bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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.