bluuebunny/crossref_metadata_2025 huggingface dataset:
Do Atypical Femoral Fractures Have Atypical Blood Tests? A Comparison of Atypical vs Typical Femoral Fractures
Authors: Brolchain Aongus O , Engelbrecht Zander , Steer Richard , Phillips Alfred , Lin Chen-i
Published: December 2024

Purpose: Atypical femoral fractures (AFFs) are a rare but important complication of anti-resorptive therapy (ART). The pathophysiology of these fractures remains poorly understood. AFFs are associated with low serum alkaline phosphatase (ALP) and other bone turnover markers, but the diagnosis is established on radiological grounds. This study investigated differences in serum biochemistry at time of hospitalisation AFFs and ‘typical’ femoral fractures (TFFs).
Methods: : Retrospective observational study across two centers in Queensland, Australia between 2012 – 2022. All femoral shaft fractures presenting across two hospitals between 2012 – 2022 were screened for inclusion. Two groups comprising AFFs and TFFs were identified for comparison. Blood results at the time of hospital admission were reviewed from the electronic medical record.
Results: 143 fractures were included, with 41 patients in the AFF group and 102 in the TFF group. Significant differences were observed between AFF and TFF groups in median serum ALP (56IU/L vs 83IU/L, p=<0.001), vitamin D level (86.8nmol/L vs 69.5nmol/L, p = 0.01), albumin (38g/L vs 36g/L, p = 0.015), globulin (27g/L vs 29g/, p = 0.02), creatinine (68 vs 77, p = 0.05) and B12 (360pg/ml vs 250pg/ml, p = 0.03). In the AFF group, 22.5% patients had a serum ALP <40IU/L compared with 3.9% in the TFF group. There was no significant difference observed in the remaining markers of liver function, electrolytes, blood group or coagulation profile.
Conclusion: Most datapoints were similar between groups. These data demonstrate that AFFs are associated with low serum ALP levels. Lower creatinine levels in the AFF group may reflect reduced muscle mass and increased frailty in these patients.
Association Between Estimated glucose disposal rate and Erectile Dysfunction in US Adults：a cross- sectional analysis of the NHANES 2001-2004
Authors: Xu+ Ningning , Wang+ Kexin , Xu Huanying , Zou Haoxi , Chen Yanfen , Wu Suzhen
Published: December 2024

Background
Erectile dysfunction (ED) is a sexual health issue affecting approximately 152 million men worldwide. Diabetes is a significant risk factor for ED, with insulin resistance playing a pivotal role in its pathogenesis. The Estimated Glucose Disposition Rate (eGDR), has been validated as a convenient and non-invasive indicator for assessing insulin resistance in diabetic patients. However, no studies have yet explored the relationship between eGDR and ED.
Objective
The purpose of this study was to determine the association between eGDR and ED in U.S. men from the National Health and Nutrition Examination Survey (NHANES).
Design:
The study analyzed data from 1,844 men aged 20 years and older in the 2001–2004 NHANES. Multivariate logistic regression with sampling weights assessed the association between eGDR and ED. Smoothed curve fitting were employed to explore the linearity of the eGDR-ED relationship. Subgroup analyses and interaction tests were performed to ensure the robustness of the result.
Result
We found a negative connection between eGDR and ED in men. Each unit increase in eGDR is associated with a 22% reduction in the risk of ED [odds ratio (OR) = 0,78 ,95% confidence interval (95% CI): 0.72–0.85, P < 0.0001].
Conclusion
Estimated glucose disposal rate was related to risk of Erectile Dysfunction in the United State adults, increase in eGDR is associated with a reduction in the risk of ED.
Methyl acrylate Functionalized Hyper-Crosslinked Polymers and Their Efficient Adsorptive Removal of Aromatic Small Molecule Compounds from Water
Authors: Huang Xiaobei , Wang Xiaolin , Zhu Shibao , Zhang Qingyuan , Wang Yutong , Fu Yuli , Xiao Zisheng , Xu Mancai , Zhong Shihua
Published: December 2024

Herein, methyl acrylate functionalized hyper-crosslinked polymers (HSDMs) were synthesized using the suspension polymerization method and they were employed to adsorb aromatic small molecule compounds. Low-crosslinked precursor polymers were prepared using styrene (St) and divinylbenzene (DVB) as crosslinking agents and different ratios of methyl acrylate (MA, 20, 15, 10, 5%) as functional monomers. Subsequently, the Friedel-Crafts reaction was conducted at 313 K to yield products characterized by hyper-crosslinked interpenetrating polymer networks abundant in rigid methylene bridges. The resulting polymers were promising for the adsorption of aromatic small molecule compounds, and the maximum capacities (qmax) for aniline, phenol and salicylic acid arrived at 103.79, 98.75 and 229.98 mg/g. The kinetic experiments demonstrated that adsorption aniline, phenol and SA reached the equilibrium within 60, 60 and 150 min, and the kinetic results were accurately described by the pseudo-second-order (PSO) rate model, exhibiting kinetic rates of 8.34×10-4, 1.01×10-3, and 5.00×10-4 g/(mg·min), respectively. Dynamic adsorption aniline capacity of 50.06 mg/g on HSDM-5 and desorption efficiency of 90.74 %. The adsorption mechanism discovered that pore-filling, hydrogen bonding, hydrophobic interaction and π-π stacking were important for the adsorption.
Working Conditions and Environment of Maternal and Neonatal Healthcare Providers in the Context of Armed Conflicts and Humanitarian Crises: The Case of Eastern DR Congo
Authors: Lembebu Corneille , Ngaboyeka Gaylord , Bisimwa Ghislain , Ndokabilya Eustache , Makali Samuel , Zalinga Christian Chiribagula , Bugugu Bony , Byamungu Christian Mugisho , Murhima’alika Christine Chimanuka , Bigirinama Rosine N. , Dramaix Michèle , Hermans Michel P , Mwene-Batu Pacifique
Published: December 2024

Introduction
Healthcare worker (HCW) play a crucial role in reducing maternal and infant mortality. However, in contexts of endemic armed conflicts, such as in the Democratic Republic of Congo (DRC), these professionals must operate under extreme working conditions, which can affect the quality of care. This study aims to assess the working environment and challenges faced by maternal and neonatal HCW in the DRC.
Methodology
We conducted a cross-sectional study in the North and South Kivu provinces in Eastern DRC. The study primarily targeted healthcare facilities in eight health zones. An evaluation aligned with the structure/process dimensions (profile and perception of the work environment of HCW) according to Donabedian was conducted. A descriptive and comparative analysis of the HZs (using the Chi-square test and T test) was performed. Informed consent was obtained for participation in the study.
Results
A total of 200 HCW were enrolled in the study, 71% of whom were women, with an average age of 37.5 years. Nurses were the majority, followed by midwives, while general practitioners represented 10.67%. On average, HCW worked approximately 67 hours per week. A third of HCW did not feel well-prepared and are dissatisfied with their work environment, reporting gaps in discussions about interpersonal skills, promotion opportunities, and professional development. Disparities in treatment were observed, with notable inequalities in training, time off, work hours, function, and promotions, often exacerbated by gender. Less than 30% received bonuses, and 90% did not receive non-monetary incentives. Verbal threats and assaults, humiliations, and physical assaults from colleagues and patients were common, with a higher incidence in North Kivu. Finally, nearly a quarter of HCW felt exposed to insecurity in and around their facilities, a perception more pronounced in North Kivu than in South Kivu.
Conclusion
This study shows that HCW in the DRC, particularly in conflict zones, work under extremely difficult conditions, characterized by intensive hours, lack of training, professional inequalities, and high insecurity. These challenges may compromise quality of care and the well-being of providers, underscoring the urgency of strengthening their protection and support to maintain the resilience of the healthcare system.
Differential effects of NMDAR antagonists on working memory and gamma oscillations, and the mediating role of the GluN2D subunit
Authors: Hill Rachel , Vinnakota Chitra , Hudson Matthew , Ikeda Kazutaka , Ide Soichiro , Mishina Masayoshi , Sundram Suresh , Jones Nigel
Published: December 2024

Working memory relies on synchronised network oscillations involving complex interplay between pyramidal cells and GABAergic interneurons. NMDA receptor (NMDAR) antagonists influence both network oscillations and working memory, but the relationship between these two consequences has not been elucidated. This study aimed to determine the effect of NMDAR antagonists on network oscillations during a working memory task in mice, and the contribution of the GluN2D receptor subunit.
After training wildtype (WT) and GluN2D-knockout (KO) mice on the Trial-Unique-Non-match to Location (TUNL) touchscreen task of working memory, recording electrodes were implanted into the prefrontal cortex (PFC) and hippocampus. Mice were challenged with either (S)-ketamine (30mg/kg), (R)-ketamine (30mg/kg), phencyclidine (PCP, 1mg/kg), MK-801 (0.3mg/kg) or saline prior to TUNL testing while simultaneous local field potential recordings were acquired.
PCP disrupted working memory accuracy in WT (p=0.001) but not GluN2D-KO mice (p=0.79). MK-801 (p<0.0001), (S)-ketamine (p<0.0001) and (R)-ketamine (p=0.007) disrupted working memory accuracy in both genotypes. PCP increased baseline gamma (30-80Hz) power in the hippocampus in WT (p=0.0015) but not GluN2D-KO mice (p=0.92). All drugs increased baseline gamma power in the PFC in both genotypes (p<0.05). Low gamma was induced during the maintenance phase of the TUNL task and increased when mice correctly completed the task (p=0.024). MK-801 disrupted task-induced low gamma in both genotypes (p=0.04).
In summary, PCP action involves the GluN2D subunit of the NMDA receptor in the hippocampus to alter baseline gamma power and working memory. Task-induced low gamma activity during maintenance aligns with task performance, and is disrupted specifically by MK-801.
Risk Factors of Decisional Conflict in People Living with Chronic Pain: a pan-Canadian survey.
Authors: Naye Florian , Tousignant-Laflamme Yannick , Sasseville Maxime , Cachinho Chloé , Gérard Thomas , Toupin-April Karine , Dubois Olivia , Paquette Jean-Sébastien , LeBlanc Annie , Gaboury Isabelle , Poitras Marie-Eve , Li Linda C. , Hoens Alison , Poirier Marie-Dominique , Légaré France , Décary Simon
Published: December 2024

Making decisions about chronic pain care is often challenging due to uncertainties, leading to decisional conflict when individuals do not receive the support and information they need. Shared decision-making interventions can help meet these needs; however, their effectiveness is inconsistent in the context of chronic pain. This study aimed to identify the decisional needs influencing decisional conflict among adults with chronic pain in Canada, to guide the development of more comprehensive interventions. In this pan-Canadian online survey, we measured decisional conflict related to the most difficult decision using the Decisional Conflict Scale (≥ 37.5 indicating clinically significant conflict) and assessed decisional needs based on the Ottawa Decision Support Framework. Of the 1,649 participants, 1,373 reported a Decisional Conflict Scale score. The mean age was 52 (SD = 16.4), with half of respondents being men (49.5%) and pain duration ranging from 3 months to 59 years. One-third (33.7%) experienced clinically significant decisional conflict. Seventeen risk factors were identified, including difficulty understanding healthcare information (OR = 2.43) and lack of prior knowledge of available options (OR = 2.03), while role congruence in decision-making was associated with reduced conflict (OR = 0.57). Future SDM interventions could be enhanced by targeting multiple risk factors of decisional conflict.
Digital chest drainage versus traditional chest drainage in children after pulmonary resection: A systematic review and meta-analysis
Authors: Ahmed Rakesh , Durr Anna , Healy David
Published: December 2024

Background
Pulmonary resection is commonly performed as curative treatment for congenital thoracic malformations. There is a plethora of high-quality evidence showing improved outcomes with digital chest drainage systems compared to traditional water-seal systems in adults. By contrast, there is a relative paucity of research with children and therefore much uncertainty in post-operative chest drain management in paediatrics.
Methods
A systematic review and meta-analysis was conducted to assess the effect of digital chest drainage systems in paediatric patients after pulmonary resection. Data sources included PubMed, Cochrane Central Register of Controlled Trials, EMBASE, and SCOPUS, with information from 1 January 2007 to 20 July 2024. The qualitative analysis included three observational studies. The quantitative analysis included 74 patients across two observational studies that compared digital and traditional chest drainage systems. A fixed effects model was used to produce a pooled estimate for a meta-analysis of means if the studies were homogenous, otherwise a random effects model was used.
Results
The meta-analysis showed a statistically significant reduction in hospital length of stay (SMD − 0.63 days, [95% CI: -1.1;-0.16, p = < 0.01]) and number of chest x-rays performed (SMD − 1.2 x-rays, [95% CI: -1.7;-0.7, p = < 0.0001]) in the digital group compared to the traditional group. Although a reduction in chest tube duration was seen in the digital group, this was not statistically significant (SMD − 2.2 days, [95% CI: -14.5;10.07, p = 0.2622]). There were no significant differences in development of pulmonary complications between the digital and traditional drainage groups (p = 0.8392).
Conclusion
The use of digital chest drainage systems demonstrated a shortened hospital length of stay and quantity of chest x-rays performed in paediatric patients following pulmonary resection. The overall certainty of these findings is limited by the low quality of the available evidence.
Investigation of the Effects of Galectin-1 on Enzalutamide Sensitivity and Cellular Functions in Prostate Cancer Cells and Its Clinical Diagnostic Value
Authors: Lee Ya-Che , Yang Kai-Wu , Lai Ya-Yan , Tung Chun-Liang , Shen Cheng-Huang , Chen Jui-Chieh
Published: December 2024

Prostate cancer (PCa) is the most common malignancy in men worldwide, with an increasing incidence rate, and many patients are diagnosed at an advanced stage with metastasis, where bone metastasis is the most frequent. Enzalutamide (ENZ) is the first-line treatment for castration-resistant prostate cancer (CRPC) and has shown efficacy in prolonging survival; however, some patients develop drug resistance. Additionally, benign prostatic hyperplasia (BPH) is a common prostate condition in aging men, with symptoms similar to PCa, highlighting the need for improved diagnostic and therapeutic approaches. In the present study, we integrated public databases, RNA sequencing (RNA-Seq), and bioinformatics tools, utilizing CRISPR-Cas9 technology to knock out galectin-1 (LGALS1) in PCa cells to comprehensively investigate its impact on ENZ sensitivity, cellular functions, and the underlying mechanisms. Clinical tissue samples were also analyzed to assess the clinical significance of LGALS family members. Our findings indicated that ENZ sensitivity depends on AR expression, and LGALS1 knockout in AR-expressing cells enhances ENZ sensitivity. RNA-Seq revealed that LGALS1 knockout suppresses energy metabolism and disrupts oxidative stress balance. Additionally, LGALS1 knockout in high-expression cells reduced proliferation, altered the cell cycle, and decreased migration and adhesion. Clinically, both AR and LGALS1 were overexpressed in bone-metastatic PCa, suggesting their potential as therapeutic targets and biomarkers.
Epidemiological features of hypertension in a high-altitude population in Tibet, China: a cross-sectional study
Authors: Yu Yue , Peng Jieru , Zhaxi Zongji , Jimei Quzhen , Shi Heng , Bai Guoxia , Yang Chunxia
Published: December 2024

Objectives To explore the present epidemiological status of hypertension in the high-altitude regions of Tibet, China, and offer insights for the prevention and control strategies of hypertension in this population.
Design A cross-sectional study was designed to be conducted in seven cities (localities) in the Tibet Autonomous Region (TAR).
Participants and settingThe survey employed a multi-stage stratified cluster sampling method and enrolled 8,992 residents aged ≥35 years from seven cities in Tibet.
Main outcome measures Present status of the epidemiology of hypertension.
Results The prevalence of hypertension in Tibet was 46.5 % and the weighted prevalence was 46.7 %. Hypertension at stage 2 and above accounted for 49.8% of all cases. Of the hypertensive subjects included in this study, 45.2 % had been diagnosed with hypertension before the study, 30.8 % were taking antihypertensive medication, and only 3.0 % had effective blood pressure control. Aging, urban population, alcohol consumption, overweight, obesity, diabetes mellitus and central obesity were risk factors for hypertension (all p < 0.05 ). Moreover, 94.2% of the individuals using antihypertensive drugs received treatment with only one medication, and calcium channel blockers were the most frequently prescribed antihypertensive drug for single-drug therapy.Women were more likely to use calcium channel blockers compared to men, while beta-blockers were less commonly used by women in comparison to men (p<0.05), nifedipine was the most commonly used calcium channel blocker drug in patients with hypertension.
Conclusion Hypertension is a key public health problem in Tibet, associated with multiple factors and with low rates of awareness, treatment and control. The government needs to strengthen basic medical care and health promotion for high-altitude populations in Tibet.
Optimising Caesarean section use in Nepal through hospital generated and population-based data on Caesarean section rates to inform policy and practice
Authors: Iang Maureen Dar , Rath Alison Dembo , Devkota Madhu Dixit , Sapkota Vishnu , Mahendra Shanti
Published: December 2024

Background:
The dual problem of lack of access to life-saving caesarean section (C-section) and the negative effects of over-intervention when it is not medically required, is well established. The health burden plus additional direct and indirect costs for households and the health system, create a ‘triple burden.’ In Nepal, whilst C-section rates have rapidly escalated, our data suggests an opportunity to avert a C-section epidemic and reduce unmet need for C-section among women with very low income.
Methods
We analysed C-section rates from 29 public and private hospitals across Nepal using the Robson Ten Group Classification System and assessed how each group compared with the Robson reference groups. Using the WHO C-Model we estimated the gap between observed and predicted facility C-section rates, adjusted for the obstetric case-mix at each facility. We generated estimates for four categories of hospitals: public with Aama (the government demand-side financing programme); public without Aama; private with Aama; private without Aama.
Results
We found that Robson groups 1 and 3 (nulliparous or multiparous women with single cephalic pregnancy, ≥ 37-week gestation, spontaneous onset of labour), together account for 66.5% of C-sections of total institutional deliveries. All four hospital categories had higher C-section rates than predicted rates. The percentage points difference between observed and predicted rates was greater for private hospitals (with Aama 18.6 percentage points and non-Aama 19.7 percentage points), than government hospitals (with Aama 10.8 percentage points and non-Aama 13.9 percentage points). The biggest gap was for private hospitals (non-Aama with observed C-section rate at 42% compared with 23% predicted.
Conclusions
Our hospital-based study data provides evidence that C-section rates are too high relative to need and are not just a function of late arrivals or complicated births, as is often claimed by facilities. C-section rates can be controlled by introducing measures in both public and private sectors. Policy needs to continue to focus on increasing uptake of the life-saving intervention among populations where C-section rates fall below optimal levels, while also ensuring that they are avoided if not indicated medically. Resources for maternal and newborn health need to be reallocated to achieve uptake of medically required C-sections equitably across population groups and steer Nepal towards optimal rates.
Clinical trial number: Not applicable.
Systems Biology-Based Assessment of Immune Responses to Whole Cell and Acellular Pertussis Vaccines: Rationale, Methodology and Enrollment Procedures for Omics Workflows
Authors: Leguia Mariana , Vila-Sanjurjo Antón , Juarez Diana , Garcia-Glaessner Alejandra , Gil Ana I. , Alvarez Mayita , Cornejo Rubelio , Cherikh Sami , Gelber Casey E. , Goll Johannes B. , Howard Leigh M. , Jimenez-Truque Natalia , Edwards Kathryn M. , Creech C. Buddy , Lanata Claudio F.
Published: December 2024

Given the local and systemic adverse reactions associated with whole cell pertussis vaccines combined with diphtheria and tetanus toxoids (DTP), acellular pertussis vaccines combined with the same toxoids (DTaP) were developed in the 1990s. In comparison to DTP, DTaP vaccines demonstrated reduced reactogenicity and equivalent or improved immunogenicity and efficacy. However, there has been a resurgence of pertussis disease, particularly in DTaP-vaccinated children, suggesting that immunity wanes more quickly with DTaP vaccination. To elucidate the differences in immune responses to DTP and DTaP vaccines, we employed a systems biology-based strategy to compare global changes in gene expression following primary vaccination with either DTP or DTaP. We used RNA-Seq and ribosome profiling (RP) to identify transcriptional and translational signatures, respectively, in peripheral blood mononuclear cells (PBMCs) collected from 50 infant recipients of DTP or DTaP at two time-points (baseline (pre-vaccination at Day 1) and either Day 2 or 8 post-vaccination). We also used standard serologic methods to assess immunogenicity, and correlated these results with transcriptional and translational signatures. Here, we provide a detailed description of the rationale, experimental design, methodology and enrollment procedures used. Given the technical complexity of our approach, our objective is to fill knowledge gaps, describe key quality metrics and support future publications. In brief, we recovered 4–12 million PBMCs (average 8.9 million) with 99% viability per 2.5 mL blood sample, enabling excellent nucleic acid recovery yields for preparation of high-quality sequencing libraries. In turn, these generated RNA-Seq and RP datasets with sufficient genome coverage breadth and depth to enable differential gene expression analyses, demonstrating the validity of this approach to study pertussis vaccine immunology specifically, and its utility to characterize mechanisms of the human immune response to vaccination generally.
Effect of treating mild hyperglycemia in early pregnancy on maternal and neonatal clinical outcomes
Authors: Zhang Yue , Qu Lei , Jin Yan , Sun Wenguang
Published: December 2024

Background: Maternal hyperglycemia during pregnancy can lead to adverse maternal and neonatal outcomes. Although early treatment is recommended, several randomized controlled trials did not show significant benefits from early intensified treatment, meaning that the benefits of treatment for early abnormal glucose remain unclear. Therefore, in this study, we aimed to evaluate the effect of medical nutritional treatment during early pregnancy of women with mild hyperglycemia on maternal and neonatal clinical outcomes.
Methods: We assigned women who had mild hyperglycemia (6.1 mmol/L >fasting plasma glucose ≥5.1 mmol/L and hemoglobin A1 <5.9%) in the first trimester and a diagnosis of gestational diabetes mellitus after an oral glucose tolerance test at 24–28 weeks to control and treatment groups depending on whether they receive medical nutritional treatment during early pregnancy. We compared the maternal and neonatal outcomes.
Results: A total of 344 women were enrolled, and 309 participants were available for analysis (170 in the treatment group and 139 in the control group). Compared with the control group, fewer women in the treatment group had cesarean deliveries (44.7% vs. 61.2%; relative risk [RR], 0.70; 95% confidence interval [CI], 0.54–0.90, P = 0.004) and required insulin therapy (2.9% vs. 8.6%; RR, 0.94; 95% CI, 0.88–0.99, P = 0.004). Women in the treatment group exhibited lower glucose levels and weight gain. Newborns in the treatment group had a higher gestational age at birth than those in the control group (39.1 [39.5, 40.0] vs. 38.8 [38.1, 39.5], P = 0.005). No significant differences were observed in other maternal and neonatal outcomes.
Conclusions: Immediate medical nutritional treatment for pregnant women with mild hyperglycemia during early pregnancy led to a lower incidence of cesarean delivery and insulin therapy during pregnancy than those without treatment. However, no significant differences were observed in neonatal outcomes, except for a higher gestational age at birth of the newborns in the treatment group.
Association between alkaline phosphatase to albumin ratio and 28-day mortality among geriatric patients with sepsis: a cohort study
Authors: Zhou Yiwen , Cai Yuxi , Zheng Pengfei , Chen Xinglin , Xu Chenyang , Mao Shanhua
Published: December 2024

The primary objective of our study was to investigate the relationship between alkaline phosphatase to albumin ratio (APAR) and the risk of 28-day mortality in geriatric patients with sepsis. This was a retrospective cohort study of patients with sepsis in the eICU Collaborative Research Database (eICU-CRD) from 208 distinct ICUs across the United States between 2014 and 2015 that explored all-cause mortality within 28 days after ICU admission. The association between APAR and 28-day mortality was assessed through multivariate logistic regression. We explored the non-linear connection between APAR and 28-day mortality in septic patients using a generalized additive model and smooth curve fitting. Our study uncovered that APAR serves as an independent risk factor for 28-day mortality in geriatric patients with sepsis. Furthermore, we identified inflection points in APAR at 4.2. These findings emphasize a non-linear relationship between APAR and the risk of 28-day mortality in geriatric patients with sepsis. In the context of a period of rapidly increasing mortality with an APAR of less than 4.2, the prognosis of elderly patients with sepsis may be optimized through a monitoring strategy for this indicator and timely implementation of appropriate medical intervention.
MIRACLE - Medical Information Retrieval using Clinical Language Embeddings for Retrieval Augmented Generation at the point of care
Authors: Arzideh Kamyar , Schäfer Henning , Idrissi-Yaghi Ahmad , Eryılmaz Bahadır , Bahn Mikel , Schmidt Cynthia Sabrina , Pollok Olivia Barbara , Hartmann Eva , Winnekens Philipp , Borys Katarzyna , Haubold Johannes , Nensa Felix , Hosch René
Published: December 2024

Most sentence transformer models have been trained in English on publicly accessible datasets. Integration of these models into Retrieval Augmented Generation systems is limited in terms of their ability to retrieve relevant patient-related information. In this study, multiple embedding models were fine-tuned on approximately eleven million question and chunk pairs from 400,000 documents documented in diverse medical categories. The questions and corresponding answers were generated by prompting a large language model. The fine-tuned model demonstrated superior performance on real-world German and translated English evaluation datasets, surpassing the state-of-the-art multilingual-e5-large model. Furthermore, models were trained on a pseudonymized dataset and made publicly available for other healthcare institutions to utilize.
Mechanisms of Manganese Transport by SLC30A10 in Maintaining Mitochondrial Homeostasis
Authors: Yang Hanting , Shen Xurui , Zhang Jinlun , Sun Peixin , Zhong Huiwen , He Rui , Wang Shiliang , Tian Zihan
Published: December 2024

Manganese (Mn) is an essential trace element required for various physiological processes, yet excessive levels induce oxidative stress and lead to severe health issues. The transporter SLC30A10 is crucial for maintaining Mn homeostasis by exporting Mn from cells to prevent toxic accumulation. Mutations in the SLC30A10 gene disrupt this function, resulting in manganese accumulation, which leads to disorders such as hypermanganesemia with dystonia 1 (HMNDYT1). Here, we show that SLC30A10 mediates Mn efflux under elevated Mn conditions, alleviating oxidative stress and preserving mitochondrial integrity. High-resolution cryo-EM structures reveal a unique Mn-binding site in SLC30A10, setting it apart from other SLC30 family transporters. We further demonstrate that the HMNDYT1-linked D40A mutation disrupts the binding and transport of Mn, identifying D40 as a potential therapeutic target. These findings provide structural insights into Mn transport and potential avenues for targeting Mn toxicity.
Exploring the Significance of Physical Activity to Enhance Quality of Life Among Hemiplegic Elderly: A Novel Approach Using Mixed-Methods Grounded Theory (MM-GT)
Authors: Sawangjaithum Kanokthip , Riewpaiboon Wachara , Sirirungruang Issavara , Sunsern Ratchanee
Published: December 2024

Background
Elderly stroke survivors commonly live a sedentary life with some degree of mobility disability despite their independent functional ability in performing activities of daily living (ADL) and ambulation. The perception and meanings given to physical activity (PA) play a significant role in promoting active aging for better quality of life (QoL). This study aims to explore the QoL-related meanings of PA given by hemiplegic older adults living in Thailand's rural community to construct an explorative theoretical model.
Methods
A mixed-methods grounded theory (MM-GT) exploratory embedded research design was used with case-by-case purposive theoretical sampling for qualitative data collection and grounded analysis from community-dwelling elderlies who were hemiplegic stroke survivors. Quantifying the PA level of respondents was embedded using Global Physical Activity Questionnaires (GPAQ), whereas World Health Organization Quality of Life-Brief (WHOQOL-BREF) and Stroke Impact Scale (SIS) were used for measuring functional impacts and QoL.
Results
The constructive theoretical model displayed three hierarchical meaningful PA categories. Firstly, initial PA refers to activities that positively drive to more independent living and negatively drive to avoid burdening the family. Secondly, identity PA refers to what they do regarding the accountabilities of prior family roles instead of living a sedentary and empty life. Thirdly, optimizing PA is defined as what PAs do to maintain and balance their meaningful existence within the wider community. The more meaningful PA was the more possibility to turn into action and contribute to the QoL of elderly hemiplegic stroke survivors. The MM-GT exploratory embedded research design with the lens of the Theory of Everything (TOE) helped to disclose the multidimensional QoL-related meanings of the PA behaviors of older people with mobility disability. Meanwhile, the Social Cognitive Learning Theory (SCLT) enhanced its learning property and explanatory power.
Conclusions
These findings have significant implications for geriatrics, rehabilitation, and public health areas, providing insights into the role of meaningful PA in improving the QoL of elderly stroke survivors and using it as a strategy for promoting active aging and improving QoL within their living community. The gender distribution of respondents and the particular semi-urban context of this study limited its generalizability.
Green design of Circuit Breaker electrical life to improve resource utilization
Authors: Zhou Jungang , Shang Zhaoxia , Liang Weiwei , Liu Jia
Published: December 2024

The qualified circuit breaker has its inherent electrical life when leaving the factory. In the course of use, the electrical life is gradually reduced due to various reasons. The electrical life of circuit breaker is reasonably designed according to service conditions, and the resource reserve is reduced when the circuit breaker is passively eliminated, to realize the green design of efficient utilization of electrical life. Analyzed the mechanism of arc erosion on the contact, and calculated the wear loss of the contact by arc erosion. Part of the heat released by arc combustion is used for contact wear, and the electrical life prediction model of circuit breaker is established based on heat utilization efficiency. The Monte Carlo method is used to test and analyze the electrical life prediction model of circuit breaker, and the correctness of model is verified. Based on the electric life prediction model, the green design model of electric life is proposed. Through the rational distribution of electrical life, the resource reserve is reduced and the resource utilization rate is improved.
Remote Surgery with 5G or 6G: Knowledge Production and Diffusion Globally and in the German Case
Authors: Martinelli Marina , Furtado André Tosi
Published: December 2024

This paper is a comprehensive exploring of technology capability in 5G/6G TIS, explicitly focusing on the potential of remote surgery globally and in Germany. The paper's main contribution is its ability to anticipate new debates on the interplay between TIS and contexts, with particular emphasis on the national and international levels. Our findings, derived from a Bibliometrics study of industry-academic relationships, highlight crucial collaborations in Germany, positioning the country as a strategic actor in international TIS and, by extension, in applying 5G/6G technological systems to remote surgery due to its knowledge production capability. We propose policies that can stimulate interaction between smaller suppliers and larger companies, which can act as intermediaries and provide access to international markets. The German government may adopt innovation, science and technology policies on 5G and 6G networks, such as targeted incentive policies for patent creation and publications and R&D activities focused on 5G and 6G in the medical field.
Upregulation of circ-0069561 promotes diabetic kidney disease progression
Authors: Chen Chaoyi , Liu Xinran , Zhu Sai , Liu Xueqi , Wang Yukai , Ma Yu , Hu Ziyun , Wu Yonggui , Jiang Ling
Published: December 2024

Circular RNAs (circRNAs) are non-coding RNAs that play a critical role in disease etiology. But the role of circRNAs in diabetic kidney disease (DKD) remains unknown. We performed whole high-throughput RNA sequencing (RNA-seq) of kidney tissues from clinical DKD patients and controls. The top 10 up-regulated circular RNAs were selected by RT-PCR validation, and the findings showed a substantial increase in the expression level of circ-0069561. RT-PCR and fluorescent in situ hybridization (FISH) confirmed that circ-0069561 expression increased both renal tissues of type 2 diabetic mice and DKD patients, with a glomerulus-specific location. Circ-0069561 expression in kidney tissue was significantly correlated with UACR, glomerular lesions, arteriolar hyalinosis and arteriosclerosis. The expression level of circ-0069561 and plasma albumin (ALB) level were independent risk factors for macroalbuminuria. Circ-0069561 demonstrated a strong diagnostic value in major proteinuria, according to the ROC curves (area under the curve = 0.889). CircRNA-miRNA-mRNA network indicated that the pathophysiology of DKD may involve ferroptosis. Podocyte damage and ferroptosis caused by high glucose were attenuated by silencing circ-0069561, according to in vitro examinations. Together, the findings suggest that circ-0069561 may influence the progression of DKD by causing ferroptosis of podocytes. The findings of this study provide new insights into the cause and progression of DKD.
The mediating role of trait mental fatigue in cognitive decline among PwMS: Implications for verbal memory and information processing speed
Authors: Tsoukaki Nefeli , Anagnostopoulou Alexandra , Kartsidis Panagiotis E. , Karagianni Maria , Liozidou Athanasia , Nikolaidis Ioannis , Grigoriadis Nikolaos , Bamidis Panagiotis D. , Styliadis Charis
Published: December 2024

Trait mental fatigue (MF) and cognitive dysfunction significantly impair the quality of life in people with multiple sclerosis (PwMS), particularly impacting information processing speed (IPS) and verbal learning-memory (VL/M). We assessed 66 PwMS and 38 healthy controls (HC) via the oral form of the Symbol Digit Modalities Test (SDMT-Of) for IPS, the Greek Verbal Learning Test (GVLT) for VL/M, and the cognitive subscale of the Modified Fatigue Impact Scale (MFIS-c) for MF. This aimed at investigating the mediating role of MF in the relationship between IPS and VL/M in PwMS. PwMS performed significantly worse than HC across all domains. Mediation analysis, controlling for age, sex, education, disease duration, and MS-type, revealed a significant effect of IPS on VL/M in PwMS. This effect became non-significant once MF was introduced, whereas the indirect effect of IPS on VL/M through MF remained significant. No significant mediation effects were observed in HC, even after controlling for age, sex, and education, underscoring the unique impact of MF on MS. This study highlights the mediating role of trait MF in cognitive deficits among PwMS, suggesting that interventions targeting MF could enhance cognitive performance. The study is registered with ClinicalTrials.gov Identifier NCT04806568 (https://www.clinicaltrials.gov/study/NCT04806568).
Graphene-based glucose sensors with an attomolar limit of detection
Authors: Lopes Vicente , Abreu Tiago , Abrantes Mafalda , Nemala Siva , De Boni Francesco , Prato Mirko , Alpuim Pedro , Capasso Andrea
Published: December 2024

Diabetes mellitus, a prevalent metabolic disorder affecting hundreds of millions worldwide, demands continuous glucose monitoring for effective management. Current blood glucose monitoring methods, such as commercial glucometers, though accurate, are invasive and uncomfortable, highlighting the need for non-invasive, ultra-sensitive alternatives. Here, we present a glucose sensing platform based on electrolyte-gated graphene field-effect transistors (EG-GFETs) functionalized with glucose oxidase enzymes for ultra-sensitive detection. Detailed material characterization by Raman and X-ray photoelectron spectroscopies confirms successful enzyme immobilization, with a marked increase in nitrogen content from 0.9% to 7.6% atomic concentration on the graphene surface, indicating substantial glucose oxidase coverage. Raman analysis reveals significant p-type doping and tensile strain on the graphene channel directly correlating with glucose concentration from 1 nanomolar to 1 millimolar. The EG-GFETs demonstrate an ultra-low limit-of-detection of 1 attomolar, with a consistent Dirac point voltage shift of +26 ± 4 mV and a linear response across six orders of magnitude (up to 1 picomolar, with a sensitivity of 10.6 mV/decade). The sensor maintains high selectivity in complex media, such as artificial tears (with a limit-of-detection of 100 attomolar), underscoring its potential for non-invasive continuous glucose monitoring applications, also in wearable format.
Ethnographic Analysis of Phenomena of South Asian Forced Migration in Greece
Authors: Taukeer Mohammed
Published: December 2024

The matter of forced migration and refugees is a global phenomenon because it is considered a crisis on global level. In these consequences, a major theme of this research paper is based on a study of forced migration from Pakistan and Bangladesh to Greece from the perspective of the cultural intention of return to the homeland. The major objective of this research paper is based on a study of the process, determinants and consequences of forced migration and their return intention. The methodology of the research paper is based on an ethnographic field survey among South Asian refugees in Athens in August 2017. Qualitative data was collected through personal interviews, focus group discussions and informal interviews under the saturation stage of information. Collected qualitative data is analyzed by case studies, narratives and descriptions under the content analysis of ethnographic technique. The findings of the study show that there is a function of culturalization of forced migration from Pakistan and Bangladesh to Greece and these consequences developed a form of assimilation and integration between South Asian and Greek culture. It developed a form of South Asian hybrid cultural diaspora through the in-direct return of South Asian refugees through the formation of building capacity of South Asian culture in Athens with the existence of contradictions, discriminations, and challenges about recreation of identity. Therefore, the findings of this research paper would encourage researchers, policymakers, and academicians to conduct further research in the area of forced migration and refugees related studies on a global level.
FRAME: A phase I trial of defactinib (FAK inhibitor) in combination with avutometinib (RAF-MEK clamp) in patients with solid tumours including low grade serous ovarian cancer
Authors: Banerji Udai , Banerjee Susana , Krebs Matthew , Greystoke Alastair , Garces Alvaro Inglese , Perez Vicky Sanchez , Terbuch Angelika , Shinde Rajiv , Caldwell Reece , Grochot Rafael , Ruddle Ruth , Gurel Bora , Swales Karen , Tunariu Nina , Prout Toby , Parmar Mona , Symeonides Stefan , Rekowski Jan , Yap Christina , Sharp Adam , Paschalis Alec , Lopez Juanita , Minchom Anna , Bono Johann
Published: December 2024

We describe the first-in-human trial of avutometinib (RAF/MEK clamp) and defactinib (FAK inhibitor) in patients with solid tumors. The trial met its primary endpoint and recommended a phase 2 dose/schedule is avutometinib 3.2 mg OD 2/7 days and defactinib 200 mg BID 7/7 days, both drugs administered orally for 3 weeks every 4 weeks. The pharmacokinetics and pharmacodynamics were consistent with previous reports of avutometinib and defactinib used as single agents. Key findings include an objective response rate (ORR) and median progression free survival (mPFS) of 42.3% (11/26; 95% confidence interval (CI): 23.4%-63.1%) and 20.1 months (95% CI: 11.2-43.9) respectively in patients with low grade serous ovarian cancer (LGSOC). This study demonstrates importance of novel combinations of targeted therapies targeting the MAPK and FAK involving intermittent dosing schedules to improve tolerability (NCT03875820/EudraCT number 2017-001035-39).
Targeting PKMYT1 enhances antitumor immune responses in castration-resistant prostate cancer
Authors: Han Bo , Gao Lin , Wang Baozhen , Liu Hui , Liu Ping , Liu Long , Han Jingying , Wang Xin , Dou Baokai , Liu Wenyao , Wang Xinpei , Sun Feifei , Feng Tingting , Zhao Ru , Chen Weiwen , Hu Jing
Published: December 2024

Immunotherapy has achieved significant success in treating various cancers, yet its efficacy in castration resistant prostate cancer (CRPC) is minimal, partly due to the lack of intratumoral immune effector cells in CRPC. Understanding the mechanisms of immune evasion and identifying potential therapeutic strategies to activate innate antitumor immunity are crucial for enhancing the response to immunotherapy. Here we demonstrate that PKMYT1, a member of the WEE1 family, is overexpressed in CRPC tissues. Patients with high PKMYT1 expression exhibit low CD8+ T cells infiltration and resistance to immune checkpoint blockade (ICB). Targeting PKMYT1 can suppress CRPC progression, accompanied with increased intratumoral CD8+ T cells. Selective PKMYT1 inhibitor, RP-6306, augments ICB at the presence of CD8+ T cells. PKMYT1 inhibitor alone or in combination with PD-L1 blockade increases infiltration of CD8+ T cell and remarkable tumor suppression in vivo. Mechanically, targeting PKMYT1 activates the cGAS-STING pathway, enhances interferon signaling, and elevates key immune modulators, including CCL5 and CXCL10. These findings highlight a key role of PKMYT1 in CRPC progression and suggest PKMYT1 as a potential therapeutic target in combination with ICB.
Incongruent Virtual Reality Attenuates Breathlessness and Leg Fatigue During Stationary Cycling
Authors: Biller Lara R , Starling Lucy , Sinha Ayush , Dearlove David , Bruce Richard M , Runswick Oliver R , Taylor Stephen , Finnegan Sarah , Pattinson Kyle
Published: December 2024

Previously we showed that discordant stimulation in virtual reality (VR) could manipulate feelings of breathlessness during stationary cycling. We were interested in developing this as a tool to help respiratory and cardiac patients better engage with exercise rehabilitation. Therefore, in a cohort of healthy volunteers we tested whether the paradigm could attenuate (rather than simply manipulate) feelings of breathlessness and leg fatigue. We explored factors associated with interindividual differences in response. We subsequently investigated clinical acceptability in cardiac and respiratory patients through extensive engagement with relevant stakeholders and a feasibility study.
Healthy participants study: 48 healthy people took part in a double-blind, randomised controlled study with two sessions. Participants cycled with a VR headset to compare discordant VR, where visual slope was always less than pedal resistance, against a concordant control. Physical and mental wellbeing were also assessed via questionnaires. Patient and Public Involvement (PPI): The paradigm was demonstrated to 66 patients and caregivers from relevant clinical communities, who then gave feedback in focus groups, panels or one-to-one structured interviews. Patient Study: 9 patients took part in a single session, observational study with a scaled-down version of the cycling paradigm to assess tolerance and acceptability.
Healthy participants study: Discordant VR was associated with reduced breathlessness and leg fatigue (breathlessness: effect size estimate = 0.39, SE = 0.04, p<0.00; leg fatigue: effect size estimate = 0.39, SE = 0.04, p<0.001). Further, that depression and health anxiety may influence this effect (breathlessness, Center for Epidemiological Studies Depression score: effect size estimate = 0.29, SE = 0.138, p = 0.04; leg fatigue, Health Anxiety Index: effect size estimate = 0.44, SE = 0.135, p = 0.002).
PPI and Patient study: Widespread enthusiasm for concept, identifying a clinical need for novel physical therapy tools. The scaled-down paradigm was mostly well tolerated in a group of relevant patients, with discordant VR approaching significance (effect size: -0.166 , p = 0.06) as a factor in reducing breathlessness, despite small N.
Discordant VR has the potential to attenuate breathlessness and effort perception during cycling exercise. This may have clinical utility in cardiac/pulmonary rehabilitation programmes or similar and our findings suggest a formal clinical trial would be merited.