bluuebunny/crossref_metadata_2025_split huggingface dataset:
PEMBELAJARAN APBRA BERORIENTASI INVITATION IN TO INQUIRY SEBAGAI ALTERNATIF SOLUSI PEMBELAJARAN SAINS BAGI SISWA TUNAGRAHITA
Authors: Wardana Rendy Wikrama , Buyung Buyung 
Published: July 2022

ABSTRAK Terbatasnya penelitian yang mengkaji pembelajaran sains bagi siswa Tunagrahita pada konteks metode pembelajaran. Tujuan penelitian ini adalah menggambarkan alternatif metode pembelajaran sains bagi siswa tunagrahita. Penelitian merupakan penelitian kualitatif dengan desain studi pustaka atau literature review. Pengumpulan data dilakukan melalui kajian dan sintesis terhadap sumber-sumber referensi bacaan baik artikel jurnal, buku maupun referensi terkait Pembelajaran APBRA dan metode Invitation in to inquiry. Analisis data dilakukan dengan menganalisis dan sintesis jurnal yang kemudian ditarik sebuah kesimpulan. Hasil penelitian menunjukkan beberapa metode pembelajaran yang dapat menjadi alternatif dalam pembelajaran sains bagi siswa Tunagrahita. Alternatif metode pembelajaran sains bagi siswa tunagrahita yakni APBRA dan invitation in to inquiry..Kata Kunci : Pembelajaran, APBRA, Invitation in to inquiry, Sains, Tunagrahita ABSTRACT The Limited research that examines science learning for mentally retarded students in the context of learning methods.This research aims to description of Alternative science learning methods for Tunagrahita students. This research was qualitative research with literature review design. Data collection was conducted by collecting some literatures either articles or books related to APBRA and invitation in to inquiry method. Data analysis was done by conducting analysis and articles and books synthesis and then drew a conclusion. The research results show that some learning methods can be an alternative in science learning for Tunagrahuta students. Alternative science learning methods for Tunagrahita students are APBRA and invitation in to inquiry. Keywords— Learning, APBRA, Invitation in to inquiry, Sains, Tunagrahita
The correlation between transcription factor 7-like 2 gene polymorphisms and susceptibility of gestational diabetes mellitus in the population of central China: A case–control study
Authors: Zhang Pei , Deng Mengyao , Li Wei , Dai Qiong , He Hua , Zheng Wenpei , She Lu , Xiang Bing , Zeng Jing , Zhou Feng , Guo Yan , Yang Mei 
Published: July 2022

ObjectiveTo investigate the correlation between transcription factor 7-like 2 (TCF7L2) gene polymorphisms and gestational diabetes mellitus (GDM) risk in the central Chinese population.MethodsThis case–control study examined the association of seven TCF7L2 gene single-nucleotide polymorphisms (SNPs) (rs11196218, rs4506565, rs7895340, rs7901695, rs11196205, rs12243326, and rs290487) with GDM risk in the central Chinese population (843 GDM and 877 controls). The clinical information and blood samples were collected by trained interviewers and nurses. Genotyping of SNPs was conducted on the Sequenom MassARRAY platform. Statistical analyses including t-test, ANOVA, chi-square test, Fisher’s exact test, and logistic regression were performed.ResultsDifferences in age, pre-pregnant body mass index (BMI), and family history of type 2 diabetes mellitus (T2DM) between the case and control groups were significant (p &lt; 0.05). Compared with the wild-type genotype, pregnant women with genotypes of rs4506565-AT (OR = 1.89, 95%CI: 1.18–3.02), rs7895340 GA (OR = 1.93, 95%CI: 1.06–3.54), rs7901695-TC (OR = 1.79, 95%CI: 1.11–2.88), and rs11196205-GC (OR = 2.15, 95%CI: 1.16–3.98) had a significantly higher risk of GDM, adjusted by age, pre-pregnant BMI, and family history of T2DM. Functional annotation showed that all these four SNPs fell in the functional elements of human pancreatic islets. Further cumulative effects analysis concluded that when participants carried all these four risk genotypes, the risk of GDM was 3.51 times (OR = 3.51, 95%CI: 1.38–8.90) than that of those without any risk genotypes.ConclusionsThe findings of this study suggested that rs4506565, rs7895340, rs7901695, and rs11196205 were the genetic susceptibility SNPs of GDM in the central Chinese population. Further studies are needed to validate our findings and clarify the underlying mechanisms.
NOTCH4 mutation as predictive biomarker for immunotherapy benefits in NRAS wildtype melanoma
Authors: Li Hongxia , Zhang Qin , Duan Qianqian , Tan Yuan , Sun Tingting , Qi Chuang 
Published: July 2022

BackgroundNRAS wildtype melanoma accounts for approximately 80% of melanomas. Previous studies have shown that NRAS wildtype melanoma had higher response rates and better prognoses than NRAS-mutant patients following immunotherapy, while as major actors in tumor cells and tumor microenvironment (TME), the association between NOTCH family genes and response to immunotherapy in NRAS wildtype melanoma remains indistinct.ObjectiveWe aim to explore whether NOTCH family gene variation is associated with genomic factors in immune checkpoint inhibitor (ICI) response in NRAS wildtype melanoma and with clinical results in these patients.MethodThis research used genomic data of 265 NRAS wildtype ICI-pretreatment samples from five ICI-treated melanoma cohorts to analyze the relationship between NOTCH family gene mutation and the efficacy of ICI therapy.ResultsNRAS wildtype melanomas with NOTCH4-Mut were identified to be associated with prolonged overall survival (OS) in both the discovery (HR: 0.30, 95% CI: 0.11–0.83, P = 0.01) and validation cohorts(HR: 0.21, 95% CI: 0.07–0.68, P = 0.003). Moreover, NOTCH4-Mut melanoma had a superior clinical response in the discovery cohort (ORR, 40.0% vs 13.11%, P = 0.057) and validation cohort (ORR, 68.75% vs 30.07%, P = 0.004). Further exploration found that NOTCH4-Mut tumors had higher tumor mutation burden (TMB) and tumor neoantigen burden (TNB) (P &lt;0.05). NOTCH4-Mut tumors had a significantly increased mutation in the DNA damage response (DDR) pathway. Gene set enrichment analysis revealed NOTCH4-Mut tumor enhanced anti-tumor immunity.ConclusionNOTCH4 mutation may promote tumor immunity and serve as a biomarker to predict good immune response in NRAS wildtype melanoma and guide immunotherapeutic responsiveness.
Circulating exo-miR-154-5p regulates vascular dementia through endothelial progenitor cell-mediated angiogenesis
Authors: Han Xue , Zhou Li , Tu Yu , Wei Jiajia , Zhang Jiajia , Jiang Guojun , Shi Qiaojuan , Ying Huazhong 
Published: July 2022

BackgroundVascular dementia (VaD) mainly results from cerebral vascular lesions and tissue changes, which contribute to neurodegenerative processes. Effective therapeutic approaches to targeting angiogenesis may reduce mortality of VaD. Endothelial progenitor cells (EPCs) play a key role in postnatal angiogenesis. Many exosomal microRNAs (exo-miRNAs) have been reported to involve in the development of dementia. The present study was designed to investigate whether the expression profile of the exo-miRNAs is significantly altered in patients with VaD and to reveal the function of differentially expressed miRNAs and the relevant mechanisms in EPC-mediated angiogenesis in VaD rat model.ResultsExosomes isolated from serum of patients with VaD (n = 7) and age-matched control subjects (n = 7), and miRNA sequencing and bioinformatics analysis found that circulating exosome miRNA-155-5p, miRNA-154-5p, miR-132-5p, and miR-1294 were upregulated in patients with VaD. The expression of miRNA-154-5p was further verified to be upregulated in clinical samples (n = 23) and 2-vessel occlusion-induced VaD rat model by reverse transcription quantitative PCR (RT-qPCR). Notably, miRNA-154-5p inhibition in bone marrow-EPCs (BM-EPCs) from VaD rats improved EPC functions, including tube formation, migration, and adhesion, and elevated concentrations of vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1α (SDF-1α). The mRNA levels of ICAM-1, VCAM-1, and MCP-1 were reduced in miRNA-154-5p-inhibited EPCs. In addition, miRNA-154-5p inhibition increased the level of superoxide dismutase (SOD), and decreased reactive oxygen species (ROS) in EPCs. PRKAA2 was chosen as a promising target gene of miR-154-5p, and miRNA-154-5p inhibition upregulated the protein expression of AMPKα2. Furthermore, upregulation of miR-154-5p markedly diminished EPC functions and inhibited angiogenesis following EPC transplantation in VaD rats.ConclusionCirculating exo-miR-154-5p was upregulated in patients with VaD, and miR-154-5p upregulation was associated with impaired EPC functions and angiogenesis in VaD rat model. Therefore, miR-154-5p is a promising biomarker and therapeutic strategy for VaD.
Effect of atrial fibrillation on outcomes after mechanical thrombectomy and long-term ischemic recurrence in patients with acute basilar artery occlusion
Authors: Zhao Chenhao , Luo Weidong , Liu Xing , Luo Jun , Song Jiaxing , Yuan Junjie , Liu Shuai , Huang Jiacheng , Kong Weilin , Hu Jinrong , Yang Jie , Sun Ruidi , Yue Chengsong , Xie Dongjing , Li Linyu , Sang Hongfei , Qiu Zhongming , Li Fengli , Wu Deping , Zi Wenjie , Yang Qingwu 
Published: July 2022

IntroductionAccording to the literature on anterior circulation, comorbid atrial fibrillation (AF) is not associated with a worse functional outcome, lower reperfusion rates, or higher rates of intracranial hemorrhage after mechanical thrombectomy (MT) compared to intravenous thrombolysis (IVT) or treatment with supportive care. However, data are limited for the effect of comorbid AF on procedural and clinical outcomes of acute basilar artery occlusion (ABAO) after MT. This study aimed to investigate the effect of atrial fibrillation on outcomes after MT and long-term ischemic recurrence in patients with ABAO.MethodsWe performed a registered study of the Endovascular Treatment for Acute Basilar Artery Occlusion Study (BASILAR, which is registered in the Chinese Clinical Trial Registry, http://www.chictr.org.cn; ChiCTR1800014759) from January 2014 to May 2019, which included 647 patients who underwent MT for ABAO, 136 of whom had comorbid AF. Prospectively defined baseline characteristics, procedural outcomes, and clinical outcomes were reported and compared.ResultsOn multivariate analysis, AF predicted a shorter puncture-to-recanalization time, higher first-pass effect rate, and lower incidence of angioplasty and/or stenting (p &lt; 0.01). AF had no effect on intracranial hemorrhage incidence [adjusted odds ratio (aOR), 1.093; 95% confidence interval (CI), 0.451–2.652], 90-day functional outcomes (adjusted common odds ratio, 0.915; 95% CI, 0.588–1.424), or mortality (aOR, 0.851; 95% CI, 0.491–1.475) after MT. The main findings were robust in the subgroup and 1-year follow-up analyses. Comorbid AF was the remaining predictor of ischemic recurrence (aOR, 4.076; 95% CI, 1.137–14.612).ConclusionsThe study revealed no significant difference in the safety and efficacy of MT for ABAO regardless of whether patients had comorbid AF. However, a higher proportion of patients with AF experienced ischemic recurrence within 1 year after MT.
Lnc-PKD2-2-3/miR-328/GPAM ceRNA Network Induces Cholangiocarcinoma Proliferation, Invasion and 5-FU Chemoresistance
Authors: Zhang Lei , Ma Donglai , Li Fujun , Qiu Gongcai , Sun Dongsheng , Zeng Zhaolin 
Published: July 2022

PurposeOur previous study observed that long non-coding RNA PKD2-2-3 (lnc-PKD2-2-3) is related to advanced tumor features and worse prognosis in cholangiocarcinoma (CCA). Then, this study aimed to further explore the linkage between lnc-PKD2-2-3, miR-328, and GPAM, as well as their effects on regulating CCA viability, mobility, and chemosensitivity.MethodsLnc-PKD2-2-3, miR-328, and GPAM expression in 30 pairs of CCA tumor and adjacent tissues, as well as in CCA cell lines, were determined. Two CCA cell lines (HuCCT1 and TFK1) were transfected by lnc-PKD2-2-3 overexpression plasmid, lnc-PKD2-2-3 siRNA, miR-328 inhibitor, and GPAM siRNA alone or in combination, followed by cell proliferation, apoptosis, invasion, and 5-FU chemosensitivity detection. Besides, xenograft mice were established for validation.ResultsLnc-PKD2-2-3 and GPAM were higher, whereas miR-328 was lower in CCA tissues versus adjacent tissues and also in CCA cell lines versus control cells; meanwhile, they were correlated with each other (all P &lt;0.05). Lnc-PKD2-2-3 knockdown decreased CCA cell proliferation, invasion, and increased apoptosis (all P &lt;0.05), but lnc-PKD2-2-3 overexpression exhibited the opposite and weaker effect. MiR-328 knockdown induced CCA cell proliferation and invasion and also attenuated the effect of lnc-PKD2-2-3-knockdown in these functions (all P &lt;0.05). Subsequently, GPAM knockdown reduced CCA cell proliferation and invasion and also weakened the effect of miR-328-knockdown in these functions (all P &lt;0.05). Additionally, lnc-PKD2-2-3 positively regulated GPAM while negatively regulating miR-328. MiR-328 negatively modified GPAM in CCA cells. Luciferase gene reporter assays verified that lnc-PKD2-2-3 directly bound miR-328 and miR-328 directly bound GPAM. Finally, the lnc-PKD2-2-3/miR-328/GPAM network also regulated the 5-FU chemosensitivity of CCA cells. In vivo experiments further revealed that lnc-PKD2-2-3 overexpression promoted tumor volume and weight but repressed tumor apoptosis in xenograft mice; meanwhile, it increased GPAM expression but decreased miR-328 expression (all P &lt;0.05). Conversely, lnc-PKD2-2-3 knockdown exhibited the opposite effects (all P &lt;0.05).ConclusionLnc-PKD2-2-3/miR-328/GPAM ceRNA network promotes CCA proliferation, invasion, and 5-FU chemoresistance.
WNT4 overexpression and secretion in thymic epithelial tumors drive an autocrine loop in tumor cells in vitro
Authors: Zhang Xiaonan , Schalke Berthold , Kvell Krisztian , Kriegsmann Katharina , Kriegsmann Mark , Graeter Thomas , Preissler Gerhard , Ott German , Kurz Katrin , Bulut Elena , Ströbel Philipp , Marx Alexander , Belharazem Djeda 
Published: July 2022

BackgroundWNT4-driven non-canonical signaling is crucial for homeostasis and age-related involution of the thymus. Abnormal WNT signaling is important in many cancers, but the role of WNT signaling in thymic tumors is largely unknown.Materials &amp; MethodsExpression and function of WNT4 and FZD6 were analyzed using qRT–PCR, Western blot, ELISA, in biopsies of non-neoplastic thymi (NT), thymoma and thymic carcinomas. ShRNA techniques and functional assays were used in primary thymic epithelial cells (pTECs) and TC cell line 1889c. Cells were conventionally (2D) grown and in three-dimensional (3D) spheroids.ResultsIn biopsy, WHO classified B3 thymomas and TCs showed increased WNT4 expression compared with NTs. During short-term 2D culture, WNT4 expression and secretion declined in neoplastic pTECs but not in 3D spheroids or medium supplemented with recombinant WNT4 cultures. Under the latter condition, the growth of pTECs was accompanied by increased expression of non-canonical targets RAC1 and JNK. Down-regulation of WNT4 by shRNA induced cell death in pTECs derived from B3 thymomas and led to decreased RAC1, but not JNK protein phosphorylation. Pharmacological inhibition of NF-κB decreased both RAC1 and JNK phosphorylation in neoplastic pTECs.ConclusionsLack of the age-related decline of non-canonical WNT4 expression in TETs and restoration of declining WNT4 expression through exogeneous WNT4 or 3D culture of pTECs hints at an oncogenic role of WNT4 in TETs and is compatible with the WNT4 autocrine loop model. Crosstalk between WNT4 and NF-κB signaling may present a promising target for combined interventions in TETs.
Association between sleep disturbance and mental health of healthcare workers: A systematic review and meta-analysis
Authors: Liu Ying , Zhang Qin , Jiang Fugui , Zhong Hua , Huang Lei , Zhang Yang , Chen Hong 
Published: July 2022

ObjectivesSleep disturbance and mental health are challenges for healthcare workers (HCWs). Especially during the COVID-19 pandemic, they experienced more severe sleep and mental health problems. However, the association between sleep disturbance and the mental health of HCWs is still controversial. This study aimed to systematically review the relationship by conducting a systematic review and meta-analysis.MethodTwo researchers retrieved the literature from Web of Science, PubMed, EMBASE, CINAHL, Psyclnfo, and Cochrane Library from the establishment of the databases until November 20, 2021. We used the New Castle-Ottawa Scale (NOS) and Agency for Healthcare Research and Quality (AHRQ) to evaluate the risk of bias in prospective research and cross-sectional research, respectively. The major exposure was HCWs’ sleep disturbance, and the major outcome was mental health. The correlation coefficients (r), regression coefficients (β) and odds ratios (OR) of the included studies were integrated.ResultFifty-nine studies were included for qualitative analysis, of which 30 studies could be combined and entered into quantitative analysis. There were 23 studies during the COVID-19 pandemic among the 59 included studies. The results of the meta-analysis showed that the correlation coefficient between sleep disturbance and mental health was 0.43 (95% CI: 0.39–0.47). HCWs with sleep disturbance had a 3.74 (95% CI: 2.76–5.07) times higher risk of mental health problems than those without sleep disturbance. The correlation coefficient during the COVID-19 epidemic was 0.45 (95% CI: 0.37–0.53), while it was 0.40 (95% CI: 0.36–0.44) during the non-epidemic period. Subgroup analysis compared the OR results in epidemic and non-epidemic periods of COVID-19, which were 4.48 (95% CI: 2.75–5.07) and 3.74 (95% CI: 2.74–7.32), respectively.ConclusionSleep disturbance and mental health problems were positively correlated among HCWs. Particularly in the COVID-19 pandemic, more attention should be given to this issue.
Perceived Stress, Resilience, and Wellbeing in Seasoned Isha Yoga Practitioners Compared to Matched Controls During the COVID-19 Pandemic
Authors: Upadhyay Preeti , Narayanan Shilpa , Khera Tanvi , Kelly Lauren , Mathur Pooja A. , Shanker Akshay , Novack Lena , Pérez-Robles Ruth , Hoffman Kim A. , Sadhasivam Senthil Kumar , Subramaniam Balachundhar 
Published: July 2022

BackgroundYoga practices, including breathing, meditation, and posture protocols (asanas), have been shown to facilitate physical and mental wellbeing.MethodsSeasoned yoga practitioners were recruited from the Isha Foundation. Recruitment of the comparison group was achieved using snowball sampling and were not yoga practitioners. Participants in the non-yoga group were randomized to a 3-min Isha practice or a comparator group asked to perform 15-min of daily reading. Participants completed a series of web-based surveys (REDCap) at baseline, 6, and 12 weeks. These surveys include validated scales and objective questions on COVID-19 infection and medical history. The validated questionnaires assess for: perceived stress (PSS), mood states [anxiety and depression (PHQ-4), joy (DPES-Joy subscale)], mindfulness attention and awareness (MAAS), resilience (BRS), mental wellbeing (WEMWBS) and recovery from traumatic event (PTGI). Weekly activity diaries were employed as a tool for collecting compliance information from study participants. Perceived stress scale scores were identified as primary outcome for this study.FindingsThe median Perceived Stress Scale (PSS) score for the yoga practitioners compared to the active and placebo comparators was significantly lower at all time-points: baseline: 11 [IQR 7–15] vs. 16 [IQR 12–21] in both the active and placebo comparators (p &lt; 0.0001); 6 weeks: 9 [IQR 6–13] vs. 12 [IQR 8–17] in the active comparator and 14 [IQR 9–18] in the placebo comparator (p &lt; 0.0001); and 12 weeks: 9 [IQR 5–13] vs. 11.5 [IQR 8–16] in the active comparators and 13 [IQR 8–17] in the placebo comparator (p &lt; 0.0001). Among the randomized participants that were compliant for the full 12 weeks, the active comparators had significantly lower median PSS scores than the placebo comparators 12 weeks [10 (IQR 5–14) vs. 13 (IQR 8–17), p = 0.017]. Further, yoga practitioners had significantly lower anxiety at all three-time points (p &lt; 0.0001), lower depression at baseline and 6 weeks (p &lt; 0.0003), and significantly higher wellbeing (p &lt; 0.0001) and joy (p &lt; 0.0001) at all three-time points, compared to the active and placebo comparator groups.InterpretationThe lower levels of stress, anxiety, depression, and higher level of wellbeing and joy seen in the yoga practitioners compared to the active and placebo comparators illustrate the impact of regular yoga practices on mental health even during the pandemic.Trial RegistrationClinicalTrials.gov, identifier: NCT 04498442.
Antiviral treatment in outpatients with herps zoster in six major areas of China, 2010–2019
Authors: Yu Zhenwei , Zhao Yuhua , Jin Jiayi , Zhu Jianping , Yu Lingyan , Han Gang 
Published: July 2022

ObjectiveThe objective of this study was to assess the status and trends of antiviral treatment in outpatients with herpes zoster in China.MethodsPrescription data on antiviral drugs were extracted from the database of the Hospital Prescription Analysis Program of China according to the inclusion criteria. Yearly prescriptions and costs were calculated, and trends were analyzed. The trends were further stratified by age, sex, and specific drug use. The distribution of defined daily costs (DDCs) of valaciclovir and famciclovir were analyzed, and trends in the median DDCs were identified.ResultsA total of 132,911 prescriptions from 49 hospitals located in six major areas of China were included in the analysis. The yearly prescriptions containing antivirals increased from 8,819 in 2010 to 16,361 in 2019. The percentage of prescriptions for patients aged 65 years and above also increased (27.7% in 2010 to 31.0% in 2019), and the number of prescriptions for females was higher than those for males (P &lt; 0.001). The average cost of antivirals per prescription decreased; thus, the yearly cost showed no increasing trend. The main prescribed antivirals were valaciclovir and famciclovir, which progressively increased in prescriptions. The use of acyclovir decreased during the study period. Prescriptions containing topical formulations, acyclovir and penciclovir, both increased. The DDCs of valaciclovir and famciclovir decreased dramatically.ConclusionThe use of antivirals has increased over the decade, while the cost has not. Antiviral treatments adhere well to recent recommendations, except for the use of topical antivirals. The findings of this study may benefit the healthcare source allocation and management of herpes zoster in China.
The Use of Androgen Deprivation Therapy in Combination With Radiation for Localized Prostate Cancer
Authors: Anderson Eric M. , McBride Sean M. 
Published: July 2022

ContextThe combined use of androgen deprivation therapy (ADT) and radiotherapy in the initial treatment of intermediate- and high-risk prostate cancer is well established.ObjectivesThis study aims to review level 1 evidence and post-hoc analyses from prospective studies to determine the benefit of the addition of ADT to curative radiotherapy in prostate cancer and provide suggestions for future combinatorial trials in localized disease.Evidence AcquisitionWe used PubMed with the terms “radiation”, “ADT”, and “prostate” to identify randomized controlled trials that compared curative therapy alone to curative therapy with androgen deprivation therapy conducted from 1980 to the present extracted by the senior author. For critical questions for which randomized data were unavailable, we used studies selected by the senior author that relied on post-hoc analyses from prospective randomized trials in an attempt to provide substantive answers.Evidence SynthesisThere is strong and unequivocal evidence that variable-length ADT in combination with curative dose radiotherapy improves biochemical recurrence-free survival, cause-specific survival (CSS), and overall survival in intermediate- and high-risk prostate cancer.Evidence SummaryADT should be a component of treatment for most men with unfavorable intermediate- and high-risk prostate cancer receiving curative dose radiotherapy