bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can probiotic, prebiotic, and synbiotic supplementation modulate the gut-liver axis in type 2 diabetes? A narrative and systematic review of clinical trials
Authors: Al-Najjar Yousef , Arabi Maryam , Paul Pradipta , Chaari Ali 
Published: December 2022

BackgroundType 2 diabetes, one of the most common noncommunicable diseases, is a metabolic disorder that results in failed homeostatic control in several body systems, including hepatic function. Due to the gut microbiome’s potential role in diabetes’ pathogenesis, prebiotics, probiotics, and synbiotics have been proposed as complimentary therapeutic approaches aimed at microbiota readjustment.MethodsA systematic review was conducted on PubMed, Scopus, Web of Science, Embase, and the Cochrane Library examining the effect of probiotics, prebiotics, and synbiotics on hepatic biomarkers in patients with diabetes.ResultsFrom 9,502 search hits, 10 studies met the inclusion criteria and were included in this review. A total of 816 participants (460 intervention and 356 control) were investigated for the effects of nine different hepatic biomarker measurements including aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total protein, bilirubin, liver steatosis, liver stiffness, fatty liver index, and gamma-glutamyl transferase levels. Of the 13 intervention groups analyzed from the 10 studies, 3 were prebiotic interventions, 3 were single species probiotic interventions, 3 were multi-species probiotic interventions, and 4 were synbiotic interventions. Nutraceuticals used in these trials included six genera of bacteria (Lactobacillus, Bifidobacterium, Streptococcus, Acetobacter, Lactococcus, and Propionibacterium), five different prebiotic formulations (inulin, inulin and beta carotene, chicory inulin enriched with oligofructose, galacto-oligosaccharides syrup, and powdered cinnamon), or a combination of these to form multi-species probiotics or synbiotics.ConclusionAlthough some studies showed insignificant changes in hepatic biomarkers, generally the results yielded a decrease in liver damage due to reduced oxidative stress, pro-inflammatory cytokines, gut dysbiosis, and insulin resistance which led to improvements in hepatic biomarker levels.
Segmental bioelectrical impedance analysis for Korean older population with cold pattern
Authors: Doan Dieu Ni Thi , Kim Kahye , Kim Seul Gee , Lee Siwoo , Lee Kun Ho , Kim Jaeuk 
Published: December 2022

ObjectiveThis study examined the association of whole-body composition and segmental bioimpedance variables with cold pattern (CP) in different sexes.MethodsWe assigned 667 older individuals to a CP group (n = 488) and a non-CP group (n = 179) by using an eight-item self-administered questionnaire. Seven body composition variables and three pairs of segmental bioimpedance variables for the upper and lower extremities, which were obtained from a segmental multifrequency bioimpedance analyzer, were employed to investigate their association with CP. Participants’ characteristics were first described. Then we compared the selected body composition and bioimpedance variables between the CP and non-CP groups. Finally, their association with CP was investigated using univariate and multivariate regression analyses. All analyses were performed separately for women and men.ResultsBoth women and men exhibited a comparable mean age in the CP and non-CP groups; however, women with CP had significantly lower blood pressures, whereas men with CP showed a higher proportion of osteoarthritis than those without CP. Compared with the non-CP group, individuals with CP exhibited significantly smaller body sizes indicated by shorter height and smaller weight, lower body mass index, and smaller volume-to-body surface area ratio in both sexes. After controlling for age, height, weight, and other covariates, we found significant reductions in body lean mass such as fat-free mass and body cell mass, basal metabolic rate per unit mass, total body water, and intra-to-extracellular water ratio in the CP group. With regard to segmental bioimpedance analysis, the resistance ratios and phase angles in the upper and lower extremities yield significant associations with CP incidence, as demonstrated by the odds ratio (95% confidence interval) of 1.72 (1.16–2.57), 1.69 (1.18–2.48), 0.60 (0.40–0.89), and 0.57 (0.39–0.82), respectively. However, these results did not emerge in men.ConclusionAbnormal cellular water distribution and deterioration in body cell mass and/or cell strength are associated with CP prevalence, regardless of age, height, weight. These findings are similar in the upper and lower extremities and are more pronounced in women. The abovementioned patterns may be considered effective indicators for identifying CP in the older adult population.
Predictive factors for relapse in triple-negative breast cancer patients without pathological complete response after neoadjuvant chemotherapy
Authors: Toss Angela , Venturelli Marta , Civallero Monica , Piombino Claudia , Domati Federica , Ficarra Guido , Combi Francesca , Cabitza Eleonora , Caggia Federica , Barbieri Elena , Barbolini Monica , Moscetti Luca , Omarini Claudia , Piacentini Federico , Tazzioli Giovanni , Dominici Massimo , Cortesi Laura 
Published: December 2022

IntroductionTriple-negative breast cancer (TNBC) patients who do not obtain pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) present higher rate of relapse and worse overall survival. Risk factors for relapse in this subset of patients are poorly characterized. This study aimed to identify the predictive factors for relapse in TNBC patients without pCR after NACT.MethodsWomen with TNBC treated with NACT from January 2008 to May 2020 at the Modena Cancer Center were included in the analysis. In patients without pCR, univariate and multivariable Cox analyses were used to determine factors predictive of relapse.ResultsWe identified 142 patients with a median follow-up of 55 months. After NACT, 62 patients obtained pCR (43.9%). Young age at diagnosis (&lt;50 years) and high Ki-67 (20%) were signi!cantly associated with pCR. Lack of pCR after NACT resulted in worse 5-year event-free survival (EFS) and overall survival (OS). Factors independently predicting EFS in patients without pCR were the presence of multifocal disease [hazard ratio (HR), 3.77; 95% CI, 1.45–9.61; p=0.005] and residual cancer burden (RCB) III (HR, 3.04; 95% CI, 1.09–9.9; p=0.04). Neither germline BRCA status nor HER2-low expression were associated with relapse.DiscussionThese data can be used to stratify patients and potentially guide treatment decision-making, identifying appropriate candidates for treatment intensi!cation especially in neo-/adjuvant setting.
Germline and somatic variants in ovarian carcinoma: A next-generation sequencing (NGS) analysis
Authors: Andrikopoulou Angeliki , Zografos Eleni , Apostolidou Kleoniki , Kyriazoglou Anastasios , Papatheodoridi Alksistis-Maria , Kaparelou Maria , Koutsoukos Konstantinos , Liontos Michalis , Dimopoulos Meletios-Athanasios , Zagouri Flora 
Published: December 2022

BackgroundGermline BRCA1/2 mutations are identified in 13-15% of ovarian cancers, while an additional 5-7% of ovarian cancers harbor somatic BRCA1/2 mutations. Beyond these mutations, germline or somatic aberrations in genes of the homologous recombination (HR) pathway such as RAD51B/C/D, PALB2, ATM, BRIP1 may confer an HR deficiency in up to 50% of ovarian tumors. Next-generation sequencing (NGS) is a high-throughput massive parallel sequencing method that enables the simultaneous detection of several mutations in entire genomes.MethodsWe performed NGS analysis in 86 patients with ovarian cancer treated in the Oncology Department of Alexandra University Hospital in order to identify the molecular landscape of germline and somatic mutations in ovarian cancer.ResultsThe genes with the highest number of pathogenic somatic mutations in high grade serous carcinoma (HGSC) patients were TP53 [68%; 34/50] and BRCA1 [22%; 11/50] followed by somatic mutations in RB1 [2%; 1/50], NF1 [2%; 1/50], BRCA2 [2%; 1/50], AKT1 [2%; 1/50], RAD50 [2%; 1/50], PIK3CA [2%; 1/50] genes. Of note, the most common TP53 genetic polymorphism was c.524G&gt;A p.Arg175His in exon 5. Variants of unknown significance (VUS) detected in HGSC included ROS1 [26%; 13/50], RAD50 [6%; 3/50], BRCA2 [6%; 3/50], NOTCH1 [6%; 3/50], TP53 [6%; 3/50], AR [6%; 3/50]. As for germline mutations, BRCA1 [8/30; 27%] and BRCA2 [4/30; 13%] were the most common genes bearing pathogenic alterations in HGSC, while VUS germline mutations commonly affected HRR-related genes, including ATM (c.7816A&gt;G), BRIP (c.2327 C&gt;A), CHEK2 (c.320-5T&gt;A).ConclusionOverall, genetic testing should be offered in most patients with ovarian cancer to identify mutations in HRR genes and determine the population that would be susceptible to poly ADP ribose polymerase (PARP) inhibitors.
Development and validation of a predictive model for diagnosing prostate cancer after transperineal prostate biopsy
Authors: Ren Wenming , Xu Yujie , Yang Congcong , Cheng Li , Yao Peng , Fu Shimin , Han Jie , Zhuo Dong 
Published: December 2022

ObjectiveThis study aimed to develop and validate a nomogram to predict the probability of prostate cancer (PCa) after transperineal prostate biopsy by combining patient clinical information and biomarkers.MethodsFirst, we retrospectively collected the clinicopathologic data from 475 patients who underwent prostate biopsy at our hospital between January 2019 to August 2021. Univariate and multivariate logistic regression analyses were used to select risk factors. Then, we established the nomogram prediction model based on the risk factors. The model performance was assessed by receiver operating characteristic (ROC) curves, calibration plots and the Hosmer–Lemeshow test. Decision curve analysis (DCA) was used to evaluate the net benefit of the model at different threshold probabilities. The model was validated in an independent cohort of 197 patients between September 2021 and June 2022.ResultsThe univariate and multivariate logistic regression analyses based on the development cohort indicated that the model should include the following factors: age (OR = 1.056, p = 0.001), NEUT (OR = 0.787, p = 0.008), HPR (OR = 0.139, p &lt; 0.001), free/total (f/T) PSA (OR = 0.013, p = 0.015), and PI-RADS (OR = 3.356, p &lt; 0.001). The calibration curve revealed great agreement. The internal nomogram validation showed that the C-index was 0.851 (95% CI 0.809-0.894). Additionally, the AUC was 0.851 (95% CI 0.809-0.894), and the Hosmer–Lemeshow test result presented p = 0.143 &gt; 0.05. Finally, according to decision curve analysis, the model was clinically beneficial.ConclusionHerein, we provided a nomogram combining patients’ clinical data with biomarkers to help diagnose prostate cancers.
Novel use of riociguat in infants with severe pulmonary arterial hypertension unable to wean from inhaled nitric oxide
Authors: Domingo L. T. , Ivy D. D. , Abman S. H. , Grenolds A. M. , MacLean J. T. , Breaux J. A. , Minford K. J. , Frank B. S. 
Published: December 2022

IntroductionRiociguat, an oral soluble guanylate cyclase stimulator, has been approved for use in adults with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension. However, there is limited data on its therapeutic use in children.Case PresentationWe report the case of two infants with severe suprasystemic pulmonary hypertension who were successfully treated with riociguat after failure to wean off inhaled nitric oxide (iNO) despite combination PAH therapy. Case 1 is a 6-month-old term male with TBX4 deletion who presented with severe hypoxemic respiratory failure and severe PAH immediately after birth. Initial cardiac catheterization showed PVRi 15.5 WU*m2. Marked hypoxemia and PAH persisted despite aggressive therapy with sildenafil, bosentan, intravenous treprostinil, and milrinone. The infant required high doses of inhaled nitric oxide (60 ppm) and manifested significant post-ductal hypoxemia and hemodynamic instability with any attempt at weaning. After discontinuation of sildenafil, initiation, and very slow uptitration of riociguat, the patient was able to maintain hemodynamic stability and wean from nitric oxide over 6 weeks with persistently severe but not worsened pulmonary hypertension. Case 2 is a 4-month-old term male with compound heterozygous SLC25A26 mutation and severe pulmonary hypertension. Initial cardiac catheterization showed PVRi 28.2 WU*m2. After uptitration of sildenafil, bosentan, and IV treprostinil, serial echocardiograms continued to demonstrate near-systemic pulmonary hypertension. He failed multiple attempts to wean off typical doses of iNO (10–20 ppm) over the following weeks with tachypnea, hypoxemia, and worsening pulmonary hypertension on echocardiogram despite continued aggressive combination targeted therapy. After a 24-h sildenafil washout, he was initiated and uptitrated on riociguat with concomitant, successful wean of nitric oxide over one week that was well tolerated. No serious adverse effects in the titration period were observed.ConclusionRiociguat may be considered as an adjuvant therapeutic agent in selected children with severe PAH who are poorly responsive to sildenafil therapy and unable to wean from iNO.
Efficacy and safety of the dexamethasone implant in vitrectomized and nonvitrectomized eyes with diabetic macular edema: A systematic review and meta-analysis
Authors: Yuan Qiongzhen , Liu Yanling , Gou Yueqin , Xu Hanyue , Gao Yunxia , Liu Yilin , Chen Yi , Zhang Ming 
Published: December 2022

Purpose: To compare the efficacy and safety of the intravitreal dexamethasone (DEX) implant for the treatment of diabetic macular edema (DME) in vitrectomized and nonvitrectomized eyes.Methods: We performed a literature search in four electronic databases (PubMed, EMBASE, MEDLINE, and Cochrane Library) from inception to 22 May 2022. Studies comparing the efficacy of the DEX implant in vitrectomized and nonvitrectomized eyes with DME with at least 3 months of follow-up were included. The main outcomes included comparison of the mean change in the best-corrected visual acuity (BCVA) and central macular thickness (CMT) from baseline to different follow-up endpoints between the vitrectomized and nonvitrectomized groups. The secondary outcomes were the mean duration of action for the first DEX implantation and the number of required injections throughout the follow-up period. Safety data were collected and compared.Results: The final analysis included 7 studies involving 582 eyes, 208 vitrectomized eyes and 374 nonvitrectomized eyes. The mean between-group differences in BCVA improvement were not significant at any endpoint, with averages difference of −0.07 logarithm of the minimum angle of resolution (logMAR) (p = 0.088) at 1 month, −0.03 logMAR (p = 0.472) 3 months, −0.07 logMAR (p = 0.066) 6 months, and −0.04 logMAR (p = 0.486) 12 months. The mean between-group differences in CMT reduction were not statistically significant, with mean differences of 7.17 μm (p = 0.685) at 1 month, 20.03 μm (p = 0.632) 3 months, −1.80 μm (p = 0.935) 6 months, and −25.65 μm (p = 0.542) 12 months. However, the vitrectomized group had a significantly shorter duration of action during the first DEX implantation than the nonvitrectomized group, with a mean difference of 0.8 months (p = 0.005). No significant between-group differences were detected for the number of required injections or safety profile.Conclusion: This meta-analysis showed similar efficacy and safety of the sustained-release DEX intravitreal implant for vitrectomized and nonvitrectomized eyes with DME. The intravitreal DEX implant could be considered an effective choice for DME treatment in eyes with prior vitrectomy.
The safety and efficacy of esketamine in comparison to dexmedetomidine during drug-induced sleep endoscopy in children with obstructive sleep apnea hypopnea syndrome: A randomized, controlled and prospective clinical trial
Authors: Yongping Zheng , Xinyi Li , Aming Sang , Qiang Xie , Tianqi Zhou , Mengmeng Shen , Xiong Chen , Xuemin Song 
Published: December 2022

Background and Purpose: Data and high-quality studies of anesthetic methods for children with obstructive sleep apnea hypopnea syndrome (OSAHS) who undergo drug-induced sleep endoscopy (DISE) are limited. Research on pediatric DISE using esketamine has never been reported before. To test the safety and efficacy of esketamine during DISE in children with OSAHS, we compare esketamine (Group K) with dexmedetomidine (Group D) in this study.Methods: 100 children with ASA Ⅰ∼Ⅱ grade, prepared for an elective adenotonsillectomy under general anesthesia, were enrolled in this study and randomized into two groups. Midazolam 0.1 mg/kg was administered intravenously for both groups. In Group D a 1 μg/kg bolus of dexmedetomidine was given over 10 min followed by the infusion rate 1 μg/kg/hr to the end of DISE. Group K received a 1.0 mg/kg IV bolus of esketamine over 10 s followed by the infusion rate 1 mg/kg/hr to the end of DISE.Results: Group K had a higher percentage of success than Group D (p = 0.008). The onset time of Group K was shorter than that of Group D (p = 0.000). The University of Michigan Sedation Scale (UMSS) score of Group K was higher than that of Group D (p = 0.005). The risk of adverse effects (AEs) was lower in Group K (p = 0.000). In Group D, systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR) all decreased, while in Group K, SBP, DBP, and HR hardly changed.Conclusion: Esketamine in comparison to dexmedetomidine provides more effective and safer depth of anesthesia for OSAHS pediatric DISE by ensuring short onset time, deep sedation, and few AEs.Clinical Trial Registration: ClincalTrials.gov, identifier NCT04877639
HIF-1 signalling pathway was identified as a potential new pathway for Icariin’s treatment against Alzheimer’s disease based on preclinical evidence and bioinformatics
Authors: You Mingyao , Yuan Ping , Li Liangqian , Xu Hongbei 
Published: December 2022

Aim: Alzheimer’s disease (AD) is a neurodegenerative condition that is characterized by the gradual loss of memory and cognitive function. Icariin, which is a natural chemical isolated from Epimedii herba, has been shown to protect against AD. This research examined the potential mechanisms of Icariin’s treatment against AD via a comprehensive review of relevant preclinical studies coupled with network pharmacology.Methods: The PubMed, Web of Science, CNKI, WANFANG, and VIP databases were used to identify the relevant studies. The pharmacological characteristics of Icariin were determined using the SwissADME and TCMSP databases. The overlapping targets of Icariin and AD were then utilized to conduct disease oncology (DO) analysis to identify possible hub targets of Icariin in the treatment of AD. The hub targets were then used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and the interactions of the targets and Icariin were assessed via molecular docking and molecular dynamics simulation (MDS).Results: According to the literature review, Icariin alleviates cognitive impairment by regulating the expression of Aβ1-42, Aβ1-40, BACE1, tau, hyperphosphorylated tau, and inflammatory mediators. DO analysis revealed 35 AD-related hub targets, and the HIF-1 signalling pathway was ranked first according to the KEGG pathway analysis. Icariin effectively docked with the 35 hub targets and HIF-1α, and the dynamic binding of the HIF-1-Icariin complex within 100 ns indicated that Icariin contributed to the stability of HIF-1α.Conclusion: In conclusion, our research used a literature review and network pharmacology methods to identify the HIF-1 signalling pathway as a potential pathway for Icariin’s treatment against AD.
Precipitation and temperature regulate species diversity, plant coverage and aboveground biomass through opposing mechanisms in large-scale grasslands
Authors: Yao Zhenyu , Xin Yue , Yang Liu , Zhao Liqing , Ali Arshad 
Published: December 2022

IntroductionAlthough the relationships between species diversity and aboveground biomass (AGB) are highly debated in grassland ecosystems, it is not well understood how climatic factors influence AGB directly and indirectly via plant coverage and species diversity in large-scale grasslands along a topographic gradient. In doing so, we hypothesized that climatic factors would regulate plant coverage, species diversity and AGB due to maintaining plant metabolic and ecological processes, but the relationship of plant coverage with AGB would be stronger than species diversity due to covering physical niche space. MethodsTo test the proposed hypothesis, we collected data for calculations of species richness, evenness, plant coverage and AGB across 123 grassland sites (i.e., the mean of 3 plots in each site) dominated by Leymus chinensis in northern China. We used a structural equation model for linking the direct and indirect effects of topographic slope, mean annual precipitation and temperature on AGB via plant coverage, species richness, and evenness through multiple complex pathways. ResultsWe found that plant coverage increased AGB, but species evenness declined AGB better than species richness. Topographic slope influenced AGB directly but not indirectly via plant coverage and species diversity, whereas temperature and precipitation increased with increasing topographic slope. Regarding opposing mechanisms, on the one hand, precipitation increased AGB directly and indirectly via plant coverage as compared to species richness and evenness. On the other hand, temperature declined AGB indirectly via plant coverage but increased via species evenness as compared to species richness, whereas the direct effect was negligible. DiscussionOur results show that niche complementarity and selection effects are jointly regulating AGB, but these processes are dependent on climatic factors. Plant coverage promoted the coexistence of species but depended greatly on precipitation and temperature. Our results highlight that precipitation and temperature are two key climatic drivers of species richness, evenness, plant coverage and AGB through complex direct and indirect pathways. Our study suggests that grasslands are sensitive to climate change, i.e., a decline in water availability and an increase in atmospheric heat. We argue that temperature and precipitation should be considered in grassland management for higher productivity in the context of both plant coverage and species diversity which underpin animals and human well-being.