bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors associated with systemic inflammatory response syndrome negativity at the early stage of sepsis among nonsurviving sepsis patients in intensive care unit
Authors: Fu Chunyi , Luo Jingchao , Wang Xiaogang , Xu Yuan , Liu Taotao 
Published: September 2024

AbstractObjectivesThis study aims to investigate the factors associated with systemic inflammatory response syndrome (SIRS) negativity during the early stage of sepsis in deceased septic patients.MethodsAdult septic patients were included from the Medical Information Mart for Intensive Care IV (MIMIC‐IV) database between 2008 and 2019. Patients who did not survive after 28 days were assigned to the SIRS‐negative or SIRS‐positive group according to whether the SIRS score was less than two points within 24 h of intensive care unit admission. Logistic regression and a restricted cubic spline model were used to analyze factors and dose–response relationships.ResultsA total of 53,150 patients were screened in the MIMIC‐IV database, and 2706 sepsis nonsurvivors were ultimately included, 101 of whom were negative for SIRS. There were significant differences in sequential organ failure assessment (SOFA) scores between groups (8.18 ± 3.58 vs. 9.75 ± 4.28, p < 0.001). Logistic regression analysis indicated that lactate (odds ratio [OR] = 0.75 [95% CI = 0.62–0.90], p = 0.002), SOFA score (OR = 0.93 [95% CI = 0.87–1.00], p = 0.046), and age (OR = 1.04 [95% CI = 0.88–1.15], p = 0.012) were independent factors related to SIRS negativity in septic patients. Analysis with a restricted cubic spline model showed that the OR of SIRS negativity continued to increase with age, particularly for those over 80 years old (p for nonlinearity = 0.024). The OR of SIRS negativity was more than 1 when the SOFA score was <4 (p for nonlinearity = 0.149) and when the lactate was <1 (p for nonlinearity = 0.014).ConclusionsFor sepsis patients with poor prognoses, elderly individuals are more likely to be SIRS negative when they have mild organ dysfunction damage or mild tissue hypoperfusion in the early stage of sepsis. This warranted an opportunity to provide early diagnosis for elderly population with negative SIRS score in order to prevent poor outcomes.
Waiting for surgery after hip fracture—Health and/or economic risk?
Authors: Saxer Franziska , Hatz Christoph , Vach Werner ,   the PROFI Study Group
Published: September 2024

AbstractObjectivesWaiting for surgery is a disconcerting experience. It can have a negative impact on patients' outcomes and length of stay (LOS) as driver for treatment costs. Process‐optimisation may be a strategy to improve quality and cost‐efficacy. The study investigates the correlation between waiting for hip fracture surgery and patient characteristics, organisational variables, outcomes, LOS, and the distribution of waiting times and LOS over time, including cost estimates. Thereby the study aims to identify the potential for organisational improvements with respect to managing the waiting time.MethodsTen‐year routine health data (patient characteristics and follow‐up information) and process‐indicators that is, waiting time and LOS from a Swiss trauma‐centre were analysed retrospectively. Cost‐estimates were calculated based on Swiss diagnosis related groups and daily costs to evaluate hospital revenues.ResultsIn total, 2572 patients aged ≥60 years with low‐energy hip fractures were included. Waiting times >48 h were associated with sub‐optimal outcomes. Over the years long waiting times decreased. This reduction was not reflected by a reduction in LOS which remained stable around 10 days, primarily driven by late discharge to in‐patient rehabilitation. Reimbursement persisted at an average revenue in the low 4–5‐digit range, depending on implant costs.ConclusionsWhile there has been a reduction of waiting times, this has not translated into a reduction of LOS or potential savings in health care costs, due to the various dependencies along the patient journey. Managing waiting times may be an area for improvement, increasing cost‐efficacy, especially since long waiting times are still associated with inferior outcomes and LOS.
Patient and care partner perspectives and preferences related to myasthenia gravis treatment: A qualitative study
Authors: Yung Margaret , Narayanaswami Pushpa , Pesa Jacqueline , Choudhry Zia , Jackson Louis , Deering Kathleen L. , Sebaaly Jamie , Richardson Jordan , Feldman Josh , Peters Wesley , Taylor Melina , Foss Allison , West Bruce , Shea Lisa , Geonnotti Gabrielle , Govindarajan Raghav 
Published: September 2024

AbstractBackground and AimsDue to the high symptom and treatment burden in myasthenia gravis (MG), understanding patient and care partner perspectives and preferences is crucial.MethodsThis study used voice analysis and virtual focus groups to understand patient and care partner experiences with MG‐related symptoms, treatments, and preferences. The voice analysis via social media listening used artificial intelligence‐powered tools to gather and structure public digital conversations on MG. Focus groups included people living with MG and care partners who completed a questionnaire and participated in a 1‐h virtual session facilitated using a semi‐structured interview guide. Qualitative data were aggregated, transcribed, and thematically analyzed.ResultsThe voice analysis examined 11,554 posts from 8321 individuals, discussing MG symptoms, treatments, and burden. Of 7563 symptom‐related posts, 5902 (78%) conveyed negative, 1427 (19%) neutral, and 234 (3%) positive sentiment. The most frequently mentioned symptoms were categorized as dysarthria, muscle weakness, and dysphagia. MG treatment sentiment analysis identified 6667 posts (67%) as neutral, 2887 (29%) as negative, and 350 (4%) as positive. For the focus groups, 15 individuals (12 patients and 3 care partners) completed the questionnaire and 14 participated in the virtual focus group sessions. The 15 participants who completed the questionnaire prioritized treatment convenience, symptom control for improved quality of life, and preventing potential MG crises in their current treatment. New treatment expectations included increased effectiveness, less frequent dosing, faster onset, and fewer side effects. Participants were also receptive to wearable medication delivery systems placed on the body and valued direct involvement in treatment decisions.ConclusionPatients and care partners are often negatively impacted by MG symptoms and value convenient and fast‐acting treatments that control symptoms with minimal side effects. Considering patient preferences may help optimize treatment decisions and improve patients' overall well‐being and satisfaction in their care.
Effect of noninertial acceleration on heat transfer by Rayleigh–Bénard magnetoconvection: Exploring nonlinear dynamics
Authors: Aruna A. S. , Kavitha N. 
Published: September 2024

AbstractBuoyancy‐driven Rayleigh–Bénard convection in the presence of a magnetic field, rotation, and temperature‐dependent viscosity has applications in the field of crystal growth, space laboratory experiments, and atmospheric convection. It also has potential applications in heat transfer and magnetohydrodynamics, which can occur in planetary and stellar interiors. The present work aims to study the combined effect of magnetic fields and rotation on the onset of Rayleigh–Bénard convection in temperature‐dependent viscosity Newtonian liquids with internal heat sources/sinks. Both linear and weak nonlinear stability analyses of convection are performed in the problem. The minimal representation of the Fourier series for the stream function and the magnetic potential allows us to derive the analytical expression for the thermal Rayleigh number () and the generalized Lorenz model. In linear theory, the critical Rayleigh number and the wave number are tabulated for different values of the Chandrasekhar number (), the Taylor number (), and the thermorheological parameter (), and the onset of stability is analyzed. It is found that the instability manifests at when for stress‐free and isothermal boundaries. In nonlinear theory, the generalized Lorenz model obtained is not amenable to analytical treatment; therefore, the classical fourth‐order Runge–Kutta method is applied to solve the Lorenz model. It is found that the internal Rayleigh number, the thermorheological parameter, and the Taylor number influence the onset of convection and heat transfer coefficient. It is also demonstrated that the joint increase in rotational force and magnetic field strength stabilizes the system strongly, thereby reducing heat transfer. However, increasing the heat source and the variable viscosity parameter have antagonistic influences.
Ascorbyl palmitate/hydroxypropyl‐β‐cyclodextrin inclusion complex loaded nanofibrous membrane for accelerated diabetic wound healing
Authors: Zhao Dan , Liu Jingchong , Liu Guotao , Hou Liangxuan , Zhou Liping , Wang Changtao , Wen Yongqiang 
Published: September 2024

AbstractReactive oxygen species (ROS) accumulation in chronic skin wounds impedes the healing process, thus it is necessary to eliminate the ROS from the vicinity of the wound in time. Ascorbyl palmitate (AP) is a potent antioxidant that suffers from solubility constraints, which largely limits its application. This study aims to improve AP's solubility by encapsulating it within 2‐hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) to acquire AP/CD inclusion complex (IC). This advancement facilitates the development of antioxidant and antibacterial nanofibrous membranes via electrospinning, utilizing polyvinyl alcohol (PVA) and quaternary ammonium chitosan (QCS). The developed PVA/QCS combined with AP/CD‐IC (PVA/QCS‐IC) nanofibers increase the release of AP, boasting good antioxidant property. In comparison to the PVA/QCS combined with AP counterparts (PVA/QCS‐AP), where AP is not encapsulated in HP‐β‐CD, the PVA/QCS‐IC nanofibers provide notable protection against oxidative stress in human skin fibroblasts and increased Col‐I expression levels. Additionally, the PVA/QCS‐IC nanofibers are able to suppress the growth of E. coli, S. aureus, and P. aeruginosa. Furthermore, the PVA/QCS‐IC nanofibers could effectively promote diabetic wound healing, facilitate collagen deposition, and reduce skin inflammation response when applied as a wound dressing in diabetic mice. The results suggest that the PVA/QCS‐IC nanofibers represent a promising solution for both enhancing AP solubility and its therapeutic potential, positioning them as potential candidates for diabetic wound care applications.
The risk of treatment‐related toxicities with PD‐1/PD‐L1 inhibitors in patients with lung cancer
Authors: Hu Hao , Zhu Qian , Tang Hua , Zhang Si‐Cai , Huang Yan‐Ze , Wang Ya‐Fang , Xu Zhi‐Yong , Yang Xiong‐Wen , Zheng Ji‐Hua , Guo Chang‐Ying 
Published: September 2024

AbstractThe risk of treatment‐related toxicities with programmed cell death 1 and its ligand (PD‐1/PD‐L1) inhibitors in patients with lung cancer is unclear and inconclusive. PubMed, EMBASE, and the Cochrane Library databases were systematically searched without language restrictions from inception to May 31, 2024 to identify Phase 3 randomized controlled trials of lung cancer comparing PD‐1/PD‐L1 inhibitors versus placebo/best supportive care (alone or in combination with nontargeted chemotherapy) that had available data regarding treatment‐related adverse events (TRAEs) or incidence and sample size. Random‐effect models were employed to study the pooled relative risk (RR) and 95% confidence intervals (CIs). Finally, 36 trials, involving 19,693 participants, fulfilled the inclusion criteria. PD‐1/PD‐L1 inhibitors significantly augmented the likelihood of developing all‐grade (RR, 1.03; 95% CI, 1.01–1.04, p < .01) and grade ≥3 TRAEs (RR, 1.16; 95% CI, 1.10 to 1.23, p < .01). PD‐1/PD‐L1 inhibitors substantially augmented the odds of developing treatment‐related serious adverse events (SAEs) (RR, 1.48; 95% CI, 1.27–1.71, p < .01) and fatal adverse events (FAEs) (RR, 1.42; 95% CI, 1.11–1.82, p < .01). Subgroup analyses indicated that the RR of SAEs and FAEs were generally consistent, regardless of treatment type, tumor type, treatment setting, PD‐1/PD‐L1 inhibitors type and study design. The most common causes of FAEs were respiratory failure/insufficiency (33.3%), cardiac events (16.1%), and hematological disorders (10.1%). We demonstrated that PD‐1/PD‐L1 inhibitors were significantly correlated with higher possibility of developing treatment‐related toxicities, especially SAEs and FAEs, compared with placebo/best supportive care controls.
Potentially functional variants of PARK7 and DDR2 in ferroptosis‐related genes predict survival of non‐small cell lung cancer patients
Authors: Wang Huilin , Liu Hongliang , Tang Xiaozhun , Lu Guojun , Luo Sheng , Du Mulong , Christiani David C. , Wei Qingyi 
Published: September 2024

AbstractFerroptosis, a form of regulated cell death, is characterized by iron‐dependent lipid peroxidation. It is recognized increasingly for its pivotal role in both cancer development and the response to cancer treatments. We assessed associations between 370,027 single‐nucleotide polymorphisms (SNPs) within 467 ferroptosis‐related genes and survival of non‐small cell lung cancer (NSCLC) patients. Data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial served as our discovery dataset, while the Harvard Lung Cancer Susceptibility Study used as our validation dataset. For SNPs that remained statistically significantly associated with overall survival (OS) in both datasets, we employed a multivariable stepwise Cox proportional hazards regression model with the PLCO dataset. Ultimately, two independent SNPs, PARK7 rs225120 C>T and DDR2 rs881127 T>C, were identified with adjusted hazard ratios of 1.32 (95% confidence interval = 1.15–1.52, p = .0001) and 1.34 (95% confidence interval = 1.09–1.64, p = .006) for OS, respectively. We aggregated these two SNPs into a genetic score reflecting the number of unfavorable genotypes (NUG) in further multivariable analysis, revealing a noteworthy association between increased NUG and diminished OS (ptrend = .001). Additionally, an expression quantitative trait loci analysis indicated that PARK7 rs225120T genotypes were significantly associated with higher PARK7 mRNA expression levels in both whole blood and normal lung tissue. Conversely, DDR2 rs881127C genotypes were significantly associated with lower DDR2 mRNA expression levels in normal lung tissue. Our findings suggest that genetic variants in the ferroptosis‐related genes PARK7 and DDR2 are associated with NSCLC survival, potentially through their influence on gene expression levels.
Cationic Polystyrene Latex Nanocarriers for Immunostimulatory Long Double‐Stranded RNA Delivery to Ovarian Cancer Cells
Authors: Aldor N. L. , Jadaa N. A. , Miller S. Y. , Alla I. , Richardson S. , Kitaev V. , Poynter S. J. 
Published: September 2024

ABSTRACTLong double‐stranded (ds)RNA, a potent stimulator of type I interferon and the innate immune response. In the present study, we demonstrated, for the first time, the efficacy of cationic polystyrene latex nanostructures (clNPs) as a dsRNA carrier, improving cellular delivery and robustly potentiating the immunostimulatory capacity of dsRNA in the ovarian cancer cell line SKOV3. The clNPs complexed with an in vitro transcribed dsRNA molecule, were bound by SKOV3 cells, and had increased cellular association compared to uncomplexed clNPs. clNPs complexed with dsRNA induced a more robust innate immune response compared to dsRNA alone. Transcript expression of two interferon‐stimulated genes, were increased 47‐ and 108‐fold over dsRNA and induced a significant antiviral state against vesicular‐stomatitis virus, resulting in a 3.3‐fold improvement on the efficacy of dsRNA. These data highlight the potential of polystyrene latex nanostructures as dsRNA carriers for anticancer immunotherapies, improving the uptake and efficacy of the nucleic acid.
Sub‐acute bisphenol A exposure induces proteomic alterations and impairs male reproductive health in mice
Authors: Yadav Shiv K. , Kumar Arvind , Yadav Bal G. , Bijalwan Vandana , Yadav Suresh , Patil Gajanan P. , Sarkar Kamalesh , Palkhade Rajendra , Das Santasabuj , Singh Dhirendra P. 
Published: September 2024

AbstractBisphenol A (BPA) is one of the most prevalent endocrine disrupting chemicals (EDCs) and there is widespread concern about the adverse effects of EDCs on human health. However, the exact mechanism of these toxicities has still not been fully deciphered. Additionally, studies have reported the toxicological effects at far low doses to the generally considered no‐observed‐adverse‐effect level (NOAEL) dose. The present study investigates the effects of a sub‐acute (28 days) exposure to BPA (10, 50 and 100 mg/kg/day) in adult male mice on various hormones levels, sperm motility, sperm count, functional integrity of sperm plasma membrane, testicular histological changes, oxidative stress markers and DNA damage. The key proteome signatures were quantified by LC‐MS/MS analysis using Orbitrap Fusion Lumos Tribrid Mass Spectrometer equipped with nano‐LC Easy‐nLC 1200. Data suggest that the BPA exposure in all doses (below/above NOAEL dose) have greatly impacted the hormone levels, sperm parameters (sperm count, motility and membrane integrity) and testicular histology. Mass spectrometry‐based proteomics data suggested for 1352 differentially expressed proteins (DEPs; 368 upregulated, 984 downregulated) affecting biological process, cellular component, and molecular functions. Specifically searched male reproductive function related proteins suggested a complex network where 46 potential proteins regulating spermatogenesis, sperm structure, activity and membrane integrity while tackling oxidative stress responses were downregulated. These potential biomarkers could shed some more light on our current understanding of the reproductive toxicological effects of BPA and may lead to exploration of novel interventions strategies against these targets for male infertility.
The ameliorative effect of carvacrol on sodium arsenite‐induced hepatotoxicity in rats: Possible role of Nrf2/HO‐1, RAGE/NLRP3, Bax/Bcl‐2/Caspase‐3, and Beclin‐1 pathways
Authors: Gencer Selman , Gür Cihan , İleritürk Mustafa , Küçükler Sefa , Akaras Nurhan , Şimşek Hasan , Kandemir Fatih M. 
Published: September 2024

AbstractArsenic is a toxic environmental pollutant heavy metal, and one of its critical target tissues in the body is the liver. Carvacrol is a natural phytocompound that stands out with its antioxidant, anti‐inflammatory, and antiapoptotic properties. The current study aims to investigate the protective feature of carvacrol against sodium arsenite‐induced liver toxicity. Thirty‐five Sprague‐Dawley male rats were divided into five groups: Control, Sodium arsenite (SA), CRV, SA + CRV25, and SA + CRV50. Sodium arsenite was administered via oral gavage at a dose of 10 mg/kg for 14 days, and 30 min later, CRV 25 or 50 mg/kg was administered via oral gavage. Oxidative stress, inflammation, apoptosis, autophagy damage pathways parameters, and liver tissue integrity were analyzed using biochemical, molecular, western blot, histological, and immunohistological methods. Carvacrol decreased sodium arsenite‐induced oxidative stress by suppressing malondialdehyde levels and increasing superoxide dismutase, catalase, glutathione peroxidase activities, and glutathione levels. Carvacrol reduced inflammation damage by reducing sodium arsenite‐induced increased levels of NF‐κB and the cytokines (TNF‐α, IL‐1β, IL‐6, RAGE, and NLRP3) it stimulates. Carvacrol also reduced sodium arsenite‐induced autophagic (Beclin‐1, LC3A, and LC3B) and apoptotic (P53, Apaf‐1, Casp‐3, Casp‐6, Casp‐9, and Bax) parameters. Carvacrol preserved sodium arsenite‐induced impaired liver tissue structure. Carvacrol alleviated toxic damage by reducing sodium arsenite‐induced increases in oxidative stress, inflammation, apoptosis, and autophagic damage parameters in rat liver tissues. Carvacrol was also beneficial in preserving liver tissue integrity.
USP1‐mediated deubiquitination of KDM1A promotes the malignant progression of triple‐negative breast cancer
Authors: Su Yang , Du Yan , He Wenguang 
Published: September 2024

AbstractPrevious research has indicated the highly expressed lysine‐specific histone demethylase 1A (KDM1A) in several human malignancies, including triple‐negative breast cancer (TNBC). However, its detailed mechanisms in TNBC development remain poorly understood. The mRNA levels of KDM1A and Yin Yang 1 (YY1) were determined by RT‐qPCR analysis. Western blot was performed to measure KDM1A and ubiquitin‐specific protease 1 (USP1) protein expression. Cell proliferation, apoptosis, invasion, migration and stemness were evaluated by MTT assay, EdU assay, flow cytometry, transwell invasion assay, wound‐healing assay and sphere‐formation assay, respectively. ChIP and dual‐luciferase reporter assays were conducted to determine the relationship between YY1 and KDM1A. Xenograft tumor experiment and IHC were carried out to investigate the roles of USP1 and KDM1A in TNBC development in vivo. The highly expressed KDM1A was demonstrated in TNBC tissues and cells, and KDM1A knockdown significantly promoted cell apoptosis, and hampered cell proliferation, invasion, migration, and stemness in TNBC cells. USP1 could increase the stability of KDM1A via deubiquitination, and USP1 depletion restrained the progression of TNBC cells through decreasing KDM1A expression. Moreover, YY1 transcriptionally activated KDM1A expression by directly binding to its promoter in TNBC cells. Additionally, USP1 inhibition reduced KDM1A expression to suppress tumor growth in TNBC mice in vivo. In conclusion, YY1 upregulation increased KDM1A expression via transcriptional activation. USP1 stabilized KDM1A through deubiquitination to promote TNBC progression.
MEOX1 triggers myofibroblast apoptosis resistance, contributing to pulmonary fibrosis in mice
Authors: Jin Ling , Bao Bo , Huang Xiao‐Ting , Tao Jia‐Hao , Duan Jia‐Xi , Zhong Wen‐Jin , Zhang Chen‐Yu , Liu Yu‐Biao , Chen Hui , Yang Nan‐Shi‐Yu , Guan Cha‐Xiang , Zhou Yong 
Published: September 2024

AbstractThe apoptosis resistance of myofibroblasts is a hallmark in the irreversible progression of pulmonary fibrosis (PF). While the underlying molecular mechanism remains elusive. In this study, we unveiled a previously unrecognized mechanism underlying myofibroblast apoptosis resistance during PF. Our investigation revealed heightened expression of mesenchyme homeobox 1 (MEOX1) in the lungs of idiopathic pulmonary fibrosis (IPF) patients and bleomycin‐induced PF mice. Silencing MEOX1 significantly attenuated PF progression in mice. In vitro, we found a notable increase in MEOX1 expression in transforming growth factor‐β1 (TGF‐β1)‐induced myofibroblasts. Silencing MEOX1 enhanced apoptosis of myofibroblasts. Mechanistically, we identified G‐protein signaling pathway regulatory factor 4 (RGS4) as a critical downstream target of MEOX1, as predicted by bioinformatics analysis. MEOX1 enhanced apoptosis resistance by upregulating RGS4 expression in myofibroblasts. In conclusion, our study highlights MEOX1 as a promising therapeutic target for protecting against PF by modulating myofibroblast apoptosis resistance.