HF, and we show that PFKP is a conserved failure-induced gene that can modulate the CM stress response.
The BRAIN Initiative and Neuroethics: Enabling and Enhancing Neuroscience Advances for Society

Abstract As the Brain Research through Advancing Neurotechnologyies, better known as the BRAIN Initiative moves forward at a rapid pace increasing attention has focused on neuroethics. The National Institutes of Health recently mandated a review of the progress of the BRAIN Initiative progress with the goal of fine-tuning its future directions. The BRAIN Working Group 2 focused its discussion on science while the BRAIN Neuroethics Subgroup focused on neuroethics. The Brain Neuroethics Subgroup deliberated for over a year collecting information and recommendations through in person and video meetings, a public one-day neuroethics symposium and soliciting input from neuroscientists and neuroethicist’s. The resulting report entitled “The BRAIN Initiative and Neuroethics: Enabling and Enhancing Neuroscience Advances for Society” was accepted by Director of NIH in October of 2019. The recommendations span many BRAIN research neuroethics concerns including privacy considerations, the use of nonhuman primate model systems, neural modulation and enhancement, subject participation in BRAIN research and equity in neuroscience research. Further the group recommended a transformative project whose goal of detailing the scientific mechanisms and ethical underpinnings of consciousness is one of the most daunting issues that impact our perceptions of ourselves. It is anticipated that the report? s recommendations will provide a foundation or “roadmap” for ensuring that neuroethics and BRAIN research move forward as an integrated effort thereby insuring that BRAIN research is of the highest quality. Video Abstract Read the transcript Watch the video on Vimeo
Hypothermia‐related Deaths: A 10‐year Retrospective Study of Two Major Metropolitan Cities in the United States*

Hypothermia‐related deaths affect vulnerable populations and are preventable. They account for the vast majority of weather‐related deaths in the United States. The postmortem diagnosis of hypothermia can be challenging, as there are no pathognomonic signs. The electronic databases of the New York City Office of Chief Medical Examiner and Harris County Institute of Forensic Sciences were searched for all fatalities where the primary cause of death included hypothermia, between January 2009 and July 2019. There were 139 hypothermia deaths in New York City (NYC) with an average annualized rate of 1.7 per million. During this same time, there were 50 hypothermia deaths in Houston with an average annualized rate of 2.4 per million. Males were more likely to die of hypothermia compared to females in both cities. The rate ratio (RR) in NYC was 3.55 (95% CI 2.40, 5.25), while the RR in Houston was 2.83 (95% CI 1.50, 5.32). Age‐ and sex‐specific standardized hypothermia mortality rates were 18.2 (95% CI 15.1, 21.2) per million in NYC and 30.1 (95% CI 21.7, 38.6) per million in Houston. The comparative hypothermia death ratio was 1.66 (95% CI 1.19, 2.30), indicating hypothermia mortality in Houston was 66% higher than in NYC. There was no correlation between zip code poverty rates and hypothermia‐related deaths. The most consistent autopsy finding was Wischnewski spots (56.6%), and ethanol was the most common toxicological finding (36.5%). Local agencies can use this data to target these higher‐risk populations and offer appropriate interventions to try to prevent these deaths.