bluuebunny/crossref_metadata_2025_split huggingface dataset:
The synergism of cytosolic acidosis and reduced NAD+/NADH ratio is responsible for lactic acidosis-induced vascular smooth muscle cell impairment in sepsis
Authors: Terpe Philipp , Ruhs Stefanie , Dubourg Virginie , Bucher Michael , Gekle Michael 
Published: January 2024

Abstract
Background
During sepsis, serve vascular dysfunctions lead to life-threatening multiple organ failure, due to vascular smooth muscle cells (VSMC) impairments, resulting in vasoplegia, hypotension and hypoperfusion. In addition, septic patients have an altered cell metabolism that leads to lactic acidosis. Septic patients suffering from lactic acidosis have a high risk of mortality. In addition, septic survivors are at risk of secondary vascular disease. The underlying mechanisms of whether and how lactic acidosis leads to the changes in VSMCs is not well understood. The aim of this study was to comprehensively investigate the effect of lactic acidosis on VSMCs and additionally compare the effects with those induced by pure acidosis and sodium lactate.

Methods
Primary human aortic smooth muscle cells (HAoSMCs) were treated for 48 h with lactic acidosis (LA_pH 6.8), hydrochloric acid (HCl_pH 6.8), sodium lactate (Na+-lactate_pH 7.4) and the respective controls (ctrl._pH 7.4; hyperosmolarity control: mannitol_pH 7.4) and comparatively analyzed for changes in (i) transcriptome, (ii) energy metabolism, and (iii) phenotype.

Results
Both types of acidosis led to comparable and sustained intracellular acidification without affecting cell viability. RNA sequencing and detailed transcriptome analysis revealed more significant changes for lactic acidosis than for hydrochloric acidosis, with lactate being almost ineffective, suggesting qualitative and quantitative synergism of acidosis and lactate. Bioinformatic predictions in energy metabolism and phenotype were confirmed experimentally. Lactic acidosis resulted in strong inhibition of glycolysis, glutaminolysis, and altered mitochondrial respiration which reduced cellular ATP content, likely due to increased TXNIP expression and altered NAD+/NADH ratio. Hydrochloric acidosis induced significantly smaller effects without changing the NAD+/NADH ratio, with the ATP content remaining constant. These metabolic changes led to osteo-/chondrogenic/senescent transdifferentiation of VSMCs, with the effect being more pronounced in lactic acidosis than in pure acidosis.

Conclusions
Overall, lactic acidosis exerted a much stronger effect on energy metabolism than pure acidosis, whereas lactate had almost no effect, reflecting the qualitative and quantitative synergism of acidosis and lactate. As a consequence, lactic acidosis may lead to acute functional impairments of VSMC, sustained perturbations of the transcriptome and cellular dedifferentiation. Moreover, these effects may contribute to the acute and prolonged vascular pathomechanisms in septic patients.
Remnant cholesterol and the risk of aortic valve calcium progression: insights from the MESA study
Authors: Li Ze-Hua , Hao Qing-Yun , Zeng Yu-Hong , Guo Jing-Bin , Li Shi-Chao , Gao Jing-Wei , Yang Ping-Zhen 
Published: January 2024

Abstract
Background
Remnant cholesterol (RC) is implicated in the risk of cardiovascular disease. However, comprehensive population-based studies elucidating its association with aortic valve calcium (AVC) progression are limited, rendering its precise role in AVC ambiguous.

Methods
From the Multi-Ethnic Study of Atherosclerosis database, we included 5597 individuals (61.8 ± 10.1 years and 47.5% men) without atherosclerotic cardiovascular disease at baseline for analysis. RC was calculated as total cholesterol minus high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), as estimated by the Martin/Hopkins equation. Using the adjusted Cox regression analyses, we examined the relationships between RC levels and AVC progression. Furthermore, we conducted discordance analyses to evaluate the relative AVC risk in RC versus LDL-C discordant/concordant groups.

Results
During a median follow-up of 2.4 ± 0.9 years, 568 (10.1%) participants exhibited AVC progression. After adjusting for traditional cardiovascular risk factors, the HRs (95% CIs) for AVC progression comparing the second, third, and fourth quartiles of RC levels with the first quartile were 1.195 (0.925–1.545), 1.322 (1.028–1.701) and 1.546 (1.188–2.012), respectively. Notably, the discordant high RC/low LDL-C group demonstrated a significantly elevated risk of AVC progression compared to the concordant low RC/LDL-C group based on their medians (HR, 1.528 [95% CI 1.201–1.943]). This pattern persisted when clinical LDL-C threshold was set at 100 and 130 mg/dL. The association was consistently observed across various sensitivity analyses.

Conclusions
In atherosclerotic cardiovascular disease-free individuals, elevated RC is identified as a residual risk for AVC progression, independent of traditional cardiovascular risk factors. The causal relationship of RC to AVC and the potential for targeted RC reduction in primary prevention require deeper exploration.
Laparoscopic versus open distal gastrectomy for advanced gastric cancer in elderly patients: a propensity-score matched analysis
Authors: Yao Qing , Sun Qian-Nan , Wang Dao-Rong 
Published: January 2024

Abstract
Background
Scarce research has reported the efficacy and safety of laparoscopic distal gastrectomy in elderly patients. This retrospective study aimed to compare the outcomes of laparoscopic and open distal gastrectomy for advanced gastric cancer in elderly patients.

Methods
A total of 303 elderly patients who underwent distal gastrectomy for advanced gastric cancer from June 2017 to June 2021 were enrolled. Variables used to calculate propensity score matching included sex, age, body mass index, American Society of Anesthesiologists, history of diabetes, and history of hypertension. The statistical significance of continuous variables was tested using an independent sample t test. chi-square or Fisher’s exact tests were used for categorical variables. Kaplan–Meier curve and log-rank test were used for the evaluation of 3-year overall survival and recurrence-free survival.

Results
After performing 1:1 propensity score matching, 248 patients were included for analysis (laparoscopic = 124, open = 124). Compared with the open group, the laparoscopic group showed significant advantages in estimated blood loss (P < 0.001), pain scale on the first postoperative day (P = 0.002), time to first flatus (P = 0.004), time to first liquid diet (P = 0.005), hospital stays (P < 0.001), and total complications (P = 0.011), but devoted much more operation time (P < 0.001). No statistical difference was observed between the two groups in 3-year recurrence-free survival (P = 0.315) or overall survival (P = 0.159).

Conclusions
Our analysis demonstrated that laparoscopic surgery had the advantages of less intraoperative blood loss, fewer postoperative complications, and faster postoperative recovery in distal gastrectomy for advanced gastric, indicating that laparoscopic distal gastrectomy is safe and effective for treating elderly patients with distal gastric cancer.
Survival outcomes of malignant peripheral nerve sheath tumors (MPNSTs) with and without neurofibromatosis type I (NF1): a meta-analysis
Authors: Lim Zhixue , Gu Tian Yuan , Tai Bee Choo , Puhaindran Mark Edward 
Published: January 2024

Abstract
Introduction
Malignant peripheral nerve sheath tumors (MPNSTs) are malignancies that demonstrate nerve sheath differentiation in the peripheral nervous system. They can occur sporadically or be associated with neurofibromatosis type 1 (NF1), an autosomal dominant neurocutaneous disorder, with up to 13% of patients developing MPNSTs in their lifetimes. Previous studies have suggested conflicting findings regarding the prognosis of NF1 for patients with MPNSTs. The elucidation of NF1 as an independent prognostic factor on mortality has implications for clinical management. We aim to investigate the role of NF1 status as an independent prognostic factor of overall survival (OS) and disease-specific survival (DSS) in MPNSTs.

Methods
An electronic literature search of PubMed and MEDLINE was performed on studies reporting OS or DSS outcomes of MPNSTs with and without NF1. A grey literature search by reviewing bibliographies of included studies and review articles was performed to find pertinent studies. Data was extracted and assessed in accordance with the PRISMA guidelines. A meta-analysis was performed to calculate hazard ratios (HRs) using a random-effects model. The primary and secondary outcomes were all-cause and disease-specific mortality, respectively, with NF1 as an independent prognostic factor of interest.

Results
A total of 59 retrospective studies involving 3602 patients fulfilled the inclusion criteria for OS analysis, and 23 studies involving 704 MPNST patients were included to evaluate DSS outcomes. There was a significant increase in the hazard of all-cause mortality (HR 1.63, 95% CI 1.45 to 1.84) and disease-specific mortality (HR 1.52, 95% CI 1.24 to 1.88) among NF1 as compared to sporadic cases. Subgroup analyses and meta-regression showed that this result was consistent regardless of the quality of the study and year of publication.

Conclusion
NF1 is associated with a substantially higher risk of all-cause and disease-specific mortality. This finding suggests that closer surveillance is required for NF1 patients at risk of developing MPNSTs.
Participatory policy analysis in health policy and systems research: reflections from a study in Nepal
Authors: Sapkota Sujata , Rushton Simon , van Teijlingen Edwin , Subedi Madhusudan , Balen Julie , Gautam Sujan , Adhikary Pratik , Simkhada Padam , Wasti Sharada P. , Karki Jiban K. , Panday Sarita , Karki Alisha , Rijal Barsha , Joshi Saugat , Basnet Srijana , Marahatta Sujan B. 
Published: January 2024

Abstract
Background
Participatory policy analysis (PPA) as a method in health policy and system research remains underexplored. Using our experiences of conducting PPA workshops in Nepal to explore the impact of the country’s move to federalism on its health system, we reflect on the method’s strengths and challenges. We provide an account of the study context, the design and implementation of the workshops, and our reflections on the approach’s strengths and challenges. Findings on the impact of federalism on the health system are beyond the scope of this manuscript.

Main body
We conducted PPA workshops with a wide range of health system stakeholders (political, administrative and service-level workforce) at the local and provincial levels in Nepal. The workshops consisted of three activities: river of life, brainstorming and prioritization, and problem-tree analysis. Our experiences show that PPA workshops can be a valuable approach to explore health policy and system issues – especially in a context of widespread systemic change which impacts all stakeholders within the health system. Effective engagement of stakeholders and activities that encourage both individual- and system-level reflections and discussions not only help in generating rich qualitative data, but can also address gaps in participants’ understanding of practical, technical and political aspects of the health system, aid policy dissemination of research findings, and assist in identifying short- and long-term practice and policy issues that need to be addressed for better health system performance and outcomes. Conducting PPA workshops is, however, challenging for a number of reasons, including the influence of gatekeepers and power dynamics between stakeholders/participants. The role and skills of researchers/facilitators in navigating such challenges are vital for success. Although the long-term impact of such workshops needs further research, our study shows the usefulness of PPA workshops for researchers, for participants and for the wider health system.

Conclusions
PPA workshops can effectively generate and synthesize health policy and system evidence through collaborative engagement of health system stakeholders with varied roles. When designed with careful consideration for context and stakeholders’ needs, it has great potential as a method in health policy and systems research.
A pre-existing Toxoplasma gondii infection exacerbates the pathophysiological response and extent of brain damage after traumatic brain injury in mice
Authors: Baker Tamara L. , Wright David K. , Uboldi Alessandro D. , Tonkin Christopher J. , Vo Anh , Wilson Trevor , McDonald Stuart J. , Mychasiuk Richelle , Semple Bridgette D. , Sun Mujun , Shultz Sandy R. 
Published: January 2024

AbstractTraumatic brain injury (TBI) is a key contributor to global morbidity that lacks effective treatments. Microbial infections are common in TBI patients, and their presence could modify the physiological response to TBI. It is estimated that one-third of the human population is incurably infected with the feline-borne parasite, Toxoplasma gondii, which can invade the central nervous system and result in chronic low-grade neuroinflammation, oxidative stress, and excitotoxicity—all of which are also important pathophysiological processes in TBI. Considering the large number of TBI patients that have a pre-existing T. gondii infection prior to injury, and the potential mechanistic synergies between the conditions, this study investigated how a pre-existing T. gondii infection modified TBI outcomes across acute, sub-acute and chronic recovery in male and female mice. Gene expression analysis of brain tissue found that neuroinflammation and immune cell markers were amplified in the combined T. gondii + TBI setting in both males and females as early as 2-h post-injury. Glutamatergic, neurotoxic, and oxidative stress markers were altered in a sex-specific manner in T. gondii + TBI mice. Structural MRI found that male, but not female, T. gondii + TBI mice had a significantly larger lesion size compared to their uninfected counterparts at 18-weeks post-injury. Similarly, diffusion MRI revealed that T. gondii + TBI mice had exacerbated white matter tract abnormalities, particularly in male mice. These novel findings indicate that a pre-existing T. gondii infection affects the pathophysiological aftermath of TBI in a sex-dependent manner, and may be an important modifier to consider in the care and prognostication of TBI patients.
Using meta-analysis and CNN-NLP to review and classify the medical literature for normal tissue complication probability in head and neck cancer
Authors: Lee Tsair-Fwu , Hsieh Yang-Wei , Yang Pei-Ying , Tseng Chi-Hung , Lee Shen-Hao , Yang Jack , Chang Liyun , Wu Jia-Ming , Tseng Chin-Dar , Chao Pei-Ju 
Published: January 2024

Abstract
Purpose
The study aims to enhance the efficiency and accuracy of literature reviews on normal tissue complication probability (NTCP) in head and neck cancer patients using radiation therapy. It employs meta-analysis (MA) and natural language processing (NLP).

Material and methods
The study consists of two parts. First, it employs MA to assess NTCP models for xerostomia, dysphagia, and mucositis after radiation therapy, using Python 3.10.5 for statistical analysis. Second, it integrates NLP with convolutional neural networks (CNN) to optimize literature search, reducing 3256 articles to 12. CNN settings include a batch size of 50, 50–200 epoch range and a 0.001 learning rate.

Results
The study's CNN-NLP model achieved a notable accuracy of 0.94 after 200 epochs with Adamax optimization. MA showed an AUC of 0.67 for early-effect xerostomia and 0.74 for late-effect, indicating moderate to high predictive accuracy but with high variability across studies. Initial CNN accuracy of 66.70% improved to 94.87% post-tuning by optimizer and hyperparameters.

Conclusion
The study successfully merges MA and NLP, confirming high predictive accuracy for specific model-feature combinations. It introduces a time-based metric, words per minute (WPM), for efficiency and highlights the utility of MA and NLP in clinical research.
Variety of femoral anteversion and its measurement in cementless total hip arthroplasty: Does robotic technology improve accuracy?
Authors: Shao Hongyi , Huang Yong , Yang Dejin , Deng Wang , Wu Xiang-Dong , Zhou Yixin 
Published: January 2024

Abstract
Background
High-performance total hip arthroplasty (THA) depends on the accurate position of components. However, femoral anteversion is variable, and current studies only used traditional instruments to evaluate it, such as protractor and spirit level with limited cases. This study aimed to identify the variability in the measured femoral native anteversion and intraoperative stem anteversion under different measurement methods, including intraoperative robotic method. We hypothesized that robotic technology was more accurate than traditional instruments for femoral anteversion evaluation.

Methods
This study included 117 hips of patients who underwent robotic-assisted THA between November 2019 and March 2021. Preoperative native femoral anteversion was measured using a robotic system. Intraoperative femoral stem anteversion was evaluated visually, and then measured with a goniometer and a robotic system, respectively. Variability in the measured femoral native anteversion and intraoperative femoral stem anteversion was calculated and compared. Intraclass correlation coefficient (ICC) and Pearson correlation analysis were used to assess the consistency and correlation of anteversion of different measurements and postoperative CT-measured stem anteversion, respectively.

Results
The result of measurement for preoperative native femoral anteversion was more variable than the intraoperative robotic-measured stem anteversion. Intraoperative robotic-measured stem version showed the highest correlation with postoperative CT measurement of stem version (r = 0.806, P < 0.001), while intraoperative surgeon estimation had the lowest correlation coefficient (r = 0.281, P = 0.025). As for the consistency with postoperative CT measurement of femoral stem anteversion, the intraoperative robotic-measured femoral stem version also had the highest value (ICC = 0.892, P < 0.001).

Conclusion
Native femoral anteversion was variable preoperatively. Using cementless stems, anteversion was also highly variable. Robotic assessment for stem anteversion during surgery was more consistent with the final position than the preoperative assessment and conventional intraoperative estimation.
Premature ovarian insufficiency: a review on the role of tobacco smoke, its clinical harm, and treatment
Authors: Cui Jinghan , Wang Ying 
Published: January 2024

AbstractPremature ovarian insufficiency (POI) is a condition in which the quantity of follicles and the quality of oocytes gradually decrease. This results in an estrogen secretion disorder and abnormal follicle development, which can lead to related diseases, early onset of menopause, sexual dysfunction, and an increased risk of cardiovascular issues, osteoporosis, and depression, among others. This disease significantly impacts the physical and mental health and overall quality of life of affected women. Factors such as genetic abnormalities, oophorectomy, radiotherapy for malignancy, idiopathic conditions, and an unhealthy lifestyle, including smoking, can accelerate the depletion of the follicular pool and the onset of menopause. Extensive research has been conducted on the detrimental effects of tobacco smoke on the ovaries. This article aims to review the advancements in understanding the impact of tobacco smoke on POI, both in vivo and in vitro. Furthermore, we explore the potential adverse effects of common toxicants found in tobacco smoke, such as polycyclic aromatic hydrocarbons (PAHs), heavy metals like cadmium, alkaloids like nicotine and its major metabolite cotinine, benzo[a]pyrene, and aromatic amines. In addition to discussing the toxicants, this article also reviews the complications associated with POI and the current state of research and application of treatment methods. These findings will contribute to the development of more precise treatments for POI, offering theoretical support for enhancing the long-term quality of life for women affected by this condition.
Multi-UAV-assisted Internet of Remote Things communication within satellite–aerial–terrestrial integrated network
Authors: Yao Yuanyuan , Dong Dengyang , Cai Changjun , Huang Sai , Yuan Xin , Gong Xiaocong 
Published: January 2024

AbstractDue to the limited transmission capabilities of terrestrial intelligent devices within the Internet of Remote Things (IoRT), this paper proposes an optimization scheme aimed at enhancing data transmission rate while ensuring communication reliability. This scheme focuses on multi-unmanned aerial vehicle (UAV)-assisted IoRT data communication within the satellite–aerial–terrestrial integrated network (SATIN), which is one of the key technologies for the sixth generation (6G) networks. To optimize the system’s data transmission rate, we introduce a multi-dimensional coverage and power optimization (CPO) algorithm, rooted in the block coordinate descent (BCD) method. This algorithm concurrently optimizes various parameters, including the number and deployment of UAVs, the correlation between IoRT devices and UAVs, and the transmission power of both devices and UAVs. To ensure comprehensive coverage of a large-scale randomly distributed array of terrestrial devices, combined with machine learning algorithm, we present the Dynamic Deployment based on K-means (DDK) algorithm. Additionally, we address the non-convexity challenge in resource allocation for transmission power through variable substitution and the successive convex approximation technique (SCA). Simulation results substantiate the remarkable efficacy of our CPO algorithm, showcasing a maximum 240% improvement in the uplink transmission rate of IoRT data compared to conventional methods.