bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prophylactic use of interleukin 6 monoclonal antibody can reduce CRS response of CAR-T cell therapy
Authors: Dou Baitao , Ren Shihui , Qiu Ling , Zhang Xupai , Zhang Nan , Cai Jiao , Chen Dan , Zhang Qian , Yao Hao , Fan Fangyi 
Published: January 2024

BackgroundChimeric antigen receptor T (CAR-T) cell immunotherapy is becoming one of the most promising treatments for hematological malignancies, however, complications such as cytokine release syndrome (CRS) seriously threaten the lives of patients. Interleukin 6(IL-6) monoclonal antibody is the common and useful treatment of CRS, however, it is not clear whether prophylactic use IL-6 monoclonal antibody before CAR-T therapy can reduce the incidence of CRS.PurposeThis study aims to systematically evaluate whether the prophylactic use of IL-6 monoclonal antibody can reduce the incidence of CRS.Data sources and methodsWe searched the PubMed, Embase, web of Science, and Cochrane Library databases for studies that reported the prophylactic use of IL-6 monoclonal antibody in the treatment of CRS-related complications of CAR-T cell immunotherapy before December 2022. The literature is screened according to the established inclusion and exclusion criteria, relevant data are extracted, and the quality of the literature is evaluated using the scale Cochrane bias risk assessment tool, and the Review Manager 5.3 is used to draw for related charts. Since the two experimental data only provide the median, the maximum and minimum values of the data, the mean and standard (Standard Deviation, SD) are calculated by this document Delai, and finally use Review Manager for data processing, and STATA software for supplementation.ResultsA total of 2 trials with a total of 37 participants were included in this study. Meta-analysis showed that compared with no use of IL-6 monoclonal antibody to prevent CRS, IL-6 monoclonal antibody was given to patients at 8 mg/kg one hour before CAR-T cell infusion, which reduced the incidence of CRS [RR: 0.41 95% confidence interval (0.20, 0.86) I[2] = 0.0% P = 0.338 z = −2.369 (p = 0.018)]. In subgroup analysis, compared with those who did not use IL-6 monoclonal antibody to prevent CRS, IL-6 monoclonal antibody was given to patients at 8 mg/kg one hour before CAR-T cell infusion, which reduced lactate dehydrogenase (LDH)[MD: −617.21, 95% confidence interval (−1104.41, −130.01) I[2] = 0% P = 0.88 Z = 2.48 (P = 0.01)], prophylactic use of IL-6 monoclonal antibody has a significant effect on reducing peak C-reactive protein (CRP) after CAR-T therapy [MD: −11.58, 95% confidence interval (−15.28, −7.88) I[2] = 0.0% P = 0.73 z = 6.14 (p &lt; 0.00001)].ConclusionThe prophylactic use of IL-6 monoclonal antibody can significantly reduce the incidence of CRS complications after CAR-T therapy, can also reduce LDH vaule and peak CRP vaule after CAR-T therapy.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023487662, identifier CRD42023487662.
Fasting glucose variability and risk of dementia in Parkinson’s disease: a 9-year longitudinal follow-up study of a nationwide cohort
Authors: Kang Sung Hoon , Choi Yunjin , Chung Su Jin , Moon Seok-Joo , Kim Chi Kyung , Kim Ji Hyun , Oh Kyungmi , Yoon Joon Shik , Seo Sang Won , Cho Geum Joon , Koh Seong-Beom 
Published: January 2024

BackgroundDiabetes is associated with an increased risk of Parkinson’s disease dementia (PDD); however, it is unknown whether this association is dependent on continuous hyperglycemia, hypoglycemic events, or glycemic variability. We aimed to investigate the relationship between visit-to-visit fasting glucose variability and PDD development in patients with Parkinson’s disease (PD).MethodsUsing data from the Korean National Health Insurance Service, we examined 9,264 patients aged ≥40 years with de novo Parkinson’s disease (PD) who underwent ≥3 health examinations and were followed up until December 2019. Glucose variability was measured using the coefficient of variation, variability independent of the mean, and average real variability. Fine and Gray competing regression analysis was performed to determine the effect of glucose variability on incident PDD.ResultsDuring the 9.5-year follow-up period, 1,757 of 9,264 (19.0%) patients developed PDD. Patients with a higher visit-to-visit glucose variability had a higher risk of future PDD. In the multivariable adjusted model, patients with PD in the highest quartile (subdistribution hazard ratio [SHR] = 1.50, 95% CI 1.19 to 1.88), quartile 3 (SHR = 1.29, 95% CI 1.02 to 1.62), and quartile 2 (SHR = 1.30, 95% CI 1.04 to 1.63) were independently associated with a higher risk of PDD than those in the lowest quartile.ConclusionWe highlighted the effect of long-term glucose variability on the development of PDD in patients with PD. Furthermore, our findings suggest that preventive measures for constant glucose control may be necessary to prevent PDD.
Vibration-induced postural reactions: a scoping review on parameters and populations studied
Authors: Bertrand-Charette Michaël , Perron Marie-Pier , da Silva Rubens A. , Beaulieu Louis-David 
Published: January 2024

ObjectiveMechanical vibration is an effective way for externally activating Ia primary endings of the muscle spindles and skin mechanoreceptors. Despite its popularity in proprioception and postural control studies, there is still no review covering the wide variety of vibration parameters or locations used in studies. The main purpose of this scoping review was thus to give an overview of general vibration parameters and to identify, if available, the rationale for justifying methodological choices concerning vibration parameters.MethodsThree databases (Pubmed, CINHAL, and SPORTDiscus) were searched from inception to July 2022. Included articles were to focus on the study of muscle spindles and skin mechanoreceptors vibration in humans and assess postural control. Following inclusion, data regarding demographic information, populations, vibration parameters and rationale were extracted and summarized.ResultsOne hundred forty-seven articles were included, mostly targeting lower extremities (n= 137) and adults (n= 126). The parameters used varied widely but were most often around 80 Hz, at an amplitude of 1 mm for 10–20 s. Regarding rationales, nearly 50% of the studies did not include any, whereas those including one mainly cited the same two studies, without elaborating specifically on the parameter's choice.ConclusionThis scoping review provided a comprehensive description of the population recruited and parameters used for vibration protocols in current studies with humans. Despite many studies, there remain important gaps of knowledge that needs to be filled, especially for vibration amplitude and duration parameters in various populations.
Comparing quality of life in lower extremity tumor patients undergoing limb salvage surgery and amputation: a meta-analysis
Authors: Banskota Nishant , Lei Senlin , Yuan Dechao , Fang Xiang , Banskota Sonali , Zhang Wenli , Duan Hong 
Published: January 2024

PurposeLimb salvage surgery and amputation are two commonly performed procedures for lower extremity tumors. When comparing these procedures in tumor patients, it is important to consider their impact on quality of life (QOL) and functional mobility. These patients often experience physical, emotional, and psychological challenges, making these factors crucial in determining the most suitable treatment approach.MethodThe outcomes of lower extremity tumors patients for QOL were collected from PubMed, MEDLINE, EMBASE, Cochrane, and Google Scholar until 28 February 2023. The physical function, mental health, role function, social function, emotional function, Toronto Extremity Salvage Score, and Musculoskeletal Tumor Society Score outcomes were analyzed to determine the differences between the two procedures.ResultsFive articles were included according to the selection criteria with a total of 245 patients. The standard mean difference (SMD) values of each parameter were slightly higher in limb salvage surgery patients but not higher enough to produce statistically significant results; the SMD values for physical function and mental health were 0.72 and 0.04, respectively. This study did not report any heterogeneity or publication bias.ConclusionsQOL is a large and enhanced term, which carries its importance and is challenging to compare between any procedures. The minimal rise in SMD of different QOL parameters highlighted only a slight advantage of limb salvage surgery over amputation. Therefore, further research is required to explore the impact of this crucial topic.
Fraisinib: a calixpyrrole derivative reducing A549 cell-derived NSCLC tumor in vivo acts as a ligand of the glycine-tRNA synthase, a new molecular target in oncology
Authors: Ben Toumia Iméne , Bachetti Tiziana , Chekir-Ghedira Leila , Profumo Aldo , Ponassi Marco , Di Domizio Alessandro , Izzotti Alberto , Sciacca Salvatore , Puglisi Caterina , Forte Stefano , Giuffrida Raffaella , Colarossi Cristina , Milardi Danilo , Grasso Giuseppe , Lanza Valeria , Fiordoro Stefano , Drago Giacomo , Tkachenko Kateryna , Cardinali Barbara , Romano Paolo , Iervasi Erika , Vargas Gabriela Coronel , Barboro Paola , Kohnke Franz Heinrich , Rosano Camillo 
Published: January 2024

Background and purpose: Lung cancer is the leading cause of death in both men and women, constituting a major public health problem worldwide. Non-small-cell lung cancer accounts for 85%–90% of all lung cancers. We propose a compound that successfully fights tumor growth in vivo by targeting the enzyme GARS1.Experimental approach: We present an in-depth investigation of the mechanism through which Fraisinib [meso-(p-acetamidophenyl)-calix(4)pyrrole] affects the human lung adenocarcinoma A549 cell line. In a xenografted model of non-small-cell lung cancer, Fraisinib was found to reduce tumor mass volume without affecting the vital parameters or body weight of mice. Through a computational approach, we uncovered that glycyl-tRNA synthetase is its molecular target. Differential proteomics analysis further confirmed that pathways regulated by Fraisinib are consistent with glycyl-tRNA synthetase inhibition.Key results: Fraisinib displays a strong anti-tumoral potential coupled with limited toxicity in mice. Glycyl-tRNA synthetase has been identified and validated as a protein target of this compound. By inhibiting GARS1, Fraisinib modulates different key biological processes involved in tumoral growth, aggressiveness, and invasiveness.Conclusion and implications: The overall results indicate that Fraisinib is a powerful inhibitor of non-small-cell lung cancer growth by exerting its action on the enzyme GARS1 while displaying marginal toxicity in animal models. Together with the proven ability of this compound to cross the blood–brain barrier, we can assess that Fraisinib can kill two birds with one stone: targeting the primary tumor and its metastases “in one shot.” Taken together, we suggest that inhibiting GARS1 expression and/or GARS1 enzymatic activity may be innovative molecular targets for cancer treatment.
Iron scavenging and suppression of collagen cross-linking underlie antifibrotic effects of carnosine in the heart with obesity
Authors: Berdaweel Islam A. , Monroe T. Blake , Alowaisi Amany A. , Mahoney Jolonda C. , Liang I-Chau , Berns Kaitlyn A. , Gao Dylan , McLendon Jared M. , Anderson Ethan J. 
Published: January 2024

Oral consumption of histidyl dipeptides such as l-carnosine has been suggested to promote cardiometabolic health, although therapeutic mechanisms remain incompletely understood. We recently reported that oral consumption of a carnosine analog suppressed markers of fibrosis in liver of obese mice, but whether antifibrotic effects of carnosine extend to the heart is not known, nor are the mechanisms by which carnosine is acting. Here, we investigated whether oral carnosine was able to mitigate the adverse cardiac remodeling associated with diet induced obesity in a mouse model of enhanced lipid peroxidation (i.e., glutathione peroxidase 4 deficient mice, GPx4+/−), a model which mimics many of the pathophysiological aspects of metabolic syndrome and T2 diabetes in humans. Wild-type (WT) and GPx4+/−male mice were randomly fed a standard (CNTL) or high fat high sucrose diet (HFHS) for 16 weeks. Seven weeks after starting the diet, a subset of the HFHS mice received carnosine (80 mM) in their drinking water for duration of the study. Carnosine treatment led to a moderate improvement in glycemic control in WT and GPx4+/−mice on HFHS diet, although insulin sensitivity was not significantly affected. Interestingly, while our transcriptomic analysis revealed that carnosine therapy had only modest impact on global gene expression in the heart, carnosine substantially upregulated cardiac GPx4 expression in both WT and GPx4+/−mice on HFHS diet. Carnosine also significantly reduced protein carbonyls and iron levels in myocardial tissue from both genotypes on HFHS diet. Importantly, we observed a robust antifibrotic effect of carnosine therapy in hearts from mice on HFHS diet, which further in vitro experiments suggest is due to carnosine’s ability to suppress collagen-cross-linking. Collectively, this study reveals antifibrotic potential of carnosine in the heart with obesity and illustrates key mechanisms by which it may be acting.
Cardiac miRNA expression during the development of chronic anthracycline-induced cardiomyopathy using an experimental rabbit model
Authors: Adamcova Michaela , Parova Helena , Lencova-Popelova Olga , Kollarova-Brazdova Petra , Baranova Ivana , Slavickova Marcela , Stverakova Tereza , Mikyskova Petra Sauer , Mazurova Yvona , Sterba Martin 
Published: January 2024

Background: Anthracycline cardiotoxicity is a well-known complication of cancer treatment, and miRNAs have emerged as a key driver in the pathogenesis of cardiovascular diseases. This study aimed to investigate the expression of miRNAs in the myocardium in early and late stages of chronic anthracycline induced cardiotoxicity to determine whether this expression is associated with the severity of cardiac damage.Method: Cardiotoxicity was induced in rabbits via daunorubicin administration (daunorubicin, 3 mg/kg/week; for five and 10 weeks), while the control group received saline solution. Myocardial miRNA expression was first screened using TaqMan Advanced miRNA microfluidic card assays, after which 32 miRNAs were selected for targeted analysis using qRT-PCR.Results: The first subclinical signs of cardiotoxicity (significant increase in plasma cardiac troponin T) were observed after 5 weeks of daunorubicin treatment. At this time point, 10 miRNAs (including members of the miRNA-34 and 21 families) showed significant upregulation relative to the control group, with the most intense change observed for miRNA-1298-5p (29-fold change, p &lt; 0.01). After 10 weeks of daunorubicin treatment, when a further rise in cTnT was accompanied by significant left ventricle systolic dysfunction, only miR-504-5p was significantly (p &lt; 0.01) downregulated, whereas 10 miRNAs were significantly upregulated relative to the control group; at this time-point, the most intense change was observed for miR-34a-5p (76-fold change). Strong correlations were found between the expression of multiple miRNAs (including miR-34 and mir-21 family and miR-1298-5p) and quantitative indices of toxic damage in both the early and late phases of cardiotoxicity development. Furthermore, plasma levels of miR-34a-5p were strongly correlated with the myocardial expression of this miRNA.Conclusion: To the best of our knowledge, this is the first study that describes alterations in miRNA expression in the myocardium during the transition from subclinical, ANT-induced cardiotoxicity to an overt cardiotoxic phenotype; we also revealed how these changes in miRNA expression are strongly correlated with quantitative markers of cardiotoxicity.
Renal and survival benefits of seventeen prescribed Chinese herbal medicines against oxidative-inflammatory stress in systemic lupus erythematosus patients with chronic kidney disease: a real-world longitudinal study
Authors: Chen Hsiao-Tien , Tung Chien-Hsueh , Yu Ben-Hui , Chang Ching-Mao , Chen Yi-Chun 
Published: January 2024

Background: Systemic lupus erythematosus (SLE) significantly links to LN, a type of CKD with high mortality despite modern Western treatments. About 70% of SLE patients develop LN, and 30% advance to end-stage renal disease (ESRD). Concerns about glucocorticoid side effects and LN worsening due to oxidative stress prompt alternative treatment searches. In Taiwan, over 85% of SLE patients opt for complementary methods, especially Chinese herbal medicine (CHM). We pinpointed seventeen CHMs for SLE (PRCHMSLE) with antioxidative and anti-inflammatory properties from national health insurance data (2000–2017). Our primary aim was to assess their impact on renal and survival outcomes in SLE patients progressing to CKD (SLE-CKD), with a secondary focus on the risks of hospitalization and hyperkalemia.Methods: We established a propensity-matched cohort of 1,188 patients with SLE-CKD, comprising 594 PRCHMSLE users and 594 nonusers. We employed Cox proportional hazards models and restricted mean survival time (RMST) analyses to assess the renal and survival outcomes of PRCHMSLE users. Moreover, we performed pooling and network analyses, specifically focusing on the renal effects linked to PRCHMSLE.Results: PRCHMSLE use was associated with decreased adjusted hazard ratios for ESRD (0.45; 95% confidence interval, 0.25–0.79, p = 0.006), all-cause mortality (0.56; 0.43–0.75, p &lt; 0.0001), non-cardiovascular mortality (0.56; 0.42–0.75, p &lt; 0.0001), and hospitalization (0.72; 0.52–0.96, p = 0.009). Hyperkalemia risk did not increase. Significant differences in RMST were observed: 0.57 years (95% confidence interval, 0.19–0.95, p = 0.004) for ESRD, 1.22 years (0.63–1.82, p &lt; 0.0001) for all-cause mortality, and 1.21 years (0.62–1.80, p &lt; 0.0001) for non-cardiovascular mortality, favoring PRCHMSLE use. Notably renoprotective PRCHMSLE included Gan-Lu-Ying, Anemarrhena asphodeloides Bunge [Asparagaceae; Rhizoma Anemarrhenae] (Zhi-Mu), Rehmannia glutinosa (Gaertn.) DC. [Orobanchaceae; Radix Rehmanniae] (Sheng-Di-Huang), Jia-Wei-Xiao-Yao-San, and Paeonia suffruticosa Andr. [Paeoniaceae; Cortex Moutan] (Mu-Dan-Pi). Network analysis highlighted primary treatment strategies with central components like Liu-Wei-Di-Huang-Wan, Paeonia suffruticosa Andr. [Paeoniaceae; Cortex Moutan] (Mu-Dan-Pi), Anemarrhena asphodeloides Bunge [Asparagaceae; Rhizoma Anemarrhenae] (Zhi-Mu), Rehmannia glutinosa (Gaertn.) DC. [Orobanchaceae; Radix Rehmanniae] (Sheng-Di-Huang), and Zhi-Bai-Di-Huang-Wan.Conclusion: This work underscores the pronounced renal and survival benefits associated with the seventeen PRCHMSLE in the treatment of SLE-CKD, concurrently mitigating the risks of hospitalization and hyperkalemia. This highlights their potential as alternative treatment options for individuals with this condition.
Nernst-Planck-Gaussian modelling of electrodiffusional recovery from ephaptic excitation between mammalian cardiomyocytes
Authors: Morris Joshua A. , Bardsley Oliver J. , Salvage Samantha C. , Jackson Antony P. , Matthews Hugh R. , Huang Christopher L-H. 
Published: January 2024

Introduction: In addition to gap junction conduction, recent reports implicate possible ephaptic coupling contributions to action potential (AP) propagation between successive adjacent cardiomyocytes. Here, AP generation in an active cell, withdraws Na+ from, creating a negative potential within, ephaptic spaces between the participating membranes, activating the initially quiescent neighbouring cardiomyocyte. However, sustainable ephaptic transmission requires subsequent complete recovery of the ephaptic charge difference. We explore physical contributions of passive electrodiffusive ion exchange with the remaining extracellular space to this recovery for the first time.Materials and Methods: Computational, finite element, analysis examined limiting, temporal and spatial, ephaptic [Na+], [Cl−], and the consequent Gaussian charge differences and membrane potential recovery patterns following a ΔV∼130 mV AP upstroke at physiological (37°C) temperatures. This incorporated Nernst-Planck formalisms into equations for the time-dependent spatial concentration gradient profiles.Results: Mammalian atrial, ventricular and purkinje cardiomyocyte ephaptic junctions were modelled by closely apposed circularly symmetric membranes, specific capacitance 1 μF cm-2, experimentally reported radii a = 8,000, 12,000 and 40,000 nm respectively and ephaptic axial distance w = 20 nm. This enclosed an ephaptic space containing principal ions initially at normal extracellular [Na+] = 153.1 mM and [Cl−] = 145.8 mM, respective diffusion coefficients DNa = 1.3 × 109 and DCl = 2 × 109 nm2s-1. Stable, concordant computational solutions were confirmed exploring ≤1,600 nm mesh sizes and Δt≤0.08 ms stepsize intervals. The corresponding membrane voltage profile changes across the initially quiescent membrane were obtainable from computed, graphically represented a and w-dependent ionic concentration differences adapting Gauss’s flux theorem. Further simulations explored biological variations in ephaptic dimensions, membrane anatomy, and diffusion restrictions within the ephaptic space. Atrial, ventricular and Purkinje cardiomyocytes gave 40, 180 and 2000 ms 99.9% recovery times, with 720 or 360 ms high limits from doubling ventricular radius or halving diffusion coefficient. Varying a, and DNa and DCl markedly affected recovery time-courses with logarithmic and double-logarithmic relationships, Varying w exerted minimal effects.Conclusion: We thereby characterise the properties of, and through comparing atrial, ventricular and purkinje recovery times with interspecies in vivo background cardiac cycle duration data, (blue whale ∼2000, human∼90, Etruscan shrew, ∼40 ms) can determine physical limits to, electrodiffusive contributions to ephaptic recovery.