bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementing and evaluating the comprehensive integration of physical activity into a major health system: study design and protocol
Authors: Stoutenberg Mark , Estabrooks Paul A , Brooks John M , Jindal Meenu , Wichman Christopher , Rosemeyer James , Schumacher Leah M , McNulty Lia K , Ewing Alex , Eskuri Stephanie , Bennett Frankie , Trilk Jennifer L
Published: January 2025

Introduction

The healthcare sector has great potential for promoting physical activity (PA) for chronic disease prevention, treatment and management; however, multiple adoption and implementation barriers exist, ranging from practice integration to information flow. In 2016, Exercise is Medicine Greenville (EIMG), a comprehensive clinic-to-community approach that involves PA assessment, recommendation and/or prescription and provider-based referral of patients to community-based PA programmes, was launched by Prisma Health in Greenville, South Carolina, USA. Since inception, variability has emerged in adoption and implementation, impacting patient reach, referral rates and engagement in the community-based PA programmes, highlighting the need for closer evaluation and refinement of strategies to maximise programme impact.

Methods and analysis

This pragmatic study will examine the adoption, implementation and reach of EIMG. 20 Prisma Health primary care clinics will be invited to adopt EIMG. In Phase I, adopting clinics will receive a standardised EIMG instructional video followed by EIMG activation, allowing providers to refer eligible patients to a 12-week evidence-informed PA programme offered at local community facilities. In Phase II, adopting clinics will receive a more in-depth EIMG onboard training. At adopting clinics, referral rates of eligible patients will be tracked over both phases (each lasting 4 months). A mixed-methods approach will explore factors related to EIMG adoption, achieving optimal implementation and reach, and patient enrolment in the PA programmes. The Reach, Effectiveness, Adoption, Implementation and Maintenance framework will inform the assessment of implementation outcomes, while the integrated Promoting Action on Research Implementation in Health Services framework will be used to explore contextual factors influencing patient-level and clinic-level outcomes.

Ethics and dissemination

We received ethical approval to conduct this study from the Prisma Health IRB Committee A (#1963762). The results of this study have the potential to significantly enhance clinical practice and improve health outcomes related to integrating a clinic-to-community PA model in health systems to connect patients with community-based PA resources. Information gained from this study will lead to the refinement of a generalisable approach to inform future implementation strategies on optimising and scaling up the integration of comprehensive PA models in US health systems and be disseminated through conference presentations, publication in peer-reviewed journals and direct work with health systems.

Trial registration number

NCT06073041.
Association between primary dysmenorrhoea on quality of life, mental health and academic performance among medical students in Indonesia: a cross-sectional study
Authors: Situmorang Herbert , Sutanto Reynardi Larope , Tjoa Kevin , Rivaldo Rivaldo
Published: January 2025

Objectives

To investigate the association between primary dysmenorrhoea and quality of life, mental health and academic performance among medical students in Indonesia.

Design

A cross-sectional study using an online survey was conducted among Indonesian medical students. Primary dysmenorrhoea occurrence and severity, as well as their associations with quality of life, mental health and academic performance, were assessed using validated questionnaires. The associations of dysmenorrhoea occurrence and severity were analysed alongside other potential independent variables, including age, region, stage of study and parental income. Statistical analyses included χ2tests, t-tests and multiple regression models to adjust for confounders (p<0.05).

Setting and participants

Indonesia (June–July 2021: n=630 medical students).

Outcomes

The primary outcomes were quality of life, mental health and academic performance, assessed as dependent variables. Quality of life was measured using the Quality of Life Scale, mental health was assessed through depression and stress scores from the Depression Anxiety Stress Scales-42; and academic performance was evaluated through concentration and activity disruption, absenteeism andcum laudegrade point average (GPA). The independent variables were primary dysmenorrhoea occurrence and severity, categorised as mild or moderate-to-severe using the Verbal Multidimensional Scoring System.

Results

Primary dysmenorrhoea was significantly associated with reduced quality of life, mental health challenges and academic disruptions. Students with dysmenorrhoea had significantly lower Quality of Life scores (–1.82, 95% CI: –2.63 to –1.02; p<0.001), with moderate-to-severe pain linked to an even more significant reduction (–2.09, 95% CI: –2.54 to –1.63; p<0.001). Dysmenorrhoea occurrence was significantly associated with depression (OR 2.16, 95% CI: 1.23 to 3.81; p=0.007), while severity was associated with both depression (OR 2.07, 95% CI: 1.47 to 2.92; p<0.001) and stress (OR 1.82, 95% CI: 1.26 to 2.62; p<0.001). Dysmenorrhoea occurrence and severity significantly disrupted concentration (OR 12.92, 95% CI: 6.14 to 27.22; p<0.001 and OR 7.24, 95% CI: 4.68 to 11.19; p<0.001, respectively), activities (OR 34.95, 95% CI: 4.77 to 256.16; p<0.001 and OR 6.92, 95% CI: 4.63 to 10.36; p<0.001) and absenteeism (OR 12.10, 95% CI: 1.65 to 88.83; p=0.014 and OR 5.65, 95% CI: 3.32 to 9.63; p<0.001).Cum laudeGPA was not significantly associated.

Conclusions

Primary dysmenorrhoea is significantly associated with the quality of life, mental health and academic performance of medical students in Indonesia. Addressing its implications can enhance student well-being and academic outcomes.
NCHD handover in the acute mental health setting: a quality improvement initiative implementing an electronic handover tool
Authors: Naxakis Stelios , Wafer Megan , Gardezi Syeda , Sadia Aamina , Mujahid Rimsha , O’Connor Karen
Published: January 2025

Background

Cork University Hospital, Ireland’s largest teaching hospital, faced challenges in maintaining consistent handover processes in its Acute Mental Health Unit (AMHU). Prior to 2019, handovers relied on informal methods, risking information loss and compromising patient care. This quality improvement (QI) initiative aimed to standardise handover practices using an electronic tool integrated with the ISBAR communication protocol.

Objectives

The project aimed to ensure accurate clinical information recording, improve patient care and safety, centralise handover material, enhance clinical transparency and accountability, and measure handover quality using the electronic tool.

Methods

Using a Plan-Do-Study-Act (PDSA) model, the initiative began with a critical incident in July 2020, prompting the creation and piloting of an electronic ‘handover tool’ aligned with ISBAR. Subsequent PDSA cycles included mandatory policy implementation and educational interventions to reinforce tool usage and adherence to communication standards.

Results

The electronic handover tool improved handover practices, with increased compliance to recommended criteria and enhanced tool utilisation. Notable improvements followed targeted educational interventions, leading to more comprehensive and standardised handover entries. These improvements enhanced communication and information transfer among NCHDs, contributing to better continuity of care and patient safety.

Conclusions

The QI initiative successfully standardised handover processes and improved communication among NCHDs in the AMHU. While improvements were observed, ongoing efforts are needed to address challenges and sustain effectiveness. Continuous training, feedback mechanisms and further refinement of the handover tool are essential for long-term success. Future directions include exploring additional technological solutions and reinforcing a culture of effective communication.
Piloting an external quality assurance program (QAP) for COVID-19 antigen rapid diagnostic tests (Ag-RDTs): findings and lessons learned from Cambodia
Authors: Phoeung Chan Leakhena , Prestedge Jacqueline , Ninan Marilyn , Cunningham Philip , Bory Sothavireak , Seang Kennarey , Heng Kanika , Williamson Deborah , Markby Jessica , Valley Andrew , Kaldor John , Saphonn Vonthanak
Published: January 2025

Rapid antigen diagnostic tests (Ag-RDTs) that quickly and accurately identify SARS-CoV-2 are an essential part of the COVID-19 response, but multiple factors can affect the validity of Ag-RDTs results. In Cambodia, several commercial Ag-RDTs have become available since the COVID-19 outbreak, but quality control (QC) and external quality assurance (EQA) of these rapid tests have yet to be fully and systematically implemented. We collaborated with laboratory experts in Australia and piloted an EQA programme of the commonly used COVID-19 Ag-RDTs at the University of Health Sciences’ MERIEUX Laboratory (Tier 1 site—responsible for the in-country receipt and distribution of QA material) and four other participating laboratories (Tier 2—healthcare facility based) between November 2021 and November 2022. The preimplementation training including the Khmer-translated documentation was conducted virtually for Tier 1 laboratories and in-person for Tier 2 laboratories. All QC (n=290) and EQA (n=60) specimens were distributed to the laboratories and testing was performed according to the frequency of Ag-RDTs use in each laboratory. All National Reference Laboratory-provided EQA and QC specimens were tested and results were submitted via the EDCNet portal using QR code scanning. The Tier 1 laboratory reported 100% concordance with the EQA reference result, while some of Tier 2 laboratories’ results were discordant. While continued capacity building and support with troubleshooting have been key to the successful EQA piloting at the UHS laboratory, the programme experienced delays in the shipping/delivery of EQA and QC panels due to customs and border requirements, which could have hindered implementation and potentially impacted the quality of the QA materials. The pilot EQA programme demonstrated potential scalability and provided data on the reliability of test results at the site. However, to ensure sustainability and practicability of this activity, in-country EQA panel preparation may need to be considered.
Reusable menstrual hygiene products may lead to underdiagnosis of heavy menstrual bleeding: a randomised trial
Authors: Samuelson Bannow Bethany , Ramsey Katrina , Courchaine Katherine , Edelman Alison , Colwill Alyssa C
Published: January 2025

Background

Clinical diagnosis of heavy menstrual bleeding (HMB) is dependent on patient report of menstrual product usage of pads and tampons, but it is unknown if newer reusable menstrual products (cup and underwear) are similarly diagnostic.

Methods

We enrolled 20 regularly menstruating individuals with HMB for two menstrual cycles. Participants completed a retrospective baseline Pictorial Blood loss Assessment Chart (PBAC) at the time of enrolment (eligibility PBAC score ≥100) as well as several different measures with each study cycle. In cycle 1, participants used study-provided disposable pads and tampons. For cycle 2, participants were randomised to menstrual cup or underwear and collected their menstrual fluid on their heaviest 2 days. We compared the two cycles with respect to the weight of menstrual fluid collected and the frequency of product changes and leaks during the heaviest days in cycles 1 and 2, as well as questionnaire responses.

Results

Overall, the mean rate of product changes per heaviest day were 5.5 disposable product changes (range 1.5–11), 3.6 cup changes (range 1.3–6.2), and 3.5 underwear changes (range 2.7–6.9). Both groups (cup users and underwear users) reported a median 3.5 leaks (range 1–5) per heaviest day in cycle 2, while using the menstrual cup or underwear.

Discussion

Participants reported fewer daily changes of reusable products compared with disposable ones, but more leaks, suggesting that ‘rate of product change’ with reusable products may result in missed diagnoses of HMB.
Growing problem: frailty in midlife adult trauma patients in the USA
Authors: Bloeser Colleen , Engelbart Jacklyn Maye , Ten Eyck Patrick , Torner James C , Galet Colette , Skeete Dionne A
Published: January 2025

Background

Unintentional falls are the greatest cause of injury-related hospitalisation in adult patients. Frailty is an important contributor to fall risk and poor outcomes in both midlife and older adult trauma patients. Despite this, the incidence of frailty remains understudied among midlife adults, and the CDC fall screening guidelines are limited to older adults. Here, we assessed the incidence of frailty among midlife and older trauma patients in the USA.

Methods

This was a retrospective study using the Trauma Quality Improvement Program database in midlife (aged 50–64 years) and older adult (aged 65 years and older) trauma patients from 2012 to 2021. Frailty was assessed using the five-item Modified Frailty Index. The adjusted change of frailty incidence over the study period was evaluated via Poisson regression.

Results

Frailty incidence in midlife trauma patients rose from 2.4% in 2012 to 5.1% in 2021. The adjusted annual incidence rate ratio (IRR) for midlife frailty was 1.08 (95% CI 1.08, 1.09). Among older adult patients, frailty incidence rose from 6.4% to 14.7%, with an adjusted annual frailty IRR of 1.10 (95% CI 1.10, 1.10).

Conclusion

Frailty is rising in both the midlife and older adult populations, indicating that these groups present increasing risk for unintentional falls and further morbidity and mortality. This underscores the necessity of fall screening in both midlife and older adult patients alongside further explorations into methods to delay the onset of frailty.
GP73 reinforces cytotoxic T-cell function by regulating HIF-1α and increasing antitumor efficacy
Authors: Liu Jialong , Feng Chao , Zhao Ruzhou , Song Hongbin , Huang Linfei , Jiang Nan , Yang Xiaopan , Liu Lanlan , Duan Cuijuan , Wan Luming , Gao Qi , Sun Lijuan , Hou Xufeng , Liu Muyi , Zhang Yanhong , Zhang Xuemiao , Zhang Dandan , Wang Yufei , Li Yong , Ma Xueping , Zhong Hui , Min Min , Wei Congwen , Cao Yuan , Yang Xiaoli
Published: January 2025

Background

Immunotherapy that targets immune checkpoints has achieved revolutionary success, but its application in solid tumors remains limited, highlighting the need for reliable enhancement of the efficacy of immunotherapy. Golgi protein 73 (GP73), a Golgi membrane protein, has been implicated in various cellular processes, including immune regulation. Recent studies suggested that GP73 may play a role in modulating the immune response in patients with cancer. In this study, we investigated the mechanism by which GP73 regulates T-cell-mediated antitumor immunity within the tumor microenvironment.

Methods

We used T-cell specific GP73 knockout mice to establish MC38 and B16 tumor models to investigate the impact of GP73-deficient T cells on tumor growth. Single-cell sequencing was subsequently employed to classify tumor-infiltrating immune cells and assess changes in cytokines and metabolic genes. Through RNA sequencing, real-time quantitative PCR, western blotting, flow cytometry, seahorse analysis, glucose uptake, and L-lactic acid secretion assays, we explored how GP73 regulates hypoxia-inducible factor 1α (HIF-1α) to influence T-cell antitumor functionality. Furthermore, we established adoptive transfer experiments to study the ability of GP73-overexpressing T cells to combat tumors. Blood samples of patient with clinical tumor were collected to assess the relationship between immunotherapy efficacy and T-cell GP73 levels.

Results

In this study, the absence of GP73 in mouse T cells promoted tumor growth and metastasis, accompanied by a decrease in the proportion of cytotoxic CD8+T cell subsets infiltrating the tumor and an increase in exhausted CD8+ T-cell subsets. Further analysis revealed that the effector function of CD8+T cells in tumors relies on glycolysis regulated by HIF-1α rather than immune checkpoints. GP73-deficient T cells exhibit severely impaired glycolysis in hypoxic environments, whereas ectopic GP73 expression restores HIF-1α levels. In adoptive immunotherapy, overexpression of GP73 in T cells inhibits tumor growth. In cytotoxicity assays, knockdown of GP73 affected the ability of CD8+T cells to kill target cells. Clinically, tumor immunotherapy partial response patients present significantly elevated levels of GP73 expression in T cells.

Conclusions

These findings reveal the role of GP73 in regulating T-cell glycolysis and may lead to new therapeutic strategies for the prognosis and treatment of clinical tumor immunotherapy.
Lipid metabolic remodeling delays senescence of T cells to potentiate their immunity against solid tumors
Authors: Xu Yemin , Ding Li , Wu Mengyue , Wang Xiya , Wang Lu , Xu Zhou , Xia Yinhe , Cao Zhennan , Zhang Yanqing , Song Ruilong , Deng Bin , Chen Gang
Published: January 2025

Background

Tumor cells can drive the senescence of effector T cells by unbalancing their lipid metabolism, thereby limiting adoptive T cell therapy and contributing to tumor immune evasion. Our objective is to provide a feasible strategy for enhancing T cell treatment efficacy against solid tumors.

Methods

In this study, liposomal arachidonyl trifluoromethyl ketone (ATK) was anchored onto the adoptive T cell surface via bioorthogonal reactions, aiming to specifically inhibit the group IVA cytosolic phospholipase A2α (cPLA2α), a key enzyme facilitating phospholipid metabolism and senescent state of T cells.

Results

The surface engineering exerted rare side effects on the activation and migration of T cells, but local and sustained extravasation of ATK downregulated cPLA2α expression, reprogrammed lipid metabolism, and inhibited lipid droplet accumulation. This endows T cells with delayed senescence and declined apoptosis to maintain their tumor-killing potency. Systemic administration of surface-engineered T cells resulted in superior infiltration in solid tumors and improved antitumor efficacy by enhancing the secretion of cytotoxic molecules, thereby prolonging the survival of mice bearing colorectal carcinoma and melanoma xenografts.

Conclusions

Lipid-metabolically remodeled T cells with delayed senescence increase efficacy in tumor microenvironment, highlighting a novel strategy for solid tumor immunotherapy.
Belimumab versus telitacicept in sequential treatment after rituximab for refractory lupus nephritis: a real-world multicentre study
Authors: Chen Yiting , Lei Xin , Xu Jianhang , Chen Xiaochan , Pan Hong , Zhang Qiankun , Wang Junni , Ren Pingping , Lan Lan , Shi Nan , Chen Liangliang , Wang Yaomin , Chen Jianghua , Jin Lie , Yang Yi , Xue Jing , Han Fei
Published: January 2025

Objective

Both belimumab and telitacicept are recognised blockers for B lymphocyte activation, both of which have been approved as add-on therapies for SLE in China. The aim of this study is to compare the efficacy of rituximab (RTX) followed by belimumab or telitacicept in a real-world cohort.

Methods

A total of 49 refractory lupus nephritis patients were enrolled from four independent centres, subsequently categorised into two treatment groups: belimumab group (n=35) and telitacicept group (n=14) based on their treatment following RTX. The outcomes of renal response rates were evaluated.

Results

In this study cohort, 63.3% presented with anti-dsDNA antibody positivity and 79.6% exhibited hypocomplementemia, with a mean Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Score of 13±6, estimated glomerular filtration rate (eGFR) of 76.2 (30.2, 113.7) mL/min and urinary protein creatinine ratio (uPCR) of 2.45 (0.77, 5.19) g/g. There was no significant differences between groups. After a follow-up duration of 26±12 months, renal objective remission rate was 80.0% (28 patients) in belimumab group and 85.7% (12 patients) in telitacicept group (difference, 5.7 percentage points, 95% CI, −25.8 to 26.8, p=1.000). Renal complete response was 54.3% (19 patients) in belimumab group and 78.6% (11 patients) in telitacicept group (difference, 24.3 percentage points, 95% CI, 9.7 to 47.8, p=0.194). The anti-dsDNA antibody, complement, eGFR, uPCR and SLEDAI-2K Score were improved in both groups with a significant reduction in prednisone dose. Major adverse effects included immunoglobulin deficiency, respiratory tract infection and urinary tract infection. No death occurred.

Conclusions

The sequential treatment of belimumab or telitacicept following RTX may represent a promising therapeutic approach in the management of refractory lupus nephritis. Further investigation is necessary to establish optimal protocols and long-term benefits.
Passant Elagroudy
Authors: Elagroudy Passant
Published: January 2025

This section of the magazine features SIGCHI Chapters volunteers who are having an impact on the ground for HCI globally. ---
Jeni Paay and Elizabeth F. Churchill, Editors
The Memory Game
Authors: Sturdee Miriam
Published: January 2025

Eva Wolfangel is a journalist, author, speaker, and moderator who has worked for
ZEIT, Deutschlandfunk
, and
Technology Review
, among others. She combines complex topics with creative storytelling to reach a broad audience. Here, she discusses the future of memory capture and manipulation.
Electroreduction of Magnetite for Steel Production from Ceramic Suspensions Containing Metallic Iron
Authors: Fumo Adélio , Lopes Daniela V. , Starykevich Maksim , Kovalevsky Andrei V.
Published: January 2025

The presence of impurities in the iron oxides feedstock introduces significant challenges during the electrowinning process for green steelmaking, leading to unpredictable effects. In the present study, the impact of metallic iron content on the Faradaic efficiency and microstructure of iron deposits obtained through the electroreduction of iron-magnetite powders in alkaline suspensions (10 M NaOH) at low temperature (80 °C) was evaluated. The findings reveal that the presence of metallic iron may negatively impact the reduction process. A comparative analysis of suspensions with and without iron content showed that the Faradaic efficiency for iron-free samples (63%–76%) significantly exceeds that of iron-containing suspensions (37%–57%). This demonstrates that the presence of metallic iron in the suspension can hinder the electroreduction of magnetite to Fe, with the effect becoming more pronounced at higher Fe concentration. Changes were observed in the microstructure of iron deposits, with the dendrites becoming less sharp and more disordered in iron-containing suspensions. Particle size distribution analysis further revealed that larger metallic iron particles may contribute to the sedimentation and entrapment of magnetite particles, which negatively affect the current density and Faradaic efficiency.
Runx2-NLRP3 axis orchestrates matrix stiffness-evoked vascular smooth muscle cell inflammation
Authors: Li Zhiqing , Wu Hao , Yao Fang , Li Yiran , Li Yanjie , Xie Si-an , Yu Fang , Fu Yi , Wang Li , Zhou Jing , Kong Wei
Published: January 2025

As a hallmark of chronic kidney disease (CKD), arterial stiffening is related to increased vascular inflammation and cardiovascular morbidity, whereas the underlying mechanism is unclear. The study demonstrates that increased arterial stiffness precedes the onset of vascular inflammation, and matrix stiffness stimulates the transdifferentiation of vascular smooth muscle cells (VSMCs) to an inflammatory phenotype via activating Runx2-NLRP3 signaling, which provides novel insights into CKD-related cardiovascular disorder treatment.
Macrophage immunometabolism: emerging targets for regrowth in aging muscle
Authors: Fennel Zachary J. , O’Connell Ryan M. , Drummond Micah J.
Published: January 2025

The recovery from muscle atrophy is impaired with aging as characterized by improper muscle remodeling and sustained functional deficits. Age-related deficits in muscle regrowth are tightly linked with the loss of early pro-inflammatory macrophage responses and subsequent cellular dysregulation within the skeletal muscle niche. Macrophage inflammatory phenotype is regulated at the metabolic level, highlighting immunometabolism as an emerging strategy to enhance macrophage responses and restore functional muscle regrowth. Accordingly, metabolic targets with an emphasis on glycolytic, hypoxia, and redox-related pathways stand out for their role in promoting macrophage inflammation and enhancing muscle regrowth in aging. Here we highlight promising immuno-metabolic targets that could be leveraged to restore optimal pro-inflammatory macrophage function in aging and enhance muscle regrowth following muscular atrophy.
Short-term estradiol administration does not restore endothelin‐B receptor‐mediated vasodilation in postmenopausal women
Authors: Nuckols Virginia R. , Shoemaker Leena N. , Kuczmarski Andrew V. , Haigh Katherine M. , McGinty Shane J. , Del Vecchio Angelica R. , Schwab Allyson I. , Edwards David G. , Taylor Hugh S. , Wenner Megan M.
Published: January 2025

The vascular endothelial endothelin-B receptor (ETBR) mediates vasodilation in premenopausal women, an effect modulated by estradiol. ETBR-mediated vasodilation is lost in postmenopausal women, but the effect of exogenous estradiol administration on ETBR function in postmenopausal women is not known. During estradiol administration, ETBR blockade did not affect cutaneous microvascular vasodilatory response to local heating. We demonstrate that exogenous estradiol administration does not restore ETBR-mediated vasodilation in postmenopausal women.
Pathogenesis of fibrosis in patella-patellar tendon junction induced by jumping load in a rabbit model
Authors: Liu Haitao , Liang Xiaotian , Li Haiwei , Wang Lin
Published: January 2025

The temporal pattern of fibrosis in the patella-patellar tendon junction (PPTJ) was determined by observing changes in histology and fibrosis-related factors at different time points in an overused jumping rabbit model. The results revealed that 1) the peak fibrotic changes in the PPTJ occurred at week 6 of jump training; 2) fibrosis in PPTJ may be associated with the changes in TGF-β1/Smad3. This study contributes to the development of targeted early interventions.
Stability Domain Construction and Tuning for External Loop Controller Parameters Based on Permanent Magnet Wind Power Generation Systems
Authors: Liang Hao , He Fei , Zhang Guangtao , Qin Chuan
Published: January 2025

Based on the closed‐loop frequency domain model of permanent magnet synchronous generator–based wind power generation system (PMSG‐WPGS), the stability domain of the control parameters is constructed through the D‐partition method in this paper to acquire the range of machine‐side converter (MSC) and grid‐side converter (GSC) parameters. First, the basic stability domain of the controller parameters is established according to the control structure and transfer function of the back‐to‐back converter. Then, based on the frequency domain performance indexes, amplitude margin and phase angle margin, the obtained basic stability domain is adjusted to further gain the control parameter values that meet the frequency domain index. Furthermore, the rationality of the stability domain range is verified by drawing root locus curves of variable controller parameters on the machine side and grid side. Finally, the low‐power scale experimental platform of PMSG‐WPGS is built in the lab to validate the feasibility of the proposed stability domain construction method.
Navigating the Complexities of Molar Incisor Hypomineralization: Challenges and Strategies in Pediatric Dentistry
Authors: Al-Nerabieah Zuhair , AlKhouli Muaaz , Dashash Mayssoon
Published: January 2025

Background: Molar incisor hypomineralization (MIH) presents a multifaceted challenge in pediatric dentistry, impacting diagnostics, clinical management, resource accessibility, and psychosocial care. The condition’s complexity is exacerbated by diagnostic variability, overlapping clinical symptoms, and the need for tailored treatment approaches.

Objectives: This study aims to explore the key challenges associated with the management of MIH in pediatric dentistry, including diagnostic precision, clinical management, resource limitations, interdisciplinary care, long‐term follow‐up, and psychosocial impact, and to propose strategies for overcoming these obstacles.

Methods: A comprehensive literature review was conducted to identify and synthesize existing evidence on MIH’s etiology, diagnosis, treatment, and prognosis. The review highlighted the barriers encountered in providing optimal care, particularly in resource‐constrained settings, and explored potential solutions through clinical and interdisciplinary approaches.

Results: The key findings included the need for standardized diagnostic criteria, the role of individualized treatment plans, and the importance of resource allocation. Limited access to specialized equipment and education hampers care, especially in under‐resourced areas. Long‐term management complexities were further compounded by the necessity for interdisciplinary collaboration and attention to psychosocial factors affecting pediatric patients.

Conclusion: Effective MIH management requires standardized diagnostic protocols, resource advocacy, interdisciplinary collaboration, and holistic patient care. Advancements in research, education, and policy are essential to improve outcomes in pediatric patients. By addressing both clinical and psychosocial challenges, the overall well‐being of MIH‐affected children can be enhanced.
Multiscale Features Integrated Model for Generalizable Deepfake Detection
Authors: Gu Siqi , Qin Zihan , Xie Lizhe , Wang Zheng , Hu Yining
Published: January 2025

Within the domain of Artificial Intelligence Generated Content (AIGC), technological strides in image generation have been marked, resulting in the proliferation of deepfake images that pose substantial security threats. The current landscape of deepfake detection technologies is marred by limited generalization across diverse generative models and a subpar detection rate for images generated through diffusion processes. In response to these challenges, this paper introduces a novel detection model designed for high generalizability, leveraging multiscale frequency and spatial domain features. Our model harnesses an array of specialized filters to extract frequency‐domain characteristics, which are then integrated with spatial‐domain features captured by a Feature Pyramid Network (FPN). The integration of the Attentional Feature Fusion (AFF) mechanism within the feature fusion module allows for the optimal utilization of the extracted features, thereby enhancing detection capabilities. We curated an extensive dataset encompassing deepfake images from a variety of GANs and diffusion models for rigorous evaluation. The experimental findings reveal that our proposed model achieves superior accuracy and generalization compared to existing baseline models when confronted with deepfake images from multiple generative sources. Notably, in cross‐model detection scenarios, our model outperforms the next best model by a significant margin of 29.1% for diffusion‐generated images and 15.1% for GAN‐generated images. This accomplishment presents a viable solution to the pressing issues of generalization and adaptability in the field of deepfake detection.
Research on the Digital Twin Polder Area System Driven by Integrating the Xin’anjiang Model and the N‐BEATS Model
Authors: Ye Feng , Jin Zishuo , Zhang Peng , Xu Dong , Lan Lin , Sun Jian
Published: January 2025

Digital twins are propelling the next generation of the industrial revolution and serve as a key technology in enabling intelligent water conservancy. However, due to the diversity of objects within water conservancy scenarios and the complexity of related factors, research and application of digital twins in the field of water conservancy remain immature. There are still significant challenges in constructing fine‐grained, high‐fidelity digital twin for water conservancy objects and their corresponding scenarios. In this context, taking polder areas as research subjects, a digital twin polder area system is proposed, which includes the data representation of the main elements in the polder area; based on 3D engine Unity, the modeling and rendering of the polder area’s terrain, water body, water conservancy projects, and different weather conditions are achieved; the Xin’anjiang model, N‐BEATS model, and the feature engineering model we proposed are integrated to predict water level and flow rate, thereby driving the visual scenario to simulate the extent of the impact of waterlogging at different future moments. Based on satellite imagery data, actual water level data, and flow rate data from a polder area in the Lixiahe river network of Jiangsu Province in China, we measure the efficiency of scene rendering and the accuracy of the prediction models. The results show that the performance and model accuracy of the digital twin polder area system meet the practical requirements. It is more comprehensive by comparing with other works, which can be used as a reference for the construction of a digital twin system or scenario in the water conservancy field.
Immune Tolerance Regulation Is Critical to Immune Homeostasis
Authors: Han Lei , Wu Tianxiang , Zhang Qin , Qi Anning , Zhou Xiaohui
Published: January 2025

The body’s immune response plays a critical role in defending against external or foreign antigens while also preserving tolerance to self‐antigens. This equilibrium, referred to as immune homeostasis, is paramount for overall health. The regulatory mechanisms governing the maintenance of this delicate immune balance are notably complex. It is currently accepted that immune tolerance is a dynamic outcome regulated by multiple factors, including central and peripheral mechanisms. Its induction or elimination plays a significant role in autoimmune diseases, organ transplantation, and cancer therapy, markedly impacting various major diseases in modern clinical practice. Overall, our current understanding of immune tolerance is still very limited. In this review article, we summarized the main mechanisms that have been known to mediate immune tolerance so far, including endogenous immune tolerance, adaptive immune tolerance, other immune tolerance mechanisms, and the homeostasis of immune tolerance, identified the key factors that regulate immune tolerance, and provided new clues for immune system recovery in many autoimmune diseases, organ transplantation, and tumor therapy.
Alfieri Stitch (Edge To Edge) in Degenerative Mitral Valve Repair: Characteristics and Late Durability in 648 Patients
Authors: Zwischenberger Brittany A. , Gaca Jeffrey G. , Carr Keith , Cosme Caitlin , Bishawi Muath , Wang Andrew , Glower Donald D.
Published: January 2025

Background: Mitral valve repair with the edge‐to‐edge technique (Alfieri stitch) has been described for over 20 years, yet little is published on late durability and potential risk of mitral stenosis remains controversial. The primary objective of this study is to describe characteristics and late durability of Alfieri stitch in mitral valve repair.

Methods: From 2004 to 2019, we reviewed data from our prospectively maintained institutional database on 1175 consecutive patients with degenerative mitral regurgitation (MR) who underwent repair. Patients undergoing concomitant operations were included. Propensity score matching was performed on patients with and without Alfieri stitch to compare clinical (survival and reoperation) and echocardiographic (moderate or severe MR [“moderate or more MR”], severe MR, and mitral stenosis) outcomes up to 10 years.

Results: Overall, 1175 patients underwent mitral valve repair; 55.1% (n = 648) received the Alfieri stitch. The median follow‐up was 4.7 (2.0, 8.2) years. Matched patients with and without Alfieri stitch had similar cumulative incidence (CI) of moderate or more MR (24% ± 5% vs. 17% ± 4%, p = 0.2, respectively), severe MR (5% ± 2% vs. 4% ± 2%, p = 0.3), and mitral reoperation (9% ± 3% vs. 2% ± 1%, p = 0.06) with no difference in survival (84% ± 3% vs. 81% ± 3%, p = 0.2). The Alfieri stitch resulted in a slightly higher mean mitral valve gradient (3.9% ± 1.5 mmHg vs. 3.6% ± 1.6 mmHg, p = 0.0003). The CI of mitral stenosis at 10 years was negligible (one patient with Alfieri stitch and two patients without Alfieri stitch).

Conclusions: In selected patients with degenerative mitral regurgitation, mitral valve repair with Alfieri stitch is durable with late outcomes comparable with other repair techniques. The Alfieri stitch may be a useful tool in selecting complex mitral pathology with minimal increased incidence of mitral stenosis. Further investigation is needed to delineate best indications for the use of Alfieri stitch.
A Novel Follow‐Up Model for Type 1 Diabetes in Children Leads to Higher Glycemic Control
Authors: Vonasek Julia , Larsen Isabelle M. , Nikontovic Amar , Thorvig Camilla Maria
Published: January 2025

Background: Poor glycemic control in type 1 diabetes (T1D) in children leads to a higher risk of diabetic complications. In the pediatric department at the North Denmark Regional Hospital, only one‐third of all children with diabetes were well‐regulated, defined as HbA1c no more than 58 mmol/mol (7.5%), in 2016. Therefore, a novel follow‐up model was developed to increase the proportion of children with well‐regulated T1Ds. The aim of this study was to evaluate the effect of a standardized follow‐up model for poorly regulated diabetes on mean HbA1c.

Methods: All children aged 0–18 with T1Ds were included in this study. A novel standardized follow‐up model was developed if HbA1c was greater than 58 mmol/mol (7.5%), in which children were followed more closely until improvement in glycemic control.

Results: In the reference year, only one‐third of children with diabetes were well‐regulated and 19% were poorly regulated (HbA1c greater than 75 mmol/mol (9.0%)). After fully implementing the model, two‐thirds of the children had well‐regulated diabetes, and only a few percent had poorly regulated diabetes. The mean HbA1c decreased by almost 10 mmol/mol (or 0.8%) from the reference year to the following years when the model was fully implemented.

Conclusion: This follow‐up model for poorly regulated diabetes increased the fraction of children with well‐regulated diabetes in our clinic and significantly decreased mean HbA1c.
Effects of an initial anti-CD19 CAR T-cell therapy on subsequent anti-CD22 CAR T-cell manufacturing and clinical outcomes in patients with r/r LBCL
Authors: Su Yi-Jiun , Kramer Anne Marijn , Hamilton Mark P. , Agarwal Neha , Srinagesh Hrishikesh K. , Baird John H. , Sahaf Bita , Kuo Adam , Ehlinger Zachary J. , Desai Moksha H. , Rietberg Skyler P. , Tunuguntla Ramya , Patel Shabnum , Chinnasamy Harshini , Gkitsas-Long Nikolaos , Klysz Dorota D. , Brown Annie Kathleen. , Bharadwaj Sushma , Dahiya Saurabh , Smith Melody , Muffly Lori , Mackall Crystal L. , Good Zinaida , Feldman Steven A. , Miklos David B. , Frank Matthew J.
Published: January 2025

Patients with large B-cell lymphoma (LBCL) progressing after anti-CD19 CAR T-cell (CAR19) therapy have poor outcomes. Subsequent CAR T-cell therapy shows promise, but the impact of residual CAR19 and early relapse remains unclear. We evaluated 37 CAR19-refractory LBCL patients who received anti-CD22 CAR T-cell (CAR22) in a phase 1b trial (NCT04088890). Residual CAR19 was unquantifiable in 17 of 33 evaluable patients post-CAR22 infusion. Single-cell RNA sequencing revealed minimal CAR19/CAR22 co-transduction. Peak CAR19 transgene levels did not affect CAR22 efficacy or toxicities. CAR22 products from patients undergoing leukapheresis > 6 months post-CAR19 had higher CD4+ naïve T and CD4+/CD8+ T- central memory (TCM) cells, with lower CD4+ T-effector memory cells. High and low percentages of CAR22 TCM and TEM, respectively, were correlated with CAR22 transduction efficiency and achieving complete response. Residual CAR19 and leukapheresis timing did not significantly affect outcomes, while CAR22 product composition was significantly correlated with treatment response.
Supplementary Figure 8 from Claudin-4 Stabilizes the Genome via Nuclear and Cell-Cycle Remodeling to Support Ovarian Cancer Cell Survival
Authors: Villagomez Fabian R. , Lang Julie , Nunez-Avellaneda Daniel , Behbakht Kian , Dimmick Hannah L. , Webb Patricia G. , Nephew Kenneth P. , Neville Margaret , Woodruff Elizabeth R. , Bitler Benjamin G.
Published: January 2025

Reactive oxygen species positive control in cell lines.
Supplementary Figure 2 from Claudin-4 Stabilizes the Genome via Nuclear and Cell-Cycle Remodeling to Support Ovarian Cancer Cell Survival
Authors: Villagomez Fabian R. , Lang Julie , Nunez-Avellaneda Daniel , Behbakht Kian , Dimmick Hannah L. , Webb Patricia G. , Nephew Kenneth P. , Neville Margaret , Woodruff Elizabeth R. , Bitler Benjamin G.
Published: January 2025

Claudin-4 dependent cell cycle and Lamin expression.
Figure 4 from Claudin-4 Stabilizes the Genome via Nuclear and Cell-Cycle Remodeling to Support Ovarian Cancer Cell Survival
Authors: Villagomez Fabian R. , Lang Julie , Nunez-Avellaneda Daniel , Behbakht Kian , Dimmick Hannah L. , Webb Patricia G. , Nephew Kenneth P. , Neville Margaret , Woodruff Elizabeth R. , Bitler Benjamin G.
Published: January 2025

Claudin-4’s effect on the actin cytoskeleton. Ovarian tumor cells were treated with CMP (400 µmol/L) for 48 hours and stained to mark the actin cytoskeleton using phalloidin. In addition, cells were engineered to express LifeAct to mark the actin cytoskeleton in living cells. Afterward, we performed a morphologic and kymograph analysis. A, Top, reconstructions of perinuclear F-actin and genomic DNA (from confocal z-stacks) for OVCAR8, OVCA429 (B), and OVCAR3 cells (C). Bottom, corresponding quantification of perinuclear F-actin for A–C, respectively. OVCAR8, 1711 cells; OVCA429, 2630 cells; OVCAR3, 2365 cells; two-tailed Mann–Whitney test, Kruskal–Wallis test with Dunn’s multiple comparisons). D, Remodeling effect of claudin-4 in the nuclear architecture, considering both nuclear lamina and perinuclear F-actin. E and F, left, Quantification of junctional F-actin from reconstructions (from confocal z-stacks). Right, confocal images (maximum projection) and zoom, followed by reconstruction of selected ROIs (at junctional F-actin) from OVCA429 cells (top) and OVCAR3 cells (bottom), respectively (n = OVCA429, 783 cells; OVCAR3, 825 cells; Kruskal–Wallis test with Dunn’s multiple comparisons). G and H, Kymographs illustrating the movement of junctional F-actin (vertical gray arrow) over time (horizontal blue arrow), generated from different ROIs during confocal live-cell imaging of transduced OVCA429 cells (top; n = 142) with LifeAct to mark F-actin (without any stimuli and cultured for 24 hours) and OVCAR3 cells (bottom; n = 116), respectively (two-tailed Mann–Whitney test; three independent experiments; significance, P < 0.05). Graphs show mean and SEM. KD, knockdown; MFI, mean fluorescence intensity; ROI, regions of interest; Veh, vehicle.
5-Methoxytryptophan Protects against Toll-Like Receptor 2-Mediated Renal Tissue Inflammation and Fibrosis in a Murine Unilateral Ureteral Obstruction Model
Authors: Wu Jing-Yiing , Lee Guan-Lin , Chueh Yu-Fan , Kuo Cheng-Chin , Hsu Yu-Juei , Wu Kenneth K.
Published: January 2025

Introduction: 5-Methoxytryptophan (5-MTP) is a cellular metabolite with anti-inflammatory properties. Several recent reports indicate that 5-MTP protects against post-injury tissue fibrosis. It was unclear how 5-MTP controls tissue fibrosis. We postulated that 5-MTP attenuates renal interstitial fibrosis by blocking toll-like receptor 2 (TLR2) and transforming growth factor β (TGFβ) signaling pathways. Methods: In vivo experiments were carried out in a well-established unilateral ureteral obstruction (UUO) model in wild-type (WT) and tlr2−/− mice. The effect of 5-MTP on renal fibrosis was evaluated by pretreatment of WT UUO mice with intraperitoneal administration of 5-MTP. To determine whether 5-MTP attenuates fibrosis by inhibiting TLR2 and TGFβ signaling pathways, we evaluated the effect of 5-MTP on TLR2-induced fibroblast phenotypic switch in NRK-49F fibroblasts and TLR2 and TGFβ signaling pathways in human proximal tubular epithelial cells (HPTECs) and RAW264.7 macrophages stimulated with Pam3CSK4 (Pam3) or TGFβ1. Results: UUO-induced renal fibrosis was abrogated in tlr2−/− mice consistent with a crucial role of TLR2 in UUO-induced renal fibrosis. UUO-induced macrophage infiltration and pro-fibrotic cytokine production in renal tissues were suppressed by tlr2 knockout. 5-MTP administration attenuated renal tissue fibrosis accompanied by reduction of macrophage infiltration and IL-6 and TGFβ levels. 5-MTP inhibits TLR2 upregulation and blocks TLR2-MyD88-TRAF6 signaling pathway in macrophages. Furthermore, 5-MTP blocked Pam3- and TGFβ1-induced phenotypic switch of NRK-49F to myofibroblasts and inhibited Pam3- and TGFβ1-induced signaling pathways in HPTECs and RAW264.7 cells. Conclusion: 5-MTP is effective in protecting against UUO-induced renal interstitial fibrosis by blocking TLR2 and TGFβ signaling pathways.
Identification of Biomarkers for Cervical Cancer Radiotherapy Sensitivity and Survival Prognosis
Authors: Huang Han , Ma Jianguang , Cui Hekai , Liang Tiantian , Ma Qingqing
Published: January 2025

Introduction
Radiotherapy resistance leads to treatment failure and disease progression in patients with cervical cancer. This study aims to elucidate the molecular underpinnings of radiotherapy response in cervical cancer by identifying radiotherapy sensitivity genes (RSGs).
Methods
We utilized two GEO expression profiling datasets (GSE3578 and GSE6213) comprising cervical cancer biopsy samples taken before and during radiotherapy to identify differentially expressed genes (DEGs) using the RankProd meta-analysis approach. Subsequent analysis was conducted using data from the TCGA-CESE project to further determine the RSGs and investigate their associations with survival prognosis, immune cell infiltration, and drug sensitivities. The differential expressions of the candidate RSGs were validated in an independent set of cervical cancer patients by qPCRs.
Results
A total of 518 DEGs were identified, with 305 genes up-regulated and 213 genes down-regulated during radiotherapy. Six key RSGs were identified as significantly associated with radiotherapy response. Cox regression analysis revealed that up-regulations of IL1RAP and GPR15 were associated with an increased risk of poor survival prognosis. Functional enrichment analysis highlighted the involvement of these genes in critical biological processes such as cytokine signaling and immune regulation. Correlation analyses demonstrated significant associations between RSG expressions and M2 Macrophage and γδT cell abundances in tumor microenvironment, as well as drug sensitivities. The expression of IL1RAP was significantly higher in the complete response group, supporting the bioinformatic finding.
Conclusion
Our findings on RSGs could potentially serve as potential biomarkers for predicting radiotherapy response and as therapeutic targets to enhance the efficacy of radiotherapy.