bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical-scale, modular manufacturing of tumor-reactive TILs using a closed and automated culture system
Authors: Völzke Christina , Ehrhardt Lisa , Fischer Laura , Maul Peter , Wenzel Carina , Riabinska Arina , Criado-Moronati Elvira , Dienstbier Mike , Hassel Jessica , Zhang Danmei , Haanen John B. , Handgretinger Rupert , Hardy Ian R. , Heemskerk Bianca , Dzionek Andrzej
Published: December 2024

Recent studies have revealed the potential of tumor-infiltrating lymphocytes (TILs) to treat solid tumors effectively and safely. However, the translation of TIL therapy for patients is still hampered by non-standardized and laborious manufacturing procedures that are expensive and produce highly variable cellular products. To address these limitations, the CliniMACS Prodigy® Tumor Reactive T cell (TRT) Process has been developed. The TRT Process allows the automated isolation, transduction, and expansion of tumor-reactive T cells in a clinically compliant and closed system under GMP conditions. The TRT Process can generate tumor-reactive T cells using several methodologies which reflect clinically relevant applications. It can manage an automated Rapid Expansion Protocol (REP) using GMP-compliant reagents to generate a TIL cell product from solid tumors, including melanoma. Additionally, the TRT Process automates the closed selection of CD137-expressing TILs directly from tumor digest followed by the direct expansion of selected cells. Enriched CD137+ TILs could be robustly expanded even when as few as 1x104 TILs were used to seed the REP phase. These data provide proof-of-concept for the isolation and expansion of tumor-reactive T cells from tumor digest in a closed, automated manner in the CliniMACS Prodigy, allowing for an efficient, simple, and reproducible manufacturing of TIL products. The direct selection of CD137+ TILs from tumor digest removes the need for the pre-REP phase, selects for therapeutically relevant cells, and can dramatically shorten the manufacturing time compared to conventional methods.
Integrating necroptosis into pan-cancer immunotherapy: a new era of personalized treatment
Authors: Gao Yan , Chen Sheng , Li Lei
Published: December 2024

Introduction

Necroptosis has emerged as a promising biomarker for predicting immunotherapy responses across various cancer types. Its role in modulating immune activation and therapeutic outcomes offers potential for precision oncology.

Methods

A comprehensive pan-cancer analysis was performed using bulk RNA sequencing data to develop a necroptosis-related gene signature, termed Necroptosis.Sig. Multi-omics approaches were employed to identify critical pathways and key regulators of necroptosis, including HMGB1. Functional validation experiments were conducted in A549 lung cancer cells to evaluate the effects of HMGB1 knockdown on tumor proliferation and malignancy.

Results

The Necroptosis.Sig gene signature effectively predicted responses to immune checkpoint inhibitors (ICIs). Multi-omics analyses highlighted HMGB1 as a key modulator of necroptosis, with potential to enhance immune activation and therapeutic efficacy. Functional experiments demonstrated that HMGB1 knockdown significantly suppressed tumor proliferation and malignancy, reinforcing the therapeutic potential of targeting necroptosis.

Discussion

These findings underscore the utility of necroptosis as a biomarker to guide personalized immunotherapy strategies. By advancing precision oncology, necroptosis provides a novel avenue for improving cancer treatment outcomes.
Efficacy and safety of misoprostol compared with dinoprostone for labor induction at term: an updated systematic review and meta-analysis of randomized controlled trials
Authors: Lakho Nusrat , Hyder Mahrukh , Ashraf Taimoor , Khan Sajida , Kumar Ajay , Jabbar Maheen , Kumari Madhurta , Qammar Asfia , Kumar Sateesh , Kumari Muskan , Deepak Fnu , Raj Kapil , Ali Azzam
Published: December 2024

Background

Labor induction is a common obstetric intervention, increasingly performed worldwide, often using prostaglandins like misoprostol and dinoprostone.

Objective

This study aims to compare the effectiveness and safety of intravaginal misoprostol versus dinoprostone for inducing labor, examining their impact on various maternal and neonatal outcomes.

Methods

A systematic review and meta-analysis were conducted using four databases—PubMed, Google Scholar, EBSCO, and the Cochrane Library—from January 2000 to April 2023. We included randomized controlled trials (RCTs) involving singleton pregnancies at term (37–42 weeks) with unfavorable cervices, where intravaginal misoprostol was compared to dinoprostone. Key outcomes evaluated for effectiveness included vaginal delivery within 24 h, overall vaginal delivery rate, and need for oxytocin augmentation. Safety outcomes assessed were tachysystole, uterine hyperstimulation, abnormal cardiotocography, NICU admissions, cesarean delivery, and APGAR scores. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects model in Review Manager (RevMan) version 5.4.1.

Results

Eight RCTs with a total of 1,801 participants (937 in the misoprostol group and 864 in the dinoprostone group) met the inclusion criteria. Misoprostol required a significantly less oxytocin augmentation than dinoprostone [RR = 0.83; 95% CI (0.71, 0.97), p = 0.02]. Other outcomes, including rates of cesarean delivery, uterine tachysystole, hyperstimulation, and NICU admissions, showed no significant differences between the two groups, indicating comparable safety and efficacy profiles.

Conclusion

This meta-analysis demonstrates that intravaginal misoprostol is an effective and safe alternative to dinoprostone for labor induction at term. Misoprostol achieved comparable efficacy and safety outcomes while requiring less oxytocin augmentation, supporting its potential as a practical induction agent in clinical settings.
The impact of zinc pre-exposure on ciprofloxacin resistance development in E. coli
Authors: Suprenant Mark P. , Ching Carly , Gross Neila , Sutradhar Indorica , Anderson Jessica E. , El Sherif Nourhan , Zaman Muhammad H.
Published: December 2024

Introduction

Antimicrobial resistance (AMR) is a global health crisis that is predicted to worsen in the coming years. While improper antibiotic usage is an established driver, less is known about the impact of other endogenous and exogeneous environmental factors, such as metals, on AMR. One metal of interest is zinc as it is often used as a supplement for diarrhea treatment prior to antibiotics.

Materials and methods

Here, we probed the impact of zinc on ciprofloxacin resistance in E. coli via altering zinc exposure time and order. We found that the order of exposure to zinc impacted resistance development. These impacted samples then underwent whole genome and RNA sequencing analysis.

Results

Zinc pre-exposure led to a subsequent acceleration of ciprofloxacin resistance. Specifically, we saw that 5 days of zinc pre-exposure led samples to have nearly a 4× and 3× higher MIC after 2 and 3 days of subinhibitory antibiotics, respectively, compared to samples not pre-exposed to zinc, but only if ciprofloxacin exposure happened in the absence of zinc. Additionally, for samples that underwent the same pre-exposure treatment, those exposed to a combination of zinc and ciprofloxacin saw delayed ciprofloxacin resistance compared to those exposed to only ciprofloxacin resulting in up to a 5× lower MIC within the first 2 days of antibiotic exposure. We did not observe any genetic changes or changes in antibiotic tolerance in cells after zinc pre-exposure, suggesting changes in gene expression may underlie these phenotypes.

Discussion

These results highlight the need to reexamine the role of zinc, and supplements more broadly, on antibiotic resistance evolution.
Investigating the crosstalk between ABCC4 and ABCC5 in 3T3-L1 adipocyte differentiation
Authors: Laddha Ankit P. , Wahane Aniket , Bahal Raman , Manautou José E.
Published: December 2024

Introduction

The plasma membrane-bound protein, multi-drug resistance-associated protein 4 (MRP4/ABCC4), has gained attention for its pivotal role in facilitating the efflux of a wide range of endogenous and xenobiotic molecules. Its significance in adipogenesis and fatty acid metabolism has been brought to light by recent studies. Notably, research on ABCC4 knockout (ABCC4−/−) mice has established a link between the absence of ABCC4 and the development of obesity and diabetes. Nevertheless, the specific contribution of ABCC4 within adipose tissue remains largely unexplored.

Methods

To address this gap, we conducted a study to elucidate the role of the ABCC4 transporter in mature adipocytes, using siRNA constructs to silence its gene function.

Results

The successful knockdown of ABCC4 significantly altered lipid status and adipogenic gene expression in mature 3T3-L1 adipocytes. Intriguingly, this knockdown also altered the gene expression patterns of other ABCC transporter family members in 3T3-L1 cells. The downregulation of ABCC5 expression was particularly noteworthy, suggesting potential crosstalk between ABCC transporters in mature adipocytes. Additionally, knocking down ABCC5 resulted in significantly higher adipogenic and lipogenic gene expression levels. Oil Red O staining confirmed increased lipid accumulation following the knockdown of ABCC4 and ABCC5. Surprisingly, the simultaneous knockdown of both transporters did not show a cumulative effect on adipogenesis, rather it led to higher levels of intracellular cAMP and extracellular prostaglandin metabolite, both of which are essential signaling molecules in adipogenesis.

Conclusion

These results highlight the complex interplay between ABCC4 and ABCC5 transporters in adipocyte function and suggest their individual contributions toward obesity and related disorders.
Elevated HIF-1α levels in maintenance hemodialysis patients: a potential link to increased cognitive impairment risk
Authors: Guo Lan , Jia Caiyun , Luo Ke , Liang Juanrong , Wang Lijun , Hui Tianli
Published: December 2024

Introduction

In China, an increasing number of patients with end-stage renal disease are undergoing hemodialysis treatment. While this treatment yields relatively positive outcomes, the prevalence of cognitive impairment in patients receiving maintenance hemodialysis ranges from 24 to 80%, which is significantly higher than the general population.

Method

In this retrospective study, a total of 120 patients with kidney disease undergoing maintenance hemodialysis (MHD) were enrolled. The cognitive status of these patients was assessed using the C-MoCA score, which allowed categorization into two groups: the no cognitive impairment (NCI) group and the cognitive impairment (CI) group. Relevant clinical data, laboratory test results, as well as HIF-1α levels, were collected and analyzed to determine their relationship with the cognitive status of the patients.

Results

In this study, a total of 45 patients (37.5%) developed CI, and their C-MoCA scores were significantly lower (21.6 ± 2.43) compared to patients in the NCI group (27.56 ± 1.48) (P < 0.001). The CI group was characterized by older age, lower levels of education, as well as lower levels of serum total bilirubin, serum total protein (TP), albumin, serum creatinine, and serum phosphorus in comparison to the NCI group. Additionally, CI patients exhibited higher levels of HIF-1α, received fewer monthly hemodiafiltration or hemoperfusion treatments, and had a lower rate of rosacastat treatment. Furthermore, univariate and multivariate logistic regression analyses demonstrated that older age (OR = 11.266 [95% CI: 2.775–45.747], P = 0.001) and higher HIF-1α (OR = 20.654 [4.831–88.298], P < 0.001) increased the risk of developing CI, while higher educational attainment reduced the risk of developing CI (> 12 years, OR = 0.004 [95% CI: 0.016–0.619], P≤0.001; 6–12 years, OR = 0.099 [95% CI: 0.000–0.049], P = 0.013).

Discussion

Cognitive impairment in patients undergoing maintenance hemodialysis (MHD) was found to be associated with older age, lower level of education, and higher HIF-1α levels. These factors should be taken into consideration by clinicians to monitor the cognitive status of MHD patients.
The impact of surgery with general anesthesia on cognitive function and putamen volume: a cross-sectional study among older adults
Authors: Jiang Jianjun , Zhang Zhuyun , Zheng Hong , Lu Jian , Li Wei
Published: December 2024

Background

Previous studies have shown that surgery under general anesthesia may diminish cognitive function; however, the proposed mechanisms need further elucidation. The purpose of the current study was twofold: (1) to compare overall and domain-specific differences in cognitive function between the surgery under general anesthesia group and the control group, and (2) to investigate the possible mechanisms of surgery under general anesthesia affecting cognitive function, using T1-structural magnetic resonance imaging.

Methods

A total of 194 older adults were included in this study. Patients were divided into a surgery under general anesthesia group (n = 92) and a control group (n = 104). The two groups were matched for age, sex, and educational level. All participants underwent clinical evaluation, neuropsychological testing, blood biochemistry analysis, and T1 phase structural magnetic resonance imaging.

Results

We found that older adults with a history of surgery under general anesthesia had lower Montreal Cognitive Assessment (MoCA) scores and smaller right putamen volumes (p < 0.05). Linear regression analysis (mediation model) indicated that surgery under general anesthesia affected MoCA scores by diminishing the volume of the right putamen (B = 1.360, p = 0.030).

Conclusion

We found evidence that older adults who underwent surgery under general anesthesia had poorer cognitive function, which may have been caused by an apoptotic or otherwise toxic effect of anesthetic drugs on the volume of the right putamen.
Prevalence of high-risk group for obstructive sleep apnea using the STOP-Bang questionnaire and its association with cardiovascular morbidity
Authors: Kang Jieun , Koo Hyeon-Kyoung , Kang Hyung Koo , Seo Woo Jung , Kang Jiyeon , Kim Jinseob
Published: December 2024

Objectives

Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder, yet many cases remain undiagnosed. The STOP-Bang questionnaire was developed to identify individuals at high risk of OSA. We aimed to investigate the prevalence of individuals with suspected OSA using the STOP-Bang risk stratification in the general population of South Korea. Additionally, we determined if the STOP-Bang risk stratification independently predicts cardiovascular morbidity.

Methods

Data from the eighth Korea National Health and Nutrition Examination Survey (2019–2020) were used. Participants aged ≥40 with complete data for STOP-Bang questionnaire were included. A STOP-Bang score of ≥5 classified individuals as high-risk whereas scores of 3–4 and less than 3 classified them as intermediate- and low-risk, respectively. The association between the high-risk group and cardiovascular morbidity was analyzed using complex sample logistic regression.

Results

Among the 6,630 participants included, approximately 6.7% were classified as high-risk based on the STOP-Bang questionnaire. The prevalence of diagnosed OSA in the high-risk group was 4.0%. The high-risk group showed a significantly higher prevalence of cardiovascular morbidity (11.9%) compared to those in the low- and intermediate-risk groups (3.0 and 8.1%, respectively). After adjusting for variables associated with cardiovascular risk, the high-risk group remained an independent predictor of increased likelihood of cardiovascular morbidity compared to the low-risk group (odds ratio, 2.05; p = 0.002). When stratified by sex, STOP-Bang high-risk was significantly associated with cardiovascular morbidity in men; however, the same trend was not observed in women.

Conclusion

We found a significant proportion of individuals at high risk of OSA is likely to remain undiagnosed in the general population of South Korea. The high-risk group demonstrated a higher burden of cardiovascular morbidity, and the STOP-Bang high-risk group was an independent predictor of cardiovascular morbidity.
Machine learning based algorithms for virtual early detection and screening of neurodegenerative and neurocognitive disorders: a systematic-review
Authors: Yousefi Milad , Akhbari Matin , Mohamadi Zhina , Karami Shaghayegh , Dasoomi Hediyeh , Atabi Alireza , Sarkeshikian Seyed Amirali , Abdoullahi Dehaki Mahdi , Bayati Hesam , Mashayekhi Negin , Varmazyar Shirin , Rahimian Zahra , Asadi Anar Mahsa , Shafiei Daniel , Mohebbi Alireza
Published: December 2024

Background and aim

Neurodegenerative disorders (e.g., Alzheimer’s, Parkinson’s) lead to neuronal loss; neurocognitive disorders (e.g., delirium, dementia) show cognitive decline. Early detection is crucial for effective management. Machine learning aids in more precise disease identification, potentially transforming healthcare. This comprehensive systematic review discusses how machine learning (ML), can enhance early detection of these disorders, surpassing traditional diagnostics’ constraints.

Methods

In this review, databases were examined up to August 15th, 2023, for ML data on neurodegenerative and neurocognitive diseases using PubMed, Scopus, Google Scholar, and Web of Science. Two investigators used the RAYYAN intelligence tool for systematic reviews to conduct the screening. Six blinded reviewers reviewed titles/abstracts. Cochrane risk of bias tool was used for quality assessment.

Results

Our search found 7,069 research studies, of which 1,365 items were duplicates and thus removed. Four thousand three hundred and thirty four studies were screened, and 108 articles met the criteria for inclusion after preprocessing. Twelve ML algorithms were observed for dementia, showing promise in early detection. Eighteen ML algorithms were identified for Parkinson’s, each effective in detection and diagnosis. Studies emphasized that ML algorithms are necessary for Alzheimer’s to be successful. Fourteen ML algorithms were discovered for mild cognitive impairment, with LASSO logistic regression being the only one with unpromising results.

Conclusion

This review emphasizes the pressing necessity of integrating verified digital health resources into conventional medical practice. This integration may signify a new era in the early detection of neurodegenerative and neurocognitive illnesses, potentially changing the course of these conditions for millions globally. This study showcases specific and statistically significant findings to illustrate the progress in the area and the prospective influence of these advancements on the global management of neurocognitive and neurodegenerative illnesses.
Analysis of clinical characteristics and predictive model for effective treatment of tinnitus in patients with transient compound sound therapy
Authors: Yuan Hao , Ma Peng-Wei , Chen Jia-Wei , Wang Wei-Long , Gao Wei , Lu Pei-Heng , Ding Xue-Rui , Lun Yu-Qiang , Wang Zi , Lu Lian-Jun
Published: December 2024

Purpose

This study explored the clinical characteristics of patients with tinnitus who responded to sound therapy and established a predictive model to evaluate the effectiveness of this therapy according to the clinical characteristics.

Methods

A retrospective analysis was performed on 991 subjective tinnitus patients who received compound sound therapy in the Department of Otolaryngology of the local hospital from November 2019 to January 2022.

Results

We found that tinnitus patients with different therapeutic effects had significant differences in the tinnitus side (p = 0.007), tone loudness distortion feedback test (FBT) (p = 0.000), residual inhibition test (RIT) (p = 0.000), tinnitus frequency (p = 0.012) and sensation level (p = 0.023). The corresponding variables were screened by univariate logistic regression, and the selected variables were analyzed using multivariate logistic regression. The results showed that FBT (p = 0.003), RIT (p = 0.000) and tinnitus frequency (p = 0.029) were independent risk factors affecting the efficacy of compound sound therapy. A predictive model and nomogram for the efficacy of compound sound therapy for tinnitus were constructed based on independent risk factors. The area under the curve (AUC) of the model constructed in this study was 0.766 (95% CI = 0.725–0.807), indicating a certain prediction ability. The calibration curve revealed that the predicted results were in good agreement with the actual results.

Conclusion

The model can predict the prognosis of tinnitus in patients receiving compound sound therapy and help otolaryngologists make the best clinical decisions regarding tinnitus treatment.
Advancing working memory research through cortico-cortical transcranial magnetic stimulation
Authors: Phylactou Phivos , Konstantinou Nikos , Ester Edward F.
Published: December 2024

The neural underpinnings of working memory (WM) have been of continuous scientific interest for decades. As the understanding of WM progresses and new theories, such as the distributed view of WM, develop, the need to advance the methods used to study WM also arises. This perspective discusses how building from the state-of-the-art in the field of transcranial magnetic stimulation (TMS), and utilising cortico-cortical TMS, may pave the way for testing some of the predictions proposed by the distributed WM view. Further, after briefly discussing current barriers that need to be overcome for implementing cortico-cortical TMS for WM research, examples of how cortico-cortical TMS may be employed in the context of WM research are provided, guided by the ongoing debate on the sensory recruitment framework.
Cognitive and cortical network alterations in pediatric temporal lobe space-occupying lesions: an fMRI study
Authors: Hu Bohan , Guan Xueyi , Zhai Huina , Han Xu , Hu Cuiling , Gong Jian
Published: December 2024

Background

Temporal lobe mass lesions are the most common intracranial space-occupying lesions in children, among various brain lobes. The temporal lobe is critically involved in higher cognitive functions, and surgical interventions often risk causing damage to these functions. If necessary interventions and prehabilitation can be conducted preoperatively, it might be possible to achieve a larger extent of lesion resection with minimal cognitive impairment. However, research in this area has been relatively limited in the past. Our study aims to fill this gap.

Methods

We enrolled 15 children with temporal lobe mass lesions and 15 age- and gender-matched healthy children as controls. All participants underwent cognitive assessments and functional MRI scans. The cognitive testing data and functional MRI data were then analyzed and compared between the two groups.

Results

Our findings suggest that children with temporal lobe mass lesions primarily exhibit impairments in working memory and sustained attention. Multiple brain network indices were altered in the affected children, with the most prominent change being hyperactivation of the default mode network (DMN). This hyperactivation was correlated with cognitive impairments, indicating that the overactivation of the DMN might represent an inefficient compensatory mechanism within the brain’s networks.

Conclusion

Compared to healthy children, those with temporal lobe mass lesions experience deficits in working memory and sustained attention, and the hyperactivation of the DMN may be the underlying network mechanism driving these cognitive impairments. Our research offers a unique and clinically valuable reference for future studies on preoperative interventions and prehabilitation in this population.
Myeloid antigen-presenting cells in neurodegenerative diseases: a focus on classical and non-classical MHC molecules
Authors: Afify Reham , Lipsius Katherine , Wyatt-Johnson Season J. , Brutkiewicz Randy R.
Published: December 2024

In recent years, increasing evidence has highlighted the critical role of myeloid cells, specifically those that present antigen (APCs) in health and disease. These shape the progression and development of neurodegenerative disorders, where considerable interplay between the immune system and neurons influences the course of disease pathogenesis. Antigen-presenting myeloid cells display different classes of major histocompatibility complex (MHC) and MHC-like proteins on their surface for presenting various types of antigens to a wide variety of T cells. While most studies focus on the role of myeloid MHC class I and II molecules in health and disease, there is still much that remains unknown about non-polymorphic MHC-like molecules such as CD1d and MR1. Thus, in this review, we will summarize the recent findings regarding the contributions of both classical and non-classical MHC molecules, particularly on myeloid microglial APCs, in neurodegenerative diseases. This will offer a better understanding of altered mechanisms that may pave the way for the development of novel therapeutic strategies targeting immune cell-MHC interactions, to mitigate neurodegeneration and its associated pathology.
Mechanisms of microbiota-gut-brain axis communication in anxiety disorders
Authors: Jiang Min , Kang Li , Wang Ya-Li , Zhou Bin , Li Hong-Yi , Yan Qiang , Liu Zhi-Gang
Published: December 2024

Anxiety disorders, prevalent mental health conditions, receive significant attention globally due to their intricate etiology and the suboptimal effectiveness of existing therapies. Research is increasingly recognizing that the genesis of anxiety involves not only neurochemical brain alterations but also changes in gut microbiota. The microbiota-gut-brain axis (MGBA), serving as a bidirectional communication pathway between the gut microbiota and the central nervous system (CNS), is at the forefront of novel approaches to deciphering the complex pathophysiology of anxiety disorders. This review scrutinizes the role and recent advancements in the MGBA concerning anxiety disorders through a review of the literature, emphasizing mechanisms via neural signals, endocrine pathways, and immune responses. The evidence robustly supports the critical influence of MGBA in both the development and progression of these disorders. Furthermore, this discussion explores potential therapeutic avenues stemming from these insights, alongside the challenges and issues present in this realm. Collectively, our findings aim to enhance understanding of the pathological mechanisms and foster improved preventative and therapeutic strategies for anxiety disorders.
Central mechanisms of muscle tone regulation: implications for pain and performance
Authors: Cacciatore Timothy W. , Anderson David I. , Cohen Rajal G.
Published: December 2024

Muscle tone represents a foundational property of the motor system with the potential to impact musculoskeletal pain and motor performance. Muscle tone is involuntary, dynamically adaptive, interconnected across the body, sensitive to postural demands, and distinct from voluntary control. Research has historically focused on pathological tone, peripheral regulation, and contributions from passive tissues, without consideration of the neural regulation of active tone and its consequences, particularly for neurologically healthy individuals. Indeed, simplistic models based on the stretch reflex, which neglect the central regulation of tone, are still perpetuated today. Recent advances regarding tone are dispersed across different literatures, including animal physiology, pain science, motor control, neurology, and child development. This paper brings together diverse areas of research to construct a conceptual model of the neuroscience underlying active muscle tone. It highlights how multiple tonic drive networks tune the excitability of complex spinal feedback circuits in concert with various sources of sensory feedback and in relation to postural demands, gravity, and arousal levels. The paper also reveals how tonic muscle activity and excitability are disrupted in people with musculoskeletal pain and how tone disorders can lead to marked pain and motor impairment. The paper presents evidence that integrative somatic methods address the central regulation of tone and discusses potential mechanisms and implications for tone rehabilitation to improve pain and performance.
Entacapone alleviates muscle atrophy by modulating oxidative stress, proteolysis, and lipid aggregation in multiple mice models
Authors: Zeng Rong , Xu Hanbing , Wu Mingzheng , Zhou Xianlong , Lei Pan , Yu Jiangtao , Wang Pinyi , Ma Haoli , Zhao Yan
Published: December 2024

Background

Skeletal muscle atrophy significantly affects quality of life and has socio-economic and health implications. This study evaluates the effects of entacapone (ENT) on skeletal muscle atrophy linked with oxidative stress and proteolysis.

Methods

C2C12 cells were treated with dexamethasone (Dex) to simulate muscle atrophy. Four murine models were employed: diaphragm atrophy from mechanical ventilation, Dex-induced atrophy, lipopolysaccharide (LPS)-induced atrophy, and hyperlipidemia-induced atrophy. Each model utilized entacapone (10 mg/kg), with sample sizes: Control (9), MV (11), MV + ENT (5) for diaphragm atrophy; Control (4), Dex (4), Dex + ENT (5) for Dex model; Control (4), LPS (4), LPS + ENT (5) for LPS model; and similar for hyperlipidemia. Measurements included muscle strength, myofiber cross-sectional area (CSA), proteolysis, oxidative stress markers [uperoxide dismutase 1 (SOD1), uperoxide dismutase 2 (SOD2), 4-hydroxynonenal (4-HNE)], and lipid levels.

Results

Our findings confirm Dex-induced muscle atrophy, evidenced by increased expression of muscle atrophy-associated proteins, including Atrogin-1 and Murf-1, along with decreased diameter of C2C12 myotubes. Atrogin-1 levels rose by 660.6% (p < 0.05) in the Dex group compared to control, while entacapone reduced Atrogin-1 by 84.4% (p < 0.05). Similarly, Murf-1 levels increased by 365% (p < 0.05) in the Dex group and were decreased by 89.5% (p < 0.05) with entacapone. Dexamethasone exposure induces oxidative stress, evidenced by the upregulation of oxidative stress-related proteins Sod1, Sod2, and 4-HNE. Entacapone significantly reduced the levels of these oxidative stress markers, enhancing GSH-PX content by 385.6% (p < 0.05) compared to the Dex-treated group. Additionally, ENT effectively reduced the Dex-induced increase in MDA content by 63.98% (p < 0.05). Furthermore, entacapone effectively prevents the decline in diaphragm muscle strength and myofiber CSA in mice. It also mitigates diaphragm oxidative stress and protein hydrolysis. Additionally, entacapone exhibits the ability to attenuate lipid accumulation in the gastrocnemius muscle of hyperlipidemic mice and alleviate the reduction in muscle fiber CSA.

Conclusion

Our findings suggest that entacapone is a promising therapeutic candidate for muscle atrophy, functioning through the reduction of oxidative stress, proteolysis, and lipid aggregation. Future research should explore the underlying mechanisms and potential clinical applications of entacapone in muscle-wasting conditions.
Hwa-byung (anger syndrome) as a risk factor for suicidal ideation in MZ generation: a survey study in South Korea
Authors: Kwon Chan-Young
Published: December 2024

Introduction

Suicide is a critical global public health issue, with South Korea exhibiting the highest suicide rate among OECD countries at 24.1 per 100,000 people in 2020. This study focuses on suicidal ideation (SI) within South Korea’s Millennials and Generation Z (Generation MZ) by examining the impact of anger and hwa-byung (HB), a culture-bound anger syndrome.

Methods

The online survey was conducted between June 7 and 12, 2024. The inclusion criteria for this study were the following: (1) generation MZ (i.e., those born between 1980 and 2005); (2) those without a history of mood disorders (i.e., depressive disorders or bipolar disorder); (3) those of Korean nationality and residing in South Korea. Demographic variables and clinical variables including SI, HB, and depression were investigated. The chi-square test or t-test was used to compare the differences between the SI and non-SI groups. Additionally, binary logistic regression analysis was performed to analyze factors associated with the presence of SI. Finally, Pearson’s correlation coefficients were calculated to explore HB symptoms that were highly associated with SI.

Results

Total 457 participants were included. The survey revealed an overall prevalence of SI of 38.07%, with 18.82% reporting “much” or more SI and 4.81% reporting “very much” SI. Significant differences were found between the SI and non-SI groups in HB symptoms, depression, anxiety, perceived stress, trait anger, state anger, anger-in, and anger-out (all p < 0.001). Logistic regression analysis identified HB symptoms (odds ratio [OR], 1.05; 95% CI, 1.00–1.11; p = 0.050), depression (OR, 1.41; 95% CI, 1.23–1.62; p < 0.001), and state anger (OR, 1.14; 95% CI, 1.05–1.24; p = 0.002) as significant factors for SI. The mediating factors confirmed the direct and indirect effects of HB symptoms on the presence of SI. Pearson’s correlation coefficients between HB symptoms and SI severity ranged from 0.241 to 0.536, with physical symptoms, such as heat sensation and chest pressure, showing high correlations (0.426 to 0.476).

Conclusion

These findings highlight the need for mental health policies that integrate Korean medical approaches into suicide prevention. Future research should confirm these results using larger, nationally representative samples to improve generalizability and further explore HB and suicidality in diverse populations.
Gross anatomical features of the insular cortex in affective disorders
Authors: Takahashi Tsutomu , Sasabayashi Daiki , Yücel Murat , Whittle Sarah , Suzuki Michio , Pantelis Christos , Malhi Gin S. , Allen Nicholas B.
Published: December 2024

Introduction

The number of insular gyri is elevated in patients with schizophrenia. Thus, it has potential as a marker of early neurodevelopmental abnormalities. However, currently it remains unclear whether patients with other neuropsychiatric disorders, such as affective disorders, also have this gross brain anatomical feature.

Materials and methods

The macroscopic features of the insular cortex in 26 patients with bipolar disorder (BD), 56 with major depressive disorder (MDD), and control subjects for each clinical group (24 for BD and 33 for MDD) were assessed using magnetic resonance imaging.

Results

The number of short insular gyri was higher in BD patients than in matched controls bilaterally with well-developed accessory and middle short gyri. Furthermore, the left middle short gyrus was more developed in MDD patients than in matched controls, and was weakly associated with the severity of depressive symptoms.

Discussion

The present results indicate that changes in the gross morphology of the insular cortex in BD and MDD is a potential vulnerability factor associated with their neurodevelopmental pathologies, and may also contribute to the severity of symptoms in MDD.
Explain the behavior change and maintenance in diabetic patients using MTM-HAPA framework
Authors: Wu Yibo , Yu Zhenjie , Yin Xiaoqiu , Li Yimiao , Jiang Yang , Liu Gongli , Sun Xinying
Published: December 2024

Objectives

The aim of the study was to to uncover the factors influencing the initiation and maintenance of health behaviors indiabetes mellitus (DM) patients, utilizing baseline data from a randomized controlled trial to construct a structural equation model based on the Multi-Theory Model (MTM) and Health Action Process Approach (HAPA) scales.

Methods

The study recruited participants with type 2 diabetes, aged between 18 and 75 years, from 45 distinct locations in Beijing, China.Patients [N = 406, n = 232 (57.1%) females, n = 232 (42.9%) males; Mean (SD) age = 56.7(10.9)] completed self-reported questionnaire about constructs from integrated theories concerning health behavior. To test the associations between the variables, structural equation modeling with latent variables was employed. Based on the path coefficients of Structural Equation Modeling(SEM), we verified all the hypotheses.

Results

Disadvantages, Advantages, Self-efficacy for Initiating Behavior, and Changes in Physical Environment are all prove to have an effect on intention, with the effect of Disadvantages being negative. Intention positively influenced Action Planning and Coping Planning, both of which in turn significantly predicted Initiation of Behavior Change. Practice for change, Emotional Transformation, Changes in Social Environment, and Self-efficacy for Sustaining Behavior were all affected by Outcome Expectancies and Risk Perception positively. Meanwhile, Practice for change, Emotional Transformation, Changes in Social Environment and Self-efficacy for Sustaining Behavior- would have a significant predictive effect on Maintenance of Behavioral Change.

Conclusion

The empirical evidence from this study robustly validates the majority of its theoretical constructs, affirming that MTM-HAPA possess significant explanatory capability in delineating the factors that underpin both the Maintenance of health-related behaviors and the Initiation of Behavior Changes in individuals suffering from DM.
The mediating role of rumination in the relationship between negative cognitive styles and depression among pregnant women in Guangzhou, China
Authors: Liang Min , Chen Yu , Liu Yan , Xiong Ribo
Published: December 2024

Backgrounds

Negative cognitive styles (NCSs) have been identified as risk factor for the onset of depression. However, little empirical evidence is available to support its role in psychological disorders in the perinatal period. Moreover, less is known about the underlying mechanism in the relation between NCSs and depression in pregnant women. The purpose of this study was to examine the mediation effect of rumination on the relationship between NCSs and antenatal depression (AD). Specifically, the mediation effects of two subtypes of rumination were tested.

Methods

A cross-sectional study was conducted from February to May 2023 using anonymous online questionnaire among women in their third trimester of pregnancy in the antenatal care clinic of a tertiary hospital. The Edinburgh Postnatal Depression Scale was used to screen antenatal depression. Attributional Style Questionnaire and Ruminative Responses Scale were employed to assess NCSs and rumination respectively. Correlational analysis of the associations between NCSs, rumination, and AD was conducted. Bootstrap mediation analysis and multiple mediation models were applied to investigate whether rumination, and its brooding and reflection components would mediate the relationship between NCSs and AD.

Results

NCSs had a significant positive effect on depression in pregnant women (c=1.45, SE=0.03, p<0.001, 95%CI: 0.92∼1.70). Rumination mediated the relationship between NCSs and depression in pregnant women (point estimate=0.41, 95%CI: 0.13∼0.79, effect size=0.22, K2 = 0.19). Multiple mediation analysis revealed that brooding, instead of reflection, mediated the relationship between NCSs and depression in pregnant women (point estimate=0.41, 95%CI: 0.15∼0.78).

Conclusion

This study provided novel evidence for the role of rumination, specifically its brooding subtype, in shaping the link between NCSs and depression in pregnant women, highlighting potentially useful targets for interventions aimed at preventing the onset of AD.
Impact of accelerated review policy on portfolio planning of vaccine companies
Authors: Liu Guicui , Huang Zhe
Published: December 2024

Background

With the introduction of the accelerated drug review policy in China, the clinical research and development time and the review and approval time of drugs have been shortened accordingly. Especially under the influence of the COVID-19 pandemic, the vaccine formulations released through the accelerated review policy are springing up, and the question of how the accelerated review policy affects the investment portfolio of vaccine enterprises has also attracted more and more attention.

Aims and methods

The article uses mixed-integer linear programming to develop a new model on portfolio planning for vaccine companies based on the accelerated review policy context. The model is constructed using the Gurobi extension class of .NET, and the investment decision is made and simulated by the Gurobi solver to investigate the portfolio planning decision of a vaccine company maximizing the net present value of its vaccine production portfolio with the increase of available capital over a 20-year time horizon.

Results

The NPV under the accelerated review policy is significantly higher than the net present value under the standard review policy when the available capital exceeds RMB 900 million. And the difference between the two of them peaks at RMB 1.87 billion when the available capital is RMB 1.9 billion; break-even occurs about 1.3 years earlier in the accelerated review policy than in the standard review; and when the available capital is the same, firms in the accelerated review policy choose to produce four products earlier and make the decision to invest in facility construction earlier; scenarios in the accelerated review policy are not as sensitive to changes in model parameters as they are in the standard review.

Conclusion

The accelerated review policy is effective in providing incentives for commercialisation. The results of this study will provide an effective reference for vaccine companies to make scientific portfolio planning under the accelerated review policy.
Adverse childhood experiences and 10-year depressive-symptoms trajectories among middle-aged and older adults in China: a population-based cohort study
Authors: Xu Jin , Han Guangxue , Xu Xiulian
Published: December 2024

Background

Adverse childhood experiences (ACEs) influence depressive symptoms. Depressive symptoms were heterogeneous from the perspective of life course.

Objective

To explore the effects of ACEs on the trajectory of depressive symptoms in China.

Participants

The data is from the 5 waves of the China Health and Retirement Longitudinal Study (CHARLS) and the 2014 Life Course Survey of it. A total of 17,106 individuals were included, without the people younger than 45 years.

Methods

We dealt with the missing values using multiple interpolation. The CESD-10 and a 12-item questionnaire was used to assess the depressive symptom and ACEs, respectively. We used group-based trajectory modelling (GBTM) to identify the 10-year depressive-symptoms. Logistic regression models were used to explore associations between the trajectory and the ACEs.

Results

Five depressive-symptom trajectories were identified based on the GBTM analysis (BIC = 540533.61; AIC = 540347.68; n = 17,106). Compared to the participants without depressive symptoms, the older adults who have more adverse childhood experiences have more odds of being in the other four groups, and the more ACEs the older adults experienced, the more likely it is.

Conclusion

The 10-year depressive-symptoms trajectories among middle-aged and older adults in China were different from previous features. The significance of a life-course intervention plan to prevent childhood adversity and the related mental health damage in later life is demonstrated by the long-term influence of ACEs on depressive symptoms.
Navigating the unseen peril: safeguarding medical imaging in the age of AI
Authors: Maertens Alexandra , Brykman Steve , Hartung Thomas , Gafita Andrei , Bai Harrison , Hoelzer David , Skoudis Ed , Paller Channing Judith
Published: December 2024

In response to the increasing significance of artificial intelligence (AI) in healthcare, there has been increased attention – including a Presidential executive order to create an AI Safety Institute – to the potential threats posed by AI. While much attention has been given to the conventional risks AI poses to cybersecurity, and critical infrastructure, here we provide an overview of some unique challenges of AI for the medical community. Above and beyond obvious concerns about vetting algorithms that impact patient care, there are additional subtle yet equally important things to consider: the potential harm AI poses to its own integrity and the broader medical information ecosystem. Recognizing the role of healthcare professionals as both consumers and contributors to AI training data, this article advocates for a proactive approach in understanding and shaping the data that underpins AI systems, emphasizing the need for informed engagement to maximize the benefits of AI while mitigating the risks.
Cultivating the conditions for care: it's all about trust
Authors: Kooijman Allison , Canfield Carolyn
Published: December 2024

This perspective article shares the viewpoints of two long-standing patient safety advocates who have participated first-hand in the evolution of patient engagement in healthcare quality and safety. Their involvement is motivated by a rejection of the common cruelty of institutional betrayal that compounds harm when patient safety fails. The advocates have sought to understand how it can be that fractured trust spreads so predictably after harm, just when it most needs strengthening. Instead, the abandonment of trust upends healthcare values and effectiveness at interpersonal, systemic and structural levels. They argue that authentic care (healthcare that is truly caring) transcends mere service delivery, thus embodying an inviolable commitment to mutual well-being, compassion and generosity. The advocates identify the influence of social determinants, such as culture, identity, and socioeconomic status, as critical to trust formation, where pathogenic vulnerability exacerbates existing inequalities and further impedes trust. The advocates call for a shift from transactional to relational, trust-based interactions that explore the potential for mobilizing restorative justice principles to repair harm and rebuild trust, enabling dialogue, mutual understanding and systemic improvement. Trust, they assert, is born in relationships, not transactions. The bureaucratic, legal and resource constraints that often impair meaningful interactions, also cause moral distress to healthcare providers and poor care quality for patients. They argue that central to the current healthcare crisis is the fundamental need for genuine connection and trust, framing this as both a practical necessity and a confirmation of humanity as intrinsic to healthcare. The advocates envision a future where patient engagement is integral to patient safety to prioritize epistemic justice, mutual respect and compassionate care, to restore healthcare as a cohesive, supportive and deeply human endeavor. They query what contributions a restorative approach could make to centre trust as necessary for cultivating the conditions for care in our healthcare system.