bluuebunny/crossref_metadata_2025 huggingface dataset:
Seismic vulnerability assessment of leaning U-shaped masonry fence walls
Authors: Park Dawon , Kim Sunwoo , Jin Suyeong , Choi Youngjun , Kim Homin , Hong Jung-Wuk
Published: February 2025

Masonry fences that tilt or lean have been recognized as potential dangers during earthquakes, making it essential to investigate their structural durability and ability to withstand seismic occurrences. In this study, a leaning U-shaped masonry fence wall structure is modeled by the reference of field surveys, and its seismic behavior is analyzed through dynamic shaking table tests as well as analytical approaches. The evolution of crack damage and changes in natural frequencies and hysteretic responses are analyzed to identify seismic behaviors of the leaning walls. As a result, the leaning causes asymmetric results between the side walls of the structure and introduces new concerns regarding seismic vulnerability. This study contributes to understanding the seismic characteristics and risks associated with leaning masonry fence walls, providing valuable insights for evaluating the hazards caused by leaning.
Effects of Low-Fat Food on Gallbladder Contraction and Sonographic Image Quality
Authors: Yip Jerica Hiu-Yui , Wong Kwan Shing , Leung Michelle Wing-Yee , Lee Ho Kiu , Au-Yeung Tin Lam , Yip Ching Wang , Hui Jack , Liu Kin Hung , Chiyanika Chileka
Published: February 2025

Objective:

The aim of this study was to examine the impact of consuming a navel orange, a low-fat food item, on gallbladder contraction and sonographic image quality.

Materials and Methods:

Sixty-six healthy Chinese participants underwent sonographic evaluation of their gallbladder volume (GBV) and anterior wall thickness (AWT) after fasting for at least 6 hours. This protocol was repeated 120 minutes after consuming a navel orange. An experienced sonographer rated the quality of the gallbladder images on a five-point Likert scale.

Results:

There was no significant change in GBV (14.15 cm³ preprandial vs 14.00 cm³ postprandial, p=.073), AWT (0.154 cm vs 0.157 cm, p=.101), or image quality (both rated 5, p=1.000) after orange intake. GBV correlated with body mass index ( p < .05). Among various age groups, no significant differences were noted, across the measured parameters, for both preprandial and postprandial states ( p > .05).

Conclusion:

In this cohort of participants, navel oranges served as an alternative to fasting for gallbladder sonographic preparation and did not affect image quality.
Characterization and chemoproteomic profiling of protein O-GlcNAcylation in SOD1-G93A mouse model
Authors: Hao Yi , Li Zhongzhong , Du Xinyan , Xie Qingsong , Li Dongxiao , Lei Shaoyuan , Guo Yansu
Published: February 2025

Background

Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease. Protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification has been found to affect the processing of several important proteins implicated in ALS. However, the overall level and cellular localization of O-GlcNAc during ALS progression are incompletely understood, and large-scale profiling of O-GlcNAcylation sites in this context remains unexplored.

Methods

By using immunostaining analysis and chemoenzymatic labeling-based quantitative chemoproteomics, we assayed O-GlcNAcylation dynamics of lumbar spinal cords from SOD-G93A mice and their non-transgenic (NTG) littermates, the most widely used animal model for studying ALS pathogenesis.

Results

We discovered that the global O-GlcNAcylation was significantly reduced at the disease end stage. Correlatively, a great increase of OGA was observed. Immunohistochemistry and immunofluorescence analysis showed a higher proportion of O-GlcNAc-positive neurons in the NTG group, while O-GlcNAc colocalization with astrocytes/microglia was elevated in SOD1-G93A mice. Moreover, we reported the identification of 568 high-confidence O-GlcNAc sites from end-stage SOD1-G93A and NTG mice. Of the 568 sites, 226—many of which occurred on neuronal function and structure-related proteins—were found to be dynamically regulated.

Conclusion

These data provide a valuable resource for dissecting the functional role of O-GlcNAcylation in ALS and shed light on promising therapeutic avenues for ALS. The chemoenzymatic labeling-based chemoproteomic approach is applicable for probing O-GlcNAc dynamics in various pathological processes.
Comparing two autologous bone grafting techniques to treat clavicular midshaft atrophic nonunion: a retrospective study
Authors: Ma Teng , Huang Qiang , Wang Chaofeng , Ren Cheng , Xu Yibo , Lin Hua , Zhang Kun , Zhang Congming , Li Zhao
Published: February 2025

Background

Open reduction, superior plate (SP) fixation, and autologous cancellous granular bone grafting (ACGBG) are common strategies for treating clavicular midshaft atrophic nonunion (CMAN). We aimed to compare the radiological findings and clinical effects of two autologous cancellous bone grafts (ACBGs) and those of single SP fixation, to treat CMAN.

Methods

This retrospective study comprised 62 patients admitted to our hospital with CMAN (ACGBG with single SP fixation between March 2012 and October 2017, 32 patients; autologous cancellous structured bone grafting [ACSBG] with single SP fixation between November 2017 and May 2021, 30 patients). Patient visual analog scale (VAS) scores for pain and disability of the arm, shoulder, and hand (DASH) scores, obtained preoperatively and at final follow-up, were recorded and analyzed. Statistical differences between the ACGBG and ACSBG groups were assessed using Fisher’s exact and two-sample independent t tests.

Results

No statistically significant differences were observed between the two groups in terms of patient demographics or the incidence of complications. VAS and DASH scores decreased significantly from the preoperative day to 9 months postoperatively in both groups, but this difference was not statistically significant at final follow-up. However, at 3 and 6 months postoperatively, compared with mean VAS and DASH scores in the ACGBG group, the ACSBG group showed lower pain and dysfunction scores (p < 0.05). The mean fracture healing times were 15.2 (range, 12–20) and 18.6 (range, 12–32) weeks in the ACSBG and ACGBG groups, respectively (p = 0.01). One case of plate breakage occurred in the ACGBG group at 5 months postoperatively, with recovery following ACSBG revision with single SP fixation.

Conclusions

ACSBG combined with single SP fixation is a promising and effective alternative technique for promoting bone union and postoperative early functional rehabilitation in treating CMAN.

Level of evidence

Level 3.
217 closed Salmonella reference genomes using PacBio sequencing
Authors: Luo Yan , Jang Jae Hee , Balkey Maria , Hoffmann Maria
Published: February 2025

Objectives

Whole Genome Sequencing (WGS) is widely used in food safety for the detection, investigation, and control of foodborne bacterial pathogens. However, the WGS data in most public databases, such as the National Center for Biotechnology Information (NCBI), primarily consist of Illumina short reads which lack some important information for repetitive regions, structural variations, and mobile genetic elements, and the genomic location of certain important genes like antimicrobial resistance genes (AMR) and virulence genes. To address this limitation, we have contributed 217 closed circular Salmonella enterica genomes that were generated using PacBio sequencing to the NCBI Pathogen Detection (PD) database and GenBank. This dataset provides a higher level of accuracy to genome representations in the database.

Data description

High-quality complete reference genomes generated from PacBio long reads can provide essential details that are not available in draft genomes from short reads. A complete reference genome allows for more accurate data analysis and researchers to establish connections between genome variations and known genes, regulatory elements, and other genomic features. The addition of 217 complete genomes from 78 different Salmonella serovars, each representing either a distinct SNP cluster within the NCBI PD database or a unique strain, significantly enriches the diversity of the reference genome database.
Boosting hypochlorite’s disinfection power through pH modulation
Authors: Sil Timir Baran , Malyshev Dmitry , Aspholm Marina , Andersson Magnus
Published: February 2025

Purpose

Hypochlorite-based formulations are widely used for surface disinfection. However, the efficacy of hypochlorite against spore-forming bacteria varies significantly in the literature. Although neutral or low pH hypochlorite solutions are effective sporicides due to the formation of hypochlorous acid (HOCl), their optimal conditions and the specific role of pH in disinfection remain unclear. These conditions also increase the solution’s corrosiveness and compromise its shelf life. Therefore, further research is needed to identify the pH conditions that balance solution stability and effective hypochlorite-based spore disinfection.

Results

This study investigates the impact of neutral to alkaline pH on the sporicidal efficiency of hypochlorite against a pathogenic Bacillus cereus strain. We apply a 5,000 ppm hypochlorite formulation for 10-min across a pH range of 7.0-12.0, simulating common surface decontamination practices. Our results demonstrate that hypochlorite is largely ineffective at pH levels above 11.0, showing less than 1-log reduction in spore viability. However, there is a significant increase in sporicidal efficiency between pH 11.0 and 9.5, with a 4-log reduction in viability. This pH level corresponds to 2 - 55 ppm of the HOCl ionic form of hypochlorite. Further reduction in pH slightly improves the disinfection efficacy. However, the shelf life of hypochlorite solution decreases exponentially below pH 8.5. To explore the pH-dependent efficacy of hypochlorite, Raman spectroscopy and fluorescence imaging were used to investigate the biochemical mechanisms of spore decontamination. Results showed that lower pH enhances spore permeability and promotes calcium dipicolinic acid (CaDPA) release from the core.

Conclusion

Our results highlight the complex relationship between pH, sporicidal efficacy of hypochlorite, and its shelf life. While lower pH enhances the sporicidal efficiency, it compromises the solution’s shelf life. A pH of 9.5 offers a balance, significantly improving shelf life compared to previously suggested pH ranges 7.0-8.0 while maintaining effective spore inactivation. Our findings challenge the common practice of diluting sodium hypochlorite with water to a 5,000 ppm solution, as this highly alkaline solution (pH of 11.9), is insufficient for eliminating B. cereus spores, even after a 10-min exposure. These findings are critical for improving disinfection practices, highlighting the importance of optimizing sodium hypochlorite effectiveness through pH adjustments before application.
Digitally supported physical activity counselling for people with chronic back pain: a randomised controlled parallel feasibility study
Authors: Lindner Nicole , Kornder Nele , Heisig Julia , Becker Annette , der Wardt Veronika van , Viniol Annika
Published: February 2025

Background

Guiding individuals with chronic back pain (CBP) to initiate and adhere to physical activity (PA) remains challenging. The study rationale is based on the need for innovative strategies, like digital tools, to better promote PA. The aim of this study was to evaluate the feasibility and acceptability of using the digital consultation app ExPa (Exercise against Pain) to support PA consultations for CBP and its potential for a future effectiveness trial. The ExPa app shows the effect of PA on pain and provides individually tailored support to increase PA.

Methods

In a 2-arm randomised controlled feasibility study, we recruited 9 physicians and 37 CBP patients in Hesse (Germany). Using computer assisted cluster randomisation, 14 patients received ExPa counselling from their physician, while 17 patients received standard treatment. Main outcomes focused on study procedures and software use, with secondary outcome including pre- and post-intervention measurements of PA (International Physical Activity Questionnaire (IPAQ), pain and mood (Short Form-12 (SF-12), Von Korff pain intensity and disability score and Hospital Anxiety and Depression Scale (HADS)). Additionally, project-tailored questionnaires and qualitative interviews assessed study procedures and software performance.

Results

Study procedures were generally feasible. However, they took more time and dropouts as well as missing data presented challenges. This provided valuable insights for planning an effectiveness trial. Quantitative and qualitative data indicated that ExPa could have benefits for increasing PA and reducing pain.

Conclusions

Results from the feasibility study indicate that improved procedures are necessary for a larger RCT. ExPa shows potential for positively impacting pain and PA.
Group-based trajectory modeling to describe the geographical distribution of tuberculosis notifications
Authors: Dagnew Alemnew F. , Hanrahan Colleen F. , Dowdy David W. , Martinson Neil A. , Lebina Limakatso , Nonyane Bareng A. S.
Published: February 2025

Background

Tuberculosis (TB) is a major public health problem, and understanding the geographic distribution of the disease is critical in planning and evaluating intervention strategies. This manuscript illustrates the application of Group-Based Trajectory Modeling (GBTM), a statistical method that analyzes the evolution of an outcome over time to identify groups with similar trajectories. Specifically, we apply GBTM to identify the evolution of the number of TB notifications over time across various geographic locations, aiming to identify groups of locations with similar trajectories. Locations sharing the same trajectory may be considered geographic TB clusters, indicating areas with similar TB notifications. We used data abstracted from clinic records in Limpopo province, South Africa, treating the clinics as a proxy for the spatial location of their respective catchment areas.

Methods

Data for this analysis were obtained as part of a cluster-randomized trial involving 56 clinics to evaluate two active TB patient-finding strategies in South Africa. We utilized GBTM to identify groups of clinics with similar trajectories of the number of TB patients.

Results

We identified three trajectory groups: Groups 1, comprising 57.8% of clinics; Group 2, 33.9%; and Group 3, 8.3%. These groups accounted for 30.8%, 44.4%, and 24.8% of total TB-diagnosed patients, respectively. The estimated mean number of TB-diagnosed patients was highest in trajectory group 3 followed by trajectory group 2 across the 12 months, with no overlap in the corresponding 95% confidence intervals. The estimated mean number of TB-diagnosed patients over time was fairly constant for trajectory groups 1 and 2 with exponentiated slopes of 0.979 (95% CI: 0.950, 1.004) and 1.004 (95% CI: 0.977, 1.044), respectively. In contrast, there was a statistically significant 3.8% decrease in the number of TB patients per month for trajectory group 3 with an exponentiated slope of 0.962 (95% CI: 0.901, 0.985) per month.

Conclusions

GBTM is a powerful tool for identifying geographic clusters of varying levels of TB notification when longitudinal data on the number of TB diagnoses are available. This analysis can inform the planning and evaluation of intervention strategies.
Axillary lymph node metastasis in breast cancer: from historical axillary surgery to updated advances in the preoperative diagnosis and axillary management
Authors: Wu Tong , Long Qian , Zeng Liyun , Zhu Jinfeng , Gao Hongyu , Deng Yueqiong , Han Yi , Qu Limeng , Yi Wenjun
Published: February 2025

Axillary lymph node status, which was routinely assessed by axillary lymph node dissection (ALND) until the 1990s, is a crucial factor in determining the stage, prognosis, and therapeutic strategy used for breast cancer patients. Axillary surgery for breast cancer patients has evolved from ALND to minimally invasive approaches. Over the decades, the application of noninvasive imaging techniques, machine learning approaches and emerging clinical prediction models for the detection of axillary lymph node metastasis greatly improves clinical diagnostic efficacy and provides optimal surgical selection. In this work, we summarize the historical axillary surgery and updated perspectives of axillary management for breast cancer patients.
The Pre-Medical Health Coach (PHC) program: pre-medical students as volunteer health coaches at a safety-net hospital in California, 2016–2020
Authors: Shak Emma B. , Berry Lyn , Chow Bryant , Abramowitz Sharone , Mehta Kala M.
Published: February 2025

Background

The volunteer Pre-Medical Health Coach (PHC) program engages student volunteers, in team-based primary care providing self-management support to patients with chronic conditions. Both the PHCs and the patients they serve are diverse. The aims of this study are to assess the impact of the PHC program on student outcomes and patient biomarkers.

Methods

All PHCs were students recruited from local universities, interviewed, then trained in motivational interviewing and evidence-based chronic disease self-management support. The 22 PHCs were diverse – 8 (36.3%) were underrepresented in medicine and 2 (9%) were first generation in college. The study setting was a public safety-net adult medicine outpatient clinic in Oakland, California. PHCs spent 5 h weekly, for 1–3 years, volunteering alongside primary care residents and faculty. Duties included: (1) observing the doctor-patient interview, (2) on-site health coaching, and (3) telephone follow-up. An internal medicine physician and a licensed clinical social worker supervised the program. Surveys were implemented to understand program impacts and career trajectories of the 22 PHCs and health action plans were reviewed over 4 years. In addition, a focus group was conducted with the PHCs using a deductive approach.

Results

Two years after completing the program, 90.9% of the PHCs were still on the path to health professions programs, 50% had applied to medical school, and 18.2% started medical training. Qualitative impacts on coaches included significant clinical exposure, meaningful connection with patients, ‘bridging’ between the community and health care system and having a more holistic view on health. Patient biomarkers included a decrease in hemoglobin A1c level by 1% point in diabetic patients with diabetes-focused action plans, and smoking-focused action plans led to decreased smoking or cessation.

Conclusions

The Pre-Medical Health Coach (PHC) program may benefit both PHCs and patients. PHCs were diverse and providing chronic disease self-management support to patients in a safety-net health care system. This program could be readily adapted in health care systems nationwide to increase diverse entrants to the healthcare workforce.
Effects of self-controlled feedback on learning range of motion measurement techniques and self-efficacy among physical therapy students: a preliminary study
Authors: Yamamoto Ryohei , Imai Takaki , Yoshizato Yushin , Akizuki Kazunori
Published: February 2025

Background

Measuring range of motion (ROM) accurately using a universal goniometer or visual estimation is challenging for physical therapy students. Self-controlled (SC) feedback, where learners decide whether to receive feedback, can enhance learning and foster self-efficacy (SE) by promoting self-regulation. However, the impact of SC feedback on skill acquisition in ROM measurement technique and SE in physical therapy students remains unclear. This study investigates the effects of SC feedback on skill acquisition in ROM measurement techniques and students’ SE.

Methods

Thirty physical therapy students were quasi-randomly assigned to an SC group, which chose feedback during practice, or a Yoked (Yk) group, which received feedback based on the SC group’s schedule. A goniometric measurement task, in which participants measure the ROM of left knee flexion using a universal goniometer, and a visual estimation task, in which they estimate it visually, were set as the learning tasks. After a pretest, they completed the practice (3 trials × 4 blocks) followed by short-term retention test (STRT) and LTRT (LTRT). All tests consisted of 3 trials. Measurement accuracy and time were used as test performance for both tasks. SE of ROM measurements was measured before the start of each test using a 10-point Likert scale. Feedback related to measurement errors were provided during practice in line with each group’s conditions.

Results

The SC group maintained high feedback frequency (80.0 ± 30.3%) during the practice. Both groups improved measurement accuracy and reduced time for goniometric measurement and visual estimation tasks, but no significant group differences were found. Goniometric accuracy exceeded visual estimation in both groups. SE before the pretest did not correlate with pretest accuracy. However, SE before the STRT correlated with accuracy at that time in both groups. In the SC group, SE before the LTRT test was related to the accuracy at the STRT.

Conclusion

SC feedback did not demonstrate superior effectiveness, but external feedback improved ROM measurement accuracy and reduced measurement time. Moreover, SE after the practice was temporarily associated with accuracy, suggesting a potential link between SE and performance in skill acquisition.
Why downsizing may increase sickness absence: longitudinal fixed effects analyses of the importance of the work environment
Authors: Grønstad Anniken , Bernstrøm Vilde Hoff
Published: February 2025

Background

Downsizing can often have a detrimental effect on employee health and increase sickness absence. Earlier research has theoretically argued that such negative consequences are due to taxing alterations in the work environment, but research efforts to empirically test this argument remain limited.

Methods

In this study, we investigate whether the environment for control, role clarity, and commitment in different work units can explain the relationship between unit-level downsizing and sickness absence. We combined register- and self-reported data from 19,173 employees in a large Norwegian health trust in the period 2011–2015 and conducted a longitudinal fixed effects analysis.

Results

Unit-level downsizing was found to be significantly related to increased short-term sickness absence, reduced organizational commitment, and reduced control. Reduced commitment explained a small part of the increase in short-term sickness absence after unit-level downsizing. There was no mediating effect of either control or role clarity.

Conclusion

The study contributes to a better understanding of the underlying mechanisms that help explain why downsizing leads to adverse health consequences and sickness absence by highlighting the complexity of this relationship and introducing organizational commitment as a relevant mediator.
Vascular remodeling and TSLP/angiogenin overexpression in severe mixed asthma
Authors: Bertolini Francesca , Carriero Vitina M.A. , Arrigo Elisa , Guida Giuseppe , Levra Stefano , Pizzimenti Stefano , Profita Mirella , Gnemmi Isabella , Di Stefano Antonino , Ricciardolo Fabio L.M.
Published: February 2025

Background

Asthma with neutrophilic/mixed inflammation is a difficult-to-control clinical phenotype. Currently, vascular and matrix airway remodeling in asthma with neutrophilic/mixed inflammation is not well known. We aimed to evaluate the differences in vascular/smooth muscle/matrix related asthma remodeling in eosinophilic (EOS) and mixed/neutrophilic (MIXED) bronchial phenotypes in relation to asthma severity and exacerbation frequency.

Methods

In this cross-sectional study, α-SMA+ cells (100µM beneath the basement membrane [BM]), BM thickness, vascular remodeling-related biomarkers (angiogenin, vascular endothelial growth factor [VEGF], CD31 and Protease-activated receptor 2 [PAR2]), alarmins (TSLP and Interleukin (IL)-33) were evaluated in bronchial sections from 40 mild-to-severe asthmatics (EOS: N = 19 and mixed/neutrophilic: N = 19/2) and 7 control subjects (CTRL).

Results

The number of CD31+ and angiogenin+ cells was higher in MIXED than in EOS asthmatics (p < 0.05). In severe MIXED CD31+, TSLP+, α-SMA+, and angiogenin+ cells increased compared to mild MIXED/EOS or severe EOS (p < 0.05), but BM thickness was higher in severe vs. mild EOS (p < 0.05). MIXED frequent exacerbators had higher numbers of CD31+ and TSLP+ cells, whereas MIXED non-exacerbators had increased PAR2+ cells. CD31+ cells correlated with impairment of pulmonary functions, number of exacerbations, ICS dose, bronchial neutrophils, angiogenin, α-SMA, TSLP and IL-33 (p < 0.05). Finally, CD31 > 97.17 cells/mm2, angiogenin > 35.36 cells/mm2, and functional parameters such as FEV1, FEV1/FVC, TLC and FRC (%pred.) were found to be predictors of severe MIXED asthma.

Conclusion

The severe or frequent exacerbator asthmatics with bronchial mixed inflammatory profile are characterized by increased number of vessels and overexpression of TSLP and angiogenin, suggesting a pathogenetic link between mixed eosinophilic and neutrophilic inflammation and vascular remodeling.
Severe malaria readmissions in Northern Uganda: a cross-sectional study
Authors: Olum James , Mukunya David , Nambozo Brendah , Nantale Ritah , Oguttu Faith , Epuitai Joshua , Lume Ivan , Wanume Benon , Olupot-Olupot Peter , Amanya Daphine , Kakuru Abel
Published: February 2025

Background

Malaria is a critical global health issue, particularly for children in endemic regions. However, factors associated with recurrent severe malaria in children under 5 years of age in Northern Uganda are poorly understood. This study aimed to identify factors associated with readmission due to severe malaria within six months post-discharge among children in this age group.

Methods

A cross-sectional study was conducted in Otuke district, encompassing twelve health facilities. A total of 760 caregivers of children admitted with severe malaria were interviewed, and hospital records were reviewed to verify the readmission data. The primary outcome assessed was readmission with severe malaria within six months after initial discharge. Data analysis was performed via Stata version 15.0.

Results

The prevalence of readmission with severe malaria among children under 5 years of age was 26.8% (198/739). Factors significantly associated with readmission included having sickle cell anaemia [adjusted prevalence ratio (aPR) 1.72; 95% confidence interval (CI) (1.95–3.14)], living in houses constructed with straw and thatch walls [(aPR 2.10; 95% CI (1.19–3.69)] and seeking care after 12 h when the child has a fever [aPR 2.01; 95% CI (1.23–3.29)].

Conclusion

The findings indicate a high proportion of severe malaria readmissions in children under 5 years of age. Sickle cell anaemia, living in houses built using straw and thatch walls and seeking care after 12 h when a child has fever were the key risk factors for readmission with severe malaria. This study highlights the importance of targeted post-discharge interventions, such as prophylactic anti-malarials in addition to bed nets, to prevent recurrent infections especially among children with sickle cell disease. In addition, improvements in housing quality and timely treatment of children with malaria are essential for reducing the burden of malaria, particularly in endemic regions.
The EU project Real4Reg: unlocking real-world data with AI
Authors: Peltner Jonas , Becker Cornelia , Wicherski Julia , Wortberg Silja , Aborageh Mohamed , Costa Inês , Ehrenstein Vera , Fernandes Joana , Heß Steffen , Horváth-Puhó Erzsébet , Korcinska Handest Monika Roberta , Lentzen Manuel , Maguire Peggy , Meedom Niels Henrik , Moore Rebecca , Moore Vanessa , Nagy Dávid , McNamara Hillary , Paakinaho Anne , Pfeifer Kerstin , Pylkkänen Liisa , Rajamaki Blair , Reviers Evy , Röthlein Christoph , Russek Martin , Silva Célia , De Valck Dirk , Vo Thuan , Bräuner Elvira , Fröhlich Holger , Furtado Cláudia , Hartikainen Sirpa , Kallio Aleksi , Tolppanen Anna-Maija , Haenisch Britta
Published: February 2025

Background

The use of real-world data is established in post-authorization regulatory processes such as pharmacovigilance of drugs and medical devices, but is still frequently challenged in the pre-authorization phase of medicinal products. In addition, the use of real-world data, even in post-authorization steps, is constrained by the availability and heterogeneity of real-world data and by challenges in analysing data from different settings and sources. Moreover, there are emerging opportunities in the use of artificial intelligence in healthcare research, but also a lack of knowledge on its appropriate application to heterogeneous real-world data sources to increase evidentiary value in the regulatory decision-making and health technology assessment context.

Methods

The Real4Reg project aims to enable the use of real-world data by developing user-friendly solutions for the data analytical needs of health regulatory and health technology assessment bodies across the European Union. These include artificial intelligence algorithms for the effective analysis of real-world data in regulatory decision-making and health technology assessment. The project aims to investigate the value of real-world data from different sources to generate high-quality, accessible, population-based information relevant along the product life cycle. A total of four use cases are used to provide good practice examples for analyses of real-world data for the evaluation and pre-authorization stage, the improvement of methods for external validity in observational data, for post-authorization safety studies and comparative effectiveness using real-world data. This position paper introduces the objectives and structure of the Real4Reg project and discusses its important role in the context of existing European projects focussing on real-world data.

Discussion

Real4Reg focusses on the identification and description of benefits and risks of new and optimized methods in real-world data analysis including aspects of safety, effectiveness, interoperability, appropriateness, accessibility, comparative value creation and sustainability. The project’s results will support better decision-making about medicines and benefit patients’ health.

Trial registration Real4Reg is registered in the HMA-EMA Catalogues of real-world data sources and studies (EU PAS number EUPAS105544).
‘You constantly have to be switched on’: A qualitative interview study of parents of children with STXBP1-related disorders in the Netherlands
Authors: van Till Sietske A. L. , Sybesma Sybren , Bruining Hilgo , Verhage Matthijs , Bunnik Eline M.
Published: February 2025

Background

Disorder-related variants in the STXBP1 gene are increasingly detected in children with severe developmental disorders. It is commonly acknowledged that developmental disorders significantly impact family life, but little is known about the day-to-day experiences of caregivers living with children with STXBP1-related disorders (STXBP1-RD). This knowledge gap may hinder researchers and care professionals from aligning research activities, care, and support with the perspectives of parents.

Methods

We conducted a semi-structured interview study to gain a better understanding of the impact of having a child with STXBP1-RD on daily family life. Interviews were audio-recorded, transcribed, and analyzed thematically. We developed an ‘analytical framework based on verbs’, as verbs signify action, to present our results on the experiences of parents in everyday life.

Results

We conducted 16 interviews with 21 parents of children with STXBP1-RD (2 to 18 years old), living in the Netherlands. The respondents described their caregiving responsibilities as extremely intense and demanding. They reported being constantly occupied with caring for their child, and expressed a feeling of always being ‘switched on’. Parents’ experiences are described using the following five verbs: (1) caring for their child, (2) recognizing their child’s needs and having their child’s needs recognized, (3) searching for answers and suitable care, (4) balancing delivering care while preserving other domains of life, and (5) coping with emotional impacts.

Conclusions

This study shows how parenting a child with STXBP1-RD involves continuous engagement with both child-related care responsibilities and other activities, such as arranging suitable care and coping with emotional impacts. The accumulation of these responsibilities and challenges significantly impacts the everyday lives of the entire family. To support STXBP1 patient families, a broad approach is needed, focusing not only on developing new medical treatments, but also on improving other therapies (e.g., speech therapy or physiotherapy) and providing social support for the entire family, including emotional support, assistance with administrative tasks, and improved information provision after diagnosis.
Inferring protein from transcript abundances using convolutional neural networks
Authors: Schwehn Patrick Maximilian , Falter-Braun Pascal
Published: February 2025

Background

Although transcript abundance is often used as a proxy for protein abundance, it is an unreliable predictor. As proteins execute biological functions and their expression levels influence phenotypic outcomes, we developed a convolutional neural network (CNN) to predict protein abundances from mRNA abundances, protein sequence, and mRNA sequence in Homo sapiens (H. sapiens) and the reference plant Arabidopsis thaliana (A. thaliana).

Results

After hyperparameter optimization and initial data exploration, we implemented distinct training modules for value-based and sequence-based data. By analyzing the learned weights, we revealed common and organism-specific sequence features that influence protein-to-mRNA ratios (PTRs), including known and putative sequence motifs. Adding condition-specific protein interaction information identified genes correlated with many PTRs but did not improve predictions, likely due to insufficient data. The integrated model predicted protein abundance on unseen genes with a coefficient of determination (r2) of 0.30 in H. sapiens and 0.32 in A. thaliana.

Conclusions

For H. sapiens, our model improves prediction performance by nearly 50% compared to previous sequence-based approaches, and for A. thaliana it represents the first model of its kind. The model’s learned motifs recapitulate known regulatory elements, supporting its utility in systems-level and hypothesis-driven research approaches related to protein regulation.
Neuroinflammation and pathways that contribute to tourette syndrome
Authors: Wu Xinnan , Hao Juanjuan , Jiang Keyu , Wu Min , Zhao Xin , Zhang Xin
Published: February 2025

Tourette syndrome (TS), a neurological and psychological disease, typically exhibit motor and phonic tics. The pathophysiology of TS remains controversial. Currently, the recognized pathogenesis of TS is the imbalance of neurotransmitters, involving abnormality of the cortex-striatum-thalamus-cortex circuit. Recently, clinical researches demonstrate that triggers such as infection and allergic reaction could lead to the onset or exacerbation of tic symptoms. Current studies have also suggested that neural-immune crosstalk caused by inflammation is also associated with TS, potentially leading to the occurrence of tics by inducing neurotransmitter abnormalities. Herein, we review inflammation-related factors contributing to the occurrence of TS as well as the mechanisms by which immune-inflammatory pathways mediate the onset of TS. This aims to clarify the pathogenesis of TS and provide a theoretical basis for the treatment of TS.
Dedifferentiated fat cells-derived exosomes (DFATs-Exos) loaded in GelMA accelerated diabetic wound healing through Wnt/β-catenin pathway
Authors: Dong Miao , Ma Xuan , Li Facheng
Published: February 2025

Background

Diabetic foot ulcers pose significant challenges for clinicians worldwide. Cell-free exosome therapy holds great potential for wound healing. Dedifferentiated fat cells (DFATs) have been used in tissue engineering and regeneration, but there are no reports on the use of DFATs-derived exosomes in diabetic wound repair.

Objectives

This study aims to investigate whether DFATs-Exos accelerated diabetic wound healing and explore its potential mechanism.

Methods

In vitro, DFATs-Exos were harvested from adipose tissue and used to treat endothelial cells (ECs) and fibroblasts. XAV939 was used as a Wnt/β-catenin pathway inhibitor. The biocompatibility of gelatin methacryloyl (GelMA) hydrogel was assessed. In vivo, DFAT-derived exosomes were encapsulated in 10% GelMA hydrogel and applied to a diabetic wound model. Histological analysis and wound closure rates were evaluated.

Results

DFATs-Exos promoted angiogenesis in ECs and significantly alleviated the high glucose-induced inhibition of cell proliferation and migration by activating the Wnt/β-catenin pathway. In vivo, compared to DFAT-Exos or GelMA alone, the DFAT-Exos/GelMA combination accelerated wound closure and enhanced collagen maturity.

Conclusion

The DFAT-Exos/GelMA hydrogel significantly promoted wound healing in a diabetic animal model through activation of the Wnt/β-catenin signaling pathway.
The trajectory of sleep after critical illness: a 24-month follow-up study
Authors: Henríquez-Beltrán Mario , Benítez Iván D. , Vaca Rafaela , Santisteve Sally , Aguilà Maria , Vila Anna , Minguez Olga , Rodríguez-Muñoz Carlos , Galán-González Anna , Carvalho-Brugger Sulamita , González Paula , Rodríguez Paula , Caballero Jesús , Barberà Carme , Torres Gerard , Labarca Gonzalo , Malla-Banyeres Mar , Moncusí-Moix Anna , Torres Antoni , de Gonzalo-Calvo David , Barbé Ferran , González Jessica , Targa Adriano D. S.
Published: February 2025

Background

Survivors of critical illness endure long-lasting physical and mental challenges. Despite the persistence of poor sleep quality in a considerable proportion of patients at the 12-month follow-up, studies with assessments exceeding this period are limited. We aimed to investigate the trajectory of sleep over the 24 months following critical illness.

Methods

Observational, prospective study. Patients diagnosed with SARS-CoV-2 infection were recruited during the intensive care unit stay. Evaluations of sleep (Pittsburgh Sleep Quality Index [PSQI]), mental health (Hospital Anxiety and Depression Scale [HADS]), quality of life (12-item Short Form Survey [SF-12]), and other factors were performed in the short-term, and at 12 and 24 months after hospital discharge. Good sleep quality was defined as a PSQI score of ≤ 5. Minimal clinically important improvement (MCII) was defined as a decrease of ≥ 4 points in the PSQI score between the short-term assessment and the 24-month follow-up.

Results

The cohort included 196 patients (69.9% males), with a median [p25;p75] age of 62.0 [53.0;67.2] years. The global population showed a mean (95% CI) change of − 0.91 ( − 1.50 to − 0.31) points in the PSQI score from the short-term assessment to the 24-month follow-up. Based on PSQI score trajectories, three distinct groups of patients were identified: (i) the healthy group, consisting of patients with good sleep quality in the short-term that was maintained throughout the follow-up period; (ii) the MCII group, consisting of patients with poor sleep quality in the short-term, but with improvement over time, ultimately reaching levels comparable to the healthy group; (iii) the non-MCII group, consisting of those with consistently poor sleep quality across the entire follow-up. Further analyses revealed that PSQI score trajectories were closely aligned with those of the HADS and SF-12 mental scores.

Conclusions

Our findings reveal that a subset of critical illness survivors requires up to 24 months after the acute phase to fully restore their sleep quality, while a significant proportion does not experience a clinically significant improvement in sleep quality over this period. These distinct sleep trajectories are strongly correlated with mental health status, highlighting the importance of addressing sleep alongside mental health within the framework of post-intensive care syndrome.
Roux-en-Y gastric bypass-associated fecal tyramine promotes colon cancer risk via increased DNA damage, cell proliferation, and inflammation
Authors: Glymenaki Maria , Curio Sophie , Shrestha Smeeta , Zhong Qi , Rushton Laura , Barry Rachael , El-Bahrawy Mona , Marchesi Julian R. , Wang Yulan , Gooderham Nigel J. , Guerra Nadia , Li Jia V.
Published: February 2025

Background

Fecal abundances of Enterobacteriaceae and Enterococcaceae are elevated in patients following Roux-en-Y gastric bypass (RYGB) surgery. Concurrently, fecal concentrations of tyramine, derived from gut bacterial metabolism of tyrosine and/or food, increased post-RYGB. Furthermore, emerging evidence suggests that RYGB is associated with increased colorectal cancer (CRC) risk. However, the causal link between RYGB-associated microbial metabolites and CRC risk remains unclear. Hence, this study investigated the tyrosine metabolism of Enterobacteriaceae and Enterococcaceae strains isolated from patients post-RYGB and explored the causal effects of tyramine on the CRC risk and tumorigenesis using both human colonic cancer cell line (HCT 116) and wild-type and Apc

Min/+ mice.

Results

We isolated 31 bacterial isolates belonging to Enterobacteriaceae and Enterococcaceae families from the feces of patients with RYGB surgery. By culturing the isolates in tyrosine-supplemented medium, we found that Citrobacter produced phenol as a main product of tyrosine, whereas Enterobacter and Klebsiella produced 4-hydroxyphenylacetate, Escherichia produced 4-hydroxyphenyllactate and 4-hydroxyphenylpyruvate, and Enterococcus and two Klebsiella isolates produced tyramine. These observations suggested the gut bacterial contribution to increased fecal concentrations of tyramine post-RYGB. We subsequently evaluated the impact of tyramine on CRC risk and development. Tyramine induced necrosis and promoted cell proliferation and DNA damage of HCT 116 cells. Daily oral administration of tyramine for 49 days to wild-type mice resulted in visible adenomas in 5 out of 12 mice, accompanied by significantly enhanced DNA damage (γH2AX +) and an increased trend of cell proliferation (Ki67 +) in the ileum, along with an upregulated expression of the cell division cycle gene (Cdc34b) in the colon. To evaluate the impact of tyramine on intestinal tumor growth, we treated Apc

Min/+ mice with the same doses of tyramine and duration. These mice showed larger colonic tumor size and increased intestinal cell proliferation and inflammation (e.g., increased mRNA expression of IL-17A and higher number of Ly6G + neutrophils) compared to water-treated Apc

Min/+ control mice.

Conclusions

Our results collectively suggested that RYGB-associated fecal bacteria could contribute to tyramine production and tyramine increased CRC risk by increasing DNA damage, cell proliferation, and pro-inflammatory responses of the gut. Monitoring and modulating tyramine concentrations in high-risk individuals could aid CRC prognosis and management.
Antimicrobial resistance surveillance and trends in armed conflict, fragile, and non-conflict countries of the Eastern Mediterranean Region
Authors: Moghnieh Rima , Bizri Nazih , Abdallah Dania , Sayegh Mohamed H.
Published: February 2025

Background

The WHO Eastern Mediterranean Region (EMR) faces major social, economic, and demographic challenges, with nearly half of its countries affected by conflicts that severely disrupt health systems. This study compared antimicrobial resistance (AMR) rates and surveillance efforts in conflict-affected, fragile, and non-conflict countries, further subdivided by income.

Methods

Data on bacteriologically confirmed bloodstream infections (BC-BSIs) from 2017 to 2021 were extracted from the WHO GLASS database. Countries were classified as conflict-affected, fragile, or non-conflict (subdivided by income) using World Bank criteria. Descriptive statistics (mean ± SD) were calculated, and group comparisons were performed using unpaired t-tests with Welch’s correction. Mean differences (MD) and 95% confidence intervals (CI) were reported.

Results

Conflict-affected countries reported significantly fewer surveillance sites than non-conflict countries (MD: 0.60, 95% CI: 0.361 to 0.836, P < 0.001) and fewer BC-BSIs per million population (MD: 31.00, 95% CI: 17.210 to 44.790, P < 0.001). In conflict zones, Acinetobacter spp. and S. aureus represented a higher proportion of BSIs compared to non-conflict countries (Acinetobacter spp. MD: -11.86, 95% CI: − 27.130 to 3.399, P = 0.099; S. aureus MD: − 10.68, 95% CI: − 30.030 to 8.680, P = 0.203). Carbapenem resistance in Acinetobacter spp. exceeded 65% across the groups, peaking in fragile zones (83.38%). Third-generation cephalosporin-resistant E. coli (3GCREC) prevalence ranged from 47.99% to 76.34%, peaking in conflict zones (76.34%). Carbapenem-resistant E. coli (CREC) prevalence ranged from 2.31% to 15.95%, highest in non-conflict low-middle income countries (15.95%). Third-generation cephalosporin-resistant K. pneumoniae (3GCRKP) exceeded 50% in all groups, peaking in conflict zones (80.42%). The prevalence of carbapenem-resistant K. pneumoniae (CRKP) ranged from 14.49% to 45.70%, peaking in conflict zones and non-conflict low-middle income countries (45.70%). Methicillin-resistant S. aureus (MRSA) exceeded 30%, peaking in conflict zones (70.09%).

Conclusions

Conflict-affected countries have weaker AMR surveillance and lower BC-BSI detection but a higher burden of resistant pathogens, notably carbapenem-resistant Acinetobacter spp. and MRSA. Tailored strategies are essential to restore infrastructure, strengthen surveillance, and mitigate the long-term impact of AMR in these zones.

Graphical Abstract
Wearable devices for patient monitoring in the intensive care unit
Authors: Angelucci Alessandra , Greco Massimiliano , Cecconi Maurizio , Aliverti Andrea
Published: February 2025

Wearable devices (WDs), originally launched for fitness, are now increasingly recognized as valuable technologies in several clinical applications, including the intensive care unit (ICU). These devices allow for continuous, non-invasive monitoring of physiological parameters such as heart rate, respiratory rate, blood pressure, glucose levels, and posture and movement. WDs offer significant advantages in making monitoring less invasive and could help bridge gaps between ICUs and standard hospital wards, ensuring more effective transitioning to lower-level monitoring after discharge from the ICU. WDs are also promising tools in applications like delirium detection, vital signs monitoring in limited resource settings, and prevention of hospital-acquired pressure injuries. Despite the potential of WDs, challenges such as measurement accuracy, explainability of data processing algorithms, and actual integration into the clinical decision-making process persist. Further research is necessary to validate the effectiveness of WDs and to integrate them into clinical practice in critical care environments.

Take home messages

Wearable devices are revolutionizing patient monitoring in ICUs and step down units by providing continuous, non-invasive, and cost-effective solutions.

Validation of their accuracy and integration in the clinical decision-making process remain crucial for widespread clinical adoption.