bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nox4 Mediates RANKL-induced ER-Phagy and Osteoclastogenesis via Activating ROS/PERK/eIF-2α/ATF4 Pathway
Authors: Sun Jing , chen wugui , Li Songtao , Yang Sizhen , Zhang Ying , Hu Xu , Qiu Hao , Xu Shangcheng , Chu Tongwei 
Published: June 2020

Abstract
Background: Receptor activator of nuclear factor-κB ligand (RANKL) has been found to induce osteoclastogenesis and bone resorption. However, the underlying molecular mechanisms remain unclear. Methods: Osteoclastogenesis was evaluated by number of TRAP-positive multinuclear (≥3) osteoclasts, bone resorption pits and expression levels of related genes. Autophagy activity were evaluated by LC3-II/LC3-I ratio, number of autophagic vacuoles and adenovirus-mRFP-GFP-tagged LC3 reporting system; Inhibitor chloroquine (CQ) was used to verified the role of autophagy in RANKL-induced osteoclastogenesis; Via downregulating Nox4 with inhibitor (DPI) and retrovirus-conveyed shRNA, we further explored the importance of Nox4 in RANKL-induced autophagy and osteoclastogenesis, as well as the regulatory effects of Nox4 on nonmitochondrial reactive oxygen species (ROS) and PERK/eIF-2α/ATF4 pathway. Intracellular ROS scavenger (NAC), mitochondrial-targeted antioxidant (MitoTEMPO) and inhibitor of PERK (GSK2606414) were also employed to investigate the role of ROS and PERK/eIF-2α/ATF4 pathway in RANKL-induced autophagy and osteoclastogenesis. Results: RANKL markedly increased autophagy, while CQ treatment caused reduction of RANKL-induced autophagy and osteoclastogenesis. Consistent with the increased autophagy, the protein levels of Nox4 were significantly increased, and Nox4 was selectively localized within the endoplasmic reticulum (ER) after RANKL stimulation. DPI and shRNA efficiently decreased the protein level and (or) activity of Nox4 in the ER and inhibited RANKL-induced autophagy and osteoclastogenesis. Mechanistically, we found that Nox4 regulates RANKL-induced autophagy activation and osteoclastogenesis by stimulating the production of nonmitochondrial ROS. Additionally, Nox4-derived nonmitochondrial ROS dramatically activate PERK/eIF-2α/ATF4, which is a critical unfolded protein response (UPR)-related signaling pathway during ER stress. Blocking the activation of the PERK/eIF-2α/ATF4 signaling pathway either by Nox4 shRNA, ROS antioxidant or PERK inhibitor (GSK2606414) treatment significantly inhibited endoplasmic reticulum autophagy (ER-phagy) during RANKL-induced osteoclastogenesis. Conclusions: Our findings provide new insights into the processes of RANKL-induced osteoclastogenesis and will help the development of new therapeutic strategies for osteoclastogenesis-related diseases.
The Role of Postoperative Radiotherapy After Primary Tumor Resection in Patients With De Novo Stage Iv Breast Cancer
Authors: Kim Yeon Joo , Kim Su Ssan , Ahn Seung Do , Jung Jinhong , Ahn Sei-Hyun , Son Byung Ho , Lee Jong Won , Kim Hee Jeong , Ko Beom Seok , Kim Sung-Bae , Jung Kyung Hae , Ahn Jin-hee , Kim Jeong-eun , Choi Eun Kyung 
Published: June 2020

Abstract
Background: To investigate the role of postoperative radiotherapy (PORT) in stage IV breast cancer patients who underwent planned primary tumor resection (PTR).Methods: This study enrolled 112 patients diagnosed with de novo stage IV breast cancer who were treated with potentially curative PTR with or without PORT. The primary outcome was overall survival (OS), and the secondary outcomes were locoregional recurrence-free survival (LRRFS) and distant progression-free survival (DPFS).Results: At a median follow-up of 48.9 months (range, 3.5–183.4 months), the median OS was 54.9 months (range, 5.3–185.9 months) with a 5 year OS rate of 59.6%. Luminal A or B type tumors and PORT were significantly predictive of longer OS. The 5 year LRRFS and DMFS rates were 79.0% and 34.3%, respectively. PORT was the only significant predictor of LRRFS (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.15–0.86; p = 0.021). A comparison of patients who did and did not receive PORT showed that patients with disseminated metastasis more likely did not receive PORT and were excluded from the analysis. Multivariate analysis showed that PORT was significantly predictive of LRRFS (HR, 0.31; 95% CI, 0.11–0.91; p = 0.033) but not of OS. Conclusions: De novo stage IV breast cancer patients who received planned PTR showed favorable survival outcomes compared with historical cohorts. PTR may be predictive of a good prognosis, especially in patients with luminal A or B type tumors. PORT was significantly predictive of LRRFS, suggesting that patients may benefit from this treatment.Trial registration: The present study was not registered due to its retrospective nature.
Cardiovascular Phenotyping in Breast Cancer Patients Treated With Her2 Targeted Therapies Using Informatics Approaches
Authors: Harris Michael A. , Conkright Brian , Johnson Robert , Boca Simina M. , Riazi Shahla , Torguson Rebecca , Alaoui Adil , Bhuvaneshwar Krithika , Gusev Yuriy , Asch Federico M. , Pohlmann Paula R , Barac Ana , Madhavan Subha 
Published: June 2020

Abstract
Background Cardiotoxicity is a serious adverse event associated with some of the most effective breast cancer therapies. Currently, it is difficult to predict which patients will develop cardiotoxicity due to the multiplicity of clinical, behavioral, and biological factors involved. MethodsHere we describe an effort to apply biomedical informatics approaches to patient data from MedStar Health’s EHR systems to discover and characterize factors that contribute to cardiotoxicity in a real world breast cancer population.ResultsData wrangling techniques including merging data from disparate clinical systems, data transformation, and de-identification of personal health information (PHI)were appliedto the raw clinical data to produce a structured integrated dataset for predictive analysis and hypothesis generation. Using this dataset as input, weshowed howpredictive models can be developed to identify patients at high risk for cardiotoxicity. ConclusionsWe demonstrate how suchmodels can be used for hypothesis generation and data exploration with the ultimate goal of developing applications for precision medicine.
Elevated PaCO2 Levels Increase Arterial Pulmonary Pressures
Authors: Triantaris Apostolos , Aidonidis Isaak , Chatziefthimiou Apostolia , Gourgoulianis Konstantinos , Zakynthinos Georgios , Makris Dimosthenis 
Published: June 2020

Abstract
BackgroundThe effect of elevated PCO2 in the pulmonary vasculature during mechanical ventilation is not clear. Previous studies in ARDS patients have shown that elevated PaCO2 may be associated with pulmonary hypertension however in models of spontaneously breathing animals results were contradictory.Results In this respect, we aimed to investigate the effect of increased PaCO2 on the pulmonary vasculature of rabbits using different levels of tidal volumes during mechanical ventilation. We conducted an experiment using two groups of adult male rabbits (n=30). Animals were randomly allocated in two groups of different tidal volumes either 6 ml/Kgr (LowVt group) or 9 ml/Kgr (HighVt group) and were ventilated with FiO2 0.3 (Normocapnia-1). Subsequently, animals in each Vt group inhaled an enriched in CO2 gas mixture (FiCO2 0.10.) in order to develop hypercapnia (Hypercapnia-1) and were then re-ventilated with the same conditions to develop subsequent phases of normocapnia and hypercapnia (Normocapnia-2,Hypercapnia-2). Pulmonary arterial pressures were measured with a catheter introduced in the pulmonary artery connected to piezo pressure transducers integrated in a polygraphic system.During hypercapnic conditions , both groups showed increase in PAPsyst, PAPdiast and PAPmean compared to their baseline values. PAPmean pressures increased significantly from Normocapnia-2 to Hypercapnia-2 whereas PAPmean at Hypercapnia-2 was found significantly increased compared to Hypercapnia-1.Conclusions These findings suggests that hypercapnia may augment the pressures in pulmonary vasculature during mechanical ventilation an effect that was observed either, using low or, higher tidal volumes. An effect of preconditioning of arterial pulmonary vessels in hypercapnia merits further investigation.
An AIDS Patient with Multiple Skin Crusted Ulcerations
Authors: Wang Yu , Wen Ying 
Published: June 2020

Abstract
Background: We report a rare case of AIDS patient with crusted ulcerations.Case presentation: A 22-year-old homosexual male was admitted to hospital for fever and ulcerations with overlying brown–black crusts. Then he was confirmed human immunodeficiency virus infection . Secondary syphilis was diagnosed by positive Markers and biopsy pathology. After application of benzathine penicillin for 3 weeks, the symptoms improved. Conclusions: Malignant syphilis is a rare form of secondary syphilis, but tends to occur in AIDS patients because of low immune function. It is usually treated well after regular treatment.
The necessity of radical hysterectomy (RH) for pure endometrial carcinoma combined with cervical involvement: a retrospective cohort study comparing RH with total hysterectomy (TH)
Authors: Qian Zhimin , Chen Guanhao , Wu Xin , Jiang Hua 
Published: June 2020

Abstract
Objective : The purpose of this study was to explore the necessity of radical hysterectomy (RH) for patients with pure endometrial carcinoma（PEC) combined with cervical involvement by comparing with total hysterectomy (TH).Methods : A total of 162 patients who were diagnosed as PEC combined with cervical involvement of stage II and III by postoperative pathological examination between January, 2007 and December, 2017 were included in our study. Among of them, 91 were followed up till the end of this study and 71 were lost in the follow-up. In the 91 patients with complete follow-up information, 34 patients were treated with TH and 57 patients were treated with RH. The 5-year progression free survival rate, 5-year overall survival rate, recurrence rate and postoperative complications of patients were evaluated.Results : There were no significant differences in both the overall survival curve and progression free survival curve between patients with PEC receiving RH and those receiving TH (both p > 0.05). The analysis of postoperative complications showed that patients with RH treatment may have a higher probability of postoperative lymphocyst and urinary dysfunction.Conclusions : RH may not improve the prognosis of cervical involvement in patients with PEC. The postoperative complications of patients with PEC who treated with RH may increase.
Transcriptomic time-series analysis of cold- and heat-shock response in psychrotrophic lactic acid bacteria
Authors: Duru Ilhan Cem , Ylinen Anne , Belanov Sergei , Pulido Alan Ávila , Paulin Lars , Auvinen Petri 
Published: June 2020

Abstract
Background:
Psychrotrophic lactic acid bacteria (LAB) species are the dominant species in microbiota of cold-stored modified-atmosphere-packaged food products and they are the main cause of food spoilage. But still, the cold- and heat-shock response of the spoilage-related psychrotrophic lactic acid bacteria has not been studied. Here, to study cold- and heat-shock response of spoilage lactic acid bacteria, we performed time-series RNA-seq for Le. gelidum, Lc. piscium and P. oligofermentans using temperatures of 0 °C, 4 °C, 14 °C, 25 °C and 28 °C.
Results:
We showed that the cold-shock protein A (cspA) gene was the main cold-shock protein gene among cold-shock protein genes in all three species. Our results indicated DEAD-box RNA helicase genes (cshA, cshB) play a critical role in cold-shock response in psychrotrophic LAB. In addition, several RNase genes were also involved in cold-shock response in Lc. piscium and P. oligofermentans. Moreover, gene network inference analysis provided candidate genes involved in cold-shock response. Ribosomal proteins, tRNA modification, rRNA modification, and ABC and efflux MFS transporter genes clustered with cold-shock response genes in all three species, which was a strong indication that these genes would be part of cold-shock response machinery. Heat-shock treatment caused upregulation of Clp protease and chaperone genes in all three species and we were able to identify transcription binding site motifs for heat-shock response genes in Le. gelidum and Lc. piscium. Finally, we showed that food spoilage-related genes were upregulated at cold temperatures.
Conclusions:
The results of this study provide new insights into a better understanding of the cold- and heat-shock response in psychrotrophic LAB. In addition, candidate genes involved in cold- and heat-shock response predicted using gene network inference analysis could be used as a target for future studies.
Molecular epidemiology of the first wave of severe acute respiratory syndrome coronavirus 2 infection in Thailand in 2020
Authors: Puenpa Jiratchaya , Suwannakarn Kamol , Chansaenroj Jira , Nilyanimit Pornjarim , Yorsaeng Ritthideach , Auphimai Chompoonut , Kitphati Rungrueng , Mungaomklang Anek , Kongklieng Amornmas , Chirathaworn Chintana , Wanlapakorn Nasamon , Poovorawan Yong 
Published: June 2020

Abstract
The coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major global concern. Several SARS-CoV-2 gene mutations have been reported. In the current study associations between SARS-CoV-2 gene variation and exposure history during the first wave of the outbreak in Thailand between January and May 2020 were investigated. Forty samples were collected at different timepoints during the outbreak, and parts of the SARS-CoV-2 genome sequence were used to assess genomic variation patterns. The phylogenetics of the 40 samples were clustered into L, G1, G2, O and T types. T types were predominant in Bangkok during the first local outbreak centred at a boxing stadium and entertainment venues in March 2020. Imported cases were infected with various types, including L, G1, G2 and O. In southern Thailand introductions of different genotypes were identified at different times. No clinical parameters were significantly associated with differences in genotype. The results indicated local transmission (type T, Spike protein (A829T)) and imported cases (types L, G1, G2 and O) during the first wave in Thailand. Genetic and epidemiological data may contribute to national policy formulation, transmission tracking and the implementation of measures to control viral spread.
Social Ties, Mobility, and COVID-19 spread in Japan
Authors: Fraser Timothy , Aldrich Daniel P. 
Published: June 2020

Abstract
Why are some communities documenting higher case loads of COVID-19 infections than others? Past studies have linked the resilience of communities against crisis to their social vulnerability and to the capacity of local governments to provide public goods and services like health care. Disaster studies, which frequently examine the effect of social ties and mobility, may help illuminate the current spread of COVID-19. We model the occurrence of new cases from February 17 to May 29 using 4841 prefecture-day observations, paired with daily tallies of aggregate Facebook user movement among neighborhoods. This preliminary study of Japanese prefectures finds that communities with strong bridging and linking social ties start out more susceptible to COVID-19 spread, but their rates quickly decrease over time compared to communities with stronger intra-group ties. These results imply that residents’ participation in civil society and trust in officials affect their adoption of new health behaviors like physical distancing, improving their capacity to respond and adapt to crisis. Though bridging and linking communities suffered more early on, they adapted better to new conditions, demonstrating greater resilience to the pandemic. We anticipate this study to be a starting point for broader studies of the effect of social ties and mobility on response to COVID-19 worldwide, verifying what kinds of social networks we should invest in to adapt to this pandemic.
COVID-19 relapse with prolonged viral shedding up to 60 days or re-infection, in 3 frontline healthcare workers with recurrent symptoms and persistent SARS-CoV-2 PCR positivity in Ireland, a developing diagnostic challenge: A case report
Authors: McGrath Jonathan , McGinty Tara , Lynch Maureen , O'Regan Edel , Natin Dominic , O'Gorman Peter , Lambert John S 
Published: June 2020

Abstract
Background:To date, the Corona Virus Disease-2019 (COVID-19) pandemic has resulted in more than 24,400 confirmed cases in Ireland, with more than 30% involving Healthcare Workers (HCW). As more staff become involved in the care of COVID-19 patients, many key clinical considerations remain uncertain, including the possibility of re-infection following initial illness, the clinical significance of prolonged viral shedding and the degree of protection conferred by development of anti- Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antibodies.We present 3 cases of COVID19-infected HCWs, each with distinct episodes of recurrent symptoms following initial resolution and with persistently positive SARS-CoV-2 PCR results, ranging up to 60 days post onset of illness. PCR results, cycle threshold (Ct) values and clinical assessment are provided to discuss the diagnostic difficulties in assessing relapsed COVID-19 infection, or re-infection with new virus following return to work. Case presentations: Patient 1,2 and 3 (age range 25-36) tested positive for SARS-CoV-2 via rtPCR on oro/nasopharyngeal swab with initial Ct values of 21.72, 24.52 and 26.58 respectively, following presentation with respiratory symptoms. All completed 14 day periods of self-isolation with full resolution of symptoms. Each patient has a clinical role and was involved in the management of COVID-19 patients following return to work. Patient 1 was admitted to hospital 44 days after initial illness, with cough, dyspnoea and a concurrent diagnosis of neurosyphilis. SARS-CoV-2 PCR was positive with Ct value 31.36 and remained positive for at least 60 days following initial illness onset. A full clinical recovery followed. Patients 2 and 3 represented to the Emergency Department with recurrent respiratory symptoms 29 and 40 days following initial illness onset respectively. SARS-CoV-2 PCR was demonstrated in each with Ct values 31.16 and 30.72 respectively. Each subsequently made a full recovery following a second period of self-isolation. Anti-SARS-CoV-2 IgG was demonstrated in all 3 patients. Conclusions: These cases demonstrate the diagnostic difficulties in determining intermittent presentation of COVID-19 infection with prolonged viral shedding, or re-infection with new virus following return to work. As the pandemic progresses, this represents a growing diagnostic challenge impacting patient assessment, staff deployment following illness and infection control.
Endoscopic and Surgical Treatment of T1N0M0 Colorectal Neuroendocrine Tumors: A Population-Based Comparative Study
Authors: Zhu Hanlong , Zhao Si , Ji Kun , Wu Wei , Zhou Jian , Zhang Chunmei , Tang Ruiyi , Miao Lin 
Published: June 2020

Abstract
Background: With the rapid advances in endoscopic technology, endoscopic therapy (ET) is increasingly applied to the treatment of small (≤20 mm) colorectal neuroendocrine tumors (NETs). However, long-term data comparing ET and surgery for management of T1N0M0 colorectal NETs are lacking. The purpose of this work was to compare overall survival (OS) and cancer-specific survival (CSS) of such patients with ET or surgery.Methods: Patients with T1N0M0 colorectal NETs were identified within the Surveillance Epidemiology and End Results (SEER) database (2004-2016). Demographics, tumor characteristics, therapeutic methods, and survival were compared. Propensity score matching (PSM) was used 1:3 and among this cohort, Cox proportional hazards regression models were performed to evaluate correlation between treatment and outcomes.Results: Of 4487 patients with T1N0M0 colorectal NETs, 1125 were identified in the matched cohort, among whom 819 (72.8%) underwent ET and 306 (27.2%) underwent surgery. There was no difference in the 5-year and 10-year OS and CSS rates between the 2 treatment modalities. Likewise, analyses stratified by tumor size and site showed that patients did not benefit more from surgery compared with ET. Moreover, multivariate analyses found no significant differences in OS [Hazard Ratio (HR) = 0.857, 95% Confidence Interval (CI): 0.513–1.431, P = 0.555] and CSS (HR = 0.925, 95% CI: 0.282–3.040, P = 0.898) between the 2 groups. Similar results were observed when comparisons were limited to patients with different tumor size and site.Conclusions: In this population-based study, patients treated endoscopically had comparable long-term survival compared with those treated surgically, which demonstrates ET as an alternative to surgery in T1N0M0 colorectal NETs.
The Prevalence and the Use of the Questionnaire’s Related to the Neglected Sexual Side Effects After Prostate Cancer Treatment: A Scoping Review of the Literature
Authors: Röscher Pierre , Sathiram Ronisha , Milios Joanne E , Wyk Jacqueline M van 
Published: June 2020

Abstract
Background: Early prostate cancer (PCa) treatment interventions may leave men with debilitating sexual side effects. These side effects may remain permanent, often undiagnosed, and undermanaged. The objective of this study was to map the evidence pertaining to the prevalence, and use of questionnaires, related to the neglected sexual side effects (NSSE) after PCa treatment consisting of radical prostatectomy (RP) surgery or radiation treatment (RT).Methods: This systematic scoping review’s search strategy involved the search of PubMed, Science Direct, and Google Scholar databases. Following title searching, two-independent reviewers conducted screening of abstracts and full articles. The screenings were guided by the eligibility criteria. Data were extracted from the included studies and the emerging themes were analysed. The review team analysed the implications of the findings in relation to the research question and aims of the study. The Mixed Method Appraisal Tool was employed for quality appraisal of included studies.Discussion: Twenty-three studies about the prevalence and questionnaire use for NSSE after early PCa treatment were included. Two studies investigated most of the collective group of NSSE’s, and all the other studies mostly looked at a single NSSE. No single validated questionnaire was found that investigates the NSSE after early PCa treatment. Most studies incorporated some aspects of other questionnaires. Two studies used non-validated questionnaires that picked up on the majority of the collective group of NSSE.Conclusion: NSSEs are prevalent in men after RP and RT. Peyronie’s Disease, orgasmic Dysfunction and Penile Length Shortening are all similarly prevalent after RP and RT. Anejaculation was only found to be prevalent after RT*. Orgasm associated incontinence resulted from RP and RT, but the prevalence in RP patients was 6 times that of RT patients. Study participants felt inadequately informed about possible sexual side effects caused by their treatment choices. Questionnaires are effective at detecting NSSE after PCa treatment, but there is no valid and reliable questionnaire currently available to detect all the collective NSSE after PCa treatment. There is a scope to develop a validated and reliable PCa NSSE questionnaire. The NSSE questionnaire must be quick, straightforward, and effective.