bluuebunny/crossref_metadata_2025 huggingface dataset:
Review of spatial layout planning methods for regional multi-station integration
Authors: Zhou Huiying , Zhang Liting , Yang Yongwen , Li Qifen , Qian Fanyue
Published: December 2024

In order to accelerate the high-quality development of China’s infrastructure, it is not only necessary to ensure the continuation and efficiency improvement of the original infrastructure, but also to promote the layout, implementation, improvement and quality improvement of new infrastructure. As an important part of the energy Internet and new power system, “multi-station integration” plays a role in strengthening digital transformation, intelligent upgrading, integration and innovation support, achieving the nearby integration of resources and the coordination and complementarity of operation, reducing redundant design, so that users, enterprises and industries in the region can reduce costs, energy saving and emission reduction, improve quality and efficiency. By combing the spatial layout planning methods, models and influencing factors of traditional single function station and multi-station integration in the region, the influences of the function station itself and other surrounding infrastructure on the function station are analyzed. Combined with the application scenario, load demand and integration mode of multi-station integration, it is proposed to combine common factors and characteristic factors. The objective evaluation method is introduced to improve the practicability and suitability of the layout location. Finally, the three-layer theoretical framework is proposed to improve and supplement the existing layout principles and methods, so as to provide reference suggestions for the scientific location selection and optimization of regional multi-station integration.
Dendritic cell effector mechanisms and tumor immune microenvironment infiltration define TLR8 modulation and PD-1 blockade
Authors: Ruiz-Torres Daniel A. , Wise Jillian F. , Zhao Brian Yinge , Oliveira-Costa Joao Paulo , Cavallaro Sara , Sadow Peter M. , Fang Jacy , Yilmaz Osman , Patel Amar , Loosbroock Christopher , Sade-Feldman Moshe , Faden Daniel L. , Stott Shannon L.
Published: December 2024

The potent immunostimulatory effects of toll-like receptor 8 (TLR8) agonism in combination with PD-1 blockade have resulted in various preclinical investigations, yet the mechanism of action in humans remains unknown. To decipher the combinatory mode of action of TLR8 agonism and PD-1 blockade, we employed a unique, open-label, phase 1b pre-operative window of opportunity clinical trial (NCT03906526) in head and neck squamous cell carcinoma (HNSCC) patients. Matched pre- and post-treatment tumor biopsies from the same lesion were obtained. We used single-cell RNA sequencing and custom multiplex staining to leverage the unique advantage of same-lesion longitudinal sampling. Patients receiving dual TLR8 agonism and anti-PD-1 blockade exhibited marked upregulation of innate immune effector genes and cytokines, highlighted by increased CLEC9A+ dendritic cell and CLEC7A/SYK expression. This was revealed via comparison with a previous cohort from an anti-PD-1 blockade monotherapy single-cell RNA sequencing study. Furthermore, in dual therapy patients, post-treatment mature dendritic cells increased in adjacency to CD8+ T-cells. Increased tumoral cytotoxic T-lymphocyte densities and expanded CXCL13+CD8+ T-cell populations were observed in responders, with increased tertiary lymphoid structures (TLSs) across all three patients. This study provides key insights into the mode of action of TLR8 agonism and anti-PD-1 blockade immune targeting in HNSCC patients.
Alternative splicing regulation by tumor suppressing subtransferable candidate 4: a pathway to tumor suppression
Authors: Zhao Haiping , Wu Nana , Wei Gaigai , Zhang Huiling , Ren Tingrong , Yi Jingjing , Zhang Yuqi , Wang Zixi , Wang Yihan , Guo Zhihan , Zhang Duanwu
Published: December 2024

Introduction

RNA splicing is a crucial posttranscriptional process that governs gene expression, and defects in alternative splicing contribute to various diseases, including cancer. Tumor suppressing subtransferable candidate 4 (TSSC4) is a known tumor suppressor and has been identified as part of the U5 small nuclear ribonucleoprotein (snRNP), which is involved in tri-snRNP biogenesis. However, the precise role of TSSC4 in regulating alternative splicing and its impact on tumor growth remain unclear.

Methods

To explore the link between splicing modulation and tumor suppression driven by TSSC4, we conducted transcriptome sequencing (RNA-seq) on TSSC4-knockout and wild-type HeLa cells. Additionally, we analyzed alternative splicing and gene expression in various cancer cell lines, including TSSC4-knockout A549 cells and TSSC4-knockdown PANC-1, MDA-MB-231, and MCF-7 cells. Splicing patterns and gene expression profiles were compared between TSSC4-deficient and control cells.

Results

Our RNA-seq analysis revealed that TSSC4 deficiency in HeLa cells results in widespread alterations in splicing patterns and gene expression. Specifically, the loss of TSSC4 led to abnormal alternative splicing events and dysregulation of tumor-associated genes, including several oncogenes. This effect was confirmed across multiple cancer cell lines, highlighting a consistent role of TSSC4 in splicing regulation.

Discussion

These findings demonstrate that TSSC4 plays a crucial role in regulating RNA splicing, particularly in controlling the splicing of many oncogenes. Our results reveal a novel mechanism by which TSSC4 mediates tumor suppression through the modulation of alternative splicing, which could provide implications for understanding TSSC4’s role in cancer biology.
Integrative analysis of PANoptosis-related genes in diabetic retinopathy: machine learning identification and experimental validation
Authors: Chen Han , Chen Enguang , Cao Ting , Feng Feifan , Lin Min , Wang Xuan , Xu Yu
Published: December 2024

Background

Diabetic retinopathy (DR) is a major complication of diabetes, leading to severe vision impairment. Understanding the molecular mechanisms, particularly PANoptosis, underlying DR is crucial for identifying potential biomarkers and therapeutic targets. This study aims to identify differentially expressed PANoptosis-related genes (DE-PRGs) in DR, offering insights into the disease’s pathogenesis and potential diagnostic tools.

Methods

DR datasets were obtained from the Gene Expression Omnibus (GEO) database, while PANoptosis-related genes were sourced from the GeneCards database. Differentially expressed genes (DEGs) were identified using the DESeq2 package, followed by functional enrichment analysis through DAVID and Metascape tools. Three machine learning algorithms—LASSO regression, Random Forest, and SVM-RFE—were employed to identify hub genes. A diagnostic nomogram was constructed and its performance assessed via ROC analysis. The CIBERSORT algorithm analyzed immune cell infiltration. Hub genes were validated through RT-qPCR, Western blotting, immunohistochemistry, and publicly available datasets. Additionally, the impact of FASN and PLSCR3 knockdown on HUVECs behavior was validated through in vitro experiments.

Results

Differential expression analysis identified 1,418 DEGs in the GSE221521 dataset, with 39 overlapping DE-PRGs (29 upregulated, 10 downregulated). Functional enrichment indicated that DE-PRGs are involved in apoptosis, signal transduction, and inflammatory responses, with key pathways such as MAPK and TNF signaling. Machine learning algorithms identified six PANoptosis-related hub genes (BEX2, CASP2, CD36, FASN, OSMR, and PLSCR3) as potential biomarkers. A diagnostic nomogram based on these hub genes showed high diagnostic accuracy. Immune cell infiltration analysis revealed significant differences in immune cell patterns between control and DR groups, especially in Activated CD4 Memory T Cells and Monocytes. Validation confirmed the diagnostic efficiency and expression patterns of the PANoptosis-related hub genes, supported by in vitro and the GSE60436 dataset analysis. Furthermore, experiments demonstrated that knocking down FASN and PLSCR3 impacted HUVECs behavior.

Conclusion

This study provides valuable insights into the molecular mechanisms of DR, particularly highlighting PANoptosis-related pathways, and identifies potential biomarkers and therapeutic targets for the disease.
Neutrophils in oncolytic virus immunotherapy
Authors: Zhou Danya , Zhang Chenglin , Sun Jingyi , Yuan Ming
Published: December 2024

Oncolytic viruses have emerged as a highly promising modality for cancer treatment due to their ability to replicate specifically within tumors, carry therapeutic genes, and modulate the immunosuppressive tumor microenvironment through various mechanisms. Additionally, they show potential synergy with immune checkpoint inhibitors. A study report indicates that from 2000 to 2020, 49.5% of oncolytic viruses were administered intratumorally and 35% intravenously during clinical trials. However, both administration methods face significant challenges, particularly with intravenous delivery, which encounters issues such as non-specific tissue uptake, neutralizing antibody responses, and antiviral effects mediated by various immune cells. Despite extensive research into the antiviral roles of CD8+ T cells and NK cells in oncolytic virus therapy, neutrophils—constituting approximately 50% to 70% of human peripheral blood leukocytes—have received relatively little attention. Neutrophils are the most abundant leukocyte subset in peripheral circulation, known for their phagocytic activity. Beyond their traditional roles in bacterial and fungal infections, emerging literature suggests that neutrophils also play a critical role in the body’s antiviral responses. Given the gaps in understanding the role of neutrophils in oncolytic virus therapy, this article reviews current literature on this topic. It aims to provide a theoretical foundation for developing oncolytic virus-based cancer therapies and enhancing their anti-tumor efficacy in future clinical treatments.
Siglec15 in blood system diseases: from bench to bedside
Authors: Fan Yujia , Sun Liangliang , He Juan , Chen Yuetong , Ma Hongli , Ding Haitao
Published: December 2024

Inhibiting the PD-1/PD-L1 pathway using immunomodulators has demonstrated promising outcomes in clinics. Immunomodulators can effectively target immune checkpoints with a strong preference for the tumor microenvironment (TME). Besides, immunomodulators specifically target the recently discovered inhibitory immune checkpoint, sialic acid-binding immunoglobulin-like lectin (Siglec-15). Distinctive in its molecular composition, Siglec-15 has a unique molecular composition and been shown to be highly prevalent in numerous solid tumor tissues and tumor-associated macrophages (TAMs) in human subjects. Notably, Siglec-15 is up-regulated across various cancer types. As a result, Siglec-15 has attracted significant attention due to its exclusive nature concerning PD-L1 expression, suggesting its role in immune evasion in patients lacking PD-L1. Siglec-15 predominantly appears in certain populations and can promote tumor development by repressing T lymphocyte activation and proliferation, thereby facilitating tumor cell immune escape. Furthermore, Siglec-15 is implicated in osteoclast differentiation and bone remodeling, indicating that it is a promising target for next-generation cancer immunotherapies. Additionally, Siglec-15 can modulate immune responses to microbial infections. The current treatment strategies for hematological conditions predominantly include conventional intensive chemotherapy and transplantation methods. However, emerging immunotherapeutic approaches are increasingly recognized for their overall effectiveness, indicating that specific molecular targets should be identified. The expression of Siglec-15 within tumor cells may indicate a novel pathway for treating hematological malignancies. In this study, the biological attributes, expression patterns, and pathogenic mechanisms of Siglec-15 across various diseases were reviewed. The role of Siglec-15 in the pathogenesis and laboratory diagnosis of hematological disorders was also evaluated.
High fetal risk in pregnancies of myositis patients—a Hungarian cohort study
Authors: Nagy-Vincze Melinda , Szinay Dorottya , Szabó Katalin , Molnár Deliné Sarolta , Balkay László , Béldi Tibor , Griger Zoltán
Published: December 2024

Background

Several systemic autoimmune rheumatic diseases may affect both fetal and maternal outcomes during pregnancy. However, little information is available regarding pregnancy outcomes in women with idiopathic inflammatory myopathy. Previously published articles stated that the activity of maternal disease may worsen pregnancy outcomes. A former multicenter study suggested that anti-Jo1 antibody positivity and joint involvement could distinguish a more vulnerable group regarding pregnancy complications. Our aim was to identify prognostic factors among clinical symptoms at disease onset and auto-antibody profiles for identifying a high-risk group for poor pregnancy outcome.

Methods

The clinical data of the myositis cohort of the Division of Clinical Immunology, University of Debrecen, Hungary, were reviewed retrospectively. IIM diagnoses were made by Bohan and Peter's criteria or European Alliance of Associations for Rheumatology/American College of Rheumatology (EULAR/ACR) criteria. Disease activity was evaluated based on physician opinion. Gynecological definitions were used to evaluate fetal outcomes.

Results

Reviewing clinical data of overall 763 patients (542 women and 221 men) revealed that 5.2% of female patients had pregnancies in the same time or after myositis onset. Among these, 71.4% of the mothers suffered from polymyositis (PM) and 28.6% suffered from dermatomyositis (DM). Their mean age at the time of myositis diagnosis was 25.28 years, and the average interval between myositis diagnosis and first pregnancy was 55.4 months. Maternal complications included preeclampsia in one case and pregnancy-induced myositis in 25% of cases. All cases of pregnancy-induced myositis improved after immunosuppressive treatment. Twenty-eight patients reported 60 pregnancies overall, with multiple pregnancies occurring in 57% of cases. Early or late fetal loss was detected in 41.7% of the pregnancies, and stillbirth occurred in 18.3% of deliveries. Although late fetal loss was observed mainly due to placental insufficiency in patients with anti-Jo1 positivity and complications seemed more frequent in PM cases, logistic regression analysis only confirmed that multiple pregnancies could be an independent risk factor for fetal (p = 0.0112) and interstitial lung disease of maternal complications (p = 0.02).

Conclusion

Internal organ involvement and the number of pregnancies could influence pregnancy outcomes in myositis patients. Patients’ family planning should be well organized and counseled by myositis experts. Prospective, multicenter collaborations are needed to precisely identify high-risk groups and state managing guidelines.
Full-grid bathymetry estimation in the numerical simulation of 8 tidal constituents using an ensemble adjustment Kalman filter-smoothing scheme
Authors: Wu Haowen , Li Wei , Han Guijun , Cao Lige , Cui Xudong , Liang Kangzhuang , Zhou Gongfu , Zheng Qingyu
Published: December 2024

The spatially varying geographic-parameters introduce significant uncertainty into the ocean model. Due to the impracticality of manually tuning spatial varying parameters, data assimilation methods are widely used for geographic-parameter optimization (GPO). Practically, the limited observations do not contain enough information to perform GPO directly on the entire grid. Therefore, techniques are required to reduce the complexity of the parameters. A full-grid GPO scheme based on the ensemble adjustment Kalman filter (EAKF) is developed. Via smoothing the spatial distribution of posterior parameter members, the EAKF-smoothing (EAKF-S) introduces additional spatial correlations among parameters. Meanwhile, the small-scale correlation between the state and the parameters, which exhibit strong pseudo-correlations, is filtered out. A tide model of the Bohai Sea and Yellow Sea, considering 8 principal tidal constituents. is constructed using the Princeton Ocean Model with the generalized coordinate system (POMgcs). The EAKF-S is employed for optimizing the full-grid bathymetry. In twin experiment, based on idealized water level observations, EAKF-S effectively reduced model errors and approximately inverted the “true” bathymetry. After GPO, the lowest mean absolute error of the parameter ensemble is 0.83 m. A series of practical GPO experiments based on synthetic water level observations calculated from NAO.99Jb data are performed. First, the improvement of EAKF-S in accuracy and efficiency over standard EAKF is proven using an M2 tide model. After that, a practical experiment on an 8 constituents tide model is performed. The results show that the forecasting performance of all 8 constituents is improved after GPO, indicating the efficacy of EAKF-S.
Evaluation of the effects of Argo data quality control on global ocean data assimilation systems
Authors: Ishikawa Ichiro , Fujii Yosuke , de Boisseson Eric , Wang Yiguo , Zuo Hao
Published: December 2024

A series of observing system experiments (OSEs) were conducted in order to evaluate the effects of Argo data quality control (QC), by using the three global ocean data assimilation systems. During the experimental period between 2015 and 2020, some Argo floats are affected by the abrupt salinity drifts, which caused spurious increasing trend of the global mean salinity in the reanalyses using the observations with only real-time QC applied. The spurious trend is mitigated by applying the gray list provided by the Argo Global Data Assembly Centres (GDAC), and further reduced by assimilating the delayed-mode Argo data of the Argo GDAC instead of the real-time Argo data. These impacts of the Argo QC are generally consistent among the three ocean data assimilation systems. Further investigations in the JMA’s system show that errors in the analyzed salinity with respect to the delayed-mode Argo data are smaller in the OSE with more rigorous QC, and the spatiotemporal variations in the sea-surface dynamic height are reproduced better. Additionally, QC impacts on the analyzed temperatures are shown not to directly reflect the difference in temperature observations among OSEs, and may be affected by difference in the salinity observations among OSEs through the cross-covariance relationship in the data-assimilation systems.
The current socioeconomic and regulatory landscape of immune effector cell therapies
Authors: Sainatham Chiranjeevi , Yadav Devvrat , Dilli Babu Aravind , Tallapalli Jayanth Reddy , Kanagala Sai Gautham , Filippov Evgenii , Murillo Chavez Franco , Ahmed Nausheen , Lutfi Forat
Published: December 2024

Immune cell effector therapies, including chimeric antigen receptor (CAR)-T cells, T-cell receptor (TCR) T cells, natural killer (NK) cells, and macrophage-based therapies, represent a transformative approach to cancer treatment, harnessing the immune system to target and eradicate malignant cells. CAR-T cell therapy, the most established among these, involves engineering T cells to express CARs specific to cancer cell antigens, showing remarkable efficacy in hematologic malignancies like leukemias, B-cell lymphomas, and multiple myeloma. Similarly, TCR-modified therapies, which reprogram T cells to recognize intracellular tumor antigens presented by major histocompatibility complex (MHC) molecules, offer promise for a range of solid tumors. NK-cell therapies leverage NK cells’ innate cytotoxicity, providing an allogeneic approach that avoids some of the immune-related complications associated with T-cell-based therapies. Macrophage-based therapies, still in early stages of the development, focus on reprogramming macrophages to stimulate an immune response against cancer cells in the tumor microenvironment. Despite their promise, socioeconomic and regulatory challenges hinder the accessibility and scalability of immune cell effector therapies. These treatments are costly, with CAR-T therapies currently exceeding $400,000 per patient, creating significant disparities in access based on socioeconomic status and geographic location. The high manufacturing costs stem from the personalized, labor-intensive processes of harvesting, modifying, and expanding patients’ cells. Moreover, complex logistics for manufacturing and delivering these therapies limit their reach, particularly in low-resource settings. Regulatory pathways further complicate the landscape. In the United States., the Food and Drug Administrations’ (FDA) accelerated approval processes for cell-based therapies facilitate innovation but do not address cost-related barriers. In Europe, the European Medicines Agency (EMA) offers adaptive pathways, yet decentralized reimbursement systems create uneven access across member states. Additionally, differing regulatory standards for manufacturing and quality control worldwide pose hurdles for global harmonization and access. To expand the reach of immune effector cell therapies, a multipronged approach is needed—streamlined regulatory frameworks, policies to reduce treatment costs, and international collaborations to standardize manufacturing. Addressing these socioeconomic and regulatory obstacles is essential to make these life-saving therapies accessible to a broader patient population worldwide. We present a literature review on the current landscape of immune effector cell therapies and barriers of access to currently approved standard of care therapy at various levels.
Renal function assessment in older people: comparative analysis of estimation equation with serum creatinine
Authors: Peruzzo Stefania , Ottaviani Silvia , Tagliafico Luca , Muzyka Mariya , Ponzano Marta , Marelli Cristina , Signori Alessio , Nencioni Alessio , Monacelli Fiammetta
Published: December 2024

Introduction

Age-related changes occurring in the kidney can lead to a reduction in Glomerular Filtration Rate (GFR); especially in older adults with multimorbidity and/or frailty, an accurate evaluation of kidney function is critical. For the estimation of GFR in patients over 70 years, CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) is often used. However, validated equations exist for old-age populations like BIS1 (Berlin Initiative Study 1) and FAS (Full Age Spectrum). Here we aimed to compare the performance of CKD-EPI, MDRD (Modification of Diet in Renal Disease), BIS1, and FAS in assessing eGFR in a population of patients over 70, to evaluate which equations show the most accurate performance in our setting.

Materials and methods

A total of 499 older adults were consecutively recruited in the Orthogeriatric ward and Oncogeriatrics clinic of IRCCS Polyclinic San Martino in Genoa Italy. eGFR was calculated using CKD-EPI, MDRD, BIS1, and FAS, calculating mean, median, standard deviation, and interquartile range. Bland–Altman graphs were used to evaluate how each equation performs with respect to the others and the concordance of the attribution of the KDIGO CKD stage was performed with Cohen’s K constant and chi-squared test.

Results

Patients’ mean age was 82.6 years (± 7.44), and the mean creatinine value was 0.97 (± 0.71) mg/dl. The mean value of eGFR was 70 mL/min with CKD-EPI (± 20.6) and MDRD (± 25.7), 57 mL/min with BIS1 (± 16.7) and FAS (± 19.0), respectively. BIS1 and FAS estimated lower eGFR values than CKD-EPI and MDRD. As age increases, a steady decrease in filtrate value is observed with BIS1 and FAS. MDRD and CDK-EPI do not show the same trend. The performance of the equations at a fixed eGFR value of 30 mL/min is more linear for BIS1 and FAS compared with CKD-EPI and MDRD. Upon evaluation with chi-square, the attribution of KDIGO stage was statistically different among the various equations.

Discussion

An appropriate assessment of renal function is of key clinical relevance to prevent adverse outcomes and risk of drug accumulation in older adults. Our study originally showed that in persons aged more than 70 years old BIS1 is the most accurate formula in calculating eGFR values when only serum creatinine is available.
“Busting the hidden curriculum” a realist and innovative perspective to foster professional behaviors
Authors: Guraya Shaista Salman , Kearney Grainne P. , Doyle Frank , Sadeq Asil , Bensaaud Abdelsalam , Clarke Eric , Harbinson Mark , Ryan Aine , Smyth Mary , Hand Sinead , Boland Fiona , Guraya Salman Yousuf , Harkin Denis W.
Published: December 2024

Contemporary health professions education has long delineated the desired attributes of medical professionalism in the form of standard curricula and their role in forming professional behaviors (PBs) among aspiring doctors. However, existing research has shown the contradictory and powerful role of hidden curriculum (HC) in negatively influencing medical students’ PBs through unspoken or implicit academic, cultural, or social standards and practices. These contrasting messages of formal curricula and HC lead to discordance and incongruence in future healthcare professionals developing professional identity formation. There is little research on PB modifying educational strategies and their determinants that medical schools adopt to bust the impact of HC. Consequently, it is unclear how the right PBs can be influenced, entrenched, and inculcated in undergraduate medical students, especially in their early clinical placements. The lack of such insight highlights a critical gap in the literature, nudging educators to take a realist stance to deal with this problem. Behavior psychology stresses shaping medical students’ values and beliefs as salient mediators that influence intentions to pursue future PBs. Curiosity prevails about what would guide the educational interventions to target this behavior change. To help understand this concept, we present our design-based innovative perspective about PROfessionalism in Partnership for Education Research (PROPER) shaped by pluralistic theoretical models in the context of two European medical schools with diverse medical students, highlighting its non-parochial and transferable nature.
Case report: A case of esophageal small cell carcinoma misdiagnosed as leiomyoma
Authors: Yan Junjun , Xiao Xifeng
Published: December 2024

Primary esophageal small cell carcinoma (PESC) is a rare, extremely aggressive malignancy characterized by rapid growth, early metastasis, and poor prognosis. This study presents a case of early-stage PESC that was initially misdiagnosed as an esophageal leiomyoma, which was observed as a submucosal tumor during gastroscopy. The patient subsequently underwent endoscopic submucosal dissection (ESD), which successfully achieved complete tumor resection. Histopathological analysis later confirmed the diagnosis of small cell carcinoma. Subsequent treatments were recommended; however, the patient declined these options and developed systemic metastases 16 months later, indicating progression to advanced disease and a poor prognosis. This case underscores the imperative to consider PESC in the differential diagnosis of submucosal esophageal lesions, especially when clinical suspicion is elevated, despite its rarity. Additionally, it highlights the challenges associated with the diagnosis and management of submucosal PESC and emphasizes the crucial role of early diagnosis in enhancing patient prognosis and survival rates.
Safety and efficacy of 48-week pegylated interferon-α-2b therapy in patients with hepatitis B virus-related compensated liver cirrhosis: a pilot observational study
Authors: Wang Zehong , Wang Xuanxuan , Zhou Li , Shi Shaoyuan , Hua Yongli , Feng Yinong
Published: December 2024

Background

Pegylated interferon-α (PEG-IFN-α) therapy could decrease hepatitis B surface antigen (HBsAg) and improve long-term prognosis of hepatitis B virus (HBV) infection. However, studies on safety and efficacy of PEG-IFN-α for patients with HBV-related cirrhosis are limited.

Methods

This was a single-center study. Fifty-four patients with HBV-related compensated cirrhosis were enrolled. All patients received subcutaneous injection of PEG-IFN-α-2b 180 μg per week for 48 weeks. The monotherapy of PEG-IFN-α-2b was used for treatment-naïve patients, while addition of PEG-IFN-α-2b to on-going nucleos(t)ide analogs (NAs) was used for NAs-experienced patients. Clinical symptoms, laboratory tests, examination indicators, and adverse events were collected at each observational time point.

Results

Forty-two patients achieved undetectable serum HBV DNA at 48 weeks post-therapy. HBsAg level was significantly reduced at 48 weeks post-therapy (227.2 IU/mL vs. 1,668 IU/mL; p < 0.001), especially in NAs-experienced patients (161.0 IU/mL vs. 1,207 IU/mL; p = 0.005). Three patients achieved HBsAg loss, and two of them obtained HBsAg seroconversion. There were no significant differences in liver stiffness measurement, thickness and length of spleen, or diameter of portal vein between baseline and 48 weeks post-therapy (p > 0.05). The aminotransferase levels were increased, while white blood cells, neutrophils, and platelets counts were decreased during PEG-IFN-α-2b therapy (p < 0.05), especially in treatment-naïve patients. Three patients discontinued PEG-IFN-α-2b therapy due to severe adverse events. No patients suffered with virological breakthrough or progressed to end-stage liver diseases during observational period.

Conclusion

A finite course of PEG-IFN-α-2b therapy was well-tolerated, and reduced HBsAg level without accelerating disease progression in patients with HBV-related compensated cirrhosis.

Clinical trial registration

This trial is a part of ZhuFeng Project (ClinicalTrials.gov, identifier NCT04035837).
A bibliometric analysis of studies on environmental enrichment spanning 1967–2024: patterns and trends over the years
Authors: Singhal Gaurav , Baune Bernhard T.
Published: December 2024

Environmental Enrichment (EE) has received considerable attention for its potential to enhance cognitive and neurobiological outcomes in animal models. This bibliometric analysis offers a comprehensive evaluation of the EE research spanning from 1967 to 2024, utilizing data extracted from Scopus and analyzed through R and VOSviewer. The volume of publications, citation patterns, and collaborations were systematically reviewed, highlighting important contributions and emerging trends within the field of animal research. Core concepts of EE research are mapped, revealing key themes such as neuroplasticity, cognitive function, and behavioral outcomes. A significant increase in EE research is demonstrated, particularly after the year 2000, reflecting growing scientific and public interest in EE paradigms. This analysis provides insights into the global contributions and collaborative networks that have shaped EE studies over time. The role of EE in advancing the understanding of neurobiological, neurodevelopmental, and neurodegenerative processes is underscored. Influential contributors, leading countries, and high-impact journals in the field of EE are identified, offering a valuable resource for researchers seeking to understand or extend the current knowledge base. The strategic selection of keywords and rigorous data curation methods ensure that the findings accurately reflect the most impactful aspects of EE research in animals. This study serves as an essential reference for future explorations and applications of EE across disciplines. By providing a clear and structured overview of the field, this paper aims to serve as a foundation for ongoing and future research initiatives, encouraging more robust investigations and applications of EE to enhance cognitive and neurological health globally.
Significant nocturnal wakefulness after sleep onset in metabolic dysfunction–associated steatotic liver disease
Authors: Schaeffer Sofia , Bogdanovic Andrijana , Hildebrandt Talitha , Flint Emilio , Geng Anne , Pecenko Sylvia , Lussier Paul , Strumberger Michael A. , Meyer Martin , Weber Jakob , Heim Markus H. , Cajochen Christian , Bernsmeier Christine
Published: December 2024

Metabolic dysfunction–associated steatotic liver disease (MASLD) is a multisystemic disease with a multifactorial pathogenesis involving dietary, environmental, and genetic factors. Previous mouse models suggested that circadian misalignment may additionally influence its development as it influences metabolism in diverse organs including the liver. Further, data from sleep questionnaires proved sleep-wake disruption in patients with MASLD. We objectively assessed sleep-wake rhythms in patients with biopsy-proven MASLD (n = 35) and healthy controls (HC, n = 16) using actigraphy 24/7 for 4 weeks. With the aim to re-align sleep rhythms a single standardized sleep hygiene education session was performed after 2 weeks. Actigraphy data revealed that MASLD patients had more awakenings per night (MASLD vs. HC 8.5 vs. 5.5, p = 0.0036), longer wakefulness after sleep onset (MASLD vs. HC 45.4 min vs. 21.3 min, p = 0.0004), and decreased sleep efficiency (MASLD vs. HC 86.5% vs. 92.8%, p = 0.0008) compared with HC despite comparable sleep duration. Patients with MASLD self-reported shorter sleep duration (MASLD vs. HC 6 h vs. 6 h 45 min, p = 0.01) and prolonged sleep latency contributing to poorer sleep quality. Standardized sleep hygiene education did not produce significant changes in sleep parameters. Our findings indicate fragmented nocturnal sleep in patients with MASLD, characterized by increased wakefulness and reduced sleep efficiency, perceived subjectively as shortened sleep duration and delayed onset. A single sleep hygiene education session did not improve sleep parameters.
Patient perspectives on the use of digital medical devices and health data for AI-driven personalised medicine in Parkinson’s Disease
Authors: Paccoud Ivana , Valero Mayca Marín , Marín Laura Carrasco , Bontridder Noémi , Ibrahim Alzhraa , Winkler Jüergen , Fomo Messaline , Sapienza Stefano , Khoury Fouad , Corvol Jean-Christophe , Fröhlich Holger , Klucken Jochen
Published: December 2024

Introduction

Parkinson’s Disease (PD) affects around 8.5 million people currently with numbers expected to rise to 12 million by 2040. PD is characterized by fluctuating motor and non-motor symptoms demanding accurate monitoring. Recent advancements in digital medical devices (DMDs) like wearables and AI offer promise in addressing these needs. However, the successful implementation of DMDs in healthcare relies on patients’ willingness to adopt and engage with these digital tools.

Methods

To understand patient perspectives in individuals with PD, a cross-sectional study was conducted as part of the EU-wide DIGIPD project across France, Spain, and Germany. Multidisciplinary teams including neurodegenerative clinics and patient organizations conducted surveys focusing on (i) sociodemographic information, (ii) use of DMDs (iii) acceptance of using health data (iv) preferences for the DMDs use. We used descriptive statistics to understand the use of DMDs and patient preferences and logistic regression models to identify predictors of willingness to use DMDs and to share health data through DMDs.

Results

In total 333 individuals with PD participated in the study. Findings revealed a high willingness to use DMDs (90.3%) and share personal health data (97.4%,) however this differed across sociodemographic groups and was more notable among older age groups (under 65 = 17.9% vs. over 75 = 39.29%, p = 0.001) and those with higher education levels less willing to accept such use of data (university level = 78.6% vs. 21.43% with secondary level, p = 0.025). Providing instruction on the use of DMDs and receiving feedback on the results of the data collection significantly increased the willingness to use DMDs (OR = 3.57, 95% CI = 1.44–8.89) and (OR = 3.77, 95% CI = 1.01–14.12), respectively.

Conclusion

The study emphasizes the importance of considering patient perspectives for the effective deployment of digital technologies, especially for older and more advanced disease-stage patients who stand to benefit the most.
Comparison of muscle synergies in walking and pedaling: the influence of rotation direction and speed
Authors: Tsuchiya Junko , Momose Kimito , Saito Hiroki , Watanabe Koji , Yamaguchi Tomofumi
Published: December 2024

Background

Understanding the muscle synergies shared between pedaling and walking is crucial for elucidating the mechanisms of human motor control and establishing highly individualized rehabilitation strategies. This study investigated how pedaling direction and speed influence the recruitment of walking-like muscle synergies.

Methods

Twelve healthy male participants pedaled at three speeds (60 RPM, 30 RPM, and 80 RPM) in two rotational directions (forward and backward). Additionally, they completed walking tasks at three different speeds (slow, comfortable, and fast). Surface electromyography (EMG) was recorded on 10 lower limb muscles during movement, and muscle synergies were extracted from each condition using non-negative matrix factorization. The similarities between the muscle synergies during walking and each pedaling condition were examined using cosine similarity.

Results

The results confirmed that the composition of muscle synergies during pedaling varied depending on the rotational direction and speed. Furthermore, one to three muscle synergies, similar to those observed during walking, were recruited in each pedaling condition, with specific synergies dependent on direction and speed. For instance, synergy involving the quadriceps and hip extensors was predominantly observed during pedaling at 30 RPM, regardless of the direction of rotation. Meanwhile, synergy involving the hamstrings was more pronounced during forward pedaling at 60 RPM and backward pedaling at 80 RPM.

Conclusion

These findings suggest that walking-like muscle synergies can be selectively recruited during pedaling, depending on the rotational direction and speed.
Contribution of fish to food and nutrition security in Southern Africa: challenges and opportunities in fish production
Authors: Maulu Sahya , Musuka Confred Godfrey , Molefe Montshwari , Ngoepe Tlou Kevin , Gabriel Ndakalimwe Naftal , Mphande Joseph , Phiri Msumenji , Muhala Valdemiro , Macuiane Messias Alfredo , Ndebele-Murisa Mzime Regina , Hasimuna Oliver Jolezya , Bokhutlo Thethela , Mulumpwa Mexford , Erasmus Victoria Ndinelago , Jere Wilson , Dekesa Chipo Hazel , Mubaya Chipo Plaxedes , Baloi Manecas Francisco , Iitembu Johannes Angala , Siankwilimba Enock , Zhang Lin
Published: December 2024

This study investigated the role of fish in addressing food and nutrition security challenges in Southern Africa, focusing on 10 countries including Angola, Zambia, Malawi, Mozambique, Namibia, Botswana, Zimbabwe, Lesotho, Eswatini, and South Africa. It examined the current state of food and nutrition security, fish production, and fish consumption patterns. Additionally, the study investigated the challenges and opportunities to enhance fish production in these countries thereby enhancing food and nutrition security. The findings revealed persistent challenges such as a high prevalence of food insecurity and malnutrition throughout the region. Fish production is hindered by overexploitation of fishery resources, inadequate fisheries management, susceptibility to climate-related shocks, limited investments in aquaculture, and inadequate access to input supplies such as quality fish seed and feed. Despite these obstacles, opportunities exist to promote sustainable fish production to enhance food security and nutrition. Countries endowed with extensive coastlines and inland waters exhibit significant potential for fishery development, while landlocked nations are increasingly exploring aquaculture as a viable solution. Addressing the challenges in fish production and capitalizing on opportunities requires comprehensive governance, technological innovation, policy interventions, and investment to ensure the sustainability and resilience of the fisheries and aquaculture industries in the region.
Fasting mimicking diet during neo-adjuvant chemotherapy in breast cancer patients: a randomized controlled trial study
Authors: Bahrami Alireza , Haghighi Shirin , Moghani Mona Malekzadeh , Khodakarim Nastaran , Hejazi Ehsan
Published: December 2024

Objective

Preclinical evidences suggests that while fasting can reduce the side effects and toxicity of chemotherapy, it can make cancer cells more susceptible to chemotherapy. This study aimed to examine the effects of fasting mimicking diet (FMD) during neo-adjuvant chemotherapy in breast cancer (BC) patients.

Methods

Forty-four newly diagnosed human epidermal growth factor receptor 2-negative (HER2-negative) patients with BC were randomized equally into two groups (22 each), to receive either a fasting mimicking diet (FMD) or their regular diet for 3 days prior to and during neoadjuvant chemotherapy. This FMD was repeated every 3 weeks for 8 cycles. Efficacy, toxicity, hematologic, metabolic, and inflammatory parameters were measured and compared.

Results

The occurrence of grade III vomiting and neutropenia in the control group was significantly higher than the FMD group (P = <0.001 and p = 0.04 respectively). Erythrocytes (p = 0.01) and neutrophils (p = 0.002) counts were significantly higher in FMD group compared to control group after cycle 8. There was a significant increase in median glucose and median insulin levels (p = 0.01 and p = 0.005, respectively) in the control group between baseline and after cycle 8. While, the median Insulin-like growth factor-1 (IGF1) (p = 0.006) and hs-CRP (p = 0.02) levels were significantly decreased in the FMD group. At the end of study (after cycle 8), the median glucose level was significantly higher in control group (p = 0.008), while the median hs-CRP level was significantly lower in FMD group (p = 0.01). The Miller and Payne pathological response 4/5 (90–100% tumor cell loss) and the radiologically complete or partial response, as measured by MRI or ultrasound before surgery occurred more frequently in FMD group compared to the controls (p = 0.01).

Conclusion

Fasting mimicking diet was well tolerated during chemotherapy and reduced toxicity of chemotherapy and also, had beneficial effects of some metabolic parameters.

Clinical Trial Registration

https://irct.behdasht.gov.ir/user/trial/61386/view.
The relationship between carbohydrate intake and sleep patterns
Authors: Zhao Yan , Guo Hailong
Published: December 2024

Background

A healthy dietary habit may contribute to good sleep quality. The present study investigates the correlation between the quality and quantity of daily carbohydrate consumption and poor sleep patterns.

Methods

The exposures of interest included low-and high-quality carbohydrate consumption and total daily carbohydrate consumption. Subjects were classified into four different carbohydrate consumption patterns: Pattern 1 was characterized by high-quality carbohydrates below the median and low-quality carbohydrates above the median; Pattern 2 included both high-and low-quality carbohydrates below the median; Pattern 3 was defined as high-and low-quality carbohydrates above the median; Pattern 4 referred to high-quality carbohydrates above the median and low-quality carbohydrates below the median. The comprehensive sleep patterns included three different sleep behaviors: sleep duration, daytime sleepiness, and snoring, which were used to score sleep patterns. A score ranging from 0 to 1 was classified as having a healthy sleep pattern, while a score between 2 and 3 showed poor sleep patterns. Survey-weighted multivariable logistic regression analyses were adopted.

Results

In the multivariate analysis, individuals who consumed more high-quality carbohydrates were linked to a decreased likelihood of experiencing poor sleep patterns [odds ratio (OR) 0.71; 95% confidence interval (CI) 0.62–0.81], while increased consumption of low-quality carbohydrates (OR 1.39; 95%CI 1.20–1.61) and total daily carbohydrates (OR 1.31; 95%CI 1.10–1.57) was related to an elevated risk of poor sleep patterns. Participants who adhered to carbohydrate intake pattern 4 exhibited a 36% lower risk of poor sleep patterns than those who followed carbohydrate intake pattern 1 (OR 0.64; 95%CI 0.56–0.74). There was a positive correlation between elevated added sugar consumption and an increased probability of developing poor sleep patterns. In contrast, an elevated intake of whole grains, fruits, or non-starchy vegetables was related to a decreased likelihood of experiencing poor sleep patterns.

Conclusion

The increased consumption of low-quality carbohydrates may heighten the susceptibility to poor sleep patterns, whereas the increased consumption of high-quality carbohydrates may mitigate the risk of developing poor sleep patterns.
Trust in nutrition, subjective norms and urban consumers’ purchase behavior of quinoa products: explanation based on preference heterogeneity
Authors: Wang Chan , Fu Xiaoyan , Li Caixia , Liu Zengjin , Wang Shanshan , Chen Tinggui , Jia Lei
Published: December 2024

Introduction

With the increase of disposable income and the awakening of health consciousness of Chinese residents, higher requirements have been put forward for the nutritional value of food. To meet the market demand and promote the high-quality development of the whole quinoa industry chain, this study aimed to analyze the purchase behavior of quinoa from the aspects of nutritional trust and subjective norms.

Methods

Based on 1,078 micro-survey data from 16 administrative districts in Shanghai, this paper empirically examined the influence of trust in nutrition and subjective norms on consumers’ purchase behavior and willingness to pay of quinoa products, and further investigated the moderating effect of preference heterogeneity.

Results

Results show that 38.22% of respondents have purchased quinoa products. Trust in nutrition and subjective norms can not only promote their purchasing behavior, but also improve consumers’ willingness to pay for quinoa products. The analysis of the moderating effect shows that both the purchase behavior and the willingness to pay are affected by the preference heterogeneity, and the cognitive preference will weaken the positive influence of subjective norms on the purchase behavior, while the nutritional preference of consumers can strengthen the positive influence of trust in nutrition on the willingness to pay.

Discussion

Therefore, this paper suggests that strengthens research and development of products market oriented, implements certification and labeling schemes for nutrition and other properties of products, intensifies publicity and promotion of products to enhancing consumers’ awareness of healthy diet.
Adjuvant sorafenib for hepatocellular carcinoma after radiofrequency ablation versus radiofrequency ablation: analysis of its efficacy and safety
Authors: Junxiao Wang , Rui Liu , Zhenyu Wen , Zejie Sang , Xiang Yang , Mingchao Ding , Hui Xie
Published: December 2024

Objectives

For the treatment of early hepatocellular carcinoma, we compared the efficacy and safety of radiofrequency ablation (RFA) alone and radiofrequency ablation combined with sorafenib (RFA+Sor).

Methods

A total of 164 patients with early HCC were included in the study. There were 87 patients who underwent RFA alone, and 77 patients who underwent RFA+Sor treatment. Overall survival (OS) was the primary endpoint of the study, and recurrence-free survival (RFS) and safety were the secondary endpoints.

Results

According to the RFA group, the RFS rates were 74.7%, 29.9%, and 11.5% at 1, 2, and 3 years, whereas in the RFA+Sor group, the RFS rates were 72.7%, 19.5%, and 11.7% at 1, 2, and 3 years (P>0.05). RFA and RFA+Sor groups had median OS of 35.0 and 41.0 months, respectively (P>0.05). For the RFA and RFA+Sor groups, the median RFS was 17.0 and 16.0 months, respectively (P>0.05). Based on the univariate regression analysis, there was no statistically significant difference between the subgroups (P>0.05). Skin rashes only occurred in the RFA+Sor group, and other adverse effects were not significantly different between the two groups (P>0.05).

Conclusions

Treatment with RFA+Sor treatment did not result in a longer OS than treatment with only RFA, however, the adverse effects of adjuvant Sorafenib were acceptable.