bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aberrant ROS&nbsp;Served as an Acquired Vulnerability of Cisplatin-resistant Lung Cancer
Authors: Xin Qian , Ji Qinghong , Zhang Ying , Ma Weihong , Tian Baoqing , Liu Yanli , Chen Yunsong , Wang Fei , Zhang Ran , Wang Xingwu , Yuan Jupeng 
Published: January 2021

Abstract
BackgroundLung cancer has become a global health issue in recent decades. Despite of high rate of resistance, cisplatin-base chemotherapy is still the main treatment of lung cancer patients who are not suitable for TKI-based targeted therapy and immunotherapy. Thus, overcoming cisplatin resistance is urgently needed.MethodsA small panel is established to screen chemicals and compounds overcoming cisplatin resistance. Survival fractions as well as proliferation are determined by MTT assay. Colony formation assay, JC-1 assay, EdU assay, ROS assay as well as apoptosis and cell cycle assay are performed to verify vitalities of different groups. Quantifications of NADP+/NADPH and GSH/GSSG are carried out according to standard protocols. Xenograft model is generated to evaluate the in vivo role of APR-246.ResultsIn this study, we identify NADPH metabolism and reactive oxygen species (ROS) levels as the main cause accounting for cisplatin resistance of H460. Based on a small panel consisting common chemotherapy drugs and compounds, APR-246 is proved an effective compound specifically inhibiting proliferation and colony formation of cisplatin resistant H460 (H460-Cis) cells. APR-246 significantly causes G0/G1 accumulation and S phase inhibition of H460-Cis cells. Besides, APR-246 can obviously lead to severe mitochondria dysfunction as well as elevated apoptosis by altering apoptosis-related protein expressions in H460-Cis cells. Further study proves that it is the aberrant ROS levels as well as NRF2/SLC7A11/GSH axis dysfunction accounting for the specific anti-tumor effects of APR-246. Mechanistically, NRF2 is specifically ubiquitylated degraded in APR-246 treated H460-Cis cells, which in turn decrease NRF2/SLC7A11/GSH axis activity.ConclusionOur study uncovered new insights into the biology driving cisplatin resistance of lung cancer and highlights potentials of APR-246 as future therapeutic agents again cisplatin resistance.
The long noncoding RNA AATBC promotes breast cancer migration and invasion by interacting with YBX1 and activating the YAP1/Hippo signaling pathway
Authors: Wang Maonan , Dai Manli , Wang Dan , Tang Ting , Xiong Fang , Xiang Bo , Zhou Ming , Li Xiaoling , Li Yong , Xiong Wei , Li Guiyuan , Zeng Zhaoyang , Guo Can 
Published: January 2021

Abstract
BackgroundLong noncoding RNAs (lncRNAs) play an important role in the regulation of gene expression and are involved in several pathological responses. However, many important lncRNAs in breast cancer have not been identified and their expression levels and functions in breast cancer remain unknown.MethodsWe used the microarray data to identify differentially expressed lncRNAs between breast cancer and adjacent breast epithelial tissues. In vitro and in vivo assays were used to explore the biological effects of the differentially expressed lncRNA Apoptosis-Associated Transcript in Bladder Cancer (AATBC) in breast cancer cells. The mass spectrometry and RNA pulldown were used to screen AATBC interacting proteins. Using the Kaplan-Meier method, survival analysis was performed.ResultsThe expression of AATBC was significantly high in breast cancer samples, and this high AATBC level was tightly correlated with poor prognosis in breast cancer patients. In vitro and in vivo experiments indicated that AATBC promoted breast cancer cells migration and invasion. AATBC specifically interacted with Y-box binding protein 1 (YBX1), which activated the YAP1/Hippo signaling pathway by binding to macrophage stimulating 1 (MST1) and promoting the nuclear translocation of Yes associated protein 1 (YAP1), allowing its function as a nuclear transcriptional regulator. ConclusionsAATBC is highly expressed in breast cancer and contributes to patients’ progression, indicating that it could serve as a novel prognostic marker for the disease. Mechanistically, AATBC affects migration and invasion of breast cancer cells through an AATBC-YBX1-MST1 axis, resulting in activating the YAP1/Hippo signaling pathway. This is also an important supplement to the composition of the YAP1/Hippo signaling pathway. The model of “AATBC-YAP1” may bring a new dawn to the treatment of breast cancer.
The Oncogenic Capacities of Long Noncoding RNA SNHG1 in Bladder Cancer by inducing proliferation and repressing apoptosis via upregulation of microRNA-9-3p-targeted MDM2
Authors: Xu Weizhang , Hu Yun , Xu Haifei , Liu Haofeng , Wang Xiaolin , Zou Qing , Yang Xuejian , Cai Hongzhou 
Published: January 2021

Abstract
Background

The involvement of long noncoding RNA small nucleolar RNA host gene 1 (lncRNA SNHG1) was documented in numerous cancers, including bladder, pancreatic and prostate cancers. However, the further mechanistic investigation of SNHG1 in bladder is still needed to conduct. With this purpose, tissue, cell, and animal experiments were implemented in our research to figure out the specific mechanism of SNHG1 in bladder cancer via microRNA-9-3p (miR-9-3p).
Methods

In harvested bladder cancer tissues, RNA-FISH and RT-qPCR were adopted for SNHG1 expression measurement and RT-qPCR for miR-9-3p expression determination. The impacts of SNHG1, miR-9-3p, MDM2, and PPARγ on cell viability, proliferation, and apoptosis were evaluated by gain- and loss-of-function approaches. RT-qPCR and western blot analysis were performed to detect expression of MDM2, PPARγ, and apoptosis-related factors. RNA pull-down, RIP, dual luciferase reporter gene assay, and IP experiment were utilized to assess the modulatory relationship among SNHG1, miR-9-3p, MDM2, and PPARγ. Tumorigenic ability of bladder cancer cells was measured in vivo.
Results

High SNHG1 and poor miR-9-3p expression was identified in bladder cancer tissues and cells. Mechanistically, SNHG1 bound to miR-9-3p which negatively targeted MDM2. MDM2 augmented PPARγ ubiquitination to downregulate PPARγ. Bladder cancer cell proliferation was diminished and cell apoptosis was enhanced by silencing SNHG1 or MDM2 or overexpressing miR-9-3p. Similarly, SNHG1 silencing orchestrated miR-9-3p/MDM2/PPARγ axis to depress bladder cancer cell tumorigenesis in vivo.
Conclusion

In summary, the obtained data provided the novel insight of the anti-oncogenic mechanism of silencing SNHG1 in bladder cancer by activating PPARγ via downregulation of miR-9-3p-targeted MDM2.
Diffusion Basis Spectrum Imaging Measures Anti-Inflammatory and Neuroprotective Effects of Fingolimod on Murine Optic Neuritis
Authors: Yang Ruimeng , Lin Tsen-Hsuan , Zhan Jie , Lai Shengsheng , Song Chunyu , Sun Peng , Ye Zezhong , Wallendorf Michael , George Ajit , Cross Anne. H , Song Sheng-Kwei 
Published: January 2021

Abstract
Background A readily implemented noninvasive imaging modality for evaluating underlying disease pathology of optic neuritis (ON) and effectiveness of therapeutics in people with CNS demyelinating diseases is currently lacking. This study aims to prospectively determine whether diffusion basis spectrum imaging (DBSI) detects, differentiates and quantitates coexisting inflammation, demyelination, axonal injury and axon loss in mice with ON due to experimental autoimmune encephalomyelitis (EAE), and to determine if DBSI accurately measures effects of fingolimod on underlying pathology.Methods EAE was induced in 7-week-old C57BL/6 female mice. Visual acuity (VA) was assessed daily to detect onset of ON (VA ≤ 0.25 cycle/degree of either eye) after which daily oral treatment with either fingolimod (1 mg/kg) or saline was given for ten weeks. In vivo DBSI scans of optic nerves were performed at baseline (before immunization), 2-, 6- and 10-weeks post treatment. DBSI-derived metrics including restricted isotropic diffusion tensor fraction (putatively reflecting cellularity), non-restricted isotropic diffusion tensor fraction (putative reflecting vasogenic edema), DBSI-derived axonal volume, axial diffusivity, λ∥ (putative reflecting axonal integrity), and increased radial diffusivity, λ⊥ (putatively reflecting demyelination). Mice were killed immediately after the last DBSI scan for immunohistochemical assessment.Results Optic nerves of fingolimod-treated mice exhibited significantly higher (p < 0.05) VA scores than saline-treated group at each time point. During ten-week of treatment, DBSI-derived non-restricted and restricted isotropic diffusion tensor fractions, and axonal volumes were not significantly different (p > 0.05) from the baseline values in fingolimod-treated mice, suggesting protection in the fingolimod treated mice. In contrast, in the saline-treated mice, transient DBSI-λ∥ decrease and DBSI-λ⊥ increase were also detected during Fingolimod treatment. DBSI-derived metrics assessed in vivo significantly correlated (p < 0.05) with the corresponding histological markers.Conclusions DBSI was used to assess changes of the underlying optic nerve pathologies in EAE mice with ON, exhibiting great potential as a noninvasive outcome measure for monitoring disease progression and therapeutic efficacy for MS.
Challenges in providing surgical procedures during the COVID-19 pandemic: Qualitative study among Operating Department Practitioners in Pakistan
Authors: Jafree Sara Rizvi , Momina Ain ul , Malik Nudra , Naqi Syed Asghar , Fischer Florian 
Published: January 2021

Abstract
Background

Operating Department Practitioners (ODPs) are neglected human resources for health with regard to both professional development and research for patient safety. The surgical theatre is associated with the highest mortality rates and with the onslaught of the COVID-19 pandemic. ODPs are key practitioners with respect to infection control during surgeries. Therefore, this study aims to describe challenges faced by ODPs. The secondary aim is to use empirical evidence to inform the public health sector management about both ODP professional development and improvement in surgical procedures, with a specific focus on pandemics.
Methods

A qualitative study has been conducted. Data collection was based on an interview guide with open-ended questions. Interviews with 39 ODPs in public sector teaching hospitals of Pakistan who have been working during the COVID-19 pandemic were part of the analysis. Content analysis was used to generate themes.
Results

Ten themes related to challenges faced by ODPs in delivering services during the pandemic for securing patient safety were identified: (i) Disparity in training for prevention of COVID-19; (ii) Shortcomings in COVID-19 testing; (iii) Supply shortages of personal protective equipment; (iv) Challenges in maintaining physical distance and prevention protocols; (v) Human resource shortages and role burden; (vi) Problems with hospital administration; (vii) Exclusion and hierarchy; (viii) Teamwork limitations and other communication issues; (ix) Error Management; and (x) Anxiety and fear.
Conclusions

The public health sector, in Pakistan and other developing regions, need to invest in the professional development of ODPs and improve resources and structures for surgical procedures, during pandemics and otherwise.
Non-alcoholic fatty liver disease increases the risk of biochemical recurrence in high-grade metastatic prostate cancer patients
Authors: Cui Jie , zhang Wei , Wang Zhenlong , Chang Yanxiang , Zhang Hongyi 
Published: January 2021

Abstract
Background

Non-alcoholic fatty liver disease (NAFLD) has been reported to be helpful to identify high-risk individuals of developing prostate cancer. In the retrospective cohort study, our aim is to investigate the relationship between NAFLD and biochemical recurrence in metastatic prostate cancer patients.
Methods

We retrospectively investigated 602 patients with metastatic prostate cancer receiving androgen deprivation therapy. Liver fat was estimated with liver-to-spleen ratio by CT scans. The relationship between NAFLD and biochemical recurrence was investigated with Cox models. The model for biochemical recurrence was adjusted for multiple variables.
Results

NAFLD was significantly associated with biochemical recurrence in patients with Gleason score ≥ 4 + 3 when adjusting for each of body mass index (hazards ratio [HR] = 1.38; 95% confidence interval [CI] = 1.08–1.77; p = 0.01), visceral adipose tissue (HR = 1.36; 95% CI = 1.07–1.74; p = 0.01), hypertension (HR = 1.41; 95% CI = 1.10–1.80; p = 0.01) and diabetes mellitus (HR = 1.42; 95% CI = 1.11–1.82; p = 0.01), using age and prostate-specific antigen level as potential confounder. The 2-year biochemical recurrence rate in Gleason score ≥ 4 + 3 patients with and without NAFLD was 84.0% (100/119) and 72.2% (130/180), respectively (p = 0.018). The median biochemical recurrence free survival of Gleason score ≥ 4 + 3 patients with and without NAFLD were 17 and 21 months, respectively (p = 0.005).
Conclusions

NAFLD is an independent risk factor for biochemical recurrence in patients with high-grade metastatic prostate cancer. If validated in prospective studies, future research should test whether treatment of NAFLD can lead to better prognosis.
Identification of hepatocellular carcinoma risk using a novel prognostic model based on apoptosis-related genes
Authors: Liu Renjie , Wang Guifu , Zhang Chi , Bai Dousheng 
Published: January 2021

Abstract
Background
Dysregulation of the balance between proliferation and apoptosis is the basis in human hepatocarcinogenesis. There is a possible association of apoptosis dysregulation with poor prognosis in many malignant tumors, such as hepatocellular carcinoma (HCC). However, the prognostic effect of Apoptosis-related genes (ARGs) on HCC is still unclear.
Methods
A total of 161 ARGs expression levels were analyzed based on The Cancer Genome Atlas (TCGA) database(https://cancergenome.nih.gov/) to screen for differentially expressed ARGs. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to determine the underlying molecular mechanisms of screened ARGs in HCC. ARGs prognostic values were identified using Cox regression to subsequently establish a prognostic risk model and scoring in patients. Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curves were plotted to determine the prognostic value in the model.
Results
Compared to normal specimens, 43 highly upregulated and 8 downregulated ARGs respectively and their normal counterparts in HCC specimens were screened. KEGG analysis demonstrated pathways correlated with these 51 genes which included MAPK, P53, TNF, PI3K-Akt signaling pathways. With Cox regression, 5 prognostic correlated with ARGs (PPP2R5B, SQSTM1, TOP2A, BMF, and LGALS3) were obtained to develop the prognosis model. According to the median of risk scores, patients were categorized into high-risk and low-risk groups. Patients in low-risk groups had a significantly higher two-year or five-year survival probability (p < 0.0001). The risk model had better potency than other clinical characteristics, with the area under the ROC curve (AUC = 0.741). Prognosis of HCC patients was established from a plotted nomogram.
Conclusion
This present study established a novel prognostic risk model for predicting HCC according to the expression of ARGs. The present advancement can potentially contribute to prediction prognosis and individualized treatment of HCC patients.
Neuroendocrine carcinoma of the common bile duct associated with congenital bile duct dilatation: A case report
Authors: Kiya Yoshitaka , Nagakawa Yuichi , Takishita Chie , Osakabe Hiroaki , Nishino Hitoe , Akashi Masanori , Yamaguchi Hiroshi , Nagao Toshitaka , Oono Ryo , Katsumata Kenji , Tsuchida Akihiko 
Published: January 2021

Abstract
Background

Cholangiocarcinoma is frequently seen in patients with congenital bile duct dilatation (CBD). Most cholangiocarcinomas are adenocarcinomas. Other types, especially neuroendocrine carcinomas (NECs), are rare. To the best of our knowledge, this is the third reported case of an NEC of the common bile duct associated with CBD and the first to receive adjuvant chemotherapy for advanced disease.
Case presentation

A 29-year-old woman presented with upper abdominal pain. Preoperative imaging indicated marked dilatation of the common bile duct and a tumor in the middle portion of the common bile duct. She was suspected of having distal cholangiocarcinoma associated with CBD and underwent pylorus-preserving pancreaticoduodenectomy. Pathological and immunohistological findings led to a final diagnosis of large-cell NEC (pT3aN1M0 pStageIIB). The postoperative course was uneventful, and she was administered cisplatin and irinotecan every 4 weeks (four cycles) as adjuvant chemotherapy. She has remained recurrence-free for 14 months.
Conclusion

This presentation is rare, and further reports are necessary.
Exosomal miR-1246 is Involved in Tumorigenesis by Targeting THRB in Breast Cancer
Authors: Zhu Jie , Chen Xiaoying , Xi Fengxiang , Zhao Lei , Wang Yichao , Xie Jiaogui 
Published: January 2021

Abstract
Background: Exosomal miRNAs have drawn increasing attention as tumor biomarkers involving in tumorigenesis due to their stability. The aim of this study was to analyze the role of exosomal miR-1246 in breast cancer.Methods: The differentially expressed (DE) miRNAs in exosomes from the serum of breast cancer patients and healthy controls were investigated using RNA-seq. The potential pathogenic target genes and functional enrichment of these miRNAs were explored using bioinformatics. Additionally, the role of miR-1246 in migration, invasion and proliferation were investigated in breast cancer cells. The expression of THRB were detected by QRT-PCR. Kaplan-Meier plotter was used to perform survival analysis.Results: The results showed that the level of exosomal miR-1246 was significantly higher in breast cancer than in the control. MiR-1246 mimic treatment promoted invasion and migration in MDA-MB-231 cells by targeting THRB. Kaplan-Meier survival curves showed that patients with high miR-1246 expression exhibited poor OS compared with patients with low miR-1246 expression, especially those with metastatic breast cancer.Conclusion: Our study provides a better understanding of exosomal miR-1246 in the process of breast cancer. Exosomal miR-1246 could be a potential prognostic biomarker for breast carcinoma.
Bilateral Chylothorax Following Left Neck Dissection and Literature Review
Authors: Kimizuka Sachiko , Yamada Hiroyuki , Kawaguchi Koji , Horiuchi Toshikatsu , Takeda Akira , Hamada Yoshiki 
Published: January 2021

Abstract
Background: Although chyle leakage may occur in the neck when the thoracic duct is damaged during cervical dissection, it is extremely rare for the chylothorax alone to leak chyle into the thoracic cavity. Case presentation: We report a case of bilateral chylothorax without chyle cervical leakage after left neck dissection, wherein partial left upper jaw resection and left radical neck dissection were performed in a 46-year-old woman who was diagnosed with left upper gingival cancer. The thoracic duct was ligated and cut during surgery and, although no obvious leakage of lymph was observed, dyspnea and cough reflex during deep inhalation were observed from the 3rd postoperative day. Approximately 600 mL of yellowish-white pleural effusion was aspirated during bilateral thoracentesis, and chylothorax was diagnosed based on clinical findings and biochemical analysis results. The patient was put on a low-fat diet on the 4th postoperative day, and a total of 3 neck drains were removed 8 days after the operation. Conclusions: Pleural effusion disappeared on imaging examination 16 days after thoracentesis and 5 years and 6 months have passed since the operation. At this time, there has been no evidence of tumor recurrence, metastasis, or pleural effusion.
“You Get Three Different Hats on and Try to Figure It Out:” Home-based Care Provision During a Disaster
Authors: Bell Sue Anne , Dickey Sarah , Rosemberg Marie-Anne 
Published: January 2021

Abstract
Background: Home-based care is a vital, and growing, part of the health care system that allows individuals to remain in their homes while still receiving health care. During a disaster, when normal health care systems are disrupted, home-based care remains a vital source of support for older adults. The purpose of this study was to describe the experiences of home-based care providers in providing care to older adults during a disaster in order to inform future disaster planning.Methods: Using qualitative inquiry informed by the social ecological model, five focus groups were conducted with home health nurses (n=25) in two settings affected by Hurricane Irma and Hurricane Harvey. An open-source database of home health agencies participating in Centers for Medicare and Medicaid Services programs was used to identify participants. Data were manually coded and larger themes were generated from recurring ideas and concepts using an abductive analysis approach. Results: Twenty five participants were included in one of five focus groups. Of the 22 who responded to the demographic survey, 65% were registered nurses, 20% were Licensed Vocational Nurses (LVN), and 15% were other types of health care providers. 12% of the sample was male and 88% was female. Seven themes were identified in the analysis: the importance of the community in preparedness and response, government and corporations were viewed as unreliable, disasters exacerbate inequalities, the role of the family bond, the breakdown of preparedness is at implementation, the tension between caring for self and family and caring for patients, and the resilience and adaptability of home based care providers.Conclusions: While home-based care providers faced multiple challenges to providing care during and after a disaster, the importance of community supports and existing nursing models of care in the immediate period after the disaster were emphasized. This study informs the growing body of evidence on the value of home-based care in promoting safety and well-being for older adults during a disaster.
Bacterial Profile and Drug Susceptibility among Adult Patients with Community Acquired Lower Respiratory Tract Infection at Tertiary Hospital, Southern Ethiopia
Authors: Gebre Alemitu Beyene , Begashaw Tsegaye Alemayehu , Ormago Moges Desta 
Published: January 2021

Abstract
Background: Lower respiratory tract infection is a global problem accounting over 50 million deaths annually. Here, we determined the bacterial profile and antimicrobial susceptibility pattern of lower respiratory tract infections among adult patients attending at Tertiary Hospital, Southern Ethiopia. Methods: A cross sectional study was conducted among adult patients with lower respiratory infection at the medical outpatient department of the Hospital. A sputum sample was collected and processed for bacterial culture and antimicrobial susceptibility test. Semi structured questionnaires were used to collect data. SPSS version 22 software was used for statistical analysis and a p value of < 0.05 was considered as statistically significant. Results: Out of 406 sputum samples of participants 136(33.5%) were culture positive for 142 bacterial isolates. Klebsiella pneumoniae 36(25.4%) was the predominant isolate followed by Pseudomonas species 25(17.6%). Gram-negative bacteria were sensitive to cefepime (86.0%) and ciprofloxacin (77.8%) antibiotics while gram-positive (76.5%) to clindamycin. Conclusion: Community acquired lower respiratory tract Infection was highly prevalent in the study area and the isolates showed resistant to common antibiotics such as ampicillin, augmentin, ceftazidime and tetracycline. Therefore, culture and susceptibility test is vital for appropriate management of lower respiratory tract infection in the study area