bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptome Analysis of Immune Receptor Activation and Energy Metabolism Reduction as the Underlying Mechanisms in Interleukin-6-Induced Skeletal Muscle Atrophy
Authors: Sun Hualin , Sun Junjie , Li Ming , Qian Lei , Zhang Lilei , Huang Ziwei , Shen Yuntian , Law Betty Yuen-Kwan , Liu Liang , Gu Xiaosong 
Published: September 2021

BackgroundInflammation may trigger skeletal muscle atrophy induced by cancer cachexia. As a pro-inflammatory factor, interleukin-6 may cause skeletal muscle atrophy, but the underlying molecular mechanisms have not been explored.MethodsIn this experimental study, we used adult male ICR mice, weighing 25 ± 2 g, and the continuous infusion of interleukin-6 into the tibialis anterior muscle to construct a skeletal muscle atrophy model (experimental group). A control group received a saline infusion. RNA-sequencing was used to analyze the differentially expressed genes in tissue samples after one and three days. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analysis were applied to define the function of these genes, and protein-protein interaction analysis was performed to identify potential transcription factors. Fluorescence microscopy was used to determine the muscle fiber cross-sectional area after 14 days.ResultsContinuous infusion of interleukin-6 for 14 days caused significant muscle atrophy. RNA-sequencing found 359 differentially expressed genes in the 1- and 3-day tissue samples and 1748 differentially expressed genes only in the 3-day samples. Functional analysis showed that the differentially expressed genes found in both the 1- and 3-day samples were associated with immune receptor activation, whereas the differentially expressed genes found only in the 3-day sample were associated with reduced energy metabolism. The expression of multiple genes in the oxidative phosphorylation and tricarboxylic acid cycle pathways was down-regulated. Furthermore, differentially expressed transcription factors were identified, and their interaction with interleukin-6 and the differentially expressed genes was predicted, which indicated that STAT3, NF-κB, TP53 and MyoG may play an important role in the process of interleukin-6-induced muscle atrophy.ConclusionsThis study found that interleukin-6 caused skeletal muscle atrophy through immune receptor activation and a reduction of the energy metabolism. Several transcription factors downstream of IL-6 have the potential to become new regulators of skeletal muscle atrophy. This study not only enriches the molecular regulation mechanism of muscle atrophy, but also provides a potential target for targeted therapy of muscle atrophy.
Ayurvedic vs. Conventional Nutritional Therapy Including Low-FODMAP Diet for Patients With Irritable Bowel Syndrome—A Randomized Controlled Trial
Authors: Jeitler Michael , Wottke Till , Schumann Dania , Puerto Valencia Laura M. , Michalsen Andreas , Steckhan Nico , Mittwede Martin , Stapelfeldt Elmar , Koppold-Liebscher Daniela , Cramer Holger , Wischnewsky Manfred , Murthy Vijayendra , Kessler Christian S. 
Published: September 2021

Aims: To compare the effects of Ayurvedic and conventional nutritional therapy in patients with irritable bowel syndrome (IBS).Methods: Sixty-nine patients with IBS were randomized to Ayurvedic (n = 35) or conventional nutritional therapy according to the recommendations of the German Nutrition Society including the low-FODMAP diet (n = 34). Study visits took place at baseline and after 1, 3, and 6 months. The primary outcome was IBS symptom severity (IBS-SSS) after 3 months; secondary outcomes included stress (CPSS), anxiety and depression (HADS), well-being (WHO-5) and IBS-specific quality of life (IBS-QOL). A repeated measures general linear model (GLM) for intent-to-treat-analyses was applied in this explorative study.Results: After 3 months, estimated marginal means for IBS-SSS reductions were 123.8 [95% confidence interval (95% CI) = 92.8–154.9; p &lt; 0.001] in the Ayurvedic and 72.7 (95% CI = 38.8–106.7; p &lt; 0.001) in the conventional group. The IBS-SSS reduction was significantly higher in the Ayurveda group compared to the conventional therapy group (estimated marginal mean = 51.1; 95% CI = 3.8–98.5; p = 0.035) and clinically meaningful. Sixty-eight percentage of the variance in IBS-SSS reduction after 3 months can be explained by treatment, 6.5% by patients' expectations for their therapies and 23.4% by IBS-SSS at pre-intervention. Both therapies are equivalent in their contribution to the outcome variance. The higher the IBS-SSS score at pre-intervention and the larger the patients' expectations, the greater the IBS-SSS reduction. There were no significant group differences in any secondary outcome measures. No serious adverse events occurred in either group.Conclusion: Patients with IBS seem to benefit significantly from Ayurvedic or conventional nutritional therapy. The results warrant further studies with longer-term follow-ups and larger sample sizes.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT03019861, identifier: NCT03019861.
Characteristics and Associated Factors of Flat Irregular Pigment Epithelial Detachment With Choroidal Neovascularization in Chronic Central Serous Chorioretinopathy
Authors: Su Yongyue , Zhang Xiongze , Gan Yuhong , Ji Yuying , Wen Feng 
Published: September 2021

Purpose: Flat irregular pigment epithelial detachment (FIPED) in chronic central serous chorioretinopathy (CSC) is strongly associated with type 1 choroidal neovascularization (CNV). The present study aimed to describe the multimodal imaging characteristics of FIPED in patients with chronic CSC and investigate the factors associated with vascularized FIPED.Methods: We included 55 chronic CSC eyes with vascularized FIPED (47 patients) and 55 chronic CSC eyes with avascular FIPED from age-matched patients (47 patients). None of the included eyes had a history of previous treatment with anti-vascular endothelial growth factor, photodynamic therapy, focal laser, or vitrectomy. The demographic and multimodal imaging data were reviewed. The location, angiography features, height and width, presence of retinal pigment epithelium (RPE) aggregations, RPE thickness, and choroid status of the FIPED area were compared between the groups.Results: The mean age of the included chronic CSC patients was 54.3 ± 7.8 years (range: 33–72 years), and 85.1% were male. Vascularized FIPED eyes had a larger width (1,556.4 ± 731.6 vs. 931.1 ± 486.2 μm, p &lt; 0.001), larger subfoveal RPE thickness (33.4 ± 15.3 vs. 26.3 ± 6.6 μm, p = 0.004), larger maximum RPE thickness of the FIPED area (46.3 ± 20.5 vs. 31.5 ± 8.3 μm, p &lt; 0.001), and more RPE aggregations in the FIPED area (94.5 vs. 54.5%, p &lt; 0.001) than avascular FIPED eyes. RPE aggregations in the FIPED area were an independent factor strongly associated with vascularized FIPED (OR = 7.922, 95% CI = 1.346–46.623, p = 0.022).Conclusion: FIPED with a larger width and RPE thickening may suggest the presence of an underlying type 1 CNV. FIPED with RPE aggregations had an increased occurrence of neovascularization in chronic CSC.
A Protocol for the Use of Case Reports/Studies and Case Series in Systematic Reviews for Clinical Toxicology
Authors: Nambiema Aboubakari , Sembajwe Grace , Lam Juleen , Woodruff Tracey , Mandrioli Daniele , Chartres Nicholas , Fadel Marc , Le Guillou Adrien , Valter Remi , Deguigne Marie , Legeay Marion , Bruneau Chloe , Le Roux Gaël , Descatha Alexis 
Published: September 2021

Introduction: Systematic reviews are routinely used to synthesize current science and evaluate the evidential strength and quality of resulting recommendations. For specific events, such as rare acute poisonings or preliminary reports of new drugs, we posit that case reports/studies and case series (human subjects research with no control group) may provide important evidence for systematic reviews. Our aim, therefore, is to present a protocol that uses rigorous selection criteria, to distinguish high quality case reports/studies and case series for inclusion in systematic reviews.Methods: This protocol will adapt the existing Navigation Guide methodology for specific inclusion of case studies. The usual procedure for systematic reviews will be followed. Case reports/studies and case series will be specified in the search strategy and included in separate sections. Data from these sources will be extracted and where possible, quantitatively synthesized. Criteria for integrating cases reports/studies and case series into the overall body of evidence are that these studies will need to be well-documented, scientifically rigorous, and follow ethical practices. The instructions and standards for evaluating risk of bias will be based on the Navigation Guide. The risk of bias, quality of evidence and the strength of recommendations will be assessed by two independent review teams that are blinded to each other.Conclusion: This is a protocol specified for systematic reviews that use case reports/studies and case series to evaluate the quality of evidence and strength of recommendations in disciplines like clinical toxicology, where case reports/studies are the norm.
Effect of Oral Sodium Bicarbonate Treatment on 24-Hour Ambulatory Blood Pressure Measurements in Patients With Chronic Kidney Disease and Metabolic Acidosis
Authors: Gaggl Martina , Repitz Alexandra , Riesenhuber Sonja , Aigner Christof , Sliber Christopher , Fraunschiel Melanie , Cejka Daniel , Sunder-Plassmann Gere 
Published: September 2021

Background: Sodium bicarbonate supplementation is a mainstay in the treatment of metabolic acidosis in patients with chronic kidney disease (CKD). Recent studies showed reduction of progression of CKD and reduced all-cause mortality. However, additional sodium loading could worsen arterial hypertension, a well-known contributor to progression of CKD. This patient-relevant and economically negative side effect is under-studied in prospective studies up until now.Objective: The aim of this study was to analyze the effect of sodium bicarbonate treatment on arterial blood pressure at baseline and after 8 weeks.Methods: The SoBic study is an ongoing randomized controlled trial, in which patients with CKD receive either a high dose of oral sodium bicarbonate or a rescue treatment, if necessary. We used standardized office blood pressure and 24-hour ambulatory blood pressure monitoring (24h-ABPM). Regression models were adjusted for estimated glomerular filtration rate and change of antihypertensives.Results: 47 subjects were enrolled and the mean age was 57 (±14.6) years and 18 (38%) were female. In 43 randomized subjects with sufficiently performed 24h-ABPM neither systolic 24h-ABPM (2.522; 95%CI: −2.364, 7.408; mmHg) nor diastolic 24h-ABPM (0.868; 95%CI: −2.411, 4.147; mmHg) was affected by study group allocation. When looking at the effect of individual sodium bicarbonate dose on 24h-ABPM, the fully adjusted model suggested an increase of 0.047 (95%CI: −0.026, 0.119) mmHg by each mg/kg per day increase of sodium bicarbonate dose.Conclusion: Sodium bicarbonate supplementation over 8 weeks did not significantly increase blood pressure measured by 24h-ABPM in CKD patients.Trial Registration: EUDRACT Number: 2012-001824-36; 12/07/2012 (https://www.clinicaltrialsregister.eu).
Hyponatremia Intervention Trial (HIT): Study Protocol of a Randomized, Controlled, Parallel-Group Trial With Blinded Outcome Assessment
Authors: Refardt Julie , Pelouto Anissa , Potasso Laura , Hoorn Ewout J. , Christ-Crain Mirjam 
Published: September 2021

Background: Hyponatremia is the most common electrolyte disorder with a prevalence of up to 30% in hospitalized patients. In contrast to acute hyponatremia where the need for immediate treatment is well-recognized, chronic hyponatremia is often considered not clinically relevant. This is illustrated by reports showing that appropriate laboratory tests are ordered in &lt;50% of patients and that up to 75% are still hyponatremic at discharge. At the same time, emerging evidence suggests an association between hyponatremia and adverse events including increased risk of mortality and rehospitalization.Methods: This is a randomized (1:1 ratio) controlled, superiority, parallel-group international multi-center trial with blinded outcome assessment. In total 2,278 participants will be enrolled. Participants will be randomly assigned to undergo either targeted correction of plasma sodium levels or standard of care during hospitalization. The primary outcome is the combined risk of death or re-hospitalization within 30 days.Discussion: All data on hyponatremia and mortality are derived from observational studies and often lack methodologic robustness. Consequently, the direct impact of hyponatremia on mortality and rehospitalization risk is still debated, resulting in a clinical equipoise whether in-hospital chronic hyponatremia should be treated or not. Therefore, a randomized controlled trial is required to study whether targeted plasma sodium correction reduces the risk of mortality and rehospitalization associated with hyponatremia.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03557957.
LBX2-AS1 as a Novel Diagnostic Biomarker and Therapeutic Target Facilitates Multiple Myeloma Progression by Enhancing mRNA Stability of LBX2
Authors: Jia Haipeng , Liu Yan , Lv Sulong , Qiao Ruifang , Zhang Xiaofen , Niu Fei , Shang Wenqing , Liu Shumei , Dong Jing , Zhang Zhirong 
Published: September 2021

Objective: Multiple myeloma (MM) represents a common age-associated malignancy globally. The function and underlying mechanism of antisense lncRNA LBX2-AS1 remain ambiguous in multiple myeloma (MM). Herein, we aimed to observe the biological implication of this lncRNA in MM.Methods: RT-qPCR was employed to examine circulating LBX2-AS1 and LBX2 in 60 paired MM and healthy subjects. Correlation between the two was analyzed by Pearson test. Under transfection with shLBX2-AS1, proliferation and apoptosis were evaluated in MM cells through CCK-8, colony formation and flow cytometry. LBX2 expression was examined in MM cells with shLBX2-AS1 or pcDNA3.1-LBX2 transfection. Following treatment with cycloheximide or actinomycin D, LBX2 expression was examined in pcDNA3.1-LBX2-transfected MM cells at different time points. Rescue assays were then presented. Finally, xenograft tumor models were established.Results: Circulating LBX2-AS1 was up-regulated in MM patients and positively correlated to LBX2 expression. Area under the curve (AUC) of LBX2-AS1 expression was 0.7525. Its up-regulation was also found in MM cells and primarily distributed in cytoplasm. LBX2-AS1 knockdown distinctly weakened proliferative ability and induced apoptosis in MM cells. Overexpressing LBX2-AS1 markedly strengthened LBX2 expression by increasing its mRNA stability. Rescue assays showed that silencing LBX2-AS1 distinctly weakened the pcDNA3.1-LBX2-induced increase in proliferation and decrease in apoptosis for MM cells. Silencing LBX2-AS1 markedly weakened tumor growth.Conclusion: Our data demonstrated that circulating LBX2-AS1 could be an underlying diagnostic marker in MM. Targeting LBX2-AS1 suppressed tumor progression by affecting mRNA stability of LBX2 in MM. Hence, LBX2-AS1 could be a novel therapeutic marker against MM.
Musk (Moschus moschiferus) Attenuates Changes in Main Olfactory Bulb of Depressed Mice: Behavioral, Biochemical, and Histopathological Evidence
Authors: Almohaimeed Hailah M. , Batawi Ashwaq H. , Mohammedsaleh Zuhair M. , Al Jaouni Soad , Mutlq Alsawat Samiah A. , Abd El Wahab Manal G. , AbdElfattah Amany A. , Ayuob Nasra N. 
Published: September 2021

BackgroundMusk (Moschus moschiferus) has been described to have a significant impact on the central nervous system, as well as anticonvulsion and antidepressant effects. This study was designed to evaluate the efficacy of musk in alleviating alterations induced in olfactory bulb of depressed mice exposed to chronic stress and identify the mechanism behind it.MethodsFifty male albino mice were divided into five groups (n= 10 each): control, musk, chronic unpredictable mild stress (CUMS), fluoxetine-treated, and musk-treated groups were included in this study. Behavioral changes and serum levels of corticosterone and proinflammatory cytokines included tumor necrosis factor α, interleukin 6, and oxidant/antioxidant profile were assessed at the end of the experiment. Main olfactory bulb (MOB) has been processed for histopathological examination. Gene expression of caspase-3, glial fibrillary acidic protein, and Ki67 were assessed in the MOB using quantitative real-time polymerase chain reaction.ResultsThe study showed that musk inhalation significantly reduced (p&lt; 0.001) corticosterone level, immobility time, inflammatory cytokines, and oxidative stress markers in CUMS-exposed mice compared to the untreated CUMS group. Musk lessened CUMS-associated neuronal alterations in the MOB and significantly reduced apoptosis and enhanced neural cell proliferation (p&lt; 0.001) comparable to fluoxetine. Musk significantly enhanced the level of antioxidants in the serum and significantly reduced inflammatory cytokines. The anti-inflammatory and antioxidant activity of musk and its constituents seemed to be behind its neuroprotective effect observed in this study.ConclusionMusk effectively ameliorated the chronic stress–induced behavioral, biochemical, and neuronal structural changes in MOB mostly through its antioxidant and anti-inflammatory effect.
Regional Differences in Early BP Management After Acute Ischemic Stroke in the ENCHANTED International Randomized Controlled Trials
Authors: Chen Chen , Song Lili , Yang Jie , Lindley Richard , Robinson Thompson , Arima Hisatomi , Chalmers John , Anderson Craig S. , Wang Xia 
Published: September 2021

Background and Aims: Epidemiological studies show significant variations in hypertension management within and between countries. The level of regional variation in early blood pressure (BP) management after acute stroke is uncertain.Methods: Data are from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED), a partial-factorial, international randomized controlled trial of thrombolysis-eligible acute ischemic stroke (AIS) patients with elevated systolic BP (SBP &gt;150 mmHg) assigned to intensive (target SBP 130-140 mmHg) vs. guideline-recommended (SBP &lt;180 mmHg) treatment; BP management was compared among four regions: Western countries (Italy/United Kingdom/Spain/Australia), China (mainland), other Asia (Hong Kong/Taiwan/Singapore/Thailand/Vietnam/India), and South America (Chile/Brazil/Colombia).Results: These analyses included 2,196 AIS [38% women, mean age 67 (12) years] patients. Commonly used intravenous BP-lowering agents were labetalol, nitroglycerin, and topical nitrates in Western countries; urapidil and sodium nitroprusside in China; nicardipine in other Asian countries; and sodium nitroprusside and labetalol in South America. Chinese patients were less likely to receive BP-lowering treatment in the first 24 h and be treated with multiple agents although they had smaller magnitude of SBP reduction and lower SBP variability.Conclusion: Regional variations in early BP management in acute stroke translated into differences in early BP control parameters.
Objective Assessment of Hyposmia in Alzheimer's Disease From Image and Behavior by Combining Pleasant Odor With Unpleasant Odor
Authors: Feng Quanzhi , Liu Hui , Zhang Hui , Liu Yi , Zhang Huihong , Zhou Yuying , Liu Gang , Han Tong 
Published: September 2021

Background: Olfactory functional magnetic resonance imaging (fMRI) of responses to a pleasant odor (PO) (lavender) can objectively evaluate olfactory dysfunction in Alzheimer's disease (AD) patients. The brain responses to a PO and unpleasant odor (UPO) were shown to differ in normal young people. Whether AD patients with olfactory dysfunction have the same brain response is not yet known.Objective: Our aim was to explore whether olfactory fMRI with both a PO and UPO can provide more information regarding olfactory impairment in AD than a PO alone.Methods: Twenty-five normal controls (NC), 26 individuals with mild cognitive impairment (MCI), and 22 AD patients underwent olfactory fMRI with lavender and pyridine odorants at three concentrations (0.10, 0.33, and 1.00%) with a 3.0-T MRI scanner.Results: There were no differences in the number of activated voxels in the primary olfactory cortex (POC) between PO and UPO conditions in the NC, MCI, and AD groups (SPM, paired t-test, uncorrected p &lt; 0.001, extent threshold = 70). In the right inferior frontal gyrus, orbital part (F3O), the number of activated voxels was greater with the UPO than with the PO in the NC group (SPM, paired t-test, uncorrected p &lt; 0.001, extent threshold = 70), but there were no differences in the MCI and AD groups. Regardless of PO or UPO conditions, there were significant differences in the number of activated voxels in the POC among the NC, MCI, and AD groups. With increasing odor concentration, the number of activated voxels in the POC decreased in the NC group but increased in the AD group. When 0.10% UPO was presented, the NC group (21/25) showed a lower breathing amplitude and shorter inhalation time, whereas the AD patients (0/22) did not show such changes in breathing.Conclusions: After PO and UPO inhalation, brain activation and respiratory behavior in AD patients were significantly different than in NC patients. Therefore, olfactory fMRI using both PO and UPO stimulation, compared with PO stimulation only, can provide more objective information regarding hyposmia associated with AD based on imaging and behavior.