bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in the Shape and Volume of Subcortical Structures in Patients With End-Stage Renal Disease
Authors: Gu Wen , He Ronghua , Su Hang , Ren Zhuanqin , Zhang Lei , Yuan Huijie , Zhang Ming , Ma Shaohui 
Published: December 2021

Introduction: End-stage renal disease (ESRD) typically causes changes in brain structure, and patients with ESRD often experience cognitive and sleep disorders. We aimed to assess the changes in the subcortical structure of patients with ESRD and how they are associated with cognitive and sleep disorders.Methods: We involved 36 adult patients for maintenance hemodialysis and 35 age- and gender-matched control individuals. All participants underwent neuropsychological examination and 3T magnetic resonance imaging (MRI) to acquire T1 anatomical images. The laboratory blood tests were performed in all patients with ESRD close to the time of the MR examination. We used volumetric and vertex-wise shape analysis approaches to investigate the volumes of 14 subcortical structural (e.g., bilateral accumbens, amygdala, hippocampus, caudate, globus pallidus, putamen, and thalamus) abnormalities in the two groups. Analyses of partial correlations and shape correlations were performed in order to identify the associations between subcortical structure, cognition, and sleep quality in patients with ESRD.Results: The volumetric analysis showed that compared with the healthy control group, patients with ESRD had less bilateral thalamus (left: p &lt; 0.001; right: p &lt; 0.001), bilateral accumbens (left: p &lt; 0.001; right: p = 0.001), and right amygdala (p = 0.002) volumes. In the vertex-wise shape analysis, patients with ESRD had abnormal regional surface atrophy in the bilateral thalamus, right accumbens, left putamen, and bilateral caudate. Moreover, the Montreal Cognitive Assessment (MoCA) score was associated with volume reduction in the bilateral thalamus (left: Spearman ρ = 0.427, p = 0.009; right: ρ = 0.319, p = 0.018), and the Pittsburgh Sleep Quality Index (PSQI) score was associated with volume reduction in the bilateral accumbens (left: ρ = −0.546, p = 0.001; right: ρ = −0.544, p = 0.001). In vertex-wise shape correlation analysis, there was a positive significant correlation between regional shape deformations on the bilateral thalamus and MoCA score in patients with ESRD.Conclusion: Our study suggested that patients with ESRD have subcortical structural atrophy, which is related to impaired cognitive performance and sleep disturbances. These findings may help to further understand the underlying neural mechanisms of brain changes in patients with ESRD.
Self-Administration of Right Vagus Nerve Stimulation Activates Midbrain Dopaminergic Nuclei
Authors: Brougher Jackson , Aziz Umaymah , Adari Nikitha , Chaturvedi Muskaan , Jules Aryela , Shah Iqra , Syed Saba , Thorn Catherine A. 
Published: December 2021

Background: Left cervical vagus nerve stimulation (l-VNS) is an FDA-approved treatment for neurological disorders including epilepsy, major depressive disorder, and stroke, and l-VNS is increasingly under investigation for a range of other neurological indications. Traditional l-VNS is thought to induce therapeutic neuroplasticity in part through the coordinated activation of multiple broadly projecting neuromodulatory systems in the brain. Recently, it has been reported that striking lateralization exists in the anatomical and functional connectivity between the vagus nerves and the dopaminergic midbrain. These emerging findings suggest that VNS-driven activation of this important plasticity-promoting neuromodulatory system may be preferentially driven by targeting the right, rather than the left, cervical nerve.Objective: To compare the effects of right cervical VNS (r-VNS) vs. traditional l-VNS on self-administration behavior and midbrain dopaminergic activation in rats.Methods: Rats were implanted with a stimulating cuff electrode targeting either the right or left cervical vagus nerve. After surgical recovery, rats underwent a VNS self-administration assay in which lever pressing was paired with r-VNS or l-VNS delivery. Self-administration was followed by extinction, cue-only reinstatement, and stimulation reinstatement sessions. Rats were sacrificed 90 min after completion of behavioral training, and brains were removed for immunohistochemical analysis of c-Fos expression in the dopaminergic ventral tegmental area (VTA) and substantia nigra pars compacta (SNc), as well as in the noradrenergic locus coeruleus (LC).Results: Rats in the r-VNS cohort performed significantly more lever presses throughout self-administration and reinstatement sessions than did rats in the l-VNS cohort. Moreover, this appetitive behavioral responding was associated with significantly greater c-Fos expression among neuronal populations within the VTA, SNc, and LC. Differential c-Fos expression following r-VNS vs. l-VNS was particularly prominent within dopaminergic midbrain neurons.Conclusion: Our results support the existence of strong lateralization within vagal-mesencephalic signaling pathways, and suggest that VNS targeted to the right, rather than left, cervical nerve preferentially activates the midbrain dopaminergic system. These findings raise the possibility that r-VNS could provide a promising strategy for enhancing dopamine-dependent neuroplasticity, opening broad avenues for future research into the efficacy and safety of r-VNS in the treatment of neurological disease.
Case Report: Significant Efficacy of Pyrotinib in the Treatment of Extensive Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Cutaneous Metastases: A Report of Five Cases
Authors: Wang Nan , Li Lin , Xiong Youyi , Chi Jiangrui , Liu Xinwei , Zhong Chaochao , Wang Fang , Gu Yuanting 
Published: December 2021

BackgroundBreast cancer (BC) is the most common tumor to develop cutaneous metastases. Most BCs with cutaneous metastasis are human epidermal growth factor receptor 2 (HER2)-positive subtypes. Although the molecular mechanisms of breast cancer metastasis to different sites and the corresponding treatment methods are areas of in-depth research, there are few studies on cutaneous metastasis.Case PresentationFive HER2-positive BC patients with extensive cutaneous metastases were treated with a regimen containing pyrotinib, a novel small-molecule tyrosine kinase inhibitor that irreversibly blocks epidermal growth factor receptor (EGFR), HER2, and human epidermal growth factor receptor 4 (HER4), then their cutaneous metastases quickly resolved at an astonishing speed and their condition was well controlled during the follow-up period.ConclusionsThis case series reports the significant therapeutic effect of pyrotinib on cutaneous metastases of HER2-positive BC for the first time. Based on this, we recommend that pyrotinib can be used as a supplement to trastuzumab for HER2-positive BC patients with cutaneous metastases. In addition, we should consider that the pan-inhibitory effect of pyrotinib on EGFR, HER2, and HER4 may provide a dual therapeutic effect against HER2 and mucin 1.
Inferring Homologous Recombination Deficiency of Ovarian Cancer From the Landscape of Copy Number Variation at Subchromosomal and Genetic Resolutions
Authors: Zhang Meng , Ma Si-Cong , Tan Jia-Le , Wang Jian , Bai Xue , Dong Zhong-Yi , Zhang Qing-Xue 
Published: December 2021

BackgroundHomologous recombination deficiency (HRD) is characterized by overall genomic instability and has emerged as an indispensable therapeutic target across various tumor types, particularly in ovarian cancer (OV). Unfortunately, current detection assays are far from perfect for identifying every HRD patient. The purpose of this study was to infer HRD from the landscape of copy number variation (CNV).MethodsGenome-wide CNV landscape was measured in OV patients from the Australian Ovarian Cancer Study (AOCS) clinical cohort and &gt;10,000 patients across 33 tumor types from The Cancer Genome Atlas (TCGA). HRD-predictive CNVs at subchromosomal resolution were identified through exploratory analysis depicting the CNV landscape of HRD versus non-HRD OV patients and independently validated using TCGA and AOCS cohorts. Gene-level CNVs were further analyzed to explore their potential predictive significance for HRD across tumor types at genetic resolution.ResultsAt subchromosomal resolution, 8q24.2 amplification and 5q13.2 deletion were predominantly witnessed in HRD patients (both p &lt; 0.0001), whereas 19q12 amplification occurred mainly in non-HRD patients (p &lt; 0.0001), compared with their corresponding counterparts within TCGA-OV. The predictive significance of 8q24.2 amplification (p &lt; 0.0001), 5q13.2 deletion (p = 0.0056), and 19q12 amplification (p = 0.0034) was externally validated within AOCS. Remarkably, pan-cancer analysis confirmed a cross-tumor predictive role of 8q24.2 amplification for HRD (p &lt; 0.0001). Further analysis of CNV in 8q24.2 at genetic resolution revealed that amplifications of the oncogenes, MYC (p = 0.0001) and NDRG1 (p = 0.0004), located on this fragment were also associated with HRD in a pan-cancer manner.ConclusionsThe CNV landscape serves as a generalized predictor of HRD in cancer patients not limited to OV. The detection of CNV at subchromosomal or genetic resolution could aid in the personalized treatment of HRD patients.
Protective Effect of Mannitol on Cisplatin-Induced Nephrotoxicity: A Systematic Review and Meta-Analysis
Authors: Li Songtao , He Xiuyun , Ruan Linjie , Ye Ting , Wen Yulong , Song Zhihua , Hu Siying , Chen Yu , Peng Bo , Li Shijie 
Published: December 2021

IntroductionCisplatin, a chemotherapeutic drug, is widely used for the treatment of various malignant tumors with good effects. However, cisplatin-induced nephrotoxicity is a major dose-limiting factor and a significant adverse event. Mannitol is used to reduce cisplatin-induced nephrotoxicity, which is controversial. This study aimed to evaluate the efficacy and safety of a hydration regimen containing mannitol against cisplatin-induced nephrotoxicity through a meta-analysis.MethodsPotential records from PubMed, EMBASE, Cochrane Library, and ClinicalTrials that met the inclusion criteria were included from inception to May 2021. Cochrane Collaboration tools were used to assess the risk of bias in the included studies. Jadad’s and NOS scores were applied to assess the quality of randomized controlled trials (RCTs) and case-control studies. A random-effects model or fixed-effects model was used depending on the heterogeneity. Subgroup analyses were performed to evaluate the potential study characteristics. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were evaluated.ResultsFour RCTs and seven case-control studies involving 4168 patients were included. Pooled results showed that mannitol use could reduce the incidence of cisplatin-induced nephrotoxicity (OR = 0.66, 95% CI [0.45–0.97], p = 0.03), especially reducing grade 3 nephrotoxicity events according to CTCAE 4.0 (OR = 0.37,95% CI [0.16–0.84]). Moreover, mannitol use was not significantly associated with creatinine clearance, serum creatine, and electrolyte disturbance (p &gt; 0.05). Gastrointestinal cancer (OR = 0.36, 95% CI [0.15–0.83], p = 0.02) and urinary tract cancer (OR = 0.32,95% CI [0.14–0.73], p = 0.007) may be more sensitive to mannitol, although the test for overall effect was significantly different (OR = 0.66, 95% CI [0.49–0.89], p = 0.007). For patients with diabetes and hypertension, mannitol may worsen renal function (OR = 1.80, 95% CI [1.18–2.72], p = 0.006; OR = 2.19, 95% CI [1.50, 3.19], p &lt; 0.0001, respectively). Mannitol may have a better protective effect when doses of mannitol were ≥ 25 g (OR = 0.58, 95% CI [0.39–0.88], p = 0.01) and doses of cisplatin &lt; 75 mg/m2 (OR = 0.59, 95% CI [0.36–0.94], p = 0.03). It revealed that mannitol use was likely to cause nausea or vomiting (OR = 1.86, 95% CI [1.20–2.89], p = 0.006).ConclusionCurrent evidence revealed that mannitol was an effective and safe drug to reduce cisplatin-induced nephrotoxicity events, especially Grade 3 events. However, it may cause more nausea/vomiting events and deteriorate renal function in patients with diabetes or hypertension. We also found that mannitol had the best effect when mannitol was ≥ 25 g in total or cisplatin was &lt; 75 mg/m2. Meanwhile, mannitol may have a better effect on gastrointestinal and urinary tract cancers.Systematic Review Registrationcrd. york. ac. uk/PROSPERO, CRD 42021253990
Lifestyle Clusters and Cardiometabolic Risks in Adolescents: A Chinese School-Based Study Using a Latent Class Analysis Approach
Authors: Zhao Weiying , Su Danyan , Mo Luxia , Chen Cheng , Ye Bingbing , Qin Suyuan , Liu Jie , Pang Yusheng 
Published: December 2021

Background: Unhealthy dietary and lifestyle behaviors are associated with a higher prevalence of non-communicable chronic diseases and higher mortality in adults. However, there remains some uncertainty about the magnitude of the associations between lifestyle behaviors and cardiovascular factors in adolescents.Methods: We conducted a school-based cross-sectional study of 895 Chinese adolescents aged 15–19 years. They participated in a questionnaire survey, physical examination, and blood sample collection. Latent class analysis (LCA) was used to identify heterogeneous subgroups of lifestyle behaviors. A set of 12 latent class indicators, which reflected lifestyle behaviors including dietary habits, physical activity, sleep duration, screen time, and pressure perception, were included in the analysis. Logistic regression analysis was performed to determine whether the derived classes were related to a cardiometabolic risk.Results: In total, 13.7 and 5.6% of the participants were overweight and obese, respectively, and 8.4 and 14.1% reported having pre-hypertension and hypertension, respectively. A two-class model provided the best fit with a healthy lifestyle pattern (65.8%) and a sub-healthy lifestyle pattern (34.2%). There were more female participants with a healthy lifestyle (56.2 vs. 43.8%), whereas there were more males with a sub-healthy lifestyle (45.4 vs. 54.6%), (all P = 0.002). Increased risk of cardiometabolic abnormality (BMI categories, blood pressure and lipids) was not significant across lifestyle patterns, except for waist circumference (70.5 vs 69.1 cm, P = 0.044). There was no significant difference in physical activity and intake of fruit and vegetable between the two patterns.Conclusion: Primary prevention based on lifestyle modification should target patterns of behaviors at high risk in adolescents. Due to the complex effect of lifestyle clusters on cardiometabolic risks, well-designed and prospective studies in adolescents are needed in the future.
Cost–Utility Analysis of Wide-Field Imaging as an Auxiliary Technology for Retinopathy of Prematurity Care in Brazil
Authors: Neves Luiza M , Haefeli Lorena M , Zin Andrea A , Steffen Ricardo E , Vasconcelos Zilton F. M , Pinto Márcia 
Published: December 2021

Purpose: To evaluate the cost–utility of wide-field imaging (WFI) as a complementary technology for retinopathy of prematurity (ROP) screening from the Brazilian Unified Health System's perspective.Introduction: ROP is one of the leading causes of avoidable childhood blindness worldwide, especially in middle-income countries. The current ROP screening involves indirect binocular ophthalmoscopy (IBO) by ROP expert ophthalmologists. However, there is still insufficient ROP screening coverage. An alternative screening strategy is the combination of WFI with IBO.Methods: A cost–utility analysis was performed using a deterministic decision-tree simulation model to estimate incremental cost–utility for ROP care. Two screening strategies were compared: (1) IBO and (2) combination of WFI of all eligible preterm infants and IBO for type 2 ROP or worse and for non-readable images. Eligible population included preterm infants &lt;32 weeks of gestational age or birth weight equal to or &lt;1,500 g. The temporal horizon was lifetime. Visual outcome data was converted to utility, and the health benefits were estimated on quality-adjusted life-years (QALY). Incremental cost per QALY gained was calculated from the health system perspective. Costs were estimated considering equipment, maintenance, consumables, and staff. A micro-costing approach was used for WFI. Two technician nurses were trained for imaging execution and had their time evaluated. Two ROP expert ophthalmologists had their time evaluated for imaging reading. One-way sensitivity analysis and probabilistic sensitivity analysis were performed.Results: Combined screening strategy resulted in a cost-effective program considering 90% ROP screening coverage. Costs per examination: (1) screening with IBO: US dollar (US $) 34.36; (2) screening with combination: US $58.20; (3) laser treatment: US $642.09; (4) long-term follow-up: ranged from US $69.33 to 286.91, based on the infant's visual function. Incremental cost per QALY gained was US $1,746.99/QALY per infant screened with the combination strategy. One-way sensitivity analysis resulted in cost-effectiveness for all parameters. Probabilistic sensitivity analyses yielded a 100% probability of combination being cost-effective in a willingness-to-pay threshold of US $1,800/QALY.Conclusion: The combined strategy for ROP screening was cost-effective. It enhances access for appropriate ROP care in middle-income countries and dminishes opportunity costs for ophthalmologists.
Design, Synthesis and Anti-Lung Cancer Evaluation of 1, 2, 3-Triazole Tethered Dihydroartemisinin-Isatin Hybrids
Authors: Hou Haodong , Qu Bin , Su Chen , Hou Guihua , Gao Feng 
Published: December 2021

A series of 1,2,3-triazole tethered dihydroartemisinin-isatin hybrids 8a-c and 9a-k were designed and synthesized. Their antiproliferative activity against A549, doxorubicin-resistant A549 (A549/DOX) as well as cisplatin-resistant A549 (A549/DDP) lung cancer cell lines was also investigated in this study. All hybrids (half maximal inhibitory concentration/IC50: 7.54–73.8 μM) were more potent than the parent drug dihydroartemisinin (IC50: 69.4–88.0 μM) and also non-cytotoxic towards mouse embryonic fibroblast cells NIH/3T3 (IC50: &gt;100 μM). The structure-activity relationships illustrated that the substituents on C-3 and C-5 position of isatin moiety influenced the activity significantly. Imine at C-3 position decreased the activity, whereas fluoro at C-5 position enhanced the activity. In particular, hybrids 8a,c (IC50: 7.54–12.1 μM) and 9i (IC50: 9.10–15.9 μM) were comparable to cisplatin (IC50: 7.54–15.9 μM vs 9.38–19.7 μM) against A549 and A549/DOX, but 4.6–7.6 folds more potent than that of cisplatin (IC50: 8.77–14.3 μM vs 66.9 μM) against A549/DDP cells. Moreover, hybrids 8a,c exhibited excellent stability (liver microsomes: 68–83%) in mouse/human microsomes and good pharmacokinetic properties, demonstrating their potential as a novel anti-lung cancer chemotherapeutic candidates.
Network Pharmacology-Based Investigation and Experimental Exploration of the Antiapoptotic Mechanism of Colchicine on Myocardial Ischemia Reperfusion Injury
Authors: Tang Yuanjun , Shi Chenyang , Qin Yingyi , Wang Shuowen , Pan Hui , Chen Ming , Yu Xuemei , Lou Yuefen , Fan Guorong 
Published: December 2021

Background: The beneficial effects of colchicine on cardiovascular disease have been widely reported in recent studies. Previous research demonstrated that colchicine has a certain protective effect on ischemic myocardium and has the potential to treat myocardial ischemia reperfusion injury (MIRI). However, the potential targets and pharmacological mechanism of colchicine to treat MIRI has not been reported.Methods: In this study, we used network pharmacology and experimental verification to investigate the pharmacological mechanisms of colchicine for the treatment of MIRI. Potential targets of colchicine and MIRI related genes were screened from public databases. The mechanism of colchicine in the treatment of MIRI was determined by protein-protein interaction (PPI), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Additionally, we evaluated the effect of colchicine on H9C2 cell activity using CCK-8 assays, observed the effect of colchicine on H9C2 cell apoptosis via flow cytometry, and further verified the expression of key targets after colchicine treated by Western blot.Results: A total of 626 target genes for colchicine and 1549 MIRI disease targets were obtained. 138 overlapping genes were determined as potential targets of colchicine in treating MIRI. the PPI network analysis demonstrated that the targets linked to MIRI were ALB, TNF, ACTB, AKT1, IL6, TP53, IL1B, CASP3 and these targets showed nice affinity with colchicine in molecular docking experiments. The results of GO analysis and KEGG pathway enrichment demonstrated that the anti-MIRI effect of colchicine involves in apoptotic signaling pathway. Further tests suggested that colchicine can protect H9C2 cell from Hypoxia/Reoxygenation (H/R) injury through anti-apoptotic effects. Western blot results demonstrated that colchicine can inhibited MIRI induced apoptosis of H9C2 cell by enhancing the decreased levels of Caspase-3 in myocardial injure model induced by H/R and activating the PI3K/AKT/eNOS pathway.Conclusions: we performed network pharmacology and experimental evaluation to reveal the pharmacological mechanism of colchicine against MIRI. The results from this study could provide a theoretical basis for the development and clinical application of colchicine.
Testing the Efficacy of ‘Unlearning’, a Mindfulness and Compassion-Based Programme for Cultivating Nonviolence in Teenagers: A Randomised Controlled Trial
Authors: Delgado-Suárez Irene , López-del-Hoyo Yolanda , García-Campayo Javier , Pérez-Aranda Adrián , Modrego-Alarcón Marta , Beltrán-Ruiz María , Gascón Santiago , Montero-Marín Jesús 
Published: December 2021

Background:Most programmes developed to reduce aggressive attitudes among teenagers are based on cultivating nonviolence, a construct that has been related to compassion and, more indirectly, mindfulness. This study aims at testing the efficacy of ‘Unlearning’, a mindfulness and compassion-based programme, for reducing aggressive attitudes in adolescents.Method:A sample of 164 students from three high schools in Zaragoza (Spain) participated in the study. They were randomly assigned to (1) ‘Unlearning’, or (2) relaxation programme. Three assessment points were established: baseline, post-treatment and a 4-month follow-up. The outcome variables were the subscales of the ‘Attitudes Toward Social Aggression Scale’. Mindfulness and compassion were assessed as secondary outcomes.Results:‘Unlearning’ did not produce changes in the primary outcomes, but significant effects were observed post-treatment in self-compassion; and in the follow-up, in self-compassion and mindfulness. The control group did not experience any change post-treatment, but a significant effect in mindfulness was observed in the follow-up. The intergroup analyses indicated that ‘Unlearning’ improved self-compassion, both post-treatment (t = −2.48,p = 0.014) and after 4-months (t = −2.03,p = 0.044), although these results were not statistically significant after correcting for multiple comparisons.Conclusion:‘Unlearning’ did not produce significant reductions in aggressive attitudes compared to the control group. The low baseline levels may have hindered the efficacy of the interventions. ‘Unlearning’ showed potential to improve self-compassion, which is related to nonviolence, and this may have positive implications for the adolescents. Future interventions should include teachers and families to enhance the effectiveness of the programmes.