bluuebunny/crossref_metadata_2025_split huggingface dataset:
CXCL13 promotes thermogenesis in mice via recruitment of M2 macrophage and inhibition of inflammation in brown adipose tissue
Authors: Xie Lijun , Wang Huiying , Wu Dan , Zhang Feng , Chen Wei , Ye Yuqing , Hu Fang 
Published: October 2023

IntroductionBrown adipose tissue (BAT) is mainly responsible for mammalian non-shivering thermogenesis and promotes energy expenditure. Meanwhile, similar to white adipose tissue (WAT), BAT also secretes a variety of adipokines to regulate metabolism through paracrine, autocrine, or endocrine ways. The chemokine C-X-C motif chemokine ligand-13 (CXCL13), a canonical B cell chemokine, functions in inflammation and tumor-related diseases. However, the role of CXCL13 in the adipose tissues is unclear.MethodsThe expression of CXCL13 in BAT and subcutaneous white adipose tissue (SWAT) of mice under cold stimulation were detected. Local injection of CXCL13 into BAT of normal-diet and high-fat-diet induced obese mice was used to detect thermogenesis and determine cold tolerance. The brown adipocytes were treated with CXCL13 alone or in the presence of macrophages to determine the effects of CXCL13 on thermogenic and inflammation related genes expression in vitro.ResultsIn this study, we discovered that the expression of CXCL13 in the stromal cells of brown adipose tissue significantly elevated under cold stimulation. Overexpression of CXCL13 in the BAT via local injection could increase energy expenditure and promote thermogenesis in obese mice. Mechanically, CXCL13 could promote thermogenesis via recruiting M2 macrophages in the BAT and, in the meantime, inhibiting pro-inflammatory factor TNFα level. DiscussionThis study revealed the novel role of adipose chemokine CXCL13 in the regulation of BAT activity and thermogenesis.
Circulating miRNA expression in extracellular vesicles is associated with specific injuries after multiple trauma and surgical invasiveness
Authors: Groven Rald Victor Maria , Greven Johannes , Mert Ümit , Horst Klemens , Zhao Qun , Blokhuis Taco Johan , Huber-Lang Markus , Hildebrand Frank , van Griensven Martijn 
Published: October 2023

IntroductionTwo trauma treatment principles are Early Total Care (ETC), and Damage Control Orthopedics (DCO). Cellular mechanisms that underlie the connection between treatment type, its systemic effects, and tissue regeneration are not fully known. Therefore, this study aimed to: 1) profile microRNA (miRNA) expression in plasma derived Extracellular Vesicles (EVs) from a porcine multiple trauma model at different timepoints, comparing two surgical treatments; and 2) determine and validate the miRNA’s messengerRNA (mRNA) targets.MethodsThe porcine multiple trauma model consisted of blunt chest trauma, liver laceration, bilateral femur fractures, and controlled haemorrhagic shock. Two treatment groups were defined, ETC (n=8), and DCO (n=8). Animals were monitored under Intensive Care Unit-standards, blood was sampled at 1.5, 2.5, 24, and 72 hours after trauma, and EVs were harvested from plasma. MiRNAs were analysed using quantitative Polymerase Chain Reaction arrays. MRNA targets were identified in silico and validated in vivo in lung and liver tissue.ResultsThe arrays showed distinct treatment specific miRNA expression patterns throughout all timepoints, and miRNAs related to the multiple trauma and its individual injuries. EV-packed miRNA expression in the ETC group was more pro-inflammatory, indicating potentially decreased tissue regenerative capacities in the acute post-traumatic phase. In silico target prediction revealed several overlapping mRNA targets among the identified miRNAs, related to inflammation, (pulmonary) fibrosis, and Wnt-signalling. These were, among others, A Disintegrin and Metalloproteinase domain-containing protein 10, Collagen Type 1 Alpha 1 Chain, Catenin Beta Interacting Protein 1, and Signal Transducers and Activators of Transcription 3. Validation of these mRNA targets in the lung showed significant, treatment specific deregulations which matched the expression of their upstream miRNAs. No significant mRNA deregulations were observed in the liver.DiscussionThis study showed treatment specific, EV-packed miRNA expression patterns after trauma that correlated with mRNA expressions in the lungs, target organs over distance. A systemic response to the increased surgical trauma in the ETC group was identified, with various miRNAs associated with injuries from the trauma model, and involved in (systemic) inflammation, tissue regeneration. EV-transported miRNAs demonstrated a clear role in multiple trauma, warranting further research into tissue-tissue talk and therapeutic applications of EVs after trauma.
Evaluation of the impact of reliance on the regulatory performance in the South African Health Products Regulatory Authority: implications for African regulatory authorities
Authors: Danks Lorraine , Semete-Makokotlela Boitumelo , Otwombe Kennedy , Parag Yashmika , Walker Stuart , Salek Sam 
Published: October 2023

IntroductionThe World Health Organization (WHO) advocates the use of reliance practices to enable national regulatory authorities (NRAs) to improve patients’ access to medicines. This study considered whether reliance review translates into swifter medicine authorization.MethodsAbridged review outcomes were examined for New Chemical Entity (NCE) and generic applications to the South African Health Products Regulatory Authority (SAHPRA) in Chemistry, Manufacturing and Controls (CMC) and clinical/bioequivalence (BE), as well as overall NCE authorization times.ResultsSAHPRA NCE CMC review time was 91 days (abridged) vs. 179 days (full), applicant response time was 34 vs. 105 days, respectively, and there was a &gt;2-fold time reduction for abridged vs. full CMC review (125 vs. 284 days). There was a 99-day decrease in clinical approval time through an abridged review (230 vs. 329 days) and a decrease in marketing authorization time for NCE abridged assessment (446 vs. 619 days). SAHPRA review time for generic applications was 97 days (abridged) vs. 191 days (full); applicant response time was 26 days (abridged) vs. 81 days (full) and there was a &gt;2-fold time reduction for CMC and BE abridged vs. full review (122 vs. 272 days).ConclusionThese results clearly support World Health Organization recommendations for the use of reliance-based regulatory review to expedite the worldwide availability of safe, effective and needed medications.
Soil microbial diversity under different types of interference in birch secondary forest in the Greater Khingan Mountains in China
Authors: Zhai Kaitao , Hua Yongchun , Liang Jingwen , Li Jing , Wang Zirui , Liu Lei , Gao Minglong , Sa Rula , Zhao Mingmin 
Published: October 2023

IntroductionSoil microorganisms are an important component of soil ecosystems with an indispensable role in forest ecosystems. We analyzed the soil microbial diversity in birch secondary forest formed by natural restoration or artificial reconstruction after interference by burning, clear cutting, and gradient cutting, and the Betula platyphylla Suk undisturbed forest in the Greater Khingan Mountains in China.MethodsIllumina high-throughput sequencing technology was used to analyze the characteristics of the soil microbial community during the restoration process of birch secondary forest caused by the different types of interference. The relationships between bacteria and fungi were analyzed. The gene functions of the soil bacterial community and the ecological functions of soil fungi were predicted using PICRUSt and FunGuild, respectively.ResultsAt the phylum level, the species and quantity of bacteria were more abundant than that of fungi. At the genus level, no obvious differences in the abundance of bacteria were observed; there were obvious differences in the abundance of fungi. Among the eight sample plots, the artificial larch forest belt had the highest bacterial and fungal alpha diversity, which was slightly higher than undisturbed forest, while the other sample plots were significantly lower. Gradual cutting pure birch forest bacteria and fungi had the highest beta diversity, and artificial larch forest belt bacteria and heavy burn sample plot fungi had the lowest beta diversity. Samples from the cutting and burning sample plots were significantly different from the undisturbed forest at the phylum level of Acidobacteriae, Acidimicrobiia, Mortierellomycetes and Sordariomycetes. We found statistical differences in biomarkers between bacterial and fungal communities in undisturbed forest and artificial larch forest belt and burn sample plots. PICRUSt prediction and FunGuild prediction showed that soil bacterial and fungal communities were rich in gene and ecological functions, respectively. In the microbial network, the stability or anti-interference performance of the fungal community was higher than that of bacteria.ConclusionOur data reveal the characteristics of the soil microbial community during the restoration process of Betula platyphylla Suk secondary forest under different types of disturbance, which is of great significance for understanding the role of soil microorganisms in the forest ecological cycle.
Systematic review and meta-analysis of the effects of menopause hormone therapy on risk of Alzheimer’s disease and dementia
Authors: Nerattini Matilde , Jett Steven , Andy Caroline , Carlton Caroline , Zarate Camila , Boneu Camila , Battista Michael , Pahlajani Silky , Loeb-Zeitlin Susan , Havryulik Yelena , Williams Schantel , Christos Paul , Fink Matthew , Brinton Roberta Diaz , Mosconi Lisa 
Published: October 2023

IntroductionDespite a large preclinical literature demonstrating neuroprotective effects of estrogen, use of menopausal hormone therapy (HT) for Alzheimer’s disease (AD) risk reduction has been controversial. Herein, we conducted a systematic review and meta-analysis of HT effects on AD and dementia risk.MethodsOur systematic search yielded 6 RCT reports (21,065 treated and 20,997 placebo participants) and 45 observational reports (768,866 patient cases and 5.5 million controls). We used fixed and random effect meta-analysis to derive pooled relative risk (RR) and 95% confidence intervals (C.I.) from these studies.ResultsRandomized controlled trials conducted in postmenopausal women ages 65 and older show an increased risk of dementia with HT use compared with placebo [RR = 1.38, 95% C.I. 1.16–1.64, p &lt; 0.001], driven by estrogen-plus-progestogen therapy (EPT) [RR = 1.64, 95% C.I. 1.20–2.25, p = 0.002] and no significant effects of estrogen-only therapy (ET) [RR = 1.19, 95% C.I. 0.92–1.54, p = 0.18]. Conversely, observational studies indicate a reduced risk of AD [RR = 0.78, 95% C.I. 0.64–0.95, p = 0.013] and all-cause dementia [RR = .81, 95% C.I. 0.70–0.94, p = 0.007] with HT use, with protective effects noted with ET [RR = 0.86, 95% C.I. 0.77–0.95, p = 0.002] but not with EPT [RR = 0.910, 95% C.I. 0.775–1.069, p = 0.251]. Stratified analysis of pooled estimates indicates a 32% reduced risk of dementia with midlife ET [RR = 0.685, 95% C.I. 0.513–0.915, p = 0.010] and non-significant reductions with midlife EPT [RR = 0.775, 95% C.I. 0.474–1.266, p = 0.309]. Late-life HT use was associated with increased risk, albeit not significant [EPT: RR = 1.323, 95% C.I. 0.979–1.789, p = 0.069; ET: RR = 1.066, 95% C.I. 0.996–1.140, p = 0.066].DiscussionThese findings support renewed research interest in evaluating midlife estrogen therapy for AD risk reduction.
The relationship between cognition and white matter tract damage after mild traumatic brain injury in a premorbidly healthy, hospitalised adult cohort during the post-acute period
Authors: Anderson Jacqueline F. I. , Oehr Lucy E. , Chen Jian , Maller Jerome J. , Seal Marc L. , Yang Joseph Yuan-Mou 
Published: October 2023

IntroductionRecent developments in neuroimaging techniques enable increasingly sensitive consideration of the cognitive impact of damage to white matter tract (WMT) microstructural organisation after mild traumatic brain injury (mTBI).ObjectiveThis study investigated the relationship between WMT microstructural properties and cognitive performance.Participants, setting and designUsing an observational design, a group of 26 premorbidly healthy adults with mTBI and a group of 20 premorbidly healthy trauma control (TC) participants who were well-matched on age, sex, premorbid functioning and a range of physical, psychological and trauma-related variables, were recruited following hospital admission for traumatic injury.Main measuresAll participants underwent comprehensive unblinded neuropsychological examination and structural neuroimaging as outpatients 6–10 weeks after injury. Neuropsychological examination included measures of speed of processing, attention, memory, executive function, affective state, pain, fatigue and self-reported outcome. The WMT microstructural properties were estimated using both diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) modelling techniques. Tract properties were compared between the corpus callosum, inferior longitudinal fasciculus, uncinate fasciculus, anterior corona radiata and three segmented sections of the superior longitudinal fasciculus.ResultsFor the TC group, in all investigated tracts, with the exception of the uncinate fasciculus, two DTI metrics (fractional anisotropy and apparent diffusion coefficient) and one NODDI metric (intra-cellular volume fraction) revealed expected predictive linear relationships between extent of WMT microstructural organisation and processing speed, memory and executive function. The mTBI group showed a strikingly different pattern relative to the TC group, with no relationships evident between WMT microstructural organisation and cognition on most tracts.ConclusionThese findings indicate that the predictive relationship that normally exists in adults between WMT microstructural organisation and cognition, is significantly disrupted 6–10 weeks after mTBI and suggests that WMT microstructural organisation and cognitive function have disparate recovery trajectories.
Blood-based biomarkers: diagnostic value in brain tumors (focus on gliomas)
Authors: Yang Yuting , Hu Fei , Wu Song , Huang Zhangliang , Wei Kun , Ma Yuan , Ou-Yang Qing 
Published: October 2023

BackgroundBrain tumors, especially gliomas, are known for high lethality. It is currently understood that the correlations of tumors with coagulation and inflammation have been gradually revealed.ObjectiveThis study aimed to explore the potential value of several reported peripheral blood parameters as comprehensively as possible, with preoperative diagnosis and identification of brain tumors (focus on gliomas).MethodsPatients with central nervous system tumors (craniopharyngioma, ependymoma, spinal meningioma, acoustic neuroma, brain metastases, meningioma, and glioma) or primary trigeminal neuralgia admitted to our hospital were retrospectively analyzed. The results of the routine coagulation factor test, serum albumin test, and blood cell test in peripheral blood were recorded for each group of patients on admission. Neutrophil–lymphocyte ratio (NLR), derived NLR (dNLR), platelet–lymphocyte ratio (PLR), lymphocyte–monocyte ratio (LMR), prognostic nutritional index (PNI), the systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), and their pairings were calculated. Their ability to identify brain tumors and their correlation with glioma grade were analyzed.ResultsA total of 698 patients were included in this retrospective case–control study. Glioma patients had higher NLR, SII, and PIV but lower LMR. The NLR in the brain metastasis group was lower than that in the control, meningioma, and acoustic neuroma groups, but the SII and PIV were higher than those in the ependymoma group. Fibrinogen, white blood cell count, neutrophil count, NLR, SII, and PIV in the GBM group were higher than those in the control group. In all comparisons, NLR and NLR + dNLR showed the greatest accuracy, with areas under the curve (AUCs) of 0.7490 (0.6482–0.8498) and 0.7481 (0.6457–0.8505), respectively. PIV, dNLR + PIV, and LMR + PIV ranked second, with AUCs of 0.7200 (0.6551–0.7849), 0.7200 (0.6526–0.7874), 0.7204 (0.6530–0.7878) and 0.7206 (0.6536–0.7875), respectively.ConclusionNLR, PIV, and their combinations show high sensitivity and specificity in the diagnosis of brain tumors, especially gliomas. Overall, our results provide evidence for these convenient and reliable peripheral blood markers.
Cranial radiation therapy with hippocampus avoidance in lung cancer treatment: systematic review and meta-analysis
Authors: Zheng Yue , You Liting , Feng Baijie , Tang Min , Na Feifei 
Published: October 2023

BackgroundThe role of cranial radiation therapy with hippocampus avoidance (HA-CRT) in neurocognitive function (NCF), brain metastasis (BM), and overall survival (OS) in lung cancer remains unclear.MethodsA meta-analysis was conducted to evaluate the impact of HA-CRT in lung cancer. Data from studies on hippocampal-avoidance prophylactic cranial irradiation (HA-PCI) and whole brain radiotherapy (HA-WBRT) were pooled.ResultsA total of 14 studies, including 5 randomized controlled trials, were included. The focus of NCF was mainly via the Hopkins Verbal Learning Test—Revised or the Free and Cued Selective Reminding Test. At 6 months post-radiotherapy, the pooled proportion of participants with decline in the performance of total recall, delayed recall, and discrimination in neurocognitive tests were 0.22 (95% CI 0.15, 0.29), 0.20 (95% CI 0.13, 0.27), and 0.14 (95% CI 0.05, 0.24) respectively. After 12 months, the proportion were 0.16 (95% CI 0.08, 0.23), 0.10 (95% CI 0.04, 0.16), and 0.04 (95% CI 0, 0.09) respectively. For HA zone relapse, the RR of HA-CRT versus CRT was 2.72 (95% CI 0.53, 13.87), and for 2-year BM, it was 1.20 (95% CI 0.82, 1.75). Regarding HA-PCI in SCLC, the 1-year BM rate was 0.12 (95% CI 0.07, 0.17), and the 2-year BM rate was 0.20 (95% CI 0.16, 0.25). For HA-WBRT in NSCLC with BM, the 2-year intracranial progression rate was 0.38 (95% CI 0.13, 0.62). There was no significant difference in OS between HA-CRT and CRT.ConclusionsHA-CRT appears to be safe in lung cancer, but it may not outperform conventional CRT. Larger RCTs comparing HA-CRT and CRT are warranted.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022360890, identifier CRD42022360890.
Psychometric properties of the Sport Anxiety Scale-2 for Chinese adolescent athletes taking the National Sports College Entrance Examination
Authors: Li Shichen , Tang Changfa , Guo Cheng , Bu Te 
Published: October 2023

BackgroundThis study aims to evaluate the psychometric properties of the Sport Anxiety Scale-2 (SAS-2) in Chinese adolescent sports exam candidates.MethodsOne day before the National Sports College Entrance Examination, 965 Chinese athletes rated the Chinese-language SAS-2. Confirmatory factor analysis was performed to test the three-factor structure. Factorial invariance was tested by comparing the configural invariance model to three more constrained models. Construct validity and reliability were determined.ResultsFit indices meet the critical values: CFI = 0.953, TLI = 0.943, RMSEA = 0.048 [90% CI, 0.041–0.054], and SRMR = 0.042. All path factor loadings exceed 0.5. The changes in CFI and RMSEA across the configural, metric, scalar, and uniqueness invariance are within the critical values, demonstrating strict measurement invariance across gender, years of training, and type of sports. The average variance extracted of the worry sub-scale is above the cutoff criteria, and McDonald's omega coefficients are over 0.70. Significant correlations exist between the SAS-2, SCAT, and CSAI-2. Factor correlations are all below 0.8. The measurement also distinguishes the known gender effect, with females showing a probability of 58.6% higher anxiety levels. The intraclass correlation coefficient ranges from 0.706 to 0.801.ConclusionThis study validated the Chinese-language SAS-2 in measuring competitive anxiety among Chinese adolescent athletes taking the National Sports College Entrance Examination. The development of the scale's applicability in China is discussed.
Mechanical ventilation induces brainstem inflammation in preterm fetal sheep
Authors: Vidinopoulos Kayla , Azman Zahrah , Somers Ainsley , Zahra Valerie A. , Thiel Alison , Lu Hui , Pham Yen , Tran Nhi Thao , Allison Beth J. , Herlenius Eric , Hooper Stuart , Galinsky Robert , Polglase Graeme R. 
Published: October 2023

BackgroundPreterm infants have immature respiratory drive and often require prolonged periods of mechanical ventilation. Prolonged mechanical ventilation induces systemic inflammation resulting in ventilation-induced brain injury, however its effect on brainstem respiratory centers is unknown. We aimed to determine the effects of 24 h of mechanical ventilation on inflammation and injury in brainstem respiratory centres of preterm fetal sheep.MethodsPreterm fetal sheep at 110 ± 1 days (d) gestation were instrumented to provide mechanical ventilation in utero. At 112 ± 1 d gestation, fetuses received either mechanical ventilation (VENT; n = 7; 3 ml/kg) for 24 h, or no ventilation (CONT; n = 6). At post-mortem, fetal brainstems were collected for assessment of mRNA and histological markers of inflammation and injury.ResultsIn utero ventilation (IUV) did not alter any blood-gas parameters. IUV significantly increased systemic IL-6 and IL-8 concentrations over the 24 h period compared to CONT. The number of ameboid microglia within the nucleus tractus solitarius and the raphe nucleus increased in VENT fetuses (p &lt; 0.05 for both vs. control). The % area fraction of GFAP + staining was not significantly higher within the preBötzinger complex (p = 0.067) and retrotrapezoid nucleus and parafacial respiratory group (p = 0.057) in VENT fetuses compared to CONT. Numbers of caspase-3 and TUNEL-positive cells were similar between groups. Gene expression (mRNA) levels of inflammation, injury, cell death and prostaglandin synthesis within the brainstem were similar between groups.ConclusionMechanical ventilation induces a systemic inflammatory response with only moderate inflammatory effects within the brainstem respiratory centres of preterm fetal sheep.