bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the interplay between posttraumatic stress disorder, gut microbiota, and inflammatory biomarkers: a comprehensive meta-analysis
Authors: Petakh Pavlo , Oksenych Valentyn , Kamyshna Iryna , Boisak Iryna , Lyubomirskaya Katerina , Kamyshnyi Oleksandr 
Published: February 2024

IntroductionPosttraumatic stress disorder (PTSD) is the most common mental health disorder to develop following exposure to trauma. Studies have reported conflicting results regarding changes in immune biomarkers and alterations in the abundance of bacterial taxa and microbial diversity in patients with PTSD.AimThe purpose of this meta-analysis is to summarize existing studies examining gut microbiota characteristics and changes in immune biomarkers in patients with PTSD.MethodsRelevant studies were systematically searched in PubMed, Scopus, and Embase, published in English between January 1, 1960, and December 1, 2023. The outcomes included changes in abundance and diversity in gut microbiota (gut microbiota part) and changes in immune biomarkers (immune part).ResultsThe meta-analysis included a total of 15 studies, with 9 focusing on changes in inflammatory biomarkers and 6 focusing on changes in gut microbiota composition in patients with PTSD. No differences were observed between groups for all inflammatory biomarkers (P≥0.05). Two of the six studies found that people with PTSD had less alpha diversity. However, the overall Standardized Mean Difference (SMD) for the Shannon Diversity Index was not significant (SMD 0.27, 95% CI -0.62–0.609, p = 0.110). Regarding changes in abundance, in two of the studies, a significant decrease in Lachnospiraceae bacteria was observed.ConclusionThis meta-analysis provides a comprehensive overview of gut microbiota characteristics in PTSD, suggesting potential associations with immune dysregulation. Future research should address study limitations, explore causal relationships, and consider additional factors influencing immune function in individuals with PTSD.Systematic review registrationhttps://www.crd.york.ac.uk, identifier CRD42023476590.
Effectiveness of a multicomponent exercise intervention in community-dwelling older Chinese people with cognitive frailty: protocol for a mixed-methods research
Authors: Ning Hongting , Chen Fenghui , Li Junxin , Du Yan , Chen Xi , Wu Shuang , Joseph Abigael , Gao Yinyan , Cao Zeng , Feng Hui 
Published: February 2024

AimsTo evaluate the effectiveness of a multicomponent exercise intervention and to clarify the underlying mechanisms of the program in community-dwelling older adults with cognitive frailty. Additionally, the perception of participants in the program will be explored.DesignA mixed-methods design, including a randomized controlled trial and an exploratory qualitative study, was used.MethodsEach group consists of 41 participants. The experimental group will undergo a 12-week multicomponent exercise intervention, including warm-up, exergaming aerobic exercise, elastic-band resistance exercise, and cool-down. This intervention was developed based on the Health Belief Model (HBM) and Self-Efficacy Model (SEM). The control group will not receive any intervention. Physical frailty and cognitive function will be considered as primary outcomes. Data will be collected both at baseline and at the end of the intervention period. Fisher’s exact test, analysis of covariance, and generalized linear models will be conducted to compare mean changes between the two groups. Additionally, the mediation models will be used to examine whether any intervention effects are mediated through exercise self-efficacy.DiscussionThe findings of this study are anticipated to provide valuable insights for healthcare providers, enabling them to learn about effective strategies to enhance exercise adherence and promote improved functionality, independence, and quality of life for older adults with cognitive frailty.Clinical trial registration: [https://clinicaltrials.gov/], identifier [ChiCTR2200058850].
Effects of rhythmic visual cues on cortical activation and functional connectivity features during stepping: an fNIRS study
Authors: Wu Jiajia , Zhou Huilin , Chen Hao , Jiang Wensong , Wang Xuelian , Meng Tao , Wu Chaowen , Li Li , Wu Yuemin , Fan Weinv , Shi Changcheng , Zuo Guokun 
Published: February 2024

IntroductionRhythmic visual cues (RVCs) may influence gait initiation by modulating cognition resources. However, it is unknown how RVCs modulate cognitive resources allocation during gait movements. This study focused on investigating the effects of RVCs on cortical hemodynamic response features during stepping to evaluate the changes of cognitive resources.MethodsWe recorded cerebral hemoglobin concentration changes of 14 channels in 17 healthy subjects using functional near-infrared spectroscopy (fNIRS) during stepping tasks under exposure to RVCs and non-rhythmic visual cues (NRVCs). We reported mean oxygenated hemoglobin (HbO) concentration changes, β-values, and functional connectivity (FC) between channels.ResultsThe results showed that, the RVC conditions revealed lower HbO responses compared to the NRVC conditions during the preparation and early stepping. Correspondingly, the β-values reflected that RVCs elicited lower hemodynamic responses than NRVCs, and there was a decreasing trend in stimulus-evoked cortical activation as the task progressed. However, the FC between channels were stronger under RVCs than under NRVCs during the stepping progress, and there were more significant differences in FC during the early stepping.DiscussionIn conclusion, there were lower cognitive demand and stronger FC under RVC conditions than NRVC conditions, which indicated higher efficiency of cognitive resources allocation during stepping tasks. This study may provide a new insight for further understanding the mechanism on how RVCs alleviate freezing of gait.
Transcriptomic analysis reveals prolonged neurodegeneration in the hippocampus of adult C57BL/6N mouse deafened by noise
Authors: Lee Sang-Youp , Lee Ho Sun , Park Min-Hyun 
Published: February 2024

IntroductionSeveral studies have reported a significant correlation between noise-induced hearing loss and cognitive decline. However, comprehensive analyses of this relationship are rare. This study aimed to assess the influence of hearing impairment on cognitive functions by analyzing organ samples in the afferent auditory pathway of deafened mice using mRNA sequencing.MethodsWe prepared 10 female 12-week-old C57BL/6N mice as the experimental and control groups in equal numbers. Mice in the experimental group were deafened with 120 dB sound pressure level (SPL) wideband noise for 2 h. Cochlea, auditory cortex, and hippocampus were obtained from all mice. After constructing cDNA libraries for the extracted RNA from the samples, we performed next-generation sequencing. Subsequently, we analyzed the results using gene ontologies (GOs) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway databases for differentially expressed genes (DEGs) of each organ.ResultsOur results revealed 102, 89, and 176 DEGs for cochlea, auditory cortex, and hippocampus, respectively. We identified 294, 203, and 211 GOs; 10, 7, and 17 KEGG pathways in the cochlea, auditory cortex, and hippocampus, respectively. In the long term (12 weeks) from noise-induced hearing loss, GOs and KEGG pathways related to apoptosis or inflammation persisted more actively in the order of hippocampus, auditory cortex, and cochlea.DiscussionThis implies that the neurodegenerative effects of noise exposure persist more longer time in the central regions.
Mussel oil is superior to fish oil in preventing atherosclerosis of ApoE−/− mice
Authors: Li Kelei , Song Xiaolei , Li Huiying , Kuang Xiaotong , Liu Shiyi , Liu Run , Li Duo 
Published: February 2024

ObjectivesThe present study aimed to explore the preventive effect of mussel oil (MO) on atherosclerosis and the potential mechanism in apolipoprotein E-null (ApoE−/−) mice.MethodsApoE−/− mice were fed with a high-fat and high-cholesterol chow and given corn oil (CO), fish oil (FO), MO, or aspirin (ASP, dissolved in CO) by gavage for 12  weeks. The total n-3 polyunsaturated fatty acids (PUFAs) in MO (51.01%) and FO (46.82%) were comparable (mainly C22:6n-3 and C20:5n-3). Wild-type mice were fed with a normal chow and given equivalent CO as health control (CON).ResultsCompared with the CON group, obvious atherosclerotic plaque appeared at aorta and aortic sinus in the CO group. Compared with the CO group, MO but not FO had a significantly smaller atherosclerotic plaque area in the aorta. The aortic atherosclerotic plaque area was comparable in the MO, CON, and ASP groups. The MO group had a significantly smaller atherosclerotic plaque area, lower lipid deposition, lower contents of smooth muscle cell (SMC), and slightly lower contents of macrophage at the aortic sinus than the FO group. Serum concentrations of IL-1β, NF-κB, and VCAM-1 were comparable in the MO and FO groups and were significantly lower than the CO group. Compared with the CO group, the MO group but not FO group had significantly lower aortic protein levels of p65NF-κB, p38MAPK, and VCAM-1. The aortic protein levels of p-p65NF-κB and p-p38MAPK were significantly lower in the MO group than the FO group.ConclusionIn conclusion, MO is more potent than FO in preventing atherosclerosis, and the possible mechanism may be by downregulating p38MAPK/NF-κB signaling pathway, decreasing VCAM-1 and macrophage, and inhibiting proliferation and migration of SMC.
Time to strategy failure and treatment beyond progression in pretreated metastatic renal cell carcinoma patients receiving nivolumab: post-hoc analysis of the Meet-URO 15 study
Authors: Murianni Veronica , Signori Alessio , Buti Sebastiano , Rebuzzi Sara Elena , Bimbatti Davide , De Giorgi Ugo , Chiellino Silvia , Galli Luca , Zucali Paolo Andrea , Masini Cristina , Naglieri Emanuele , Procopio Giuseppe , Milella Michele , Fratino Lucia , Baldessari Cinzia , Ricotta Riccardo , Mollica Veronica , Sorarù Mariella , Tudini Marianna , Prati Veronica , Malgeri Andrea , Atzori Francesco , Di Napoli Marilena , Caffo Orazio , Spada Massimiliano , Morelli Franco , Prati Giuseppe , Nolè Franco , Vignani Francesca , Cavo Alessia , Lipari Helga , Roviello Giandomenico , Catalano Fabio , Damassi Alessandra , Cremante Malvina , Rescigno Pasquale , Fornarini Giuseppe , Banna Giuseppe Luigi 
Published: February 2024

BackgroundImmunotherapies exhibit peculiar cancer response patterns in contrast to chemotherapy and targeted therapy. Some patients experience disease response after initial progression or durable responses after treatment interruption. In clinical practice, immune checkpoint inhibitors may be continued after radiological progression if clinical benefit is observed. As a result, estimating progression-free survival (PFS) based on the first disease progression may not accurately reflect the actual benefit of immunotherapy.MethodsThe Meet-URO 15 study was a multicenter retrospective analysis of 571 pretreated metastatic renal cell carcinoma (mRCC) patients receiving nivolumab. Time to strategy failure (TSF) was defined as the interval from the start of immunotherapy to definitive disease progression or death. This post-hoc analysis compared TSF to PFS and assess the response and survival outcomes between patients treatated beyond progression (TBP) and non-TBP. Moreover, we evaluated the prognostic accuracy of the Meet-URO score versus the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score based on TSF and PFS.ResultsOverall, 571 mRCC patients were included in the analysis. Median TSF was 8.6 months (95% CI: 7.0 – 10.1), while mPFS was 7.0 months (95% CI: 5.7 – 8.5). TBP patients (N = 93) had significantly longer TSF (16.3 vs 5.5 months; p &lt; 0.001) and overall survival (OS) (34.8 vs 17.9 months; p &lt; 0.001) but similar PFS compared to non-TBP patients. In TBP patients, a median delay of 9.6 months (range: 6.7-16.3) from the first to the definitive disease progression was observed, whereas non-TBP patients had overlapped median TSF and PFS (5.5 months). Moreover, TBP patients had a trend toward a higher overall response rate (33.3% vs 24.3%; p = 0.075) and disease control rate (61.3% vs 55.5%; p = 0.31). Finally, in the whole population the Meet-URO score outperformed the IMDC score in predicting both TSF (c-index: 0.63 vs 0.59) and PFS (0.62 vs 0.59).ConclusionWe found a 2-month difference between mTSF and mPFS in mRCC patients receiving nivolumab. However, TBP patients had better outcomes, including significantly longer TSF and OS than non-TBP patients. The Meet-URO score is a reliable predictor of TSF and PFS.
Protocol of a first-in-human clinical trial to evaluate the safety, tolerability, and preliminary efficacy of the bispecific CD276xCD3 antibody CC-3 in patients with colorectal cancer (CoRe_CC-3)
Authors: Jung Susanne , Schlenk Richard F. , Hackenbruch Christopher , Roldan Pinzon Sandra S.L. , Bitzer Michael , Pflügler Martin , Walz Juliane S. , Jung Gundram , Heitmann Jonas S. , Salih Helmut R. 
Published: February 2024

IntroductionColorectal cancer (CRC) is the third most common cancer worldwide in men and women. In the metastasized stage, treatment options and prognosis are limited. To address the high medical need of this patient population, we generated a CD276xCD3 bispecific antibody termed CC-3. CD276 is expressed on CRC cells and on tumor vessels, thereby allowing for a “dual” anticancer effect.Methods and analysisThis first-in-human clinical study is planned as a prospective multicenter trial, enrolling patients with metastatic CRC after three lines of therapy. During the dose-escalation part, initially, an accelerated titration design with single-patient cohorts is employed. Here, each patient will receive a fixed dose level (starting with 50 µg for the first patient); however, between patients, dose level may be increased by up to 100%, depending on the decision of a safety review committee. Upon occurrence of any adverse events (AEs) grade ≥2, dose-limiting toxicity (DLT), or reaching a dose level of ≥800 µg, the escalation will switch to a standard 3 + 3 dose design. After maximum tolerated dose (MTD) has been determined, defined as no more than one of the six patients experiencing DLT, an additional 14 patients receive CC-3 at the MTD level in the dose-expansion phase. Primary endpoints are incidence and severity of AEs, as well as the best objective response to the treatment according to response evaluation criteria in solid tumors (RECIST) 1.1. Secondary endpoints include overall safety, efficacy, survival, quality of life, and pharmacokinetic investigations.Ethics and disseminationThe CD276xCD3 study was approved by the Ethics Committee of the Medical Faculty of the Heinrich Heine University Düsseldorf and the Paul-Ehrlich-Institut (P00702). Clinical trial results will be published in peer-reviewed journals. Trial registration numbers: ClinicalTrials.cov Registry (NCT05999396) and EU ClinicalTrials Registry (EU trial number 2022-503084-15-00).
The novel LESS (low-cost entrainment syringe system) O2 blender for use in modified bubble CPAP circuits: a clinical study of safety
Authors: Wu Andrew G. , Luch Sreyleak , Slusher Tina M. , Fischer Gwenyth A. , Lunos Scott A. , Bjorklund Ashley R. 
Published: February 2024

BackgroundBubble continuous positive airway pressure (bCPAP) is used in resource-limited settings for children with respiratory distress. Low-cost modifications of bCPAP use 100% oxygen and may cause morbidity from oxygen toxicity. We sought to test a novel constructible low-cost entrainment syringe system (LESS) oxygen blender with low-cost modified bCPAP in a relevant clinical setting.MethodsWe conducted a clinical trial evaluating safety of the LESS O2 blender among hospitalized children under five years old in rural Cambodia evaluating the rate of clinical failure within one hour of initiation of the LESS O2 blender and monitoring for any other blender-related complications.FindingsThirty-two patients were included. The primary outcome (clinical failure) occurred in one patient (3.1%, 95% CI = 0.1–16.2%). Clinical failure was defined as intubation, death, transfer to another hospital, or two of the following: oxygen saturation &lt;85% after 30 min of treatment; new signs of respiratory distress; or partial pressure of carbon dioxide ≥60 mmHg and pH &lt;7.2 on a capillary blood gas. Secondary outcomes included average generated FiO2's with blender use, which were 59% and 52% when a 5 mm entrainment was used vs. a 10 mm entrainment port with 5–7 cm H2O of CPAP and 1–7 L/min (LPM) of flow; and adverse events including loss of CPAP bubbling (64% of all adverse events), frequency of repair or adjustment (44%), replacement (25%), and median time of respiratory support (44 h).InterpretationOverall the LESS O2 blender was safe for clinical use. The design could be modified for improved performance including less repair needs and improved nasal interface, which requires modification for the blender to function more consistently.
Real-world effects of Yishen Tongbi decoction for rheumatoid arthritis: protocol for a prospective, observational, multicenter cohort study with validation against double-blind, randomized, controlled trial
Authors: Liu Lijuan , Zhu Fangfang , Xin Yijun , Zhang Lu , Hu Congqi , Xu Yanping , Zhang Jinming , Liu Lingjie , Chen Guangxing 
Published: February 2024

Introduction: Rheumatoid arthritis (RA) is a globally challenging and refractory autoimmune disease, constituting a serious menace to human health. RA is characterized by recurrent pain and is difficult to resolve, necessitating prolonged medication for control. Yishen Tongbi decoction is a traditional Chinese herbal compound prescribed for treating RA. We have completed a 3-year RCT study that confirmed the clinical efficacy of Yishen Tongbi decoction for RA. Notably, we observed a faster clinical remission rate compared to MTX by week 4 of treatment. In our forthcoming study, we intend to conduct a comprehensive assessment of the efficacy and safety of Yishen Tongbi decoction in the real-world treatment of RA through a prospective study.Methods and analysis: This prospective, multicenter, real-world observational study will be conducted at two designated centers in China from October 2023 to August 2025. The study will include 324 patients with active rheumatoid arthritis. One group will receive Yishen Tongbi decoction combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). The other group will receive standard treatment. Standard treatment can be further divided into subgroups: csDMARDs, targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), and biologic disease-modifying antirheumatic drugs (bDMARDs). In each group, the number of tender joints, number of swollen joints, pain score, patient global assessment, physician global assessment, disease activity index (DAS28-ESR or DAS28-CRP), clinical disease activity index (cDAI), simplified disease activity index (sDAI) and relevant laboratory data will be compared. Clinical indicators and disease activity of the patients will be assessed at baseline, week 4 and week 12 after the initiation of treatment. The primary outcome will be the American College of Rheumatology 20% improvement criteria (ACR20) attainment rate among patients at week 12 after treatment. Every adverse event will be reported.Ethics and dissemination: This study has been approved by the Ethics Committee of the first affiliated Hospital of Guangzhou University of traditional Chinese Medicine (NO.K-2023-009). The results of the study will be published in national and international peer-reviewed journals and at scientific conferences. The researchers will inform participants and other RA patients of the results through health education.Clinical Trial Registration:https://www.chictr.org.cn/index.html, identifier ChiCTR2300076073
Leniolisib: a novel treatment for activated phosphoinositide-3 kinase delta syndrome
Authors: De Surya K. 
Published: February 2024

Graphical AbstractIC50 = 11 nM (PI3Kδ); 244 nM (PI3Kα); 424 nM (PI3Kβ), 2,230 nM (PI3Kγ).
Salinity change evokes stress and immune responses in Atlantic salmon with microalgae showing limited potential for dietary mitigation
Authors: van Muilekom Doret R. , Mueller Jonas , Lindemeyer Jacqueline , Schultheiß Thekla , Maser Edmund , Seibel Henrike , Rebl Alexander , Schulz Carsten , Goldammer Tom 
Published: February 2024

Smoltification was found to impact both immune and stress responses of farmed Atlantic salmon (Salmo salar), but little is known about how salinity change affects salmon months after completed smoltification. Here, we examined (1) the effect of salinity change from brackish water to seawater on the stress and immune responses in Atlantic salmon and (2) evaluated if functional diets enriched with microalgae can mitigate stress- and immune-related changes. Groups of Atlantic salmon were fed for 8 weeks with different microalgae-enriched diets in brackish water and were then transferred into seawater. Samples of the head kidney, gill, liver and plasma were taken before seawater transfer (SWT), 20 h after SWT, and 2 weeks after SWT for gene-expression analysis, plasma biochemistry and protein quantification. The salmon showed full osmoregulatory ability upon transfer to seawater reflected by high nkaα1b levels in the gill and tight plasma ion regulation. In the gill, one-third of 44 investigated genes were reduced at either 20 h or 2 weeks in seawater, including genes involved in cytokine signaling (il1b) and antiviral defense (isg15, rsad2, ifit5). In contrast, an acute response after 20 h in SW was apparent in the head kidney reflected by increased plasma stress indicators and induced expression of genes involved in acute-phase response (drtp1), antimicrobial defense (camp) and stress response (hspa5). However, after 2 weeks in seawater, the expression of antiviral genes (isg15, rsad2, znfx1) was reduced in the head kidney. Few genes (camp, clra, c1ql2) in the gill were downregulated by a diet with 8% inclusion of Athrospira platensis. The results of the present study indicate that salinity change months after smoltification evokes molecular stress- and immune responses in Atlantic salmon. However, microalgae-enriched functional diets seem to have only limited potential to mitigate the related changes.