bluuebunny/crossref_metadata_2025_split huggingface dataset:
MLN2238 exerts its anti-tumor effects via regulating ROS/JNK/mitochondrial signaling pathways in intrahepatic cholangiocarcinoma
Authors: Xu Hao , Xu Guangyu , Xu Qianhui , Xu Chang , Zhou Xiaohu , Bai Yang , Yin Lu , Ding Yuan , Wang Weilin 
Published: October 2022

Background: Intrahepatic Cholangiocarcinoma (iCCA) is a highly malignant tumor with limited treatment options that contributes largely to cancer-related deaths worldwide. Compared with traditional transcriptomic analysis, single-cell RNA sequencing (scRNA-seq) is emerging as a more advanced and popular tool for the in-depth exploration of cellular diversity and molecular complexity. As a next-generation proteasome inhibitor, MLN2238 presents better pharmacodynamics, pharmacokinetics, and therapeutic responses in various cancers. However, its effects and mechanisms of action in iCCA remain unknown.Methods: iCCA tumor heterogeneity was determined based on 4,239 qualified scRNA-seq data from 10 iCCA samples. The potential biological roles of proteasome-related genes in iCCA were investigated using a pseudo-trajectory reconstruction. The effect of MLN2238 on iCCA cell proliferation was estimated using the CCK-8, EdU, and clone formation assays. Flow cytometry was used to examine the effect of added MLN2238 on cell cycle and apoptosis levels. Autophagic flux was detected using AdPlus-mCherry-GFP-LC3B cells. ROS levels and mitochondrial membrane potential were determined using DCFH-DA probing and JC-1 staining. JNK activation and mitochondrial apoptosis were observed using western blotting and immunofluorescence microscopy, respectively. Finally, we used a tumor-bearing mouse model to validate its efficacy in vivo for iCCA treatment.Results: Proteasome-related genes were dysregulated in iCCA progression and expressed at higher levels in tumor tissues. MLN2238 suppressed cell proliferation, blocked the cell cycle in the G2/M phase, promoted apoptosis, and induced cytoprotective autophagy in iCCA cells. Furthermore, MLN2238 increased ROS levels and activated the JNK signaling pathway. Inhibition of ROS and JNK activation by NAC and SP600125 significantly reversed MLN2238-induced apoptosis. MLN2238 also suppressed the growth of iCCA tumors in vivo.Conclusion: Proteasome-related genes play pivotal roles in iCCA development. MLN2238, as a proteasome inhibitor, induces apoptosis in iCCA cells through ROS/JNK/mitochondrial signaling pathways, and hence, making MLN2238 a potential therapeutic choice for iCCA.
Baicalein prevents stress-induced anxiety behaviors in zebrafish model
Authors: Selvaraj Logesh Kumar , Jeyabalan Srikanth , Wong Ling Shing , Sekar Mahendran , Logeshwari B. , Umamaheswari S. , Premkumar Sree , Sekar Roshan Tej , Begum M. Yasmin , Gan Siew Hua , Izzati Mat Rani Nur Najihah , Chidambaram Kumarappan , Subramaniyan Vetriselvan , Al Fatease Adel , Alamri Ali , Sathasivam Kathiresan V. , Selvaraj Siddharthan , Vijeepallam Kamini , Fuloria Shivkanya , Fuloria Neeraj Kumar 
Published: October 2022

Baicalein is a flavonoid mainly obtained from plants with wide range of biological activities, including neuroprotection. An acute and unexpected chronic stress (UCS) protocol has recently been adapted to zebrafish, a popular vertebrate model in brain research. The present study was aimed to evaluate baicalein’s anti-anxiety potential in a zebrafish model by induction, which included neuropharmacological evaluation to determine behavioural parameters in the novel tank diving test (NTDT) and light-dark preference test (LDPT). The toxicity was also assessed using the brine shrimp lethality assay, and the 50% lethal concentration (LC50) was determined. The animals were then stressed for 7 days before being treated with different doses of baicalein (1 and 2 mg/L) for another 7 days in UCS condition. Due to acute stress and UCS, the frequency of entries and time spent in the 1) top region and 2) light area of the novel tank reduced significantly, indicating the existence of elevated anxiety levels. The biological activity of baicalein was demonstrated by its high LC50 values (1,000 μg/ml). Additionally, baicalein administration increased the frequency of entries and duration spent in the light region, indicating a significant decrease in anxiety levels. Overall, the present results showed that baicalein has a therapeutic advantage in reversing the detrimental consequences of UCS and acute stress, making it is a promising lead molecule for new drug design, development, and therapy for stress.
Upconverting nanoparticles as primary thermometers and power sensors
Authors: Martins Joana Costa , Skripka Artiom , Brites Carlos D. S. , Benayas Antonio , Ferreira Rute A. S. , Vetrone Fiorenzo , Carlos Luís D. 
Published: October 2022

Luminescence thermometry is a spectroscopic technique for remote temperature detection based on the thermal dependence of the luminescence of phosphors, presenting numerous applications ranging from biosciences to engineering. In this work, we use the Er3+ emission of the NaGdF4/NaGdF4:Yb3+,Er3+/NaGdF4 upconverting nanoparticles upon 980 nm laser excitation to determine simultaneously the absolute temperature and the excitation power density. The Er3+2H11/2→4I15/2 and 4S3/2→4I15/2 emission bands, which are commonly used for thermometric purposes, overlap with the 2H9/2 →4I13/2 emission band, which can lead to erroneous temperature readout. Applying the concept of luminescent primary thermometry to resolve the overlapping Er3+ transitions, a dual nanosensor synchronously measuring the temperature and the delivered laser pump power is successfully realized holding promising applications in laser-supported thermal therapies.
Restricted and repetitive behavior in children with autism during the first three years of life: A systematic review
Authors: Chaxiong Pang , Dimian Adele F. , Wolff Jason J. 
Published: October 2022

Restricted and repetitive behavior (RRB) is a core diagnostic feature of autism spectrum disorder (ASD). Previous research shows that RRB is prevalent early in life and observed in neurotypical development as well. Less is known, however, about early RRB patterns, developmental trajectories, and the relation to outcomes for autistic children. The purpose of this systematic review was to synthesize findings from studies examining RRB in autistic children from birth through age 3. A detailed protocol was designed a priori based on PRISMA guidelines for systematic reviews. From the published literature, 41 peer reviewed journal articles were identified and included in this review. Our synthesis of the literature suggests that differences in RRB are evident prior to age 2 in children with or who go onto be diagnosed with autism. These differences were evident for both frequency and intensity of RRB across multiple topographies. There were mixed results regarding functional outcomes associated with early RRB, such as cognitive and adaptive behavior, though relations appeared to become stronger as children aged beyond toddlerhood. Notably, level of RRB appears unrelated to autism severity in young autistic children. A wide range of RRB have been reported to be elevated in autistic children during the first years of life, including repetitive motor behaviors, atypical sensory behaviors, insistence on sameness (IS), and self-injurious behaviors (SIBs). In contrast to studies of older children, RRB in very young autistic children do not appear to be associated with functional outcomes but may be valuable to include in early screening efforts.Systematic review registrationhttps://osf.io/huzf3, unique identifier: doi: 10.17605/OSF.IO/HUZF3.
Revealing immune infiltrate characteristics and potential diagnostic value of immune-related genes in ulcerative colitis: An integrative genomic analysis
Authors: Huang Jinke , Zhang Jiaqi , Wang Fengyun , Zhang Beihua , Tang Xudong 
Published: October 2022

ObjectivesUlcerative colitis (UC) is an autoimmune disease of the colon. The aim of this study was to explore the characteristics of immune infiltrates in UC patients and identify immune-related diagnostic biomarkers for UC.MethodsThree gene expression profiles were acquired from the GEO database, followed by identification of differentially expressed genes (DEGs) by Linear Modeling of Microarray Data. Enrichment analysis of Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Disease Ontology (DO) were performed to analyze the biological functions of DEGs. Subsequently, the single sample gene set enrichment analysis (ssGSEA) was performed to identify immune infiltration characteristics of UC. Correlations between diagnostic genes and immune infiltration were explored to identify markers with the greatest diagnostic potential, and a UC diagnostic model was subsequently constructed. Finally, the prediction performance of the model was quantified by nomogram, non-correlated nomogram, and ROC curve.ResultsA total of 3111 DEGs (1,608 up-regulated and 1,503 down-regulated genes) were identified. DEGs were significantly involved in the immune system and UC-related pathways. Immune infiltration profiles of colonic tissue were significantly different between healthy individuals and UC patients. High proportions of resting of aDCs, B cells, CD8+ T cells, DCs, iDCs, Macrophages, Neutrophils, pDCs, T helper cells, Tfh, Th1 cells, Th2 cells, TIL and Treg were found in UC samples. A 5-gene based diagnostic prediction model was constructed and the results of nomogram, non-correlated nomogram and ROC curve suggested the powerful diagnostic value of the model.ConclusionsThis study identified the immune infiltrate characteristics and 5 immune-related genes for UC. The model based on the immune-related genes facilitates the early diagnosis of UC and provides a basis for the evaluation of the prognosis of UC.
Sex disparities in food consumption patterns, dietary diversity and determinants of self-reported body weight changes before and amid the COVID-19 pandemic in 10 Arab countries
Authors: Tayyem Reema , Ibrahim Mohammed O. , Mortada Hussein , AlKhalaf Majid , Bookari Khlood , Al Sabbah Haleama , Qasrawi Radwan , Kamel Iman , Dashti Somaia , Allehdan Sabika , Bawadi Hiba , Waly Mostafa , Abuhijleh Haya , Hammouh Fadwa , Al-Awwad Narmeen , Al-Bayyari Nahla , Cheikh Ismail Leila , Abu Al-Halawa Diala , Othman Manal ,   The Regional CORONA COOKING Survey Group, Hoteit Maha 
Published: October 2022

BackgroundThe COVID-19 pandemic along with its confinement period boosted lifestyle modifications and impacted women and men differently which exacerbated existing gender inequalities. The main objective of this paper is to assess the gender-based differentials in food consumption patterns, dietary diversity and the determinants favoring weight change before and amid the COVID-19 pandemic among Arab men and women from 10 Arab countries.MethodsA cross-sectional study was conducted based on a convenience sample of 12,447 households' family members (mean age: 33.2 ± 12.9; 50.1% females) and information from participants aged 18 years and above was collected about periods before and during the pandemic.ResultsFindings showed that, during the COVID-19 period, the dietary diversity, declined by 1.9% among females compared to males (0.4%) (p &lt; 0.001) and by 1.5% among overweight participants (p &lt; 0.001) compared to their counterparts.ConclusionsTo conclude, gender-sensitive strategies and policies to address weight gain and dietary diversity during emergent shocks and pandemics are urgently needed in the region.
Health impacts with telework on workers: A scoping review before the COVID-19 pandemic
Authors: Furuya Yuko , Nakazawa Shoko , Fukai Kota , Tatemichi Masayuki 
Published: October 2022

BackgroundTelework has dramatically increased due to the coronavirus disease 2019 (COVID-19) pandemic, and the health impacts related to telework have become major concerns. Some studies have shown that telework has both positive and negative impacts. However, during the pandemic, the influence of COVID-19 is too strong to estimate the health effects of telework. Therefore, this scoping review investigated a comprehensive overview of those impacts based on studies conducted before the COVID-19 pandemic.MethodsWe searched keywords related to telework in five databases: PubMed, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, and Ichu-Shi Web. We included articles written in English and Japanese and published from January 2009 to December 2020. One author extracted data, and four authors were paired into two groups. All authors independently conducted the first and second screening and checked the results in pairs. Any disagreements were resolved by reaching a consensus among all authors. All screening and strategies were performed with the consent of all authors.ResultsTwenty-nine quantitative studies published in 12 countries were extracted. The outcomes included 10 studies on physical and lifestyle outcomes, 25 studies on stress and mental health outcomes, and 13 studies on quality-of-life and wellbeing outcomes. Telework increased sitting time in one study, and two studies showed improvement in behavior, such as reducing smoking or drinking due to telework. While six studies reported subjective stress levels improved by telework, the results for depression, anxiety, and other disorders varied across those studies, and the social or individual factors further complicated the situation.ConclusionTelework is potentially associated with a shift to healthier lifestyles but also the potential for inverse correlation to extend sedentary time. Mental stress indicators depend on the social and individual situations, and very few intervention studies on teleworking existed prior to the COVID-19 pandemic. Our review identified a lack of intervention and comparative research on health problems with telework and revealed a need to conduct research with clear comparisons in post-COVID-19 studies.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021203104, identifier: CRD42021203104.
The role of structured exercise interventions on cognitive function in older individuals with stable Chronic Obstructive Pulmonary Disease: A scoping review
Authors: Eastus Caroline C. , Baez Daniel E. , Buckley Maria L. , Lee Jungeun , Adami Alessandra 
Published: October 2022

A decline in cognitive performance has been associated with disease severity, exacerbations rate, presence of comorbidities, and low activity level in people with chronic obstructive pulmonary disease (COPD). Participation in exercise programs appears to have neuroprotective effects and to improve cognitive performance in older people. The present work undertook a scoping review of the effects of exercise-based interventions on cognitive function in older individuals with stable COPD.MethodsThe methodological framework for scoping review was used and electronic searches of five databases performed. Original research and observational studies published between January 2010 and December 2021, administering exercise-based interventions and cognitive function evaluation, were included.ResultsOf 13 full-text manuscripts assessed for eligibility, five were allocated to analysis. Three studies administered exercise training within pulmonary outpatient rehabilitation program (PR), and one inpatient PR. The fifth study conducted a structured training intervention in which either aerobic or a combination with resistance exercises were included. Twelve cognitive function screening tools were used in the five studies included in the analysis. Results extracted were based on 245 COPD (33% female) with moderate to very-severe airflow limitation. Interventions ranged from 12 to 36 sessions. Studies reported statistically significant improvements after intervention in different cognitive function domains, such as global cognition, immediate and delayed recall ability, cognitive flexibility, verbal fluency, attention, abstract reasoning, praxis ability.ConclusionsExercise-based interventions improve several areas of cognitive function in patients with stable COPD. However, the magnitude of gain varies among studies, and this is possibly due to the heterogeneity of tests used. Future research is needed to validate the optimal battery of screening tests, and to support the definition of guidelines for cognitive function evaluation in COPD.
Development of an adolescent advisory group to inform sexual and reproductive health research for first- and second-generation immigrant adolescents in Canada: A community-based participatory action research study
Authors: Vyas Krooti , Louie-Poon Samantha , Meherali Salima 
Published: October 2022

BackgroundDespite the growing evidence supporting the benefit of engaging adolescents in research, the active engagement of immigrant adolescents in research is limited. Further, when exploring the sexual and reproductive health (SRH) needs of immigrant adolescents, utilization of adolescent advisory groups is finite. This study aimed to train and evaluate engagement of an adolescent advisory group (AAG) to inform SRH needs of immigrant adolescents in Canada.MethodsUsing purposive sampling, 13 AAG members were recruited into this study. Members were trained in content related to SRH needs of adolescents and various research methodologies such as conducting a scoping review and qualitative interviews with adolescent participants. After 10 months of member engagement, their experiences were evaluated to identify areas of success and areas for improvement. These data were collected using the Public and Patient Engagement Evaluation Tool, which consisted of a Likert survey and open-ended questions, and analyzed in accordance to the Patient Engagement in Research (PEIR) framework.FindingsTen members completed the evaluation survey. Likert survey responses were primarily positive. Majority of members showed positive demonstrations regarding various components of the PEIR framework, including contributions, support, research environment, and feeling valued.ConclusionFindings illustrated that immigrant AAGs are constructive to informing SRH research. Not only can research teams benefit, but members are also empowered. This study provided the foundation for future immigrant adolescent engagement in research and knowledge translation, and effective means of evaluating engagement by utilizing the PEIR framework.
Development and validation of a nomogram for patients with stage II/III gastric adenocarcinoma after radical surgery
Authors: Wang Lei , Han Huiqiong , Feng Liwen , Qin Yanru 
Published: October 2022

BackgroundWe aimed to construct nomograms based on clinicopathological features and routine preoperative hematological indices to predict cancer-specific survival (CSS) and disease-free survival (DFS) in patients with stage II/III gastric adenocarcinoma (GA) after radical resection.MethodsWe retrospectively analyzed 468 patients with stage II/III GA after curative gastrectomy between 2012 and 2018; 70% of the patients were randomly assigned to the training set (n = 327) and the rest were assigned to the validation set (n = 141). The nomogram was constructed from independent predictors derived from the Cox regression in the training set. Using the consistency index, the calibration and the time-dependent receiver operating characteristic curves were used to evaluate the accuracy of the nomogram. Decision curve analysis was used to assess the value of the model in clinical applications. Patients were further divided into low- and high-risk groups based on the nomogram risk score.ResultsMultivariate Cox model identified depth of invasion, lymph node invasion, tumor differentiation, adjuvant chemotherapy, CA724, and platelet-albumin ratio as covariates associated with CSS and DFS. CA199 is a risk factor unique to CSS. The nomogram constructed using the results of the multivariate analysis showed high accuracy with a consistency index of 0.771 (CSS) and 0.771 (DFS). Moreover, the area under the curve values for the 3-and 5-year CSS were 0.868 and 0.918, and the corresponding values for DFS were 0.872 and 0.919, respectively. The nomogram had a greater clinical benefit than the TNM staging system. High-risk patients based on the nomogram had a worse prognosis than low-risk patients.ConclusionThe prognostic nomogram for patients with stage II/III GA after radical gastrectomy established in this study has a good predictive ability, which is helpful for doctors to accurately evaluate the prognosis of patients to make more reasonable treatment plans.
Endoscopy-assisted high anterior cervical approach in craniovertebral junction (CVJ)
Authors: Li Pengfei , Wang Kaixuan , Ji Hongming , Zhang Gangli , Chen Shengli , Zhang Shiyuan , Dunn Ian F. , Hu Changchen 
Published: October 2022

BackgroundSurgical procedures in the craniovertebral junction (CVJ) suffer from specific challenges due to the proximity between the cranium and spine containing the critical neurovascular structures and the brainstem, respectively. Owing to the complex transitional zone, it is highly challenging for classic surgical approaches to practically acquire the additional exposure to neurovascular structures of the CVJ. Inspired by these facts, we explore the feasibility of an endoscopy-assisted high anterior cervical approach in the CVJ.MethodsTo explore the feasibility of an endoscopy-assisted approach, we quantitatively assessed the surgical corridor and extent of exposure of the CVJ in 6 cadaveric specimens using 0° and 30° endoscopes.ResultsThe applied endoscopes provided adequate exposure to neurovascular structures and the brainstem in the CVJ. Notably, the resection of the anterior arch of C1 is avoided in minimal anterior clivectomy. Further, improved exposure of the CVJ is obtained after removing the odontoid.ConclusionAn endoscope-assisted high anterior cervical approach in the CVJ significantly preserved the cervical spine stability while minimalizing the risk of neurovascular injury within the surgical corridor.
Entering the Third Decade After Kidney Transplantation: Excellent Graft Function Refers to Superior Graft but Not Patient Survival
Authors: Reimann Anna Vera , Nilsson Jakob , Wuethrich Rudolf P. , Mueller Thomas F. , Schachtner Thomas 
Published: October 2022

Kidney transplant recipients (KTRs) with ultralong-term survival represent a growing, yet insufficiently studied patient cohort. In this single-center retrospective study, we analyzed 248 ultralong-term survivors (≥20 years). KTRs were classified into those with superior graft function (defined as eGFR ≥45 ml/min + proteinuria ≤300 mg/day + eGFR-slope ≤ 2 ml/min/1.73 m2/year) and inferior graft function regarding the risk of CKD progression. 20 years post-transplant, median eGFR was 54 ml/min (11–114), proteinuria 200 mg/24 h (0–7,620), eGFR decline 0.45 ml/min/1.73 m2/year (11.7 6.5) and DSA had been detected in 19.7% of KTRs. We identified 96 KTRs (38.7%) with superior (group 1) and 152 KTRs (61.3%) with inferior graft function (group 2). Donation after cardiac death, female sex, glomerulonephritis as primary disease, and early TCMR were independently associated with inferior graft function. Graft survival was significantly better in group 1 compared to group 2 (LogRank,p&lt; 0.001). Besides group affiliation (HR 20.515,p= 0.003), multivariable analysis identified DSA development (HR 3.081,p= 0.023) and donor age (HR 1.032,p= 0.024) as independent factors. Interestingly, there was no significant difference in patient survival (LogRank,p= 0.350). In ultralong-term survivors, excellent graft function refers to superior graft survival but does not extend ultimate patient survival. DSA-formation should be taken seriously even in the ultralong-term.