bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Predictive Values of Advanced Non-Small Cell Lung Cancer Patients Harboring Uncommon EGFR Mutations—The Mutation Patterns, Use of Different Generations of EGFR-TKIs, and Concurrent Genetic Alterations
Authors: Tan Jiarong , Hu Chengping , Deng Pengbo , Wan Rongjun , Cao Liming , Li Min , Yang Huaping , Gu Qihua , An Jian , Jiang Juan 
Published: August 2021

IntroductionEpidermal growth factor receptor (EGFR) 19del and L858R mutation are known as “common mutations” in non-small cell lung cancer (NSCLC) and predict sensitivities to EGFR tyrosine kinase inhibitors (TKIs), whereas 20ins and T790M mutations confer drug-resistance to EGFR-TKIs. The role of the remaining uncommon EGFR mutations remains elusive.MethodsWe retrospectively screened a group of NSCLC patients with uncommon EGFR mutations other than 20ins and T790M. The mutation patterns, use of different generations of EGFR-TKIs, and concurrent genetic alterations were analyzed. Meanwhile, a cohort of patients with single 19del or L858R were included for comparison.ResultsA total of 180/1,300 (13.8%) patients were identified. There were 102 patients with advanced or recurrent NSCLC that received first-line therapy of gefitinib/erlotinib/icotinib and afatinib and were eligible for analysis. The therapeutic outcomes among patients with common mutations (EGFRcm, n = 97), uncommon mutation plus common mutations (EGFRum+EGFRcm, n = 52), complex uncommon mutations (complex EGFRum, n = 22), and single uncommon mutations (single EGFRum, n = 28) were significantly different (ORRs: 76.3%, 61.5%, 54.5%, and 50.0%, respectively, p = 0.023; and mPFS: 13.3, 14.7, 8.1, and 6.0 months, respectively, p = 0.004). Afatinib showed superior efficacy over gefitinib/erlotinib/icotinib in EGFRcm (ORR: 81.0% vs. 75.0%, p = 0.773; mPFS: 19.1 vs. 12.0m, p = 0.036), EGFRum+EGFRcm (ORR: 100% vs. 54.5%, p = 0.017; mPFS: NE vs. 13.6m, p = 0.032), and single EGFRum (ORR: 78.6% vs. 21.4%, p = 0.007; mPFS: 10.1 vs. 3.0m, p = 0.025) groups. Comprehensive genomic profiling by Next Generation Sequencing encompassing multiple cancer-related genes was performed on 51/102 patients; the mPFS of patients without co-mutation (n = 16) and with co-mutations of tumor-suppressor genes (n = 31) and driver oncogenes (n = 4) were 31.1, 9.2, and 12.4 months, respectively (p = 0.046). TP53 mutation was the most common co-alteration and showed significantly shorter mPFS than TP53 wild-type patients (7.0 vs. 31.1m, p &lt; 0.001). Multivariate analysis revealed that concurrent 19del/L858R and tumor-suppressor gene alterations independently predicted better and worse prognosis in patients with uncommon mutations, respectively.ConclusionsUncommon EGFR mutations constitute a highly heterogeneous subgroup of NSCLC that confer different sensitivities to EGFR-TKIs with regard to the mutation patterns. Afatinib may be a better choice for most uncommon EGFR mutations. Concurrent 19del/L858R and tumor-suppressor gene alterations, especially TP53, can be established as prognostic biomarkers.
Identification and Validation of a Five-Gene Signature Associated With Overall Survival in Breast Cancer Patients
Authors: Wang Xiaolong , Li Chen , Chen Tong , Li Wenhao , Zhang Hanwen , Zhang Dong , Liu Ying , Han Dianwen , Li Yaming , Li Zheng , Luo Dan , Zhang Ning , Yang Qifeng 
Published: August 2021

BackgroundRecent years, the global prevalence of breast cancer (BC) was still high and the underlying molecular mechanisms remained largely unknown. The investigation of prognosis-related biomarkers had become an urgent demand.ResultsIn this study, gene expression profiles and clinical information of breast cancer patients were downloaded from the TCGA database. The differentially expressed genes (DEGs) were estimated by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. A risk score formula involving five novel prognostic associated biomarkers (EDN2, CLEC3B, SV2C, WT1, and MUC2) were then constructed by LASSO. The prognostic value of the risk model was further confirmed in the TCGA entire cohort and an independent external validation cohort. To explore the biological functions of the selected genes, in vitro assays were performed, indicating that these novel biomarkers could markedly influence breast cancer progression.ConclusionsWe established a predictive five-gene signature, which could be helpful for a personalized management in breast cancer patients.
A Prospective Study of Liver Regeneration After Radiotherapy Based on a New (Su’S) Target Area Delineation
Authors: Su Ting-Shi , Li Li-Qing , Liang Shi-Xiong , Xiang Bang-De , Li Jian-Xu , Ye Jia-Zhou , Li Le-Qun 
Published: August 2021

BackgroundIn this study, we designed a new (Su’S) target area delineation to protect the normal liver during liver regeneration and prospectively evaluate liver regeneration after radiotherapy, as well as to explore the clinical factors of liver regeneration and established a model and nomogram.MethodsThirty patients treated with preoperative downstaging radiotherapy were prospectively included in the training cohort, and 21 patients treated with postoperative adjuvant radiotherapy were included in the validation cohort. The cut-off points of each optimal predictor were obtained using receiver-operating characteristic analysis. A model and nomogram for liver regeneration after radiotherapy were developed and validated.ResultsAfter radiotherapy, 12 (40%) and 13 (61.9%) patients in the training and validation cohorts experienced liver regeneration, respectively. The risk stratification model based on the cutoffs of standard residual liver volume spared from at least 20 Gy (SVs20 = 303.4 mL/m2) and alanine aminotransferase (ALT=43 u/L) was able to effectively discriminate the probability of liver regeneration. The model and nomogram of liver regeneration based on SVs20 and ALT showed good prediction performance (AUC=0.759) in the training cohort and performed well (AUC=0.808) in the validation cohort.ConclusionsSVs20 and ALT were optimal predictors of liver regeneration. This model may be beneficial to the constraints of the normal liver outside the radiotherapy-targeted areas.
Integrative Analysis Identified MCT4 as an Independent Prognostic Factor for Bladder Cancer
Authors: Zhao Yang , Zhao Bin , Yan Wei-Hua , Xia Yan , Wang Zhi-Hui , Zheng Guo-Yang , Wang Wen-Da , Zhang Yu-Shi 
Published: August 2021

BackgroundBladder cancer is the 10th most common cancer and most common urothelial malignancy worldwide. Prognostic biomarkers for bladder cancer patients are required for individualized treatment. Monocarboxylate transporter 4 (MCT4), encoded by SLC16A3 gene, is a potential biomarker for bladder cancer because of its crucial role in the lactate efflux in the aerobic glycolysis process. We aimed to study the association between MCT4 expression and the overall survival (OS) of bladder cancer patients.MethodsThe published single-cell RNA sequencing data of 49,869 bladder cancer cells and 15,827 normal bladder mucosa cells and The Cancer Genome Atlas (TCGA) bladder cancer cohort data were used to explore the mRNA expression of SLC16A3 in bladder cancer. Eighty-nine consecutive bladder cancer patients who had undergone radical cystectomy were enrolled as a validation cohort. The expression of MCT4 proteins in bladder cancer specimens was detected using immunohistochemistry staining. The Kaplan–Meier survival analysis and Cox regression were performed to analyze the association between MCT4 protein expression and OS in bladder cancer patients.ResultsSLC16A3 mRNA was upregulated in bladder cancer cells. The upregulated genes in SLC16A3-positive epithelial cells were enriched in the glycolysis process pathway and monocarboxylic acid metabolic process pathway. Patients with high SLC16A3 mRNA expression showed significantly poor OS (p = 0.016). High MCT4 protein expression was also found to be an independent predictor for poor OS in bladder cancer patients (HR: 2.462; 95% CI: 1.202~5.042, p = 0.014). A nomogram was built based on the results of the multivariate Cox analysis.ConclusionBladder cancer with high SLC16A3 mRNA expression has a poor OS. High MCT4 protein expression is an independent prognostic factor for bladder cancer patients who had undergone radical cystectomy.
HDR Brachytherapy and SBRT as Bridging Therapy to Liver Transplantation in HCC Patients: A Single-Center Experience
Authors: Walter Franziska , Fuchs Frederik , Gerum Sabine , Rottler Maya C. , Erdelkamp Robert , Neumann Jens , Nierer Lukas , Guba Markus , De Toni Enrico N. , Seidensticker Max , Ricke Jens , Belka Claus , Corradini Stefanie 
Published: August 2021

BackgroundIn the treatment of patients with HCC awaiting liver transplantation (LT), local ablative treatments (LAT) are available either for downstaging or as bridging treatment. We present our clinical experience with both available radiation-based techniques, brachytherapy (BT), and stereotactic body radiotherapy (SBRT).MethodsAll patients diagnosed with HCC and who were treated with BT or SBRT at our institution between 2011 and 2018 were retrospectively reviewed. The current analysis included all patients who subsequently underwent LT.ResultsA total of 14 patients (male=9; female=5) were evaluated. Seven underwent BT for bridging before LT, and seven were treated with SBRT. BT was performed with a prescribed dose of 1 × 15 Gy, while SBRT was applied with 37 Gy (65%-iso) in three fractions in six patients, and one patient was treated with 54 Gy (100%-iso) in nine fractions. The treatment was generally well tolerated. One case of grade 3 bleeding was reported after BT, and one case of liver failure occurred following SBRT. All patients underwent LT after a median time interval of 152 days (range 47–311) after BT and 202 days (range 44–775) following SBRT. In eight cases, no viable tumor was found in the explanted liver, while four liver specimens showed vital tumor. The median follow-up after SBRT was 41 months and 17 months following BT. Overall, no hepatic HCC recurrence occurred following LT.ConclusionBoth SBRT and BT are feasible and well tolerated as bridging to LT when applied with caution in patients with impaired liver function. Radiation-based treatments can close the gap for patients not suitable for other locally ablative treatment options.
The Transplant Evaluation Rating Scale Predicts Clinical Outcomes 1 Year After Lung Transplantation: A Prospective Longitudinal Study
Authors: Nöhre Mariel , de Zwaan Martina , Bauer-Hohmann Maximilian , Ius Fabio , Valtin Christina , Gottlieb Jens 
Published: August 2021

Objectives:It has been recommended that all candidates for lung transplantation undergo pre-transplant psychosocial evaluation for risk assessment. However, psychosocial issues are only important if they correlate with outcomes after transplantation.Methods:In this prospective study patients who were referred for lung transplantation from 2016 to 2018 (n= 352) at Hannover Medical School were evaluated using the Transplant Evaluation Rating Scale (TERS). Clinical outcomes included listing, and post-transplant outcomes including mortality, medical aspects such as lung allograft dysfunction, hospitalizations, and renal function, behavioral aspects such as BMI and adherence, and mental issues such as levels of depression, anxiety, and quality of life. TERS scores were divided into tertiles and, in addition, the impact of the two subscale scores—“defiance” and “emotional sensitivity”—was investigated.Results:Of the patients who were transplanted (n= 271) and were still alive (n= 251), 240 had already reached their 1-year assessment at the end of 2020 and were evaluated 1 year after the operation. A subgroup of 143 received an extended mental assessment. BMI, adherence scores, levels of anxiety, depression, and quality of life 1 year post-transplantation differed significantly between TERS tertiles with higher TERS scores predicting less favorable outcomes. The TERS subscale “defiance” was predictive of BMI and adherence whereas the TERS subscale “emotional sensitivity” was predictive of symptoms of anxiety and depression, and quality of life 1 year after transplantation. Patients in the lowest TERS tertile were more likely to having been listed and—as a trend—to having survived the first year after transplantationConclusions:Our findings show that psychosocial factors as measured by TERS score are predictors of behavioral and mental outcomes 1 year after lung transplantation. The TERS allows us to focus on psychosocial risk factors that can be treated or minimized before or after transplantation.
900 MHz Radiofrequency Field Induces Mitochondrial Unfolded Protein Response in Mouse Bone Marrow Stem Cells
Authors: Xie Wen , Xu Rui , Fan Caiyun , Yang Chunyu , Chen Haiyan , Cao Yi 
Published: August 2021

Objective: To examine whether exposure of mouse bone marrow stromal cells (BMSC) to 900 MHz radiofrequency fields used in mobile communication devices can induce mitochondrial unfolded protein response (UPRmt).Methods: BMSCs were exposed to continuous wave 900 MHz radiofrequency fields (RF) at 120 μW/cm2 power intensity for 4 h/d for 5 consecutive days. Cells in sham group (SH) were cultured in RF exposure system, but without RF radiation. The positive control cells were irradiated with 6 Gy X-ray at a dose rate of 1.103 Gy/min (XR). To inhibit the upstream molecular JNK2 of UPRmt, cells in siRNA + RF, and siRNA + XR group were also pretreated with 100 nM siRNA-JNK2 for 48 h before RF/XR exposure. Thirty minutes, 4 h, and 24 h post-RF/XR exposure, cells were collected, the level of ROS was measured with flow cytometry, the expression levels of UPRmt-related proteins were detected using western blot analysis.Results: Compared with Sham group, the level of ROS in RF and XR group was significantly increased 30 min and 4 h post-RF/XR exposure (P &lt; 0.05), however, the RF/XR-induced increase of ROS level reversed 24 h post-RF/XR exposure. Compared with Sham group, the expression levels of HSP10/HSP60/ClpP proteins in cells of RF and XR group increased significantly 30 min and 4 h post-RF/XR exposure (P &lt; 0.05), however, the RF/XR-induced increase of HSP10/HSP60/ClpP protein levels reversed 24 h post-RF exposure. After interfering with siRNA-JNK2, the RF/XR exposures could not induce the increase of HSP10/HSP60/ClpP protein levels any more.Conclusions: The exposure of 900 MHz RF at 120 μW/cm2 power flux density could increase ROS level and activate a transient UPRmt in BMSC cells. Mitochondrial homeostasis in term of protein folding ability is restored 24 h post-RF exposure. Exposure to RF in our experimental condition did not cause permanent and severe mitochondrial dysfunctions. However, the detailed underlying molecular mechanism of RF-induced UPRmt remains to be further studied.
Students’ and Instructor’s Perspective on the use of Blackboard Platform for Delivering an Engineering Course
Authors: Uziak Jacek , Oladiran M. Tunde , Lorencowicz Edmund , Becker Kurt 
Published: August 2021

The use of Information Technology (IT) has been growing over the years in various human endeavours. It has also been adopted in education sector for teaching and learning. Various studies have been conducted to assess the effectiveness and acceptance of e-learning strategy by students. In particular, the current research is an attempt to obtain students’ and instructor’s perspective on the use of Blackboard software. The technology is a course management system used in a blended learning mode to deliver a third year mechanical engineering course at the University of Botswana (UB). In terms of students’ views, the study covered a period of nine years and the questionnaire survey was administered to each succeeding cohort of students. Whereas in terms of the instructor’s perspective the motivation and the challenges faced during the years of use of the platform were described. Results indicate that students were generally comfortable with the use of Blackboard as they highly embraced it. Students indicate that their performance improved and communication with instructor was enhanced significantly. The respondents also recommended that Blackboard should be used in other courses in their programme of study. The instructor considered the time factor the most vital challenge related to the use of the platform. However, despite the challenges the application of the learning platform and the development of its material was a positive experience for the instructor and well received by the students.
Analysis of Factors Affecting the Auditory Attention of Non-native Speakers in e-Learning Environments
Authors: Bajaj Nikesh , Carrión Jesús Requena , Bellotti Francesco , Berta Riccardo , De Gloria Alessandro 
Published: August 2021

: One of the most striking characteristics of e-Learning audiences is their diversity. Native and non-native learners can be expected among such audiences and therefore, when developing e-Learning courses it is important to consider the impact of the language level on learning. Specifically, non-native learners are expected to have a diminished auditory perception compared to native ones and hence reduced attention capabilities that could result in a poorer performance. In this study, we assess the impact of linguistic and auditory factors on the attention of non-native learners, namely semanticity, sentence length and noise level. An English language platform mimicking real e-Learning environments is used and attention is quantified by measuring the number of English words correctly identified during a listening task. Our results show that changes in each factor affect the attention score significantly. Interestingly, the effects of semanticity are apparent in noiseless environment, but vanish in noisy ones. Results also show that in noiseless environments, a change in the length of semantic sentences from small or medium to long causes a significant drop in the attention score. Our results demonstrate the importance of carefully accounting for linguistic and auditory factors when designing effective e-Learning courses, especially when they target global audiences and learners with different language abilities are expected.
Perceptions on breast cancer
Authors: Wea Lidwina Dewiyanti 
Published: August 2021

Penelitian ini mengumpulkan informasi dari para Biarawati yang ada di Kabupaten Manggarai, yang di kategorikan sebagai kelompok nulliparitas. 6 orang Biarawati berpartisipasi dalam penelitian ini. Penelitian kualitatif digunakan untuk mencari tema-tema yang muncul berkaitan dengan pandangan tentang kanker payudara. Data dikumpulkan dengan menggunakan wawancara yang direkam menggunakan recorder. Temuan penelitian menunjukkan beberapa fakta penting yang kemudian mempengaruhi perilaku mereka dalam memberi pandangan tentang kanker payudara. Didapatkan 4 tema yang muncul. Pertama yaitu kurang pengetahuan. Tema yang mewakili itu adalah mayoritas partisipan tidak dapat menjawab pengertian, penyebab, tanda dan gejala serta pengobatan kanker. Tema kedua yaitu kepercayaan. Mayoritas partisipan meyakini bahwa mereka tidak dapat terkena kanker payudara karena mereka tidak menikah dan pola hidup mereka selama dalam biara sangat di jaga. Tema ketiga yaitu kebiasaan. Pernyataan yang mewakili adalah bahwa di dalam biara tidak ada diskusi tentang kesehatan reproduksi, mereka menganggap bahwa itu bukan merupakan suatu yang utama dalam kehidupan membiara. Tema keempat yaitu harapan. Tema ini muncul karena mayoritas partisipan menginginkan adanya sosialisasi tentang kesehatan reproduksi terutama kanker payudara. Dengan demikian, hasil temuan dalam penelitian ini menjelaskan bahwa partisipan belum mendapatkan informasi yang baik tentang kanker payudara. Keyakinan dan kebiasaan terkait kanker payudara juga muncul dalam hasil penelitian ini, yang juga ada kaitannya dengan budaya atau kebiasaan yang berlangsung lama di dalam biara. Respon harapan yang di ungkapkan merupakan temuan yang perlu mendapat perhatian dari berbagai pihak. Partisipan sangat membutuhkan informasi yang benar tentang kesehatan reproduksi terutama kanker payudara.
ANALISIS PENGETAHUAN MENGENAI HIV/AIDS DENGAN SIKAP WARGA BINAAN TERHADAP ODHA DI LEMBAGA PEMASYARAKATAN
Authors: Wijayanti Agnes Erida 
Published: August 2021

Latar Belakang: Masalah HIV/AIDS di rumah tahanan sangat kompleks terkait pengetahuan mengenai HIV/AIDS dan perilaku berisiko serta stigma bagi warga binaan yang menjadi ODHA. Penelitian ini dilakukan di Lembaga Pemasyarakatan Klas II A Yogyakarta. Penelitian dilakukan untuk keperluan program penanggulangan HIV/AIDS yang berkaitan dengan program Asuhan keperawatan paliatif warga binaan dengan HIV/AIDS. Tujuan: Mengetahui hubungan antara pengetahuan mengenai HIV/AIDS dengan sikap warga binaan. Metode Penelitian: Desain yang digunakan dalam penelitian ini merupakan penelitian kuantitatif dengan metode survei analitik, pendekatan cross sectional. Hasil: Pengetahuan warga binaan mengenai HIV/AIDS dalam kategori sedang dan tinggi, namun separuh responden masih bersikap negatif terhadap warga binaan orang dengan HIV/AIDS. Terdapat hubungan pengetahuan warga binaan mengenai HIV/AIDS dengan sikap warga binaan dengan HIV/AIDS, namun kekuatan hubungan tersebut lemah.
APAKAH AKTIVITAS HITUNG GERAKAN JANIN MEMICU KECEMASAN IBU HAMIL?
Authors: Samutri Erni 
Published: August 2021

Latar belakang: Aktivitas hitung gerakan janin dikembangkan sebagai salah satu self-screening tool bagi ibu hamil untuk memantau aktivitas janin, penurunan gerakan janin, dan menurunkan angka kematian perinatal. Namun, aktivitas ini mungkin dapat memicu kecemasan ibu hamil dan meningkatkan kunjungan antenatal yang tidak diperlukan. Tujuan: untuk mengetahui perubahan kecemasan pada ibu hamil yang melakukan aktivitas hitung gerakan janin. Metode: penelitian ini menggunakan desain pre eksperimental untuk mengukur perubahan kecemasan pada 33 ibu hamil dengan usia kehamilan 28-37 minggu yang melakukan hitung gerakan janin selama 3 minggu. Kecemasan diukur dengan Beck Anxiety Inventory pada empat periode pengukuran yaitu sebelum intervensi, segera setelah intervensi, 2 minggu dan 3 minggu setelah intervensi hitung gerakan janin. Uji Friedman digunakan untuk mengetahui perubahan kecemasan pada keempat periode pengukuran. Hasil: terdapat perubahan signifikan pada tingkat kecemasan ibu hamil setelah intervensi (p<0,001), pada periode segera setelah intervensi (p=0,001) dan 3 minggu setelah intervensi (p=0,001). Kesimpulan: Aktivitas hitung gerakan janin dapat menurunkan kecemasan ibu hamil di akhir trimester kehamilan. Jadwal kunjungan antenatal ibu hamil tidak berubaha setelah melakukan hitung gerakan janin. Penelitian lebih lanjut diperlukan untuk menilai dampak aktivitas hitung gerakan janin terhadap outcome kehamilan yang lain, termasuk kejadian kematian perinatal.
Kata kunci: kecemasan, hitung gerakan janin, kunjungan antenatal.