bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between elevated serum REG Iα levels and eGFR decline in patients with chronic kidney disease: a cross-sectional study in eastern China
Authors: Huang Nan , Zhu Xiangyun , Shu Zhiyi , Chen Sheng , Wu Xiaodong , Wang Hui , Huang Xi , Hu Xiuxiu , Sun Jinfang , Chen Pingsheng , Graf Rolf , Bai Jianling , Wang Bin , Li Ling 
Published: February 2025

ObjectivesThis study aimed to investigate the relationship between serum regenerating protein Iα (REG Iα) levels and estimated glomerular filtration rate (eGFR) and to evaluate the diagnostic efficiency of REG Iα in chronic kidney disease (CKD).DesignThis is a cross-sectional study.SettingThe study was conducted in eastern China between August 2022 and August 2023.ParticipantsA total of 880 participants aged over 18 years were enrolled, with 220 non-CKD participants (111 males, 50.45%) and 660 patients with CKD (366 males, 55.45%). CKD was diagnosed based on the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 guidelines. Exclusion criteria included participation in other trials, acute kidney injury, end-stage kidney disease undergoing renal replacement therapy, pregnancy, active infections, gastrointestinal or pancreatic inflammation, history of gastrointestinal or pancreatic resections, cancer and mental disorders.ResultsSerum REG Iα was significantly higher in the CKD group (125.54 (60.28–303.39) ng/mL) compared with those in the non-CKD group (24.62 (14.09–37.32) ng/mL, p<0.001). Positive correlations were observed between serum REG Iα and serum creatinine, cystatin C (Cys-C), and kidney injury molecule 1 (KIM-1), while a negative correlation was identified with eGFR. After adjusting for sex, diabetes, hypertension and fasting blood glucose, the multivariate regression analysis demonstrated a significant association between serum REG Iα and eGFR (OR=1.737 (1.263–2.388), p=0.001). Furthermore, serum REG Iα levels increased progressively with declining kidney function categorised by eGFR (p<0.001). In CKD screening, serum REG Iα demonstrated strong diagnostic performance, with an area under the receiver operating characteristic curves (AUC) of 0.860 (0.813–0.899), providing a sensitivity of 71.63%, a specificity of 86.89%, a positive predictive value of 94.30% and a negative predictive value of 46.85%. Additionally, serum REG Iα exhibited an AUC of 0.769 (0.712–0.819) for identifying high- and very-high-risk CKD based on KDIGO risk stratification. Its sensitivity significantly outperformed serum Cys-C and KIM-1 (82.80% vs 75.16% and 36.94%, respectively).ConclusionsThis study provided compelling evidence that serum REG Iα levels were notably elevated in patients with CKD and closely associated with kidney function. REG Iα may serve as a promising biomarker for CKD detection and risk stratification.Clinical trial registrationThe study was approved by the Ethics Committee of Zhongda Hospital (approval number: 2022ZDSYLL204-P01) and conducted in compliance with the Helsinki Declaration. The clinical trial was registered under ChiCTR2300072247.
Incidence of tuberculosis and its predictors among children on antiretroviral therapy in Amhara Region, Ethiopia: a multicentre institution-based retrospective follow-up study
Authors: Mekonnen Gebrehiwot Berie , Legesse Bruck Tesfaye , Baye Fikadie Dagnew , Wondie Wubet Tazeb 
Published: February 2025

IntroductionTuberculosis (TB) continues to be a significant public health issue, particularly in low-income and middle-income countries. Globally, the End TB Strategy targets an 80% reduction in TB incidence by 2030. Despite this strategy, there remains limited evidence on the incidence of TB among HIV-infected children after the test-and-treat strategies in Amhara Region. Hence, this study aimed to assess the incidence of TB and its predictors among children on antiretroviral therapy (ART) in Amhara Region, which is the second largest region in Ethiopia and located in the northwestern, northeastern and north-central parts of Ethiopia.MethodsA multicentre institution-based retrospective follow-up study was conducted on 421 HIV-infected children receiving ART from July 2014 to March 2022. The study participants were selected using simple random technique. National antiretroviral intake and follow-up forms were used to gather data through the KoBo Toolbox. Stata V.17 was used for data analysis. The Kaplan-Meier curve was applied to estimate failure time, and the log-rank test was employed to compare groups of predictors. To identify TB predictors, Gompertz regression models, both bivariable and multivariable, were constructed. Ultimately, a 95% CI adjusted HR (AHR) was calculated, and variables with a p value less than 0.05 were considered statistically significant.ResultsA total of 421 children with a record completeness rate of 97.9% were analysed in the study. The TB incidence rate in children on ART was 2.16 (95% CI 1.52, 3.05) per 100 child-year observations. Anaemia at baseline (AHR: 3.83; 95% CI 1.46, 10.04), never taking TB preventive treatment (TPT) (AHR: 3.78; 95% CI 1.44, 9.94), wasting (AHR: 2.53; 95% CI 1.19, 5.38) and not initiating ART within 7 days (AHR: 2.35; 95% CI 1.15, 4.78) were significant predictors of TB in children.ConclusionThe incidence of TB in children on ART was relatively high. HIV-positive children presenting with anaemia, those who never took TPT, wasted children and those with late initiation of ART were prone to the occurrence of TB. Therefore, prioritising anaemia treatment, TB preventive therapy, nutritional counselling and timely initiation of ART are essential to curb the TB burden.
Volunteer responders’ experience of attending a paediatric out-of-hospital cardiac arrest in Denmark: a qualitative study
Authors: Kjærholm Sofie Have , Kragh Astrid Rolin , Juul Grabmayr Anne , Borch-Johnsen Liv , Folke Fredrik , Poulsen Ingrid , Malta Hansen Carolina , Guldager Rikke 
Published: February 2025

ObjectiveTo explore the experiences of volunteer responders attending a paediatric out-of-hospital cardiac arrests (POHCAs) in Denmark.DesignThis qualitative study used the Reflective Lifeworld Research theoretical framework. Data were generated through nine in-depth, in-person or virtual semistructured interviews conducted with volunteer responders.SettingThe study was conducted in Denmark. We recruited volunteer responders from all of Denmark enrolled in the nationwide volunteer responder programme.ParticipantsNine volunteer responders who were dispatched in response to a POHCA from 2020 to 2023 were included in the study.ResultsThe experiences of attending a POHCA were categorised into three key themes: the mission, the situation and the aftermath. The mission refers to the altruistic drive of volunteer responders to contribute to life-saving efforts. The situation reflects the profound shock experienced when volunteer responders realise that the patient is a child, alongside their ability to act decisively and initiate cardiopulmonary resuscitation in the situation. The aftermath reveals the deep sense of fulfilment derived from being present and actively involved in attempting to save a child’s life, as well as the various emotions and reactions that the volunteer responders process after the event.ConclusionAttending a POHCA is a profoundly intense experience that can leave an emotional impact on the volunteer responders. On arriving at the location, despite the initial shock upon realising that the patient is a child, the volunteer responders engage in the resuscitation attempt and offer support to the child’s family. However, alerting the volunteer responders beforehand that the patient is a child may help mitigate the initial shock. Volunteer responders find significant meaning in their roles and express a strong commitment to saving lives, irrespective of the age of those in need.
Minimally invasive glaucoma surgery: comparison of Hydrus microstent with iStentinjectin primary open-angle glaucoma
Authors: Komzak Krishna , Allen Penelope L , Toh Tze’Yo 
Published: February 2025

BackgroundTo evaluate and compare the efficacy of a single Hydrus and double iStentinjectboth combined with cataract surgery for the treatment of primary open-angle glaucoma (POAG).MethodsThe study was designed as a prospective comparative case series. Patients with POAG undergoing trabecular microbypass stent insertion in addition to cataract surgery were recruited and consent was obtained. Baseline demographic information and preoperative, intraoperative and postoperative outcomes including intraocular pressure (IOP), visual acuity and topical glaucoma medication use were recorded and analysed. Treatment outcomes were analysed after propensity score matching to adjust for baseline differences between the two groups. Primary success was defined as an IOP of ≤18 and ≥20% IOP reduction at 12 months; other outcomes included IOP ≤15 mm Hg and ≤21 mm Hg. These were measured against complete success (no medications) and qualified success (one or more medications).ResultsThe study comprised 85 eyes in the Hydrus group and 100 eyes in the iStentinjectgroup at commencement, with 12-month follow-up for 85 and 78, respectively. When correcting for baseline differences between the two groups using propensity score matching, Hydrus eyes were not more likely to achieve primary success (average treatment effect −0.79, p=0.15).ConclusionAfter adjusting for baseline differences, there was no statistically significant difference between combined Hydrus microstent implantation and cataract surgery when compared with the iStentinjectin reducing IOP at 12-month follow-up. This study was limited by statistically significant baseline differences between the two study groups, adjusted for with propensity score matching.
Improving follow-up visits among individuals with hypertension: Quality Improvement project in the District Hospital, Seoni, Madhya Pradesh, India, 2021–2022
Authors: Bharadwaj Rupali , Kaviprawin Mogan , Neelkanth Namita , Navkar Vinod Kumar , Azarudeen Mohamed Jainul , Parasuraman Ganeshkumar , Ramalingam Archana , Kaur Prabhdeep 
Published: February 2025

BackgroundIn India, to achieve a 25% relative reduction in the prevalence of raised blood pressure (BP) by 2025, approximately 4.5 crore additional people with hypertension will need to have their BP effectively treated. We conducted a Quality Improvement (QI) initiative to improve follow-up and reduce missed visits among individuals with hypertension registered under India Hypertension Control Initiative, District Hospital, Seoni, Madhya Pradesh, India, in 2022.MethodsWe conducted a quasiexperimental study from January to September 2022 in the District Hospital in Seoni, Madhya Pradesh. Following the Ishikawa diagram, the major root causes for missed visits were identified, and countermeasures were developed. The packages under Plan-Do-Study-Act (PDSA) included (i) training urban Accredited Social Health Activists to conduct house visits for individuals with missed visits and (ii) triangulating the follow-up records from various information systems. The review meetings for QI initiatives were conducted fortnightly to follow-up PDSAs. We calculated the proportion of individuals who were followed-up monthly, and the proportion of missed visits among those registered quarterly.ResultsCumulatively, 2850 individuals were registered with hypertension till September 2022. Following the intervention, the monthly follow-up proportion increased from 21% in January to 37% in September 2022. Missed visit proportion decreased from 66% (228/345) in quarter four, 2021, to 22% (40/180) in quarter three, 2022. Of the 1438 individuals counselled by ASHA home visits, 74.9% returned for follow-up.ConclusionIn our setting, QI initiatives suggested that missed visits decreased during the intervention period. However, the interventions must be implemented continuously for better monitoring and use in similar settings.
Effect of lifestyle interventions on cognitive function, physical fitness and activity over 2 years in primary school children: results from the fit4future intervention programme
Authors: Schoenfeld Julia , Kaiser Michaela , Rieger Barbara , Haller Bernhard , Halle Martin , Siegrist Monika 
Published: February 2025

ObjectivesPhysical activity is associated with positive health effects and improved cognitive function in children. However, these data are primarily based on cross-sectional studies. We investigated changes in cognitive function, physical fitness and physical activity in children following a school-based intervention.MethodsThe ‘fit4future’ study is a prospective, interventional, long-term study conducted in Germany to evaluate the impact of a comprehensive school-based health promotion programme in children. The aims of the programme have been to increase the amount of physical activity, to support a healthy diet and to improve attention and concentration performance as well as coping strategies. Schools received equipment to support physical activity, for example, action cards, brochures as well as online materials containing information regarding physical activity, nutrition, cognitive function and stress management. Teachers were trained in six workshops to enable them to promote a systematic health promotion process at schools. Parents received brochures about healthy lifestyles with practical advice for everyday family life. Additional information was provided on the programme’s homepage. At the beginning of the second and the end of the third grade, children completed a differential performance test (Concentrated Task) for the assessment of concentration and attention in which they had to cross predetermined pictorial symbols on preprinted test sheets (average marked signs). Changes in the average marked signs were investigated and compared with age-specific and sex-specific norms. Physical fitness and activity were assessed using a six-item fitness test and questionnaire.ResultsA total of 839 children (mean age 7.5±0.6 years, 48% girls) from 32 schools participated in this study. Over 2 years, average marked signs increased from 91.6±20.7 to 138.0±27.6 (p<0.001) (n=553 children, mean age 7.5±0.6 years, 51% girls). This improvement was greater than expected compared with the age-specific and sex-specific norms. The children showed significant improvements in all fitness test items and a significant increase in physical activity (p<0.001). Age, baseline average marked signs and changes in the jump-and-reach test were associated with changes in cognitive function (regression coefficient β=0.95, SE=0.23, p<0.001).ConclusionA school-based health promotion programme improved cognitive function, physical activity and physical fitness beyond the age-related improvements expected over 2 years in a large cohort of primary school children.Trial registration numberGerman Clinical Trials Register (DRKS-ID: DRKS00020894, Date of registration: 2020-02-26).
Improving uptake of lung cancer screening: an observational study on the impact of timed appointments and reminders
Authors: Bhamani Amyn , Naidu Sindhu Bhaarrati , Patrick Tanya , Anandan Lavanya , Desai Kiran , Bojang Fanta , Verghese Priyam , Robinson Paul , Patel Shivani , Thakrar Ricky , Nair Arjun , Navani Neal , Janes Sam M 
Published: February 2025

Lung cancer screening (LCS) reduces lung cancer-related mortality; however, uptake remains low compared with other cancer screening programmes. In this observational study, we report the impact of timed appointments and reminders on participation in our regional LCS programme.Initial uptake of timed appointments was 53.0% (n=17 274/32 593), higher than previously reported in the UK, while initial uptake of open invitations was 29.8% (n=10 246/34 371). Among initial non-responders, 17.5% (n=4263/24 400) completed triage following a reminder. The increased participation following reminders only partially offset the significant difference in initial uptake between the two appointment types.Timed appointments and reminders are strongly advocated to increase participation in national LCS programmes.
Can Q-balls describe cosmological and galactic dark matter?
Authors: Mandal Susobhan , Shankaranarayanan S. 
Published: February 2025

Abstract
The Cold Dark Matter (CDM) hypothesis accurately predicts large-scale structure formation and fits the Cosmic Microwave Background temperature fluctuations (CMB). However, observations of the inner regions of dark matter halos and dwarf galaxy satellites have consistently posed challenges to CDM. On the other hand, the Modified Newtonian Dynamics (MOND) hypothesis can explain galactic phenomena but fails to account for the complex shape of the CMB and matter power spectra. CDM and MOND are effective in nearly mutually exclusive regimes, prompting the question: is there a physical mechanism where CDM and MOND share a common origin? Q-balls, which are localized, non-topological solitons, can be a bridge between the two hypotheses. Q-balls formed in the early Universe can mimic CDM at cosmological scales. Interestingly, Q-balls can exhibit MOND-like behavior in the late Universe at galactic scales, providing a unified framework. Specifically, we demonstrate that millicharged composite Q-balls formed from complex scalar fields, decoupled from the background radiation, can naturally arise during the radiation-dominated epoch. From the matter-radiation equality, we also obtain the mass of Q-balls to be 1 eV, which are much smaller than the electron mass. Using the constraints from the invisible decay mode of ortho-positronium, we obtain

$$Q < 3.4 \times 10^{-5}$$

Q
<
3.4
×

10

-
5

. We also establish an upper bound on the number density of Q-balls, which depends on the charge of the Q-ball and the small initial charge asymmetry. Furthermore, we demonstrate that the MOND naturally emerges at the galactic scale within the framework of our Q-ball model.
Effective Treatment of Disseminated Prostate Cancer Using CD46-Targeted 225Ac Therapy
Authors: Bidkar Anil P. , Peter Robin , Wadhwa Anju , Bobba Kondapa Naidu. , Bidlingmaier Scott , Meher Niranjan , Chou Jonathan , Greenland Nancy , Dasari Chandrashekhar , Naik Shubhankar , Raveendran Athira , Basak Megha , Camara Serrano Juan Antonio , Steri Veronica , Kogan Scott , Oskowitz Adam , He Jiang , Wilson David M. , Aggarwal Rahul , Sriram Renuka , VanBrocklin Henry F. , Seo Youngho , Liu Bin , Flavell Robert R. 
Published: February 2025

Abstract
Purpose: Metastatic castration-resistant prostate cancer (mCRPC) has limited treatment options and a poor prognosis. Recently, PSMA-targeted alpha particle therapy agents using Actinium-225 (225Ac) have shown promising results for prostate cancer treatment, but a significant fraction of patients with advanced mCRPC demonstrate loss of PSMA expression. We have previously reported that PSMA-null and PSMA-positive tumors can be detected and treated effectively with CD46-targeted radiopharmaceuticals. This study evaluates the CD46-targeting PET imaging agent [89Zr]DFO-YS5 and the radioimmunotherapy agent [225Ac]Macropa-PEG4-YS5 in disseminated prostate cancer tumors. Experimental Design: Microtumor lesions, primarily observed in the liver, kidneys, and lungs, were successfully detected with [89Zr]DFO-YS5 PET imaging. We used disseminated 22Rv1 tumors for biodistribution studies, dosimetry assessments, and therapeutic efficacy evaluations of [225Ac]Macropa-PEG4-YS5. Results: Quantitative digital alpha-particle autoradiography revealed high radiation dose deposition from [225Ac]Macropa-PEG4-YS5 in microtumors compared to surrounding liver tissues, although in larger lesions (&gt;1 mm diameter) the dose distribution was heterogeneous. Early treatment of smaller disseminated tumors with uniform radiation dose was more effective in ablating tumors and promoting survival. In late-stage lesions of large size, heterogeneous dose deposition limited therapeutic efficacy, requiring higher administered activity to achieve a complete response. Conclusions: Our findings highlight that [225Ac]Macropa-PEG4-YS5 holds the potential for clinical translation for metastatic prostate cancer and reinforces the value of microdosimetry in understanding the efficacy of and resistance to targeted alpha therapy.
Epigenetic dysregulation of retrotransposons in cancer
Authors: Leung Danny , Liu Kwok Yu 
Published: February 2025

Abstract
Approximately 97% of the human genome comprises non-coding sequences, with nearly half originating from transposable elements. Among these, retrotransposons represent a critical subclass that replicates via a "copy-and-paste" mechanism and significantly influences the regulation of host genomes. In both normal and pathological contexts, retrotransposons contribute a vast reservoir of regulatory elements that can modulate the expression of genes. If left unchecked, retrotransposons can substantially affect host transcriptional programs and genomic integrity. Therefore, various mechanisms, including epigenetic modifications, are employed to mitigate their potentially deleterious effects. In diseases such as cancers, the epigenome is often significantly reprogrammed, which can lead to retrotransposon dysregulation. Drawing insights from recent studies conducted in human and murine cells, this review examines how retrotransposons expand the complexity of mammalian genomes, describes the impact of their epigenetic dysregulation in cancer development, and highlights the potential of targeting these sequences for therapeutic strategies.
The Germline and Somatic Origins of Prostate Cancer Heterogeneity
Authors: Yamaguchi Takafumi N. , Houlahan Kathleen E. , Zhu Helen , Kurganovs Natalie , Livingstone Julie , Fox Natalie S. , Yuan Jiapei , Sietsma Penington Jocelyn , Jung Chol-Hee , Schwarz Tommer , Jaratlerdsiri Weerachai , van Riet Job , Georgeson Peter , Mangiola Stefano , Taraszka Kodi , Lesurf Robert , Jiang Jue , Chow Ken , Heisler Lawrence E. , Shiah Yu-Jia , Ramanand Susmita G. , Clarkson Michael J. , Nguyen Anne , Espiritu Shadrielle Melijah G. , Stuchbery Ryan , Jovelin Richard , Huang Vincent , Bell Connor , O'Connor Edward , McCoy Patrick J. , Lalansingh Christopher M. , Cmero Marek , Salcedo Adriana , Chan Eva K.F. , Liu Lydia Y. , Stricker Phillip D. , Bhandari Vinayak , Bornman Riana M.S. , Sendorek Dorota HS. , Lonie Andrew , Prokopec Stephenie D. , Fraser Michael , Peters Justin S. , Foucal Adrien , Mutambirwa Shingai B A. , Mcintosh Lachlan , Orain Michèle , Wakefield Matthew , Picard Valérie , Park Daniel J. , Hovington Hélène , Kerger Michael , Bergeron Alain , Sabelnykova Veronica , Seo Ji-Heui , Pomerantz Mark M. , Zaitlen Noah , Waszak Sebastian M. , Gusev Alexander , Lacombe Louis , Fradet Yves , Ryan Andrew , Kishan Amar U. , Lolkema Martijn P. , Weischenfeldt Joachim , Têtu Bernard , Costello Anthony J. , Hayes Vanessa M. , Hung Rayjean J. , He Housheng H. , McPherson John D. , Pasaniuc Bogdan , van der Kwast Theodorus , Papenfuss Anthony T. , Freedman Matthew L. , Pope Bernard J. , Bristow Robert G. , Mani Ram S. , Corcoran Niall M. , Reimand Jüri , Hovens Christopher M. , Boutros Paul C. 
Published: February 2025

Abstract
Newly diagnosed prostate cancers differ dramatically in mutational composition and lethality. The most accurate clinical predictor of lethality is tumor tissue architecture, quantified as tumor grade. To interrogate the evolutionary origins of prostate cancer heterogeneity, we analyzed 666 prostate tumor whole genomes. We identified a compendium of 223 recurrently mutated driver regions, most influencing downstream mutational processes and gene expression. We identified and validated individual germline variants that predispose tumors to acquire specific somatic driver mutations: these explain heterogeneity in disease presentation and ancestry differences. High-grade tumors have a superset of the drivers in lower-grade tumors, including increased frequency of BRCA2 and MYC mutations. Grade-associated driver mutations occur early in tumor evolution, and their earlier occurrence strongly predicts cancer relapse and metastasis. Our data suggest high- and low-grade prostate tumors both emerge from a common pre-malignant field, influenced by germline genomic context and stochastic mutation-timing.