bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mycobacterium
dormancy and antibiotic tolerance within the retinal pigment epithelium of ocular tuberculosis
Authors: Liu Rachel , Dang Joshua N. , Lee Rhoeun , Lee Jae Jin , Kesavamoorthy Niranjana , Ameri Hossein , Rao Narsing , Eoh Hyungjin 
Published: June 2024

ABSTRACT

Tuberculosis (TB) is a leading cause of death among infectious diseases worldwide due to latent TB infection, which is the critical step for the successful pathogenic cycle. In this stage
, Mycobacterium tuberculosis
resides inside the host in a dormant and antibiotic-tolerant state. Latent TB infection can also lead to multisystemic diseases because
M. tuberculosis
invades virtually all organs, including ocular tissues. Ocular tuberculosis (OTB) occurs when the dormant bacilli within the ocular tissues reactivate, originally seeded by hematogenous spread from pulmonary TB. Histological evidence suggests that retinal pigment epithelium (RPE) cells play a central role in immune privilege and in protection from antibiotic effects, making them an anatomical niche for invading
M. tuberculosis
. RPE cells exhibit high tolerance to environmental redox stresses, allowing phagocytosed
M. tuberculosis
bacilli to maintain viability in a dormant state. However, the microbiological and metabolic mechanisms determining the interaction between the RPE intracellular environment and phagocytosed
M. tuberculosis
are largely unknown. Here, liquid chromatography-mass spectrometry metabolomics were used to illuminate the metabolic state within RPE cells reprogrammed to harbor dormant
M. tuberculosis
bacilli and enhance antibiotic tolerance. Timely and accurate diagnosis as well as efficient chemotherapies are crucial in preventing the poor visual outcomes of OTB patients. Unfortunately, the efficacy of current methods is highly limited. Thus, the results will lead to propose a novel therapeutic option to synthetically kill the dormant
M. tuberculosis
inside the RPE cells by modulating the phenotypic state of
M. tuberculosis
and laying the foundation for a new, innovative regimen for treating OTB.

IMPORTANCE

Understanding the metabolic environment within the retinal pigment epithelium (RPE) cells altered by infection with
Mycobacterium tuberculosis
and mycobacterial dormancy is crucial to identify new therapeutic methods to cure ocular tuberculosis. The present study showed that RPE cellular metabolism is altered to foster intracellular
M. tuberculosis
to enter into the dormant and drug-tolerant state, thereby blunting the efficacy of anti-tuberculosis chemotherapy. RPE cells serve as an anatomical niche as the cells protect invading bacilli from antibiotic treatment. LC-MS metabolomics of RPE cells after co-treatment with H
2
O
2
and
M. tuberculosis
infection showed that the intracellular environment within RPE cells is enriched with a greater level of oxidative stress. The antibiotic tolerance of intracellular
M. tuberculosis
within RPE cells can be restored by a metabolic manipulation strategy such as co-treatment of antibiotic with the most downstream glycolysis metabolite, phosphoenolpyruvate.
Morphological and pathogenic investigation of the emerging fungal threat
Emergomyces africanus
Authors: Albergoni Elaine C. , Oliveira Haroldo C. , Honorato Leandro , Valdez Alessandro F. , Sena Bianca G. , Castelli Rafael F. , Rodrigues Ana Julia Curioni , Marcon Bruna H. , Robert Anny W. , Nimrichter Leonardo , Rodrigues Marcio L. 
Published: June 2024

ABSTRACT

Emergomyces africanus
is a highly fatal fungal pathogen affecting individuals with advanced HIV disease. Molecular patterns and ultrastructural aspects of
E. africanus
are unknown, and pathogenic models have not been investigated in detail. Since the cell wall of fungi is a determinant for interaction with the host and antifungal development, we characterized the ultrastructural aspects of
E. africanus
and the general properties of cell wall components under different conditions of growth
in vitro
and
in vivo
. We also tested the pathogenic potential of
E. africanus
in a
Galleria mellonella
model of infection. Transmission electron microscopy revealed the common intracellular, ultrastructural features of fungi in association with a thick cell wall. Scanning electron microscopy revealed a smooth cell surface, with no apparent decorative structures. Yeast cultures of
E. africanus
showed the distribution of chitin, chitooligomers, and mannoproteins commonly observed in fungi. However, in mixed microenvironments containing yeast and filamenting forms of
E. africanus
, the detection of chitooligomers was increased in comparison with isolated yeast cells, while the detection of these components in filamenting forms was markedly reduced. These observations were suggestive of the ability of
E. africanus
to change its cell wall composition in response to different microenvironments. Although
E. africanus
was unable to kill
G. mellonella
, this infection model allowed us to isolate infected hemocytes for further analysis of mannoproteins, chitin, and chitooligomers. Once again, the detection of
E. africanus
chitooligomers was markedly increased. These results reveal previously unknown ultrastructural features of
E. africanus
and suggest a high plasticity in the cell wall of this lethal pathogen.

IMPORTANCE

The epidemiology of fungal infections is very dynamic, and novel health emergencies are hard to predict. New fungal pathogens have been continuously emerging for the last few decades, and
Emergomyces africanus
is one of these threats to human health. This complex scenario points to the need for generating knowledge about emerging pathogens so that new therapeutic strategies can be designed. In this study, we characterized the general cellular and pathogenic properties of the emerging fungal pathogen
E. africanus
. Our results reveal that
E. africanus
manifests some of the typical properties of fungal cells but also exhibits some unique characteristics that might be helpful for the future development of therapeutic strategies.
Supplemental Material: Detrital zircon U-Pb ages and provenance of Paleogene paleochannel strata, Sierra Nevada and western Nevada: Implications for paleotopographic evolution
Authors: Tye Alexander , Niemi Nathan A. 
Published: June 2024

<p>Table S1: Compiled igneous geochronology data from NAVDAT (Farmer et al., 2009) encompassing all available single-mineral U-Pb, Ar-Ar, and K-Ar ages. Table S2: Compiled published detrital zircon U-Pb age data from Paleogene sedimentary deposits of the Sierra Nevada (Cassel et al., 2012; Cecil et al., 2010). </p>
Primary achalasia diagnosed during pregnancy: rare cause of nausea and vomiting
Authors: Mei Jenny Y , Mendoza Dorian , Gutierrez Monica , Rao Rashmi 
Published: June 2024

Nausea and vomiting during pregnancy are very common; however, when persistent symptoms lead to severe malnutrition, other conditions should be considered. We present a patient with severe postprandial nausea and vomiting resulting in 120 lb weight loss. She was treated for presumed hyperemesis gravidarum but diagnosed with achalasia type 1 upon further work-up. The pregnancy was further complicated by fetal growth restriction, shortened cervix and preterm premature rupture of membranes, and resulted in delivery at 26 weeks of gestation. Postpartum, she underwent a peroral endoscopicmyotomyprocedure and has returned to normal body mass index.The differential for nausea/vomiting is broad, and major medical conditions can manifest for the first time during pregnancy. Severe malnutrition adversely affects maternal and fetal health. Further work-up should be pursued when symptoms cannot otherwise be explained.
A randomized, placebo-controlled study of chitosan gel for the treatment of chronic diabetic foot ulcers (the CHITOWOUND study)
Authors: Slivnik Matevž , Navodnik Preložnik Maja , Fir Mojca , Jazbar Janja , Čebron Lipovec Nanča , Locatelli Igor , Liette Lauzon Hélène , Urbančič Rovan Vilma 
Published: June 2024

IntroductionTo assess the efficacy of a chitosan-based gel (ChitoCare) for the treatment of non-healing diabetic foot ulcers (DFUs).Research design and methodsForty-two patients with chronic DFUs were randomized to the ChitoCare or placebo gel for a 10-week treatment period and 4-week follow-up. The primary study end point was the rate of complete wound closure at week 10, presented as relative rate.ResultsThirty patients completed the 10-week treatment and 28 completed the 4-week follow-up. The ChitoCare arm achieved 16.7% complete wound closure at week 10 vs 4.2% in the placebo arm (p=0.297), 92.0% vs 37.0% median relative reduction in wound surface area from baseline at week 10 (p=0.008), and 4.62-fold higher likelihood of achieving 75% wound closure at week 10 (p=0.012). Based on the results of the Bates-Jensen Wound Assessment Tool, the wound state at week 10 and the relative improvement from the baseline were significantly better (median 20 vs 24 points, p=0.018, and median 29.8% vs 3.6%, p=0.010, respectively).ConclusionsChitoCare gel increased the rate of the DFU healing process. Several secondary end points significantly favored ChitoCare gel.Trial registration numberNCT04178525.
Barriers and facilitators to learning health systems in primary care: a framework analysis
Authors: Fisher Georgia , Saba Maree , Dammery Genevieve , Ellis Louise A , Churruca Kate , Mahadeva Janani , Foo Darran , Wilcock Simon , Braithwaite Jeffrey 
Published: June 2024

BackgroundThe learning health system (LHS) concept is a potential solution to the challenges currently faced by primary care. There are few descriptions of the barriers and facilitators to achieving an LHS in general practice, and even fewer that are underpinned by implementation science. This study aimed to describe the barriers and facilitators to achieving an LHS in primary care and provide practical recommendations for general practices on their journey towards an LHS.MethodsThis study is a secondary data analysis from a qualitative investigation of an LHS in a university-based general practice in Sydney, Australia. A framework analysis was conducted using transcripts from semistructured interviews with clinic staff. Data were coded according to the theoretical domains framework, and then to an LHS framework.Results91% (n=32) of practice staff were interviewed, comprising general practitioners (n=15), practice nurses (n=3), administrative staff (n=13) and a psychologist. Participants reported that the practice alignment with LHS principles was influenced by many behavioural determinants, some of which were applicable to healthcare in general, for example, some staff lackedknowledgeabout practice policies andskillsin using software. However, many were specific to the general practice environment, for example, theenvironmental contextof general practice meant that administrative staff were an integral part of the LHS, particularly in facilitating partnerships with patients.ConclusionsThe LHS journey in general practice is influenced by several factors. Mapping the LHS domains in relation to the theoretical domains framework can be used to generate a roadmap to hasten the journey towards LHS in primary care settings.
Defining the Black population in Canadian health research: a scoping review protocol
Authors: Uwamahoro Marie-Claire , Idowu James , Chowdhury Nashit , Bele Sumedh , Popeski Naomi , Boakye Francis , Odame-Ankrah Charles , King Regine , Rabi Doreen , Turin Tanvir C 
Published: June 2024

IntroductionIn the context of health research in Canada, various terms and labels have been employed to reference the Black population. This practice has had the unintended consequence of diminishing the comparability and efficiency of studies. Furthermore, using a broad term such as ‘Black’ may fail to encompass the diversity and intricacy of the ethnocultural backgrounds of people who are racialised as such. It may also obscure the subtleties of their experiences and health outcomes. This study aims to examine how health researchers have defined Black within the scope of their work and different labels used to identify the Black population in Canada.Methods and analysisWe have developed and employed a comprehensive and sensitive search strategy to identify articles concerning the health and wellness of the Black population in Canada. Both peer-reviewed and grey literature will be searched. Original articles published in both English and French will be included. The screening process will consist of two stages: the title and abstract screening, followed by a thorough examination of full-text articles. Additionally, single citation tracking and manual search of reference lists will be conducted. Study characteristics and relevant information on the definition of the Black population will be extracted, followed by reflective thematic analysis and presentation of the key findings.Ethics and disseminationThis review will not require ethical approval. We will disseminate the results through meetings with stakeholders. From the beginning, a knowledge translation approach was decided upon following consultation with citizen researchers and community champions. Our findings will also be disseminated through oral and poster presentations, peer-reviewed publications, and social media.
Knowledge, attitude and practice towards insomnia and sleep hygiene among patients with chronic insomnia in Northwest China in 2023: a cross-sectional survey
Authors: Zhu Jing , Zhang Shiping , Zhu Zhibo , Wang Jinghua , Kang Tao , Li Xin , Zhao Yikang , Zhu Lijuan 
Published: June 2024

ObjectivesTo investigate the knowledge, attitude and practice (KAP) towards insomnia and sleep hygiene among patients with chronic insomnia.DesignWeb-based cross-sectional survey.SettingShaanxi Provincial People’s Hospital (northwest China) between January 2023 and May 2023.ParticipantsPatients with chronic insomnia.Primary and secondary outcome measuresDemographic characteristics and KAP towards insomnia and sleep hygiene were collected by distributing a questionnaire developed by the authors.ResultsA total of 613 people participated in this study, with a Mean Knowledge Score of 7.63±2.56 (total score of 12), a Mean Attitude Score of 48.39±6.643 (total score of 70) and a Mean Practice Score of 42.37±8.592 (total score of 70). Knowledge was significantly correlated with attitude (r=0.447, p<0.001) and practice (r=0.327, p<0.001), and attitude was significantly correlated with practice (r=0.486, p<0.001). Multivariable logistic regression showed that higher knowledge (OR=1.181 (1.062–1.314), p=0.002) and better attitude (OR=1.171 (1.124–1.221), p<0.001) were independently associated with good practice. According to the structural equation modelling analysis, knowledge directly influenced practice (β=0.457, p=<0.001) and attitude (β=1.160, p=<0.001), while attitude influenced practice (β=0.550, p=<0.001).ConclusionThe KAP towards insomnia and sleep hygiene among patients with chronic insomnia in Northwest China in 2023 was moderate, with better practice showing signs of being influenced by better knowledge and more positive attitudes.
Phase II study in children and adults under 40 years with newly diagnosed Langerhans cell histiocytosis: protocol for an LCH-19-MSMFB clinical trial in Japan
Authors: Ono Rintaro , Sakamoto Kenichi , Kudo Ko , Sato Aki , Kudo Kazuko , Fujino Hisanori , Kawahara Yuta , Hashimoto Hiroya , Doi Takehiko , Yanagisawa Ryu , Kawamata Toyotaka , Miyazaki Osamu , Nakazawa Atsuko , Ota Yasunori , Kanegane Hirokazu , Nakazawa Yozo , Horibe Keizo , Saito Akiko M , Manabe Atsushi , Usuki Kensuke , Kiyoi Hitoshi , Morimoto Akira , Tojo Arinobu , Shioda Yoko 
Published: June 2024

IntroductionAlthough the prognosis of Langerhans cell histiocytosis (LCH) is excellent, the high recurrence rate and permanent consequences, such as central diabetes insipidus and LCH-associated neurodegenerative diseases, remain to be resolved. Based on previous reports that patients with high-risk multisystem LCH show elevated levels of inflammatory molecules, we hypothesised that dexamethasone would more effectively suppress LCH-associated inflammation, especially in the central nervous system (CNS). We further hypothesised that intrathecal chemotherapy would effectively reduce CNS complications. We administer zoledronate to patients with multifocal bone LCH based on an efficacy report from a small case series.Methods and analysisThis phase II study (labelled the LCH-19-MSMFB study) is designed to evaluate the significance of introducing dexamethasone and intrathecal chemotherapy for multisystem disease and zoledronate for multifocal bone disease in previously untreated, newly diagnosed children, adolescents (under 20 years) and adults under 40 years. The primary endpoint is the 3-year event-free survival rate by risk group of under 20 years and the 3-year event-free survival rate of 20 years and over.Ethics and disseminationThis study was approved by the Central Review Board of the National Hospital Organisation Nagoya Medical Centre (Nagoya, Japan) on 21 January 2022 and was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp/en-latest-detail/jRCTs041210027). Written informed consent will be obtained from all patients and/or their guardians.Trial registration numberjRCTs041210027.
Scoping review protocol on the perception and attitude of women on methods for collecting cervicovaginal samples for human papillomavirus testing in sub-Saharan Africa
Authors: Andrew-Bassey Uduak Ima , Oke Deborah Olamiposi , Okunlola Michael A , Morhason-Bello Imran O 
Published: June 2024

IntroductionSub-Saharan Africa (SSA) regions have the highest burden of cervical cancer (CC), accounting for nearly a quarter of global mortality. Many women in SSA are reluctant to access CC screening because they are uncomfortable exposing their private parts to healthcare providers. The perception of women who have experienced self-sampling in SSA is yet to be reviewed. This scoping review will explore the literature on the perception and attitude of women towards methods of collecting cervicovaginal samples for human papillomavirus (HPV) testing in SSA.Methods and analysisAn extensive search using the Arksey and O’Malley framework will be conducted. The search criteria will be limited to original research conducted in community or clinical settings in SSA within the last 10 years. Four databases, namely, PUBMED, Cochrane, African Journals Online and Google Scholar, will be searched. Two independent persons (UIAB and DOO) will screen the titles and abstracts and later full texts using population, intervention, comparison and outcome criteria. IOMB will serve as a tiebreaker whenever there is no agreement on the choice of eligibility criteria. The screening process will be presented using Preferred Reporting Items for Systematic Reviews and Meta-Analyses for the scoping review flow format. The descriptive analysis of eligible studies for scoping reviews will be summarised. We will describe themes of attitude and perception covering pain, embarrassment, privacy and comfortability, willingness to self-sample, anxiety and confidence.Ethics and disseminationThis is a scoping review protocol and does not require ethical approval. Findings from this review will be disseminated through peer-reviewed publications, the production of policy briefs, and presentations at local and international conferences.
PRECISE trial (Pain RElief Combination Intervention StratEgies): protocol for the clinical trial of a pregabalin–melatonin combination for fibromyalgia
Authors: Gilron Ian , DeBow Chris , Elkerdawy Hala , Khan James S , Salomons Tim V , Duggan Scott , Tu Dongsheng , Holden Ronald R , Milev Roumen , Buckley D Norman , Moulin Dwight E 
Published: June 2024

IntroductionFibromyalgia is associated with chronic widespread pain and disturbed sleep. Multidisciplinary, multimodal management often includes pharmacotherapy; however, current drugs used to treat fibromyalgia provide meaningful benefit to only 30–60% of treated individuals. Combining two or more different drugs is common in clinical practice with the expectation of better efficacy, tolerability or both; however, further research is needed to identify which combinations actually provide added benefit. Thus, we are planning a clinical trial to evaluate melatonin (MLT)–pregabalin (PGB) combination in participants with fibromyalgia.Methods and analysisThis will be a single-centre, double-blind, randomised, double-dummy, three-period, crossover trial comparing a MLT–PGB combination to each monotherapy in 54 adult participants satisfying the 2016 American College of Rheumatology criteria for fibromyalgia. Participants will receive maximally tolerated doses of MLT, PGB and MLT–PGB combination for 6 weeks. The primary outcome will be daily pain intensity (0–10); secondary outcomes will include the Fibromyalgia Impact Questionnaire, SF-36 survey, Medical Outcomes Study Sleep Scale, Beck Depression Inventory (BDI-II), adverse events and other measures. Analysis of the primary and secondary outcomes will involve a linear mixed model with sequence, period, treatment, the first-order carryover and baseline pain score as fixed effects and participant as a random effect to test whether there are any treatment differences among three treatments and to estimate the least square mean of the mean daily pain intensity for each treatment, adjusting for carryover as well as period effects (ie, stability of pain levels).Ethics and disseminationThis trial has been registered with the International Standard Randomised Controlled Trial Number Registry, ISRCTN #18278231, has been granted ethical approval by the Queen’s University Health Sciences Research Ethics Board (Queen’s HSREB Protocol #6040998) and is currently under review for a Clinical Trial Application to Health Canada Natural and Non-prescription Health Products Directorate. All participants will provide written informed consent prior to trial participation. Following trial completion, results will be disseminated in one or more biomedical journal publications and presented at one or more scientific meetings.Trial registration numberThis trial has been registered with the International Standard Randomised Controlled Trial Number Registry,ISRCTN18278231.
Players are positive regarding injury prevention exercise programmes, but coaches need ongoing support: a survey-based evaluation using the Health Action Process Approach model across one season in amateur and youth football
Authors: Lindblom Hanna , Åkerlund Ida , Waldén Markus , Sonesson Sofi , Hägglund Martin 
Published: June 2024

ObjectivesImplementation of injury prevention exercise programmes (IPEPs) in sports is challenging, and behaviour change among players and coaches is essential for success. The aim was to describe players’ and coaches’ motivation and coaches’ goal pursuit when using IPEPs in amateur and youth football across a season. A secondary aim was to describe players’ motivation to engage in IPEP use in relation to presence or absence of injury.MethodsThe study was based on questionnaires to amateur and youth, male and female football players and coaches at baseline, mid-season and post-season in a three-armed randomised trial in 2020 in Sweden. Questionnaires were based on the Health Action Process Approach (HAPA) model with questions about the motivational phase when intention for change is created (players and coaches) and a goal-pursuit phase when intention is translated into action (coaches).ResultsIn total, 455 players (126 male), mean age 20.1 years (SD±5.8, range 14–46) and 59 (52 male) coaches took part. Players generally gave positive answers in the HAPA motivational phase (Likert 6–7 on a 1–7 Likert scale). Differences in ratings between injured and uninjured players were minor. Coaches had positive or neutral ratings (Likert 4–6) in the motivational and goal-pursuit phases. Ratings deteriorated across the season, with less positive responses from 40% of players and 38-46% of coaches post-season.ConclusionPositive ratings in the HAPA motivational phase indicated fertile ground for IPEP use. Neutral ratings by coaches and deterioration across the season in players and coaches suggest a need for ongoing support for IPEP use.Trial registration numberNCT04272047.