bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune responses in rodent whole eye transplantation: elucidation and preliminary investigations into rejection diagnosis and monitoring
Authors: Li Bing , Wang Yong , Owens Charles R. , Banaee Touka , Chu Charleen T. , Jabbari Kayvon , Lee Anna D. , Khatter Neil J. , Palestine Alan G. , Su An-Jey A. , Huang Christene A. , Washington Kia M. 
Published: January 2025

BackgroundWhole Eye Transplantation (WET) offers potential for vision restoration but is hindered by the complex challenge of immune rejection. Understanding and closely monitoring these immunological responses is crucial for advancing WET. This study delves into the timeline and nature of immune responses in a rodent model of WET without immunosuppression, aiming to elucidate a detailed picture of the immune landscape post-transplantation and establish innovative diagnostic and monitoring methods.MethodsWe employed a multi-faceted approach to analyze immune responses post-WET, including assessments of gross changes in corneal transparency, thickness, and skin condition. Histopathological examinations of both ocular and surrounding skin tissues provided insights into cellular changes, complemented by ocular RT-qPCR for molecular analysis. Serological analysis was employed to quantify cytokines, chemokines, and donor-specific antibodies, aiming to identify potential biomarkers correlating with WET rejection and to validate the presence of antibody-mediated rejection. These methodologies collectively contribute to the development of non-invasive diagnostic and monitoring strategies for WET.ResultsOur study revealed a rapid and acute immune response following WET, characterized by an early innate immune response dominated by complement involvement, and infiltration of neutrophils and monocytes by post-operative day (POD) 2. This was succeeded by an acute T-cell-mediated immune reaction, predominantly involving T helper 1 (Th1) cells and cytotoxic T lymphocytes (CTLs). The presence of donor specific antibody (DSA) and indications of pyroptosis in the early phases of rejection were observed. Notably, the early elevation of serum CXCL10 by POD4, coupled with ocular CD3+ cell infiltration, emerged as a potential early biomarker for WET rejection. Additionally, corneal transparency grading proved effective as a non-invasive monitoring tool.ConclusionThis study offers a first-time comprehensive exploration of immune responses in WET, unveiling rapid and complex rejection mechanisms. The identification of early biomarkers and the development of non-invasive monitoring techniques significantly advance our understanding of WET rejection. Additionally, these findings establish an essential baseline for future research in this evolving field.
Dysfunctional β-cell autophagy induces β-cell stress and enhances islet immunogenicity
Authors: Austin Matthew C. , Muralidharan Charanya , Roy Saptarshi , Crowder Justin J. , Piganelli Jon D. , Linnemann Amelia K. 
Published: January 2025

BackgroundType 1 Diabetes (T1D) is caused by a combination of genetic and environmental factors that trigger autoimmune-mediated destruction of pancreatic β-cells. Defects in β-cell stress response pathways such as autophagy may play an important role in activating and/or exacerbating the immune response in disease development. Previously, we discovered that β-cell autophagy is impaired prior to the onset of T1D, implicating this pathway in T1D pathogenesis.AimsTo assess the role of autophagy in β-cell health and survival, and whether defects in autophagy render islets more immunogenic.MethodsWe knocked out the critical autophagy enzyme, ATG7, in the β-cells of mice (ATG7Δβ-cell) then monitored blood glucose, performed glucose tolerance tests, and evaluated bulk islet mRNA and protein. We also assessed MHC-I expression and presence of CD45+ immune cells in ATG7Δβ-cell islets and evaluated how impaired autophagy affects EndoC-βH1 HLA-I expression under basal and IFNα stimulated conditions. Lastly, we co-cultured ATG7Δβ-cell islet cells with diabetogenic BDC2.5 helper T cells and evaluated T cell activation.ResultsWe found that all ATG7Δβ-cell mice developed diabetes between 11-15 weeks of age. Gene ontology analysis revealed a significant upregulation of pathways involved in inflammatory processes, response to ER stress, and the ER-associated degradation pathway. Interestingly, we also observed upregulation of proteins involved in MHC-I presentation, suggesting that defective β-cell autophagy may alter the immunopeptidome, or antigen repertoire, and enhance β-cell immune visibility. In support of this hypothesis, we observed increased MHC-I expression and CD45+ immune cells in ATG7Δβ-cell islets. We also demonstrate that HLA-I is upregulated in EndoC β-cells when autophagic degradation is inhibited. This effect was observed under both basal and IFNα stimulated conditions. Conversely, a stimulator of lysosome acidification/function, C381, decreased HLA-I expression. Lastly, we showed that in the presence of islet cells with defective autophagy, there is enhanced BDC2.5 T cell activation.ConclusionsOur findings demonstrate that β-cell autophagy is critical to cell survival/function. Defective β-cell autophagy induces ER stress, alters pathways of antigen production, and enhances MHC-I/HLA-I presentation to surveilling immune cells. Overall, our results suggest that defects in autophagy make β-cells more susceptible to immune attack and destruction.
Changes in donor lymphocyte infusion for relapsed patients post-hematopoietic stem cell transplantation: a 30-year single-center experience
Authors: Uchibori Yusuke , Kurosawa Shuhei , Najima Yuho , Haraguchi Kyoko , Sadato Daichi , Hirama Chizuko , Sadaga Yasutaka , Kondo Kaori , Kato Chika , Sakai Satoshi , Kambara Yasuhiro , Ouchi Fumihiko , Shimabukuro Masashi , Jinguji Atsushi , Shingai Naoki , Toya Takashi , Shimizu Hiroaki , Kobayashi Takeshi , Harada Hironori , Harada Yuka , Okuyama Yoshiki , Doki Noriko 
Published: January 2025

IntroductionDonor lymphocyte infusion (DLI) is a therapeutic approach for relapse after hematopoietic stem cell transplantation (HSCT). Despite their reported efficacy, the evolution of DLI practices over time remains underexplored.MethodsThis study provided a comprehensive analysis of DLI strategies and outcomes over 30 years at a single institution. A retrospective analysis was conducted on 75 patients who underwent DLI for disease relapse between April 1994 and March 2024. The primary endpoint was the 3-year overall survival (OS) rate after DLI. Secondary endpoints included the 100-day complete remission (CR) rate and incidence of acute graft-versus-host disease (GVHD).ResultsThe median age at the first DLI was 49 years (range, 20–69 years). The most common underlying diseases in all 75 cases were acute myeloid leukemia (AML, n = 46) and myelodysplastic syndromes (MDS, n = 12). Until 2014, DLI was only performed in patients with AML (n = 14), MDS (n = 2), or chronic myeloid leukemia (n = 5). However, since 2015, patients with various diseases, including lymphoid malignancies, have also undergone DLI. Azacitidine was the most frequently used combination therapy with DLI (n = 34). Regimens including venetoclax and FLT3 inhibitors have been commonly used since 2019 (n = 18). The 3-year OS rate was 29.1% (95% CI, 18.8–40.2%). Factors negatively influencing OS included age ≥50 years and a high or very high refined disease risk index. The 100-day CR rate was 52.1%, and acute GVHD occurred in 25.3% of the patients, with no strong correlation between GVHD incidence and CR achievement. Among 18 patients who underwent three or more DLIs since 2018, 88.9% achieved remission following DLI or second HSCT, with a median follow-up of 949.5 days for survivors.ConclusionThis study highlighted the evolving trends in DLI practices and the diversification of combination therapies. Future research should focus on further validating these findings and optimizing DLI protocols to improve patient outcomes.
Emerging roles of mitochondrial sirtuin SIRT5 in succinylation modification and cancer development
Authors: Ke Zhangmin , Shen Kaikai , Wang Li , Xu Hao , Pan Xia , Qian Zhenjue , Wen Yuting , Lv Tangfeng , Zhang Xiuwei , Song Yong 
Published: January 2025

Succinylation represents an emerging class of post-translational modifications (PTMs), characterized by the enzymatic or non-enzymatic transfer of a negatively charged four-carbon succinyl group to the ϵ-amino group of lysine residues, mediated by succinyl-coenzyme A. Recent studies have highlighted the involvement of succinylation in various diseases, particularly cancer progression. Sirtuin 5 (SIRT5), a member of the sirtuin family, has been extensively studied for its robust desuccinylase activity, alongside its deacetylase function. To date, only a limited number of SIRT5 substrates have been identified. These substrates mediate diverse physiological processes such as glucose oxidation, fatty acid oxidation, ammonia detoxification, reactive oxygen species scavenging, anti-apoptosis, and inflammatory responses. The regulation of these activities can occur through either the same enzymatic activity acting on different substrates or distinct enzymatic activities targeting the same substrate. Aberrant expression of SIRT5 has been closely linked to tumorigenesis and disease progression; however, its role remains controversial. SIRT5 exhibits dual functionalities: it can promote tumor proliferation, metastasis, drug resistance, and metabolic reprogramming, thereby acting as an oncogene; conversely, it can also inhibit tumor cell growth and induce apoptosis, functioning as a tumor suppressor gene. This review aims to provide a comprehensive overview of the current research status of SIRT5. We discuss its structural characteristics and regulatory mechanisms, compare its functions with other sirtuin family members, and elucidate the mechanisms regulating SIRT5 activity. Specifically, we focus on the role of succinylation modification mediated by SIRT5 in tumor progression, highlighting how desuccinylation by SIRT5 modulates tumor development and delineating the underlying mechanisms involved.
Screening semen samples for Zika virus infection: role for serologic and RT-PCR testing
Authors: Ferraz Humberto , Akrami Kevan , de Moraes Laise , Gusmão Lais Cambuí , Coelho Genevieve , Freitas Daniele , Barral-Netto Manoel , Barral Aldina , Boaventura Viviane , Santos Luciane Amorim , Khouri Ricardo 
Published: January 2025

IntroductionZika virus (ZIKV) is primarily transmitted through mosquito bites though may act as a sexually transmitted infection. Men can shed the virus in their semen for extended periods, with reports indicating shedding for up to six months after the initial infection. This poses a concern for couples planning pregnancy, whether through natural or assisted methods due to the risk of congenital Zika disease. Human reproductive clinics typically perform serologic tests to screen for Zika infection.MethodsIn this study, we evaluated semen samples stored in a human reproduction clinic in Salvador, Brazil, during the Zika virus outbreak, using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) technique.Results36 sperm samples from 23 donors were analyzed, including 5 with positive IgG serology for ZIKV and all negative for IgM. Despite these serologic findings, all analyzed samples were negative by RT-qPCR ZIKV.DiscussionDespite the limited number of samples, this study raises further concern that the use of serology may be an unreliable surrogate method to predict the presence of ZIKV in semen.
Effect of perioperative esketamine use on emergency delirium in children undergoing tonsillectomy and adenoidectomy: a systematic review and meta-analysis of randomized controlled trials
Authors: Liu Junfeng , Liu Jinming , Sun Hong , Cheng Xue , Wang Chunhui , Lei Daoyun , Han Chao 
Published: January 2025

BackgroundEmergence delirium(ED) is a common postoperative complication in children undergoing tonsillectomy and adenoidectomy under general anesthesia. There is no high-quality evidence on the relationship between esketamine and ED. The systematic review and meta-analysis was performed to investigate the effect of perioperative esketamine use on ED in children undergoing tonsillectomy and adenoidectomy.MethodWe searched Embase, The Cochrane Library, PubMed, MEDLINE, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang, VIP, and SinoMed from inception to 1 September, 2024. Two evaluators identified randomized controlled trials comparing perioperative use of esketamine with placebo or other drugs in children undergoing tonsillectomy and adenoidectomy. Incidence of ED was the primary outcome of the study. Data synthesis was performed by using Review Manager 5.4 software.ResultsTwenty-three relevant studies involving a total of 1,996 children were identified. Perioperative use of esketamine reduced the incidence of ED in children undergoing tonsillectomy and adenoidectomy (RR = 0.33, 95% CI: [0.25, 0.44], p &lt; 0.00001, I2 = 0%). Scores of ED were lower in the esketamine group than in the control group (SMD = -1.20, 95% CI: [−1.56,-0.84], p &lt; 0.00001, I2 = 88%). Children in the esketamine group have lower postoperative pain scores (SMD = -0.51, 95% CI: [−0.80,-0.39], p &lt; 0.00001, I2 = 74%). Esketamine was also associated with a lower incidence of adverse events (RR = 0.75, 95% CI: [0.57, 0.99], p = 0.04, I2 = 62%). We also found that the use of esketamine reduced the length of stay in the post-anesthetic care unit (PACU) but had no effect on the time to extubation.ConclusionPerioperative use of esketamine could significantly reduce the incidence of ED in children undergoing tonsillectomy and adenoidectomy. However, the optimal dose and timing of esketamine administration for preventing ED remains to be explored.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=558560, PROSPERO: CRD42024558560.
Comparative the efficacy and safety of Gosuranemab, Semorinemab, Tilavonemab, and Zagotenemab in patients with Alzheimer’s disease: a systematic review and network meta-analysis of randomized controlled trials
Authors: Cai Wenting , Zhang Hui , Wu Yan , Yao Yao , Zhang Jinping 
Published: January 2025

ObjectiveThe aim of this study was to compare the efficacy and safety of anti-tau protein monoclonal antibodies for Alzheimer’s disease (AD). Tau protein aggregation, a key pathological feature of AD, is closely associated with neurodegeneration and cognitive decline. Targeting tau protein has emerged as a promising therapeutic strategy. By investigating the effects of monoclonal antibodies on cognitive function, disease progression, and overall quality of life in patients with AD, which can provide valuable insights into their potential as a therapeutic option for this devastating neurodegenerative disorder.MethodsThe randomized controlled trials (RCTs) investigating the efficacy of Gosuranemab, Semorinemab, Tilavonemab, and Zagotenemab in Alzheimer’s disease (AD) were systematically searched across PubMed, Embase, Web of Science and Cochrane Library, up to May 2024. The control group included placebo. The efficacy indicators were change in the Mini Mental State Examination (MMSE), Clinical Dementia Rating Scale Sum of Boxes (CDR-SB), Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-Cog), Alzheimer’s Disease Cooperative Study-Activities of Daily Living Scale (ADCS-ADL) from baseline until the time of efficacy observation. Statistical analysis was conducted using Stata 14 and RevMan 5.4. The purpose of data processing, including generating network evidence plots, surface under the cumulative ranking curve (SUCRA) ranking, league plots, and funnel plots, is to visually summarize and evaluate the relative effectiveness and safety and potential publication bias of multiple interventions. Mean differences (MD) and 95% confidence interval (95%CI) as effect sizes to analyze continuous variables.ResultsThis study encompassed six RCTs involving 2,193 patients. Semorinemab were more effective than placebo in MMSE and ADAS-Cog scores (MDs ranging between 0.52 and 3.21; MDs ranging between 0.17 and 3.30). Placebo showed relatively good efficacy according to SUCRA ranking on change in CDR-SB and ADCS-ADL scores (75.7 and 79.5%). Tilavonemab and Semorinemab exhibited efficacy similar to that of a placebo in the analysis of the two indicators. Tilavonemab showed a lower incidence of AE, SAE, fall, and urinary tract infections than placebo, and the differences were statistically significant. Most safety analysis results showed no statistical difference.ConclusionThe results indicated that anti-tau protein monoclonal antibodies, such as Semorinemab and Tilavonemab, showed promise in terms of efficacy and safety for managing AD. Further studies are needed to confirm these findings, assess long-term effects, and refine treatment protocols.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/#myprospero, CRD42024583388.
Body position influence on cerebrospinal fluid volume redistribution inside the cranial and spinal CSF compartments
Authors: Strbačko I. , Radoš M. , Jurjević I. , Orešković D. , Klarica M. 
Published: January 2025

IntroductionIt is generally accepted that during body position changes from horizontal to vertical there is a short-lasting shift of a certain CSF volume from the cranium into the hydrostatically lower parts of the spinal space, which leads to transitory CSF pressure decrease to negative values.MethodsIn order to test this, we performed MRI volumetry of cranial and spinal part of the CSF space in healthy volunteers of both genders (n = 22) in three different body positions [horizontal (H); elevated head and upper body (H-UP) under an angle about 30° from the base; elevated lower body (B-UP) under an angle about 30° from the base].ResultsVolumes of brain and spinal cord tissue did not change during body position changes. Significant CSF volume (ml) changes occur inside the spinal space in the tested body positions, primarily in the lumbosacral segment (H-UP – 38.1 ± 7.0; H – 34.4 ± 6.5; B-UP – 28.7 ± 6.5), while at the same time no significant CSF volume changes have been observed inside the cranium in two tested positions (H and B-UP) in which it was possible to measure intracranial CSF volume changes or if we sum up cervical and cranial CSF volumes in those positions.ConclusionObserved results suggest that during the changes of body position CSF volume redistribution occurs, primarily inside the spinal and not the cranial space. This is in accordance with the new hypothesis by which spinal intradural space can significantly change its volume due to its elasticity, thus adjusting to the influence of gravity and pressure changes.
Higher levels of oxidative balance score linked to lower risk of gallstones: findings from the 2017–2020 National Health and Nutrition Examination Survey
Authors: Xiong Ting , Chen Zhonghuo , Yi Jianwei , Yu Taozhi , Wang Kai 
Published: January 2025

Background and objectiveThe Oxidative Balance Score (OBS) has been linked to various chronic diseases; however, its association with gallstone prevalence remains underexplored. This study aimed to investigate the relationship between OBS and gallstone risk.MethodsThis cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted from 2017 to March 2020. Weighted logistic regression models were applied to examine the association between OBS and the prevalence of gallstones, complemented by subgroup and sensitivity analyses. Restricted cubic spline (RCS) was used to investigate the nonlinear association between OBS and the prevalence of gallstones.ResultsA total of 5,382 participants were included, among whom 592 reported a history of gallstones. After adjusting for confounding factors, a significant negative association was observed between OBS and gallstone prevalence (quartile 4 vs. quartile 1: odds ratio [OR] 0.63, 95% confidence interval [CI] 0.43–0.90, p = 0.019). The RCS analysis further supported a negative linear relationship between OBS and gallstone risk (nonlinear p = 0.149). The findings of the subgroup analyses exhibited considerable consistency.ConclusionThis study identified a significant negative linear association between OBS and gallstone risk, suggesting that higher OBS levels are associated with a reduced likelihood of gallstone formation.
Caffeinated chewing gum enhances maximal strength and muscular endurance during bench press and back squat exercises in resistance-trained men
Authors: Ding Li , Liu Jue , Yao Yi , Guo Li , Chen Bin , Cao Yinhang , Girard Olivier 
Published: January 2025

IntroductionCaffeinated chewing gum, known for its rapid absorption, has not been previously studied for its effects on maximal strength and muscular endurance in resistance exercise. The aim of this study was to determine the efficacy of caffeinated chewing gum on maximal strength and muscular endurance during bench press and back squat exercises.MethodsIn a randomized, double-blind design, 16 resistance-trained males (age: 21.6 ± 2.0 years, height: 176.8 ± 6.1 cm, mass: 79.6 ± 8.8 kg) chewed either caffeinated gum (3 mg/kg) or a placebo gum on two occasions, 1 week apart. After a standardized warm-up, participants chewed the gum for 5 min before performing maximal strength test (one-repetition maximum [1RM]) and muscular endurance test (60% 1RM repetitions to failure) for bench press and back squat exercises. 1RM, number of repetitions, ratings of perceived exertion and pain perception were assessed.ResultsCaffeinated chewing gum significantly improved 1RM in both bench press (105.3 ± 14.5 vs. 100.3 ± 13.4 kg, +5.0% [95% confidence interval (CI): 3.7–6.3%], p &lt; 0.01) and back squat (172.3 ± 20.2 vs. 161.9 ± 22.3 kg, +6.8% [95%CI: 4.1–9.5%], p &lt; 0.01) exercises with small effect size (Cohen’s d: 0.36 [95%CI: 0.09–0.63] and 0.49 [95%CI: 0.22–0.76], respectively), despite similar levels of pain perception and RPE (p &gt; 0.05). It also increased the number of repetitions in both bench press (20 ± 5 vs. 17 ± 4, +18.8% [95%CI: 11.5–26.1%], p &lt; 0.01) and back squat (37 ± 11 vs. 28 ± 8, +33.3% [95%CI: 23.1–43.4%], p &lt; 0.01) exercises with moderate-to-large effect size (Cohen’s d: 0.76 [95%CI: 0.48–1.03] and 0.89 [95%CI: 0.60–1.16], respectively), despite similar levels of pain perception and RPE (p &gt; 0.05).DiscussionCaffeinated chewing gum (3 mg/kg) improved both maximal strength and muscular endurance during bench press and back squat exercises in resistance-trained men. This approach offers a practical and time-efficient method to improve training performance while minimizing the risk of side effects.