bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered carbohydrate oxidation during exercise in overreached endurance athletes is applicable to training monitoring with continuous glucose monitors
Authors: Coates Alexandra M. , Thompson Kyle M. A. , Grigore Monica M. , Baker Ryleigh E. , Pignanelli Christopher , Robertson Alexa A. , Frangos Sara M. , Cheung Christian P. , Burr Jamie F. 
Published: December 2023

AbstractPurposeThe purpose of the study was to investigate whether carbohydrate utilization is altered during exercise in overreached endurance athletes and examine the utility of continuous glucose monitors (CGM) to detect overreaching status.MethodsEleven endurance athletes (M:8, F:3) completed a 5‐week training block consisting of 1 week of reduced training (PRE), 3 weeks of high‐intensity overload training (POST), and 1 week of recovery training (REC). Participants completed a Lamberts and Lambert Submaximal Cycling Test (LSCT) and 5 km time‐trial at PRE, POST, and REC time points, 15 min following the ingestion of a 50 g glucose beverage with glucose recorded each minute via CGM.ResultsPerformance in the 5 km time‐trial was reduced at POST (∆‐7 ± 10 W, p = 0.04,  = 0.35) and improved at REC (∆12 ± 9 W from PRE, p = 0.01,  = 0.66), with reductions in peak lactate (∆‐3.0 ± 2.0 mmol/L, p = 0.001,  = 0.71), peak HR (∆‐6 ± 3 bpm, p < 0.001,  = 0.86), and Hooper‐Mackinnon well‐being scores (∆10 ± 5 a.u., p < 0.001,  = 0.79), indicating athletes were functionally overreached. The respiratory exchange ratio was suppressed at POST relative to REC during the 60% (POST: 0.80 ± 0.05, REC: 0.87 ± 0.05, p < 0.001,  = 0.74), and 80% (POST: 0.93 ± 0.05, REC: 1.00 ± 0.05, p = 0.003,  = 0.68) of HR‐matched submaximal stages of the LSCT. CGM glucose was reduced during HR‐matched submaximal exercise in the LSCT at POST (p = 0.047,  = 0.36), but not the 5 km time‐trial (p = 0.07,  = 0.28) in overreached athletes.ConclusionThis preliminary investigation demonstrates a reduction in CGM‐derived glucose and carbohydrate oxidation during submaximal exercise in overreached athletes. The use of CGM during submaximal exercise following standardized nutrition could be employed as a monitoring tool to detect overreaching in endurance athletes.
Real‐time loop‐mediated isothermal amplification (real‐time LAMP) assay for rapid diagnosis of amoebic liver abscess
Authors: Khunger Sandhya , Mewara Abhishek , Kaur Upninder , Duseja Ajay , Ray Pallab , Kalra Naveen , Sharma Navneet , Sehgal Rakesh 
Published: December 2023

AbstractAmong the parasitic diseases, amoebic liver abscess (ALA) ranks second to malaria in terms of mortality. Due to the poor sensitivity of conventional diagnostic methods, there is a need for the development of effective and rapid diagnostic methods for ALA. Thus, the purpose of this work was to develop a real‐time loop‐mediated isothermal amplification (RT‐LAMP) assay specific to Entamoeba histolytica. Further, we compared the performance of real‐time LAMP with conventional and real‐time PCR (RT‐PCR) targeting 18S small subunit ribosomal RNA (18S SSU rRNA) gene of E. histolytica in patients with ALA. A total of 126 liver samples were obtained for the study. Of these, 96 aspirated pus samples were obtained from patients suffering from an ALA (serology confirmed, anti‐amoebic immunoglobulin IgG positive), 19 aspirated pus samples from patients with pyogenic liver abscess (PLA, 16S RNA gene positive) and 11 autopsy liver tissues. The results showed that the DNA of E. histolytica was detected in 81 samples by conventional PCR, 93 by RT‐PCR and 95 by RT‐LAMP. The analytical sensitivity of the RT‐LAMP assay was much higher than the other two techniques. RT‐LAMP assay was able to amplify up to one copy of the targeted gene of E. histolytica while conventional PCR and RT‐PCR could amplify up to 103 and 102 copies of the targeted gene of E. histolytica, respectively. In conclusion, RT‐LAMP proved to be a sensitive, specific and rapid test which can be utilised as an effective tool for the diagnosis of ALA.
Fever in focus: Symptoms, diagnoses and treatment of febrile children in Ghana—A longitudinal hospital study
Authors: Rautman Lydia Helen , Maiga‐Ascofaré Oumou , Eibach Daniel , Hogan Benedikt , Dekker Denise , Jaeger Anna , Akenten Charity Wiafe , Owusu‐Dabo Ellis , Boateng Felix Osei , Hanson Henry , Boahen Kennedy Gyau , Sarpong Nimako , Adu‐Sarkodie Yaw , Kreuels Benno , May Jürgen , Krumkamp Ralf 
Published: December 2023

AbstractBackgroundHealthcare resources are often limited in areas of sub‐Saharan Africa. This makes accurate and timely diagnoses challenging and delays treatment of childhood febrile illness. We explored longitudinal characteristics related to symptoms, diagnosis and treatment of hospitalised febrile children in a rural area of Ghana highly endemic for malaria.MethodsFebrile children under 15 years, admitted to the study hospital paediatric ward, were recruited to the study and clinical data were collected throughout hospitalisation. Descriptive statistics were reported for all cases; for longitudinal analyses, a subset of visits with limited missing data was used.ResultsThere were 801 hospitalised children included in longitudinal analyses. Malaria (n = 581, 73%) and sepsis (n = 373, 47%) were the most prevalent suspected diagnoses on admission. One‐third of malaria suspected diagnoses (n = 192, 33%) were changed on the discharge diagnosis, compared to 84% (n = 315) of sepsis suspected diagnoses. Among malaria‐only discharge diagnoses, 98% (n/N = 202/207) received an antimalarial and 33% (n/N = 69/207) an antibiotic; among discharge diagnoses without malaria, 28% (n/N = 108/389) received an antimalarial and 83% (n/N = 324/389) an antibiotic.ConclusionsSuspected diagnoses were largely based on clinical presentation and were frequently changed; changed diagnoses were associated with lingering symptoms, underscoring the need for faster and more accurate diagnostics. Medications were over‐prescribed regardless of diagnosis stability, possibly because of a lack of confidence in suspected diagnoses. Thus, better diagnostic tools are needed for childhood febrile illnesses to enhance the accuracy of and confidence in diagnoses, and to cut down unjustified medication use, reducing the risk of antimicrobial and malaria resistance.
Teacher-Coaches in an Australian Regional Independent School: An Exploratory Case Study
Authors: Johnson Matthew G. , Stylianou Michalis , Mallett Clifford J. 
Published: December 2023

Grounded in role socialization theory, we examined the perceptions of teacher-coaches at an Australian independent, regional school regarding the challenges and opportunities associated with performing this dual role. This interpretivist exploratory case study was conducted with 10 teacher-coaches of various backgrounds and experience levels. Data were collected through semistructured interviews and analyzed using a data-driven reflexive thematic analysis. Three themes were identified: (a) teacher-coaches preferred teaching over coaching, and a mismatch existed between administrators’ position and teacher-coaches’ perceptions of school practice; (b) participants identified enhanced relationships with students and career enhancement as opportunities in performing the dual roles; and (c) perceived challenges included time pressures, insufficient coaching preparation, and development opportunities. Findings highlight the complexities in successfully navigating the dual role in this context. Consideration of role preferences, challenges and opportunities, and localized coaching supports may help optimize teacher-coach, student, and school outcomes.
Exploring Blind and Visually Impaired Students’ Views on How to Improve Physical Education
Authors: Keene M. Ally , Haegele Justin A. , Ball Lindsay E. , Nowland Lindsey A. , Zhu Xihe 
Published: December 2023

Purpose: The purpose of this study was to explore blind and visually impaired students’ opinions on ways to improve physical education. Method: Twenty-two blind and visually impaired youth (age 12–17 years) completed one-to-one interviews. Three themes were constructed using a reflexive thematic analysis approach. Findings: The first theme depicted participants’ views that physical education was a break during the day that did not have educational benefits. In the second theme, the participants highlighted communication and collaboration as important elements that could improve their experiences. The final theme centered on the nonexistent, insufficient, or demoralizing nature of seldom existing accommodations. Discussion: Blind and visually impaired students noted aspects of curriculum content, communication, and accommodations in physical education that may be changed to enhance their experiences, which largely centered on their physical educators’ behaviors.
Oteseconazole versus fluconazole for the treatment of severe vulvovaginal candidiasis: a multicenter, randomized, double-blinded, phase 3 trial
Authors: Wang Xiaoqian , Chen Lihong , Ruan Hongjie , Xiong Zhengai , Wang Wenying , Qiu Jin , Song Weihua , Zhang Chunlian , Xue Fengxia , Qin Tianhua , Zhang Bei , An Ruifang , Luo Xiping , Wang Wei , Zhang Songling , Cai Yunlang , Kang Jiali , Deng Henan , Fan Shangrong , Cui Manhua , Wang Shijin , Luo Xiaowan , Su Zhiying , Shu Jing , Wang Quanren , Wang Fang , Bai Jianling , Liao Qinping 
Published: December 2023

ABSTRACT

Vulvovaginal candidiasis (VVC) is a common condition among women. Fluconazole remains the dominant treatment option for VVC. Oteseconazole is a highly selective inhibitor of fungal CYP51. This randomized, double-blinded, phase 3 trial was conducted to evaluate the efficacy and safety of oteseconazole compared with fluconazole in treating severe VVC. Female subjects presenting with vulvovaginal signs and symptoms score of ≥7 and positive
Candida
infection determined by potassium hydroxide test or Gram staining were randomly assigned to receive oteseconazole (600 mg on D1 and 450 mg on D2) or fluconazole (150 mg on D1 and D4) in a 1:1 ratio. The primary endpoint was the proportion of subjects achieving therapeutic cure [defined as achieving both clinical cure (absence of signs and symptoms of VVC) and mycological cure (negative culture of
Candida
species)] at D28. A total of 322 subjects were randomized and 321 subjects were treated. At D28, a statistically significantly higher proportion of subjects achieved therapeutic cure in the oteseconazole group than in the fluconazole group (66.88% vs 45.91%;
P
= 0.0002). Oteseconazole treatment resulted in an increased proportion of subjects achieving mycological cure (82.50% vs 59.12%;
P
< 0.0001) and clinical cure (71.25% vs 55.97%;
P
= 0.0046) compared with fluconazole. The incidence of treatment-emergent adverse events was similar between the two groups. No subjects discontinued study treatment or withdrew study due to adverse events. Oteseconazole showed statistically significant and clinically meaningful superiority over fluconazole for the treatment of severe VVC and was generally tolerated.
Systematic functional analysis of the Com pilus in
Streptococcus sanguinis
: a minimalistic type 4 filament dedicated to DNA uptake in monoderm bacteria
Authors: Mom Jeremy , Chouikha Iman , Valette Odile , Pieulle Laetitia , Pelicic Vladimir 
Published: December 2023

ABSTRACT

Type 4 filaments (T4F) are a superfamily of versatile nanomachines, ubiquitous in prokaryotes, which use conserved multi-protein machineries to assemble and operate filamentous polymers of type 4 pilins. In the best-studied T4F, these machineries are complex, which has posed challenges to understanding the mechanisms of filament assembly and their multiple functions. Here, we report the systematic functional analysis of the Com pilus, a widespread T4F mediating DNA uptake during natural transformation in monoderm bacteria. Using
Streptococcus sanguinis
, we show that Com pili are
bona fide
type 4 pili (T4P), representing a new pilus sub-type. We show that with only eight components necessary for pilus assembly and functioning—all “core” proteins universally conserved in this superfamily—the Com pilus epitomizes a minimalistic T4F. We further demonstrate that core T4F components are sufficient for filament assembly. Paradoxically, akin to the more elaborate T4F, the Com pilus contains four minor pilins forming a complex, probably tip-located. Our results have global implications for T4F and make the Com pilus a model for elucidating fundamental processes underpinning filament assembly.

IMPORTANCE
Type 4 filaments (T4F) are nanomachines ubiquitous in prokaryotes, centered on filamentous polymers of type 4 pilins. T4F are exceptionally versatile and widespread virulence factors in bacterial pathogens. The mechanisms of filament assembly and the many functions they facilitate remain poorly understood because of the complexity of T4F machineries. This hinders the development of anti-T4F drugs. The significance of our research lies in characterizing the simplest known T4F—the Com pilus that mediates DNA uptake in competent monoderm bacteria—and showing that four protein components universally conserved in T4F are sufficient for filament assembly. The Com pilus becomes a model for elucidating the mechanisms of T4F assembly.
Mucorales
fungi suppress nitric oxide production by macrophages
Authors: Soare Alexandra Y. , Bruno Vincent M. 
Published: December 2023

ABSTRACT

Mucormycosis is classified by the National Institute of Allergy and Infectious Diseases as an emerging disease and is caused by
Mucorales
fungi. Despite the high morbidity and mortality rates associated with the disease, little is known about the host-pathogen interactions that dictate disease progression. The recent surge of mucormycosis cases among COVID-19 patients has thrust the disease and the lack of available treatments into the spotlight. Despite severe fungal angioinvasion and tissue necrosis during infection, clinical observations suggest a lack of pro-inflammatory responses. Understanding immune evasion mechanisms in mucormycosis can help guide potential therapeutic options. In this study, we demonstrate that
Mucorales
fungi can suppress the accumulation of nitric oxide (NO) in lipopolysaccharide- and interferon gamma-stimulated macrophages despite robust expression of the
Nos2
mRNA and inducible nitric oxide synthase protein. This suppressive activity requires fungal viability and direct contact with macrophages and is not due to restricted access to L-arginine substrate. While
Mucorales
fungi appear to be able to remove NO from its environment, it does not account for the full suppression that we observe and suggests that
Mucorales
employs at least two mechanisms. Future experiments will elucidate the mechanisms by which
Mucorales
fungi deplete NO accumulation by macrophages and the implications of this depletion in mucormycosis pathogenesis.

IMPORTANCE

In October 2022,
Mucorales
fungi were listed in the “High Priority Group” on the first-ever list of fungal priority pathogens by the World Health Organization. As the causative agent of mucormycosis,
Mucorales
have become of great clinical and public health importance with growing mucormycosis numbers, notably with the exponential rise of COVID-19-associated mucormycosis cases. Despite the dire need, there are limited therapeutic options to treat mucormycosis. Our research fills in critical gaps of knowledge about how
Mucorales
fungi evade the host immune system. Specifically, we offer evidence that
Mucorales
block nitric oxide production, which is a key mediator and signaling molecule of the mammalian innate immune response to microbial pathogens. Our work offers new insight into immune evasion mechanisms by
Mucorales
fungi.
Interrelation between gut microbiota, SCFA, and fatty acid composition in pigs
Authors: Sebastià Cristina , Folch Josep M. , Ballester Maria , Estellé Jordi , Passols Magí , Muñoz María , García-Casco Juan M. , Fernández Ana I. , Castelló Anna , Sánchez Armand , Crespo-Piazuelo Daniel 
Published: December 2023

ABSTRACT

The gut microbiota is a key player in the host metabolism. Some bacteria are able to ferment non-digestible compounds and produce short-chain fatty acids that the host can later transform and accumulate in tissue. In this study, we aimed to better understand the relationships between the microorganisms and the short-chain fatty acid composition of the rectal content, including the possible linkage with the fatty acid composition in backfat and muscle of the pig. We studied a Duroc × Iberian crossbred population, and we found significant correlations between different bacterial and archaeal genera and the fatty acid profile. The abundance of n-butyric acid in the rectal content was positively associated with
Prevotella
spp. and negatively associated with
Akkermansia
spp., while conversely, the abundance of acetic acid was negatively and positively associated with the levels of
Prevotella
spp. and
Akkermansia
spp., respectively. The most abundant genus,
Rikenellaceae
RC9 gut group, had a positive correlation with palmitic acid in muscle and negative correlations with stearic acid in backfat and oleic acid in muscle. These results suggest the possible role of
Prevotella
spp. and
Akkermansia
spp. as biomarkers for acetic and n-butyric acids, and the relationship of
Rikenellaceae
RC9 gut group with the lipid metabolism, building up the potential, although indirect, role of the microbiota in the modification of the backfat and muscle fatty acid composition of the host.

IMPORTANCE

The vital role of the gut microbiota on its host metabolism makes it essential to know how its modulation is mirrored on the fatty acid composition of the host. Our findings suggest
Prevotella
spp. and
Akkermansia
spp. as potential biomarkers for the levels of beneficial short-chain fatty acids and the possible influence of
Rikenellaceae
RC9 gut group in the backfat and muscle fatty acid composition of the pig.
Suicidality Treatment Occurring in Paediatrics (STOP) Medication Suicidality Side Effects Scale in young people in two cohorts across Europe
Authors: Santosh Paramala , Sala Regina , Lievesley Kate , Singh Jatinder , Arango Celso , Buitelaar Jan K , Castro-Fornieles Josefina , Coghill David , Dittmann Ralf W , Flamarique Itziar , Hoekstra Pieter J , Llorente Cloe , Purper-Ouakil Diane , Schulze Ulrike , Zuddas Alessandro , Parnell Nathan , Mohan Mohapradeep , Fiori Federico 
Published: December 2023

ObjectivesAs part of the ‘Suicidality: Treatment Occurring in Paediatrics (STOP)’ study, we developed and performed psychometric validation of an electronic-clinical-outcome-assessment (eCOA), which included a patient-reported-outcome (ePRO), an observer-rated-outcome (eObsRO) for parents/carers and a clinician-reported-outcome (eClinRO) that allows identification and monitoring of medication-related suicidality (MRS) in adolescents.DesignSTOP: Prospective study: A two phase validation study to assess the impact of medication on suicidal ideations.SettingSix participating countries: Netherlands, UK, Germany, France, Spain and Italy that were part of the Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 261411.ParticipantsCohort 1 consisted of 41 adolescent-completions, 50 parent-completions and 56 clinician-completions. Cohort 2 consisted of 244 adolescent-completions, 198 parent-completions and 240 clinician-completions from across the six countries. The scale was administered only to participants who have screened positive for the STOP-Suicidality Assessment Scale (STOP-SAS).ResultsA total of 24 items for the development of the STOP-Medication Suicidality Side Effects Scale (STOP-MS3) were identified and three versions (for patients, parents and clinicians) of the STOP-MS3were developed and validated in two separate study cohorts comprising of adolescents, their parents and clinicians. Cronbach’s α coefficients were above 0.85 for all domains. The inter-rater reliability of the STOP-MS3was good and significant for the adolescent (ePRO), clinician (eClinRO) (r=0.613), parent (eObsRO) versions of the scale (r=0.394) and parent and clinician (r=0.347). Exploratory factor analysis identified a 3-factor model across 24 items for the adolescent and parent version of the scale: (1) Emotional Dysregulation, (2) Somatic Dysregulation and (3) Behavioural Dysregulation. For the clinician version, a 4-factor model defined the scale structure: (1) Somatic Dysregulation, (2) Emotional Dysregulation, (3) Behavioural Dysregulation and (4) Mood Dysregulation.ConclusionThese findings suggest that the STOP-MS3scale, a web-based eCOA, allows identification and monitoring of MRS in the adolescent population and shows good reliability and validity.
temas prominentes en la discusión Constitucional
Authors: Heresi José Ignacio 
Published: December 2023

A unas pocas semanas del plebiscito en que se decidirá si se acepta o rechaza la nueva propuesta de constitución, la opción “En contra” parece correr con ventaja. La encuesta CEP de septiembre y octubre de 2023 arrojó una ventaja para esta opción: si bien un 53% declara que aún no ha decidido, un 30% se manifestó en contra y un 8% a favor. La encuesta Feedback, por su parte, realizada entre el 14 y el 16 de noviembre, encuentra que el 53,2% de los encuestados votará en contra y el 33,8% a favor. Continuar leyendo-
Fimepinostat Impairs NF­κB and PI3K/AKT Signaling and Enhances Gemcitabine Efficacy in H3.3K27M-Diffuse Intrinsic Pontine Glioma
Authors: Wang Dan , Yan Kun , Yu Hongxing , Li Haocheng , Zhou Wei , Hong Yaqiang , Guo Shuning , Wang Yi , Xu Cheng , Pan Changcun , Tang Yujie , Liu Nian , Wu Wei , Zhang Liwei , Xi Qiaoran 
Published: December 2023

Abstract

Diffuse intrinsic pontine glioma (DIPG) is the most aggressive pediatric brain tumor, and the oncohistone H3.3K27M mutation is associated with significantly worse clinical outcomes. Despite extensive research efforts, effective approaches for treating DIPG are lacking. Through drug screening, we identified the combination of gemcitabine and fimepinostat as a potent therapeutic intervention for H3.3K27M DIPG. H3.3K27M facilitated gemcitabine-induced apoptosis in DIPG, and gemcitabine stabilized and activated p53, including increasing chromatin accessibility for p53 at apoptosis-related loci. Gemcitabine simultaneously induced a prosurvival program in DIPG through activation of RELB-mediated NF­κB signaling. Specifically, gemcitabine induced the transcription of long terminal repeat elements, activated cGAS-STING signaling, and stimulated noncanonical NF­κB signaling. A drug screen in gemcitabine-treated DIPG cells revealed that fimepinostat, a dual inhibitor of HDAC and PI3K, effectively suppressed the gemcitabine-induced NF­κB signaling in addition to blocking PI3K/AKT activation. Combination therapy comprising gemcitabine and fimepinostat elicited synergistic antitumor effects in vitro and in orthotopic H3.3K27M DIPG xenograft models. Collectively, p53 activation using gemcitabine and suppression of RELB-mediated NF­κB activation and PI3K/AKT signaling using fimepinostat is a potential therapeutic strategy for treating H3.3K27M DIPG.

Significance:
Gemcitabine activates p53 and induces apoptosis to elicit antitumor effects in H3.3K27M DIPG, which can be enhanced by blocking NF­κB and PI3K/AKT signaling with fimepinostat, providing a synergistic combination therapy for DIPG.