bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fluoroquinolones and rifampin combination in the backdrop of heteroresistant tuberculosis
Authors: Vogensen Vanessa B. , Singh Sanjay , Allende Christopher J. , Engelthaler David M. , Boorgula Gunavanthi D. , Thomas Tania A. , Sturkenboom Marieke G. G. , Akkerman Onno W. , Gumbo Tawanda , Srivastava Shashikant 
Published: January 2025

ABSTRACT

The impact of heteroresistance on tuberculosis (TB) treatment outcomes is unclear, as is the role of different rifampin and isoniazid exposures on developing resistance mutations. Hollow fiber system model of TB (HFS-TB) units were inoculated with drug-susceptible
Mycobacterium tuberculosis
(
Mtb
) and treated with isoniazid and rifampin exposure identified in a clinical trial as leading to treatment failure and acquired drug resistance. Systems were sampled for drug concentration measurements, estimation of total and drug-resistant
Mtb
, and small molecule overlapping reads (SMOR) analysis for the detection of heteroresistance. In the second HFS-TB study, systems were inoculated with an isoniazid-resistant clinical strain and treated with various combinations of isoniazid, rifampin, moxifloxacin, and levofloxacin for 28 days. Linear regression and exponential decline models were used for data analysis. Suboptimal isoniazid and rifampin exposures failed to kill drug-susceptible
Mtb
in the HFS-TB. Standard susceptibility methods failed to detect drug resistance, but SMOR detected isoniazid and rifampin heteroresistance, as well as fluoroquinolone, to which bacilli were not exposed.
rpoB
mutations arising from low rifampin exposures were Q513K and H526N, whereas those from regimen adequate rifampin but low isoniazid concentrations were S531L. Moxifloxacin-rifampin combination sterilized the HFS-TB units inoculated with the isoniazid-resistant
Mtb
in 14 days compared with 21 days of treatment with levofloxacin-rifampin, with no further emergence of drug resistance. Early detection of isoniazid and rifampin heteroresistance could provide an opportunity to individualize the therapy and protect fluoroquinolones when added to the MDR-TB treatment regimen.
Multiple sclerosis and infection: history, EBV, and the search for mechanism
Authors: SoRelle Elliott D. , Luftig Micah A. 
Published: January 2025

SUMMARY
Infection has long been hypothesized as the cause of multiple sclerosis (MS), and recent evidence for Epstein-Barr virus (EBV) as the trigger of MS is clear and compelling. This clarity contrasts with yet uncertain viral mechanisms and their relation to MS neuroinflammation and demyelination. As long as this disparity persists, it will invigorate virologists, molecular biologists, immunologists, and clinicians to ascertain how EBV potentiates MS onset, and possibly the disease’s chronic activity and progression. Such efforts should take advantage of the diverse body of basic and clinical research conducted over nearly two centuries since the first clinical descriptions of MS plaques. Defining the contribution of EBV to the complex and multifactorial pathology of MS will also require suitable experimental models and techniques. Such efforts will broaden our understanding of virus-driven neuroinflammation and specifically inform the development of EBV-targeted therapies for MS management and, ultimately, prevention.
Xanthomonas citri
subsp.
citri
requires a genus-specific outer membrane protein and TolB to coordinate cell membrane integrity and virulence
Authors: Wu Leilei , Zhu Xueyan , Long Hang , Huang Xinyu , Zhu Shuying , Xue Qi , Li Ziao , Zou Huasong 
Published: January 2025

ABSTRACT

Xanthomonas citri
subsp.
citri
(
Xcc
) possesses a
Xanthomonas
-specific
o
uter
m
embrane
p
rotein XAC1347 (OMP

Xan

) that exerts a role in the expression of the type III secretion system for pathogenicity. In this study, we reported that OMP

Xan

was required for salt stress tolerance and cell membrane integrity, as well as the expression of the
gum
genes for the production of extracellular polysaccharides. Pull-down and yeast two-hybrid assays revealed that OMP

Xan

interacts with TolB, a substrate of the Tol/Pal membrane protein system. The deletion of
tolB
resulted in similar phenotypic alterations as the

OMP
Xan

mutant in salt stress tolerance, cell membrane integrity, and the expression of
hrpG
,
hrpX
,
hrpD6
, and
hrcC
for pathogenicity. In contrast, the absence of TolB resulted in an increased level of expression of the
gum
genes and the production of extracellular polysaccharides. These results indicate that the interaction of OMP

Xan

and TolB coordinates multi-faceted mechanisms to manage environmental stress and pathogenicity.

IMPORTANCE

The gram-negative
Xanthomoas citri
subsp.
citri
(
Xcc
) is a causal agent of citrus canker, a serious bacterial disease on citrus plants. Our previous research reported that a
Xanthomonas
-specific outer membrane protein XAC1347 (OMP
Xan
) is necessary for type III gene expression. This manuscript provided evidence to show that OMP
Xan
interacts with Tol/Pal system substrate TolB. Moreover, OMP

Xan

and TolB are both required for cell membrane integrity, stress adaption, and virulence. The overall results support that OMP

Xan

and TolB coordinate multi-faceted mechanisms to manage environmental stress and pathogenicity.
Analysis of the growth trajectories of junior residents in Japan: a longitudinal cohort study using data from a nationwide e-portfolio system (EPOC2)
Authors: Nawa Nobutoshi , Okada Eriko , Akaishi Yu , Kashimada Ayako , Okada Hiroko , Okuhara Tsuyoshi , Kiuchi Takahiro , Takahashi Makoto , Ohde Sachiko , Fukui Tsuguya , Tanaka Yujiro , Yamawaki Masanaga 
Published: January 2025

ObjectivesAs more emphasis is placed on the acquisition of competencies in medical education, portfolios are increasingly being used for evaluation. EPOC2 (E-POrtfolio of Clinical training) is an e-portfolio system developed in Japan and is used by about 800 clinical training hospitals. The study objective is to identify the learning trajectory of junior residents to provide insights into the provision of better postgraduate and undergraduate medical education in Japan.DesignLongitudinal cohort study.SettingHospitals nationwide adopting EPOC2.Participants7671 residents who participated in clinical training programmes at hospitals adopting EPOC2 between April 2020 and March 2022.Primary outcome measureFormative evaluation scores assessed through self-evaluation by junior residents and evaluations by supervisors/senior physicians at the end of each rotation in each clinical department.ResultsFor all evaluation items, growth trajectories were divided into six groups, each with distinct characteristics based on the specific content of the evaluation form. For example, in the self-evaluation of medical knowledge and problem-solving (B-2), a lower percentage of respondents had adequate scores at the beginning of their training compared with other similar items. Compared with the self-evaluations of the other item groups (ie, forms A1–A4 and B1–B9), the self-evaluation of the item group related to seeing patients (ie, forms C1–C4) differed by showing a group that remained at or below 2 until the end, accounting for 2.8% to 7.0%, possibly indicating the relatively low confidence of the residents for these items.ConclusionsGrowth trajectories fall into six groups, each with its own characteristics depending on the content of the items. These findings offer valuable insights into the developmental trajectories of junior residents and may highlight opportunities for enhancing their training programmes in Japan. This underscores the usefulness of a nationwide evaluation system, enabling researchers to analyse clinical education outcomes across the country using uniform indicators.
Factors associated with weight loss response to GLP-1 analogues for obesity treatment: a retrospective cohort analysis
Authors: Squire Peter , Naude James , Zentner Ali , Bittman Jesse , Khan Nadia 
Published: January 2025

ObjectivesThe response to glucagon-like peptide-1 (GLP-1) analogues for weight loss varies significantly. We investigated the anthropometric, demographic and clinical characteristics associated with total body weight loss (TBWL) from subcutaneous GLP-1 analogue therapy in patients with obesity in a real-world setting.DesignRetrospective cohort analysis.SettingAn urban, multidisciplinary obesity community clinic in Vancouver, Canada, from November 2018 to April 2021.Participants483 adults with a body mass index (BMI) of ≧30 kg/m2who had filled a new prescription for subcutaneous semaglutide or liraglutide, with at least 6-month follow-up, were included (mean follow-up: 17.3 months). Individuals with prior bariatric surgery were excluded.OutcomesThe primary outcome was the %TBWL over a mean follow-up period of 520 days. Participant’s TWBL was categorised as non-response (<5% TBWL), moderate response (5%–15% TBWL) or hyper-response (>15% TBWL).ResultsThe average %TBWL in the cohort was 12.2%. Among the participants, 17.8% had a non-response, 48.4% had a moderate response and 33.8% had a hyper-response. In the multivariable regression analysis, being a woman was associated with hyper-response (adjusted OR 1.92, CI 1.01 to 3.65, p=0.048). Age, diabetes status, baseline BMI, being sedentary, anxiety and depression were not independently associated with TBWL in response to GLP-1 analogue therapy.ConclusionsIn a real-world setting, female sex was found to be associated with a hyper-response to GLP-1 analogue therapy for obesity management. Other clinical factors evaluated, including diabetes status, were not associated with the response. Future research should assess additional variables and support the development of novel biomarkers that are associated with weight loss response.
Sleep profile in patients with septo-optic-pituitary dysplasia: protocol for a prospective cohort study
Authors: Pasca Ludovica , Morelli Federica , Catalano Guido , Quaranta Carlo Alberto , Vitali Helene , Ballante Elena , Dattrino Francesca , Crema Francesca , Rota Paola , Varesio Costanza , De Giorgis Valentina , Romaniello Romina , Signorini Sabrina , Franco Valentina 
Published: January 2025

IntroductionChildren with septo-optic-pituitary dysplasia (SOD) may experience a range of visual impairments and hormonal dysfunctions beyond developmental delay/intellectual disability. The literature describes sleep fragmentation, circadian rhythm disruptions and reduced sleep efficiency. These manifestations are believed to be closely linked to both structural and functional abnormalities associated with SOD, potentially disrupting the natural circadian rhythm. Both anomalies in midline brain structures and decreased visual input could potentially impact melatonin secretion, although a distinct melatonin profile for SOD patients has yet to be identified. Furthermore, the specific contribution of these factors to sleep disturbances in SOD remains unexplored. The aim of this study is to evaluate the quality of sleep and its characteristics, along with the melatonin profile, among paediatric patients diagnosed with SOD. A comparison will be made between these findings and those of children with isolated bilateral visual impairment, as well as patients with agenesis of the corpus callosum.Methods and analysisParticipants aged between 3 and 18 years previously diagnosed with SOD will be recruited prospectively. Each participant will be assessed at baseline and at each follow-up visit scheduled to evaluate the clinical course. Sleep quality and daytime sleepiness changes will be tracked using actigraphic assessment, standardised sleep questionnaires and a sleep EEG. Additionally, plasma and salivary melatonin profiles will be assessed for each participant.Ethics and disseminationThis study has been approved by local Ethics Committee (N°0049187/23). The study findings will be shared through publication in an international peer-reviewed journal and presented at both national and international conferences.Trial registration numberNCT06262152.
Soil organic matter is responsive to short-term climate cycles
Authors: Sorenson P.T. , Bedard-Haughn A.K. 
Published: January 2025

Strong evidence exists that management practices can increase soil organic matter (SOM); however, climate is also known to affect SOM content. The objective of this study was to investigate the relationship between precipitation and SOM. Precipitation and SOM data from southeastern Saskatchewan were highly correlated ( r = 0.91, p < 0.01), with SOM contents declining during drier periods, indicating SOM is responsive to short-term climate cycles. Assessing soil organic carbon (SOC) stock changes must account for climate variability to avoid ascribing either SOC losses due to lower precipitation or gains due to higher precipitation to management practices.
Real‐World Insights Into Hypoglycemia Risk While Driving in Teens and Young Adults With Type 1 Diabetes
Authors: Pamidimukkala Kalyan , Ferm Michael L. , Erraguntla Madhav , Haridas Balakrishna , Byju Achu , Lawley Mark , Menon Sruthi , Villegas Carolina , McKay Siripoom , DeSalvo Daniel J. 
Published: January 2025

Background: Clinical guidelines on driving for people with diabetes exist, but there are limited studies analyzing glucose data and hypoglycemia risk while driving. No published studies have analyzed teenage or emerging adult drivers with type 1 diabetes (T1D). The primary aim of our pilot study was to explore the glycemic patterns of young drivers with T1D as they relate to clinical guidelines and identify trends that could be used to improve road safety.Methods: In this pilot study, we collected continuous glucose monitoring (CGM) data from five drivers with T1D (median age 19, range 17–21 years) over a 1‐month period. The driving trips were divided into two categories: (1) Short trips (<60 min) and (2) Long trips (≥60 min). Hypoglycemia was defined as <70 mg/dL as recorded by CGM for at least four consecutive readings. Trips <10 min were excluded from the analysis.Results: Data on 284 total trips with associated CGM readings were recorded. The average number of trips taken by drivers during the study was 56.8 trips (range 9–82). For short trips (n = 276), no episodes of hypoglycemia occurred when starting glucose was >90 mg/dL (n = 227). For short trips with starting glucose of 70–90 mg/dL (n = 32), each hypoglycemic event (n = 5) had a drop in the first CGM glucose value while driving. Seventeen (5.7%) of short trips started with a glucose <70 mg/dL. A total of eight long trips (>60 min) were recorded, all had a starting CGM value of >90 mg/dL, and none had hypoglycemia events.Conclusions: These real‐world findings from a small sample of teenage and young adult drivers with T1D support the American Diabetes Association (ADA) recommendation for starting glucose of >90 mg/dL when driving. Larger studies would be helpful in clearly identifying and improving road safety concerns in young drivers with T1D.
Body Composition at Diagnosis and Early Response in Pediatric Hodgkin Lymphoma
Authors: Wadhwa Aman , Dai Chen , Kessel Sandra , Richman Joshua S. , Shen Wei , Kahn Justine M. , Castellino Sharon M. , Kelly Kara M. , Friedman Debra L. , Bhatia Smita 
Published: January 2025

Abstract

Background:
The association between skeletal, muscle, and adipose tissue (body composition) and early response using PET in pediatric Hodgkin lymphoma remains unstudied.

Methods:
Patients enrolled on Children’s Oncology Group studies AHOD0031 (intermediate-risk Hodgkin lymphoma) and AHOD0831 (high-risk Hodgkin lymphoma) with digital abdominal CT scans at diagnosis and PET scans after 2 cycles (PET2) were included. Two consecutive slices at the third lumbar vertebra were identified, and skeletal muscle index (SMI; in cm2/m2) and total adipose tissue index (TATI; in cm2/m2) were calculated using sliceOmatic and height at diagnosis. SMI and TATI were divided into quintiles [Q1 (lowest) to Q5 (highest)]. Body mass index (BMI) was calculated using height and weight at diagnosis. The association between baseline body composition (SMI, TATI, and BMI) and positive PET2 was examined using logistic regression, adjusting for age at diagnosis, sex, race/ethnicity, stage, histology, bulk disease, and “B” symptoms.

Results:
Among 1,033 included patients, PET2 was positive in 314 (30.4%) patients. SMI was not associated with positive PET2. Extremes of TATI were associated with positive PET2, when compared with the middle TATI quintile [reference: Q3; ORQ1 = 1.63; 95% confidence interval (CI) = 1.03–2.60; P = 0.04; ORQ2 = 1.82; 95% CI = 1.17–2.82; P = 0.008; ORQ5 = 1.94; 95% CI = 1.23–3.05; P = 0.005]. The association between BMI in obesity range and positive PET2 trended toward significance (OR = 1.42; 95% CI = 0.98–2.04; P = 0.06; ref = normal weight).

Conclusions:
Extremes of adipose tissue at diagnosis influence early response among pediatric Hodgkin lymphoma.

Impact:
Validation of results from this study could inform studies investigating body composition–based chemotherapy dosing.
PSMA+ Extracellular Vesicles Are a Biomarker for SABR in Oligorecurrent Prostate Cancer: Analysis from the STOMP-like and ORIOLE Trial Cohorts
Authors: Andrews Jack R. , Kim Yohan , Horjeti Edlira , Arafa Ali , Gunn Heather , De Bruycker Aurélie , Phillips Ryan , Song Daniel , Childs Daniel S. , Sartor Oliver A. , Orme Jacob J. , Chaudhuri Aadel A. , Tran Phuoc , Kiess Ana , Sutera Philip , Mercier Carole , Ost Piet , Park Sean S. , Lucien Fabrice 
Published: January 2025

Abstract

Purpose:
Two randomized clinical trials (STOMP and ORIOLE) demonstrated that stereotactic ablative radiotherapy (SABR) can prolong androgen-deprivation therapy–free survival or progression-free survival (PFS) in patients with metachronous oligometastatic castration-sensitive prostate cancer (omCSPC). Although most patients with omCSPC have a more modest delay in progression, a small subset achieves a durable response following SABR. We investigated the prognostic and predictive value of circulating prostate-specific membrane antigen-positive (PSMA+) extracellular vesicles (EV) and PSA in a biomarker correlative study using blood samples from three independent patient cohorts.

Experimental Design:
Plasma samples from 46 patients with omCSPC on the ORIOLE trial and 127 patients with omCSPC on the STOMP trial protocol treated with SABR were included in the study. Pre-SABR PSMA+EV levels (EV/mL) were measured by nanoscale flow cytometry. Kaplan–Meier curves and logistic regression models were used to determine the association of PSMA+EV and PSA levels with clinical outcomes.

Results:
In the pooled cohorts, the median biochemical PFS were 26.1 and 15.0 months (P = 0.005), and the median radiographic PFS were 36.0 and 25.0 months (P = 0.003) for PSMA+EV-low and -high groups, respectively. The combination of pre-SABR low levels of both PSMA+EV and PSA was associated with a lower risk of radiographic progression (HR, 0.34, 95% confidence interval, 0.18–0.58; P = 0.0002). In the ORIOLE cohort, which included both an SABR arm and an observation arm, low PSMA+EV was predictive of benefit from SABR (P = 0.012).

Conclusions:
PSMA+EV is a novel prognostic and predictive biomarker of radiographically occult tumor burden in omCSPC. PSMA+EV may inform clinical decisions about identifying patients who will achieve a durable benefit from consolidative SABR alone.
Myt1 Kinase: An Emerging Cell-Cycle Regulator for Cancer Therapeutics
Authors: Lang Fengchao , Kaur Karambir , Zaheer Javeria , Ribeiro Diego Luis , Yang Chunzhang 
Published: January 2025

Abstract
Cell-cycle checkpoints are stringent quality control mechanisms that regulate cell-cycle progression and division. Cancer cells often develop a dependency on the G2–M cell-cycle checkpoint to facilitate DNA repair and resolve intrinsic or therapy-induced DNA damage. This dependency leads to therapy resistance, continuous cell division, and disease progression. Targeting G2–M checkpoints has been heavily pursued over the past two decades and has progressed into clinical studies. Recent genome-scale functional genomic studies have revealed that protein kinase, membrane-associated tyrosine/threonine 1, an essential but previously overlooked molecule for the G2–M checkpoint, is a promising target for multiple types of cancers. In this work, we summarize the latest discoveries in molecular targeting of protein kinase, membrane-associated tyrosine/threonine 1, and discuss the challenges and limitations in expanding its clinical application.
High Plasma Polyamine Levels Are Associated With an Increased Risk of Poststroke Cognitive Impairment: A Multicenter Prospective Study From CATIS
Authors: He Yu , Jia Yiming , Liu Yi , Chang Xinyue , Yang Pinni , Shi Mengyao , Guo Daoxia , Peng Yanbo , Chen Jing , Wang Aili , Xu Tan , He Jiang , Zhang Yonghong , Zhu Zhengbao 
Published: January 2025

Background
Polyamines have been suggested to play pivotal roles in ischemic stroke and neurodegenerative disorders, but the associations of plasma polyamines with poststroke cognitive impairment (PSCI) remain unclear. We aimed to prospectively investigate the associations of plasma putrescine, spermidine, and spermine with PSCI among patients with ischemic stroke in a multicenter cohort study.

Methods and Results

We measured plasma polyamine levels at baseline among 619 patients with ischemic stroke from a preplanned ancillary study of CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). We used the Mini‐Mental State Examination and Montreal Cognitive Assessment to evaluate cognitive function at 3‐month follow‐up after ischemic stroke, and PSCI was defined as Mini‐Mental State Examination score <27 or Montreal Cognitive Assessment score <25. According to the Mini‐Mental State Examination score, plasma polyamines were positively associated with PSCI. The adjusted odds ratios of PSCI for the highest versus lowest quartile of putrescine, spermidine, and spermine were 1.81 (95% CI, 1.09–3.00), 1.81 (95% CI, 1.09–3.01), and 1.92 (95% CI, 1.15–3.20), respectively. In addition, plasma putrescine (net reclassification improvement, 32.08%;
P
<0.001; integrated discrimination improvement, 1.62%;
P
=0.002), spermidine (net reclassification improvement, 25.29%;
P
=0.002; integrated discrimination improvement, 1.22%;
P
=0.006), and spermine (net reclassification improvement, 16.54%;
P
=0.045; integrated discrimination improvement, 1.36%;
P
=0.004) could significantly improve the risk reclassification of PSCI beyond established risk factors. There were similar significant relationships when PSCI was defined by Montreal Cognitive Assessment score.

Conclusions
Higher plasma polyamine levels were associated with increased risk of PSCI among patients with ischemic stroke. Our findings suggest that plasma polyamines should be implicated in the pathophysiologic processes of PSCI and may be the potential intervention targets for PSCI.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01840072.