bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical course of spinal pain in adolescents: a feasibility study in a chiropractic setting
Authors: Montgomery Laura RC , Kamper Steven J , Young Anika , Beynon Amber , Pohlman Katherine A , Hestbæk Lise , Hancock Mark J , French Simon D , Maher Christopher G , Swain Michael S 
Published: January 2025

DesignProspective feasibility study.ObjectivesTo inform the design and conduct of a large-scale clinical cohort study investigating adolescents with moderate-to-severe spinal pain.SettingChiropractic care in Sydney, Australia.ParticipantsAdolescents aged 12–17 years with spinal pain (≥4/10 pain intensity score).MethodsAdolescents and chiropractors completed baseline and week-12 follow-up questionnaires, with adolescents reporting pain intensity and recovery weekly via text messages during weeks 1–11. Questionnaire measures included spinal pain, pain coping, quality of life, physical activity, clinical assessment findings and care delivered. Chiropractors provided usual clinical care. We conducted a descriptive feasibility analysis.Primary outcomes(1) Recruitment rate, (2) response rate to each data collection instrument and (3) retention rate.ResultsFrom May 2021 to February 2023, 20 chiropractors from 10 clinics were enrolled (invited n=85). 10 chiropractors recruited 45 adolescents (15.4±1.4 years, 43% female) over 13.5 months, excluding an 8-month pause due to COVID-19 disruptions. The average recruitment rate was 0.6 adolescents/recruiting chiropractor/month. We achieved a 100% response to chiropractor baseline and follow-up questionnaires, 98% to adolescent baseline, 94% average response to combined weekly text messages and 93% retention of adolescents at study completion.ConclusionsOur high response and retention rates demonstrate feasible data collection methods in this population. Addressing low recruitment by expanding the number and type of clinicians is necessary for a successful larger study.
Observational study protocol: the faecal microbiome in the acute stage of new-onset paediatric type 1 diabetes in an Irish cohort
Authors: Kennedy Elaine Catherine , Ross Fiona Catherine , O’Shea Carol-Anne , Lavelle Aonghus , Ross Paul , Dempsey Eugene , Stanton Catherine , Hawkes Colin Patrick 
Published: January 2025

IntroductionType 1 diabetes (T1D) is an autoimmune-mediated disorder caused by the destruction of pancreatic beta cells. Although there is an underlying genetic predisposition to developing T1D, the trigger is multifactorial and likely includes environmental factors. The intestinal microbiome has been identified as one such factor. Previous studies have illustrated differences in the microbiota of people with T1D compared with healthy controls. This study aims to describe the evolution of the microbiome and metabolome during the first year of clinical T1D, or stage 3 T1D diagnosis, and investigate whether there are differences in the microbiome and metabolome of children who present with and without diabetic ketoacidosis. The study will also explore possible associations between the microbiome, metabolome, glycaemic control and beta cell reserve.Methods and analysisThis prospective cohort study will include children with newly diagnosed T1D and sibling controls (n=100, males and females) and their faecal microbiome will be characterised using shotgun metagenomic sequencing at multiple time points during the first year of diagnosis. We will develop a microbial culture biobank based on culturomic studies of stool samples from the healthy controls that will support future investigation. Metabolomic analysis will aim to identify additional biomarkers which may be involved in disease presentation and progression. Through this initial exploratory study, we aim to identify specific microbial biomarkers which may be used as future interventional targets throughout the various stages of T1D progression.Ethics and disseminationThis study has been approved by the Clinical Research Ethics Committee of the Cork Teaching Hospitals. Study results will be available to patients with T1D and their families, carers, support networks and microbiome societies and other researchers.Trial registration numberThe clinicaltrials.gov registration number for this trial isNCT06157736.
Real-world outcomes in patients with melanoma brain metastasis: a US multisite retrospective chart review study of systemic treatments
Authors: Glitza Oliva Isabella C , Palaia Jennell , Sakkal Leon A , Patel Divya , Moshyk Andriy , Han Natalia , Odak Shardul , Schmier Jordana K , Ning Ning , Chandra Sunandana 
Published: January 2025

ObjectiveThis study examined real-world treatment patterns and outcomes in patients with melanoma brain metastasis (MBM) treated with first-line immunotherapy consisting of nivolumab plus ipilimumab or anti-programmed death-1 (PD-1) monotherapy (nivolumab or pembrolizumab) or targeted therapy consisting of BRAF/MEK inhibitors.DesignRetrospective chart review study.SettingAcademic medical centres, community hospitals and private practice offices.ParticipantsIncluded patients diagnosed with melanoma with brain metastasis in the USA.Outcome measuresThe statistical analysis was descriptive in nature. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared between treatments in a univariate Cox proportional hazards model.ResultsIn total, 472 patients with MBM who received first-line nivolumab plus ipilimumab (n=246), anti-PD-1 monotherapy (n=112) or BRAF/MEK inhibitors (n=114) were identified. Patients receiving nivolumab plus ipilimumab, compared with patients receiving anti-PD-1 monotherapy or BRAF/MEK inhibitors, had favourable baseline prognostic factors, such as younger age, fewer or smaller brain metastases, better Eastern Cooperative Oncology Group performance status and less frequently elevated lactate dehydrogenase. Median follow-up times were 15.4 months (range 0.1 to 37.0), 13.3 months (range 0.3 to 36.6) and 13.9 months (range 1.9 to 36.5), respectively. Numerically longer OS was observed with nivolumab plus ipilimumab versus anti-PD-1 monotherapy (HR 0.47, 95% CI 0.34 to 0.67) or BRAF/MEK inhibitors (HR 0.72, 95% CI 0.50 to 1.04) and numerically longer PFS was observed with nivolumab plus ipilimumab versus anti-PD-1 monotherapy (HR 0.74, 95% CI 0.53 to 1.02) or BRAF/MEK inhibitors (HR 0.82, 95% CI 0.60 to 1.12). With nivolumab plus ipilimumab, anti-PD-1 monotherapy and BRAF/MEK inhibitors, 1-year OS rates were 79%, 60% and 72%, respectively; 1-year PFS rates were 68%, 58% and 59%.ConclusionsIn this real-world study, first-line nivolumab plus ipilimumab appeared to provide benefit versus anti-PD-1 monotherapy and BRAF/MEK inhibitors in patients with MBM, consistent with pivotal trial data. However, the observed benefit may have been due to confounding and selection bias, given that patients receiving nivolumab plus ipilimumab had favourable baseline prognostic factors compared with patients receiving anti-PD-1 monotherapy or BRAF/MEK inhibitors.
Prevalence of sudden unexpected death of infants and its subcategories in low- or middle-income countries: a systematic review protocol
Authors: Rhoda Natasha R , Turawa Eunice , Engel Mark , Ayouni Imen , Zuhlke Liesl , Coetzee David , Mathews Shanaaz 
Published: January 2025

IntroductionInfant mortality in low or middle-income countries (LoMICs) is still triple that of high-income countries (HICs), and the high mortality burden regions are also weighed down by a triple or quadruple burden of disease such as HIV and tuberculosis; chronic illness; mental health; injury and violence; and maternal, neonatal and child mortality. Emerging data suggest that the sudden unexpected death in infancy (SUDI) burden in LoMICs is at least 10-fold that in HICs. While ending preventable deaths in the neonatal period has received some global attention, the postnatal period where SUDIs occur is a poorly understood and data-poor area in LoMICs. We propose conducting a systematic review to evaluate the burden and trends of SUDIs in LoMICs since 2004.Methods and analysisWe will systematically search PubMed, Web of Science, Scopus, African Index Medicus, EBSCOHost, Google Scholar, WHOIS and WHO database to identify studies published from July 2004 until October 2024. Two reviewers will screen titles and abstracts and select full-text articles independently for review. We will use the tool developed by the South African Medical Research Council—Burden of Disease Review Manager (BODRevMan)—to assess the risk of bias for each included study. Risk of bias will be assessed for each included study. Information on the prevalence and/or incidence of SUDI and its subcategories and case definitions will be extracted from each article. Where possible, data on prevalence, incidence and subcategories will be pooled using a random effects meta-analysis to account for variability between estimates. The I2statistic will establish the level of heterogeneity due to variation in estimates rather than chance. Results will be presented in tables and graphs. The systematic review will be reported according to the PRISMA 2020 checklist.Ethics and disseminationEthical approval is not required as this is a protocol for a systematic review. Findings will be disseminated through peer-reviewed publications and conference presentations.PROSPERO registration numberCRD42023466162.
Human versus Analogue Insulin for Youth with Type 1 Diabetes in Low-Resource Settings (HumAn-1): protocol for a randomised controlled trial
Authors: Foulds Abigail , Josey Claire , Kehlenbrink Sylvia , Rollman Bruce L , Chang Chung-Chou H , Lalama Christina , Ansbro Éimhín , Prust Margaret L , Zabeen Bedowra , Ramaiya Kaushik , Ogle Graham , Chae Sae-Rom , Luo Jing 
Published: January 2025

IntroductionLong-acting insulin analogues are the standard of care for people with type 1 diabetes (T1D) in high-income countries but remain largely inaccessible and understudied in low-resource settings. In settings where glycaemic control is typically poor and food insecurity is common, long-acting insulin analogues may offer tangible clinical benefits for people with T1D. To determine whether insulin glargine, a long-acting insulin analogue, reduces the risk of serious hypoglycaemia and/or improves glycaemic time-in-range (TIR) versus human insulin regimens in this population, we are conducting the Human vs Analogue Insulin for Youth with Type 1 Diabetes in Low-Resource Settings randomised controlled trial.Methods and analysisThis is a 1:1 randomised, parallel-group clinical trial comparing biosimilar insulin glargine with human insulin (Neutral Protamine Hagedorn (NPH) or premixed 70/30 insulin) in 400 youth with type 1 diabetes (T1D) recruiting in Dhaka, Bangladesh (n=250) and Mwanza, Tanzania (n=150). Blinded continuous glucose monitors will be used to assess glycaemic control in both study arms over 14-day periods at baseline and at 3, 6 and 12 months after randomisation. The co-primary outcomes are the per cent time in serious hypoglycaemia (<54 mg/dL) and TIR (70–180 mg/dL) at 6 months of follow-up. Secondary outcomes include TIR at 12 months and time-in-hypoglycaemia, time-above-range, nocturnal hypoglycaemic events and glycaemic control (ie, haemoglobin A1C (HbA1c)) at 6- and 12-months of follow-up. Treatment satisfaction and quality of life are assessed at baseline, 6- and 12 month follow-up. Additionally, the study is conducting qualitative interviews, quantitative assessments of treatment satisfaction and quality of life, as well as assessing the cost-effectiveness of analogue insulin use in low-resource settings.Ethics and disseminationThis study was approved by the Institutional Review Board at the University of Pittsburgh (STUDY21110122), the National Health Research Ethics Committee at the National Institute for Medical Research in Tanzania (NIMR/HQ/R.8a/Vol.IX/4265) and the Ethical Review Committee (ERC) of Diabetic Association of Bangladesh (BADAS-ERC/EC/22/405). Research findings will be shared by the local partner organisations and institutions with relevant stakeholders including youth living with diabetes, policy makers, healthcare workers and the general public. Findings will also be shared at local, regional and international scientific meetings.Trial registration numberClinicalTrials.gov:NCT05614089.
Determining the incidence, risk factors and biological drivers of irritable bowel syndrome (IBS) as part of the constellation of postacute sequelae of SARS-CoV-2 infection (PASC) outcomes in the Arizona CoVHORT-GI: a longitudinal cohort study
Authors: Pogreba Brown Kristen , Austhof Erika , McFadden Caitlyn M , Scranton Caroline , Sun Xiaoxiao , Vujkovic-Cviji Ivan , Rodriguez Dominic , Falk Laura , Heslin Kelly M , Arani Gayatri , Obergh Victoria , Bessey Kate , Cooper Kerry 
Published: January 2025

IntroductionPostacute sequelae of SARS-CoV-2 infection (PASC) are extensive. Also known as long COVID, primary outcomes reported are neurologic, cardiac and respiratory in nature. However, several studies have also reported an increase in gastrointestinal (GI) symptoms and syndromes following COVID-19. This study of PASC will include extensive analyses of GI symptoms, determine if people with pre-existing irritable bowel syndrome (IBS) are at higher risk of developing PASC generally or PASC-GI, and which biomarkers are impacted and to what degree. This R01 study is being funded by the National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK135483-01) from 2023 to 2028.Methods and analysesThis study combines a longitudinal epidemiologic cohort study and in-depth, novel biologic analyses. In collaboration with a pre-existing study, the Arizona CoVID-19 Cohort (CoVHORT)-GI will recruit participants based on the history of COVID infection(s), new or ongoing GI symptoms 3–6 months postinfection, and pre-existing or incident IBS diagnosis to represent five study groups for comparison and analyses. A subset (n=1000) of those recruited will submit both stool and blood samples. Both samples will undergo a novel method to quantitate humoral and mucosal immune responses to host-derived faecal communities in conjunction with magnetic bead-based separation and high-depth shotgun microbial sequencing. Stool samples will also undergo traditional microbiome analyses (diversity and abundance) and faecal calprotectin assays. Additional serum analyses will aim to determine if a proteomics-based signature exists that differentiates a unique biomarker compositional signature discriminating PASC-GI versus no PASC. All laboratory data will be linked with in-depth epidemiologic data on demographics, symptoms and chronic conditions.Ethics and disseminationThis study involves human participants and was approved by the University of Arizona Institutional Review Board (IRB (#00002332) and has been deemed minimal risk. Participants gave informed consent to participate in the study before taking part. All publications from the study will be shared back to participants along with alternative lay summaries and webinars to communicate key findings. The data management plan has been published and is publicly available online, including protocols for data requests.
Reducing the urge to be physically active in patients with anorexia nervosa through virtual reality: protocol for a randomised-controlled feasibility trial
Authors: Halbeisen Georg , Timmesfeld Nina , Paslakis Georgios 
Published: January 2025

IntroductionWeight restoration is a primary goal in anorexia nervosa (AN) treatment. Recent studies suggest that addressing physical activity urges in patients with AN is a promising target to facilitate weight restoration. This trial will evaluate the feasibility of a virtual reality (VR)-based intervention as an add-on treatment to psychotherapy to improve activity urges and, consequently, initial treatment responses on core outcomes as targeted per AN treatment guidelines.Methods and analysisThis single-centre feasibility trial adopts the single-blind, two-arm design and outcome measures of an intended full-scale randomised controlled trial (RCT) in order to establish that all necessary trial components work together as intended. It will evaluate feasibility as the primary endpoint and compare changes in ratings of the urge to be active between patients with AN randomly assigned to receiving VR intervention sessions and patients with AN in a control procedure. The feasibility of the full-scale RCT will depend on whether patients (1) will evaluate the experience as acceptable, (2) tolerate VR side effects and (3) will adhere to the intended intervention schedule. We define a set of three-tiered, formal progression criteria and employ a ‘traffic light system’ demarcating go (green), amend (amber) and stop (red) signals for advancing to the full-scale RCT.Ethics and disseminationThe study was approved by the ethics committee of the Ruhr University Bochum’s Medical Faculty at Campus East-Westphalia (AZ 2024-1296, 9 December 2024). Patients have to provide written consent before taking part in the study. The findings will be published with open access.Trial registration numberDRKS00035681, German Clinical Trials Register.
Two-photon excited fluorescence with shaped laser pulses for refractive beams
Authors: S. Bukhari S. S. A. , Gottschalk R. , Lindinger A. 
Published: January 2025

Abstract
We report two-photon excited fluorescence of dyes for refracted laser beams by utilizing tailored laser pulses. A fluorescence contrast difference due to phase shaping could be achieved between different coumarin dyes. Particularly, an increased contrast difference is obtained for configurations close to the Brewster angle. Furthermore, by using a subsequent deformable phase plate for spatial shaping it was possible to precisely adjust the laser beam for controlled refraction at the liquid dye surface. A polarization-dependent refraction was observed when directing the shaped laser beam on the curved liquid adhesion meniscus close to the cuvette wall. This results in a refraction-dependent contrast difference. The presented method could be utilized for surface-sensitive biophotonic imaging applications.

Graphic abstract
Characterization of the Phenotypic and Genotypic Antibiotic Resistance Markers in Escherichia coli (E. coli) Associated With Diabetes and Nondiabetic Patients
Authors: Adjei David Nana , Mughogho Thomas Stuart , Michael Olu-Taiwo , Saidu Sarah , Amegatcher Gloria , Forson Akua Obeng 
Published: January 2025

Introduction: Individuals with diabetes are more susceptible to urinary tract infections (UTIs) than those without the disease. This study aimed to determine the phenotypic and genotypic antibiotic resistance profiles of Escherichia coli in diabetic and nondiabetic patients.Methodology: A total of 374 clean‐catch midstream urine specimens were screened for uropathogens, and antibiogram analysis was done on E. coli isolates by the Kirby–Bauer disc diffusion method, followed by phenotypic confirmation of extended spectrum beta‐lactamase (ESBL) production. In addition, polymerase chain reaction (PCR) assays were carried out to determine ESBL genotypes.Result: Overall, we observed UTIs prevalence of 19.8% and 10.7% in diabetic and nondiabetic patients. Females exhibited higher UTI prevalence than males in both groups ([71.8% and 28.2%] vs. [85% and 15%]) (p < 0.0001). Among women with and without diabetes, the age groups of 55–64 and 25–34 years showed the highest prevalence of UTIs (25.6% vs. 40%). The most prevalent uropathogen was E. coli (62.2% vs. 75%); multidrug‐resistant (MDR) E. coli was (61% vs. 33.3%) and ESBL–E. coli was (34.8% and 20%) in diabetic and nondiabetic patients, respectively. The most common ESBL‐mediated gene was blaCTX‐M (64.3%) with multiple ESBL genes in some E. coli isolates. High‐level resistance was observed for ampicillin (91.2%), cefuroxime (96.7%), ciprofloxacin (44.9%), and trimethoprim (59.4%), and low‐level resistance was observed for gentamicin (18.7%), ceftriaxone (20.9%), and nitrofurantoin (19.8%). There was no significant difference between antibiotic resistance in diabetic and nondiabetic patients (p > 0.05).Conclusion: We observed blaCTX‐M as the most common ESBL genotype, in combination with other ESBL genes present in some E. coli isolates. Nitrofurantoin and ceftriaxone antibiotics were efficacious. Appropriate prescription of antibiotic therapy, and the prevention of transmission of resistant genes in the context of public health can be facilitated by routine monitoring of the resistance profiles and ESBL markers in patients with and without diabetes.
Characterization of TNG348: A Selective, Allosteric USP1 Inhibitor That Synergizes with PARP Inhibitors in Tumors with Homologous Recombination Deficiency
Authors: Simoneau Antoine , Pratt Charlotte B. , Wu Hsin-Jung , Rajeswaran Shreya S. , Comer Charlotte Grace , Sudsakorn Sirimas , Zhang Wenhai , Liu Shangtao , Meier Samuel R. , Choi Ashley H. , Khendu Tenzing , Stowe Hannah , Shen Binzhang , Whittington Douglas A. , Chen Yingnan , Yu Yi , Mallender William D. , Feng Tianshu , Andersen Jannik N. , Maxwell John P. , Throner Scott 
Published: January 2025

Abstract
Inhibition of the deubiquitinating enzyme USP1 can induce synthetic lethality in tumors characterized by homologous recombination deficiency (HRD) and represents a novel therapeutic strategy for the treatment of BRCA1/2-mutant cancers, potentially including patients whose tumors have primary or acquired resistance to PARP inhibitors (PARPi). In this study, we present a comprehensive characterization of TNG348, an allosteric, selective, and reversible inhibitor of USP1. TNG348 induces dose-dependent accumulation of ubiquitinated protein substrates both in vitro and in vivo. CRISPR screens show that TNG348 exerts its antitumor effect by disrupting the translesion synthesis pathway of DNA damage tolerance through RAD18-dependent ubiquitinated PCNA. Although TNG348 and PARPi share the ability to selectively kill HRD tumor cells, CRISPR screens reveal that TNG348 and PARPi do so through discrete mechanisms. Particularly, knocking out PARP1 causes resistance to PARPi but sensitizes cells to TNG348 treatment. Consistent with these findings, combination of TNG348 with PARPi leads to synergistic antitumor effects in HRD tumors, resulting in tumor growth inhibition and regression in multiple mouse xenograft tumor models. Importantly, our data on human cancer models further show that the addition of TNG348 to PARPi treatment can overcome acquired PARPi resistance in vivo. Although the clinical development of TNG348 has been discontinued because of unexpected liver toxicity in patients (NCT06065059), the present data provide preclinical and mechanistic support for the continued exploration of USP1 as a drug target for the treatment of patients with BRCA1/2-mutant or HRD cancers.