bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting Prostate Cancer Upgrading of Biopsy Gleason Grade Group at Radical Prostatectomy Using Machine Learning-assisted Decision-support Models&nbsp;
Authors: Liu Hailang , Tang Kun , Peng Ejun , Wang Liang , Xia Ding , Chen Zhiqiang 
Published: October 2020

Abstract
Background: This study aimed to develop a machine learning (ML)-assisted model capable of accurately predicting the probability of biopsy Gleason grade group upgrading before making treatment decisions.Methods: We retrospectively collected data from prostate cancer (PCa) patients who underwent systematic biopsy and radical prostatectomy from January 2015 to December 2019 at Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology. The study cohort was divided into training and testing datasets in a 70:30 ratio for further analysis. Four ML-assisted models were developed from 16 clinical features using logistic regression (LR), logistic regression optimized by least absolute shrinkage and selection operator (Lasso) regularization (Lasso-LR), random forest (RF) and support vector machine (SVM). The area under the curve (AUC) was applied to determine the model with the highest discrimination. Calibration plots were used to investigate the extent of over- or underestimation of predicted probabilities relative to the observed probabilities in models. Results: In total, 530 PCa patients were included, with 371 patients in the training dataset and 159 patients in the testing dataset. The Lasso-LR model showed good discrimination with an AUC, accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 0.776, 0.712, 0.679, 0.745, 0.730 and 0.695, respectively, followed by SVM (AUC 0.740, 95% confidence interval [CI]: 0.690–0.790), LR (AUC 0.725, 95% CI: 0.674–0.776) and RF (AUC 0.666, 95% CI: 0.618–0.714). Validation of the model showed that the Lasso-LR model had the best discriminative power (AUC 0.735, 95% CI: 0.656–0.813), followed by SVM (AUC 0.723, 95% CI: 0.644–0.802), LR (AUC 0.697, 95% CI: 0.615–0.778) and RF (AUC 0.607, 95% CI: 0.531–0.684) in the testing dataset. Both the Lasso-LR and SVM models were well-calibrated. Conclusion: The Lasso-LR model had good discrimination in the prediction of patients at high risk of harboring incorrect Gleason grade group assignment, and the use of this model may be greatly beneficial to urologists in treatment planning, patient selection, and the decision-making process for PCa patients.
Osimertinib in Advanced EGFR-T790M&nbsp;Mutation-positive Non-small Cell Lung Cancer Patients Treated Within the Special Use Medication Program in Spain. OSIREX-spanish Lung Cancer Group
Authors: Provencio Mariano , Terrasa Josefa , Garrido Pilar , Campelo Rosario García , Aparisi Francisco , Diz Pilar , Aguiar David , García-Giron Carlos , Hidalgo Julia , Aguado Carlos , González Jorge Jose García , Esteban Emilio , Gómez-Aldavarí Lorenzo , Moran Teresa , Juan Oscar , Chara Luís Enrique , Marti Juan Luis , Castro Rafael López , Ortega Ana Laura , Moreno Elia Martínez , Coves Juan , Peña Ana M. Sánchez , Bosch-Barrera Joaquim , Gastaldo Amparo Sánchez , Núñez Natalia Fernández , Barco Edel del , Cobo Manuel , Isla Dolores , Majem Margarita , Navarro Fátima , Calvo Virginia 
Published: October 2020

Abstract
Background: AURA study reported 61% objective response rate and progression-free survival of 9.6 months with osimertinib in patients with EGFR/T790M+ non-small cell lung cancer. Due to lack of real-world data, we proposed this study to describe the experience with osimertinib in Spain.Methods: Post-authorization, non-interventional Special Use Medication Program, multicenter, retrospective study in advanced EGFR/T790M+ non-small cell lung cancer. 155 patients were enrolled (August 2016-December 2018) from 30 sites. Primary objective: progression-free survival. Secondary objectives: toxicity profile, objective response rate, and use of health service resources.Results: 70% women, median age 66. 63.9% were non-smokers and 99% had adenocarcinoma. Most had received at least one prior treatment (97%), 91.7% had received previous EGFR-tyrosine kinase inhibitors and 2.8% osimertinib as first-line treatment. At data cutoff, median follow-up was 11.8 months. 155 patients were evaluable for response, 1.3% complete response, 40.7% partial response, 31% stable disease and 11.6% progressive disease. Objective response rate was 42%. Median progression-free survival was 9.4 months. 49% reported an adverse event, the majority of which (78%) were grade 1 or 2. The resource cost study indicates early use is warranted. Conclusion: This study to assess the real-world clinical impact of osimertinib showed high drug activity in pretreated advanced EGFR/T790M+ non-small cell lung cancer, with manageable adverse events.Clinical trial registration number: NCT03790397
The Identification of the Anthracycline Aclarubicin as an Effective Cytotoxic Agent for Pancreatic Cancer
Authors: Brouwer Thomas , Zanden Sabina Y van der , Eendenburg Jaap DH van , Bonsing Bert A , de Miranda Noel FCC , Neefjes Jacques J , Vahrmeijer Alexander L 
Published: October 2020

Abstract
BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of cancer, mainly due to its delayed diagnosis and lack of effective therapeutic options. Therefore, it is imperative to find novel treatment options for PDAC. Here, we tested a series of conventional chemotherapeutics together with anthracycline compounds as single agents or in combination, determining their effectivity against established commercial and patient-derived, low passage PDAC cell lines.MethodsProliferation and colony formation assays were performed to determine the anti-cancer activity of anthracyclines; aclarubicin and doxorubicin, on commercial and patient-derived, low passage PDAC cell lines. In addition, the effect of standard of care drugs gemcitabine and individual components of FOLFIRINOX were also investigated. The assays involved short-term exposure to the drugs in order to mimic pharmacokinetics in a patient.ResultsAclarubicin showed superior anti-tumor activity compared to other anthracyclines and standard of care drugs (gemcitabine and individual components of FOLFIRINOX) in a patient-derived, low passage PDAC cell line. Importantly, the combination of gemcitabine and aclarubicin showed a synergistic effect at a dose range where the single agents by themselves were ineffective. Subsequent testing in commercial cell lines showed similar cytotoxic effects of aclarubicin in two out of three cell lines. Gemcitabine and doxorubicin had variable responses between the cell lines, but their effect never exceeded that of aclarubicin.ConclusionsAclarubicin is cytotoxic for commercial and patient-derived low-passage PDAC cell lines, at doses lower than peak serum concentrations for patient treatment. Our findings support a (re-)consideration of aclarubicin as a backbone of new combination regimens for pancreatic cancer patients.
Comprehensive Analysis of the Expression and Prognosis for IRXs&nbsp;in Non-small Cell Lung Cancer
Authors: Wang Qiongzi , Qiu Xueshan 
Published: October 2020

Abstract
Iroquoishomeobox transcription factor family （IRXs）have been increasingly reported to play roles in suppressing or promoting a variety of cancers, however, little is known about their expression and prognostic value in terms of human lung cancer. In this study, Oncomine, GEPIA, Kaplan-Meier plotter, and cBioPortal databases were used to analyze the different expression patterns and prognostic values of six IRXs in NSCLC and examine their related functions and pathways using GO enrichment. Compared with normal lung cancer tissues, the expression of IRX1 and IRX2 in NSCLC tissues was significantly lower and was positively correlated with the 10-year survival rate of patients. Higher expression of IRX4 was related to terminal tumors, and suggested a poor prognosis. It was also found that IRXs may play a tumor-suppressive role in the localization of cytoplasm in NSCLC, while localization in the nucleus suggests a more malignant behavior. Together these results suggest that IRX1 and IRX2 may be prognostic indicators of LUAD, and that IRX4 could be a potential target for LUAD treatment.
Non-lithifying microbial ecosystem dissolves peritidal lime sand
Authors: Present Theodore , Gomes Maya , Trower Elizabeth , Stein Nathan , Lingappa Usha , Naviaux John , Thorpe Michael , Cantine Marjorie , Fischer Woodward , Knoll Andrew , Grotzinger John 
Published: October 2020

Abstract
Microbialites accrete where environmental conditions and microbial metabolisms promote lithification, commonly through carbonate cementation. On Little Ambergris Cay, Turks and Caicos Islands, microbial mats occur widely in peritidal environments above ooid sand, but they do not become lithified or preserved. Sediment cores and porewater geochemistry indicate that aerobic respiration and sulfide oxidation inhibit lithification, dissolving calcium carbonate sand despite widespread aragonite precipitation from platform surface waters. In tidally pumped environments, primary productivity and respiration can negate the effects of taphonomically-favorable seawater chemistry on carbonate mineral saturation and microbialite development.
Challenges Experienced by Midwives Working in Rural Communities of the Bongo District in the Upper East Region of Ghana. A Qualitative Study
Authors: Adatara Peter , Amooba Philemon Adoliwine , Afaya Agani , Salia Solomon Mohammed , Avane Mabel Apaanye , Kuug Anthony , Maalman Raymond Saa-Eru , Atakro Confidence Alorse , Attachie Irene Torshie , Atachie Constancia 
Published: October 2020

Abstract
IntoductionGlobally, a total of 295 000 women lost their lives due pregnancy and childbirth in 2017, with sub-Saharan Africa and South Asia accounting for approximately 86% of all maternal deaths. Currently the Maternal Mortality Ratio (MMR) in Ghana is uncceptably high with about 308 deaths/100,000 live births in 2017 and most of these maternal deaths occur less in urban areas than in rural areas. As midwives play a vital role in maternity care and in the reduction of MMR, this study therefore sought to explore and describe challenges experienced by midwives working in rural communities in the Bongo District of the Upper East region of Ghana.MethodsA qualitative descriptive exploratory design was used to gain better insight into midwives’ experiences of working and providing women-centred midwifery care in rural areas of Ghana. A total of 30 midwives providing midwifery care in rural areas of the Upper East region of Ghana for at least three years were purposefully selected for this study. Data were collected using individual semi-structured interviews and analysed through qualitative content analysis. ResultsFive main themes emerged from the data analysis. These thematic areas included inadequate infrastructure (lack of bed and physical space), lack of logistics, shortage of midwifery staff, lack of motivation, and limited in-service training opportunities.ConclusionThe study concludes that although the rural midwives perform a multidisciplinary function in providing midwifery care in rural northern Ghana, they experience a myriad of challenges in providing midwifery care. There is the need for the Ghana Health Service and other stakeholders to motivate midwives working in rural areas through policy interventions such as rural incentive allowances, supportive supervision and in-service training opportunities for midwives in order to encourage them to accept posting to rural areas of Ghana to improve maternal and child health care.
Human Interferon Inducible Transmembrane Protein 3 (IFITM3) Inhibits Influenza Virus A Replication and Inflammation by Interacting with ABHD16A
Authors: Chen Liang , Limei Zhu , Jun Chen 
Published: October 2020

Abstract
Background: Studies have shown that human interferon inducible transmembrane proteins (hIFITMs) family proteins have broad-spectrum antiviral capabilities. Preliminary studies in our laboratory have preliminarily proved that hIFITMs have the effect of inhibiting influenza viruses. In order to further study its mechanism and role in the occurrence and development of influenza A, relevant studies have relevant studies have been carried out.Methods: Fluorescence quantitative polymerase chain reaction (PCR) detection, yeast two-hybrid test and optical confocal microscopy were used to investigate the effect of hIFITM3 on influenza virus A (IVA) replication, the interaction with human abhydrolase domain containing 16A (hABHD16A) and the expression of inflammation-related factors.Results: In HEK293 cells, overexpression of hIFITM3 protein significantly inhibited the replication of IVA at 24h, 48h, and 72h; yeast two-hybrid experiment proved that hIFITM3 interacts with hABHD16A; laser confocal microscopy observations showed that hIFITM3 and hABHD16A co-localized in cell membrane area; the expression level of inflammation-related factors in cells overexpressing hIFITM3 or hABHD16A was detected by fluorescence quantitative PCR, and the results showed that the mRNA levels of interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-a and for cyclooxygenase 2 (COX2) were significantly increased. But when hIFITM3/hABHD16A was co-expressed, the mRNA expression levels of these cytokines were significantly reduced except COX2. When influenza virus infected cells co-expressing hIFITM3/hABHD16A, the expression level of inflammatory factors decreased compared with the control group, indicating that hIFITM3 can play an important role in regulating inflammation balance.Conclusions: This study confirmed that hIFITM3 has an effect of inhibiting IVA replication. Furthermore, it was found that hIFITM3 interacts with hABHD16A, following which it can better inhibit the replication of influenza virus and the inflammatory response caused by the disease process.
Characterization of Genes Associated with TGA7 During the Floral Transition
Authors: Xu Xiaorui , Xu Jingya , Yuan Chen , Hu Yikai , Liu Qinggang , Chen Qianqian , Zhang Pengcheng , Shi Nongnong , Qin Cheng 
Published: October 2020

Abstract
BackgroundThe TGA family has ten members and plays vital roles in plant defence and development in Arabidopsis. However, involvement of TGAs in control of flowering time remains largely unknown and requires further investigation. ResultsTo study the role of TGA7 during the floral transition, we first tested phenotypes of tga7 mutant, which displayed delay-flowering phenotype under both long-day and short-day conditions. We then performed flowering genetic pathways analysis and found that both autonomous and thermosensory pathways may affect TGA7 expression. Furthermore, to reveal differential gene expression profiles between wild-type (WT) and tga7, cDNA libraries were generated for WT and tga7 mutant seedlings at 9 DAG (days after germination). For each library, deep-sequencing produced approximately 6.67 Gb of high-quality sequences with the majority (84.55%) of mRNAs between 500 and 3000 nucleotides in length. Three hundred and twenty-five differentially expressed genes (DEGs) were identified between WT and tga7 mutant seedlings. Among them, four genes are associated with flowering time control. Differential expression of the four flowering-related DEGs was further validated by qRT-PCR.ConclusionsTransciptomic sequencing coupled with flowering genetic pathways analysis provides a framework for further studying the role of TGA7 in promoting flowering.
Ethnic Conflict as a Risk Amplifier for Resurgent P. Vivax Malaria in Temperate Zones:&nbsp;A Case Study from the Caucasus Region.
Authors: Hirschfeld Katherine , de Beurs Kirsten , Brayfield Brad , Melkonyan Ani 
Published: October 2020

Abstract
Background: One of the most protracted post-Soviet conflicts of the 1990s was a territorial dispute between Armenia and Azerbaijan over the contested Karabakh region. Years of ethnic violence led to the displacement of nearly a million refugees, as well as a public health crisis that included epidemics of malaria, diphtheria and other preventable diseases. Malaria is not usually considered a health risk in temperate climates, but seasonal epidemics were widespread throughout the Caucasus in the early decades of the twentieth century. Methods: This paper combines qualitative historical research with geospatial analysis to explore how endemic malaria was controlled during the Soviet era, and how ethnic conflict reconfigured local ecologies to facilitate the re-emergence of P. vivax after the Soviet collapse in the 1990s. Results: This research reveals that ethnic conflicts have specific qualities that increase risks of infectious and vector borne disease outbreaks, even in places that have successfully achieved a modern health and mortality profile. The risk amplifiers of ethnic conflicts include 1) the creation of contested spaces controlled by separatists that are outside of any national public health surveillance system; 2) mass population movements and refugee outflows due to ethnic violence; and 3) changes in land use that expand potential mosquito breeding sites throughout the conflict zone. Conclusions: Ongoing hostilities between Armenia and Azerbaijan, combined with the repopulation of key vector species (specifically An. sacharovi) lead us to conclude that contemporary populations in the Caucasus remain vulnerable to resurgent outbreaks of ethno-nationalist violence as well as the return of seasonal malaria, even after decades of successful control.
Qualitative Assessment of Patients’ Perspectives and Needs from Community Pharmacists in Substance Use Disorder Management
Authors: Fatani Sarah , Bakke Daniel , D’Eon Marcel , El-Aneed Anas 
Published: October 2020

Abstract
Background: Substance use disorder (SUD) is a major health concern affecting Canadians and their health care system. SUD treatment plans addressing patients’ needs and choices have demonstrated improved treatment outcomes. It is essential for health care providers, including community pharmacists, to understand patients' needs and prioritize them. Therefore, this study explores the perspective of patients living with SUD regarding community pharmacist services and the delivery of care in a community pharmacy setting located in the small urban center of, Saskatoon, Saskatchewan, Canada.Methods: A qualitative methodology was used for this research inquiry. Four focus groups were conducted in Saskatoon, with a total of 20 individuals who had experienced substance use and accessed community pharmacy services. The discussion of the four focus groups was transcribed verbatim and analyzed independently by two researchers. Agreement on the emergent themes was reached through discussion between the two researchers. Results: Data analysis resulted in four themes that described participants' perspectives about community pharmacists. The four emergent themes are: 1) experience of people living with SUD in a community pharmacy, 2) services provided by community pharmacists, 3) the methadone maintenance program, and 4) needs from community pharmacists. Conclusion: There is significant potential for the patient-pharmacist relationship to address the varying needs of patients living with SUD and improve their overall health care experience. Patients who use substances are receptive to pharmacists' services beyond dispensary; however, respectful communication, provision of drug-related information, and counseling are among the primary demands. Future research should focus on studying the impact of meeting the needs of patients on their treatment outcomes.
A Nomogram to Predict Postoperative Complications in Elderly with Total Hip Replacement
Authors: Tan Xiujuan , Ge Fengmin , Mo Guixi , Li Zhiyi , Gu Xiaoxia , Zhang Liangqing 
Published: October 2020

Abstract
Background: By analyzing the risk factors of postoperative complications in elderly patients with hip replacement, We aimed to develop a nomogram model based on preoperative and intraoperative variables and verified the sensitivity and specificity for risk stratification of postoperative complications in elderly with total hip replacement patients.Methods: A total of 414 elderly patients who underwent surgical treatment for total hip replacement hospitalized at the Affiliated Hospital of Guangdong Medical University from March 1, 2017 to August 31, 2019 were included into this study. Univariate and multivariate logistic regression were conducted to identify independent risk factors of postoperative complication in the 414 patients. A nomogram was developed by R software and validated to predict the risk of postoperative complications.Results: Multivariate logistic regression analysis revealed that age (OR=1.05, 95%CI: 1.00-1.09) , renal failure(OR=0.90, 95% CI: 0.83～0.97) , Type2 diabetes (OR=1.05, 95% CI: 1.00～1.09) , ALB (OR=0.91, 95% CI: 0.83～0.99) were independent risk factors of postoperative complication in elderly patients with hip replacement (P＜0.05) . For validation of the nomogram, ROC curve revealed that the model predicting postoperative complication in elderly patients with hip replacement was the area under the curve of 0.8254(95% CI: 0.78～0.87) , the slope of the calibration plot was close to 1 and the model passed Hosmer-Lemeshow goodness of fit test (x2 = 10.16, P=0.4264), calibration in R Emax=0.176, Eavg=0.027, which all demonstrated that the model was of good accuracy. Conclusion: The nomogram predicting postoperative complications in patients with total hip replacement constructed based on age, type 2 diabetes, renal failure and ALB is of good discrimination and accuracy, which was of clinical significance.
Integrated CNV-seq, Karyotyping and SNP-array Analyses for Effective Prenatal Diagnosis of Chromosomal Mosaicism
Authors: Ma Na , Xi Hui , Chen Jing , Peng Ying , Jia Zhengjun , Yang Shuting , Hu Jiancheng , Pang Jialun , Zhang Yalan , Hu Rong , Wang Hua , Liu Jing 
Published: October 2020

Abstract
Background: Emerging studies suggest that low‐coverage massively parallel copy number variation sequencing (CNV-seq) provide advantage in detecting low-level mosaicism compared with chromosomal microarray analysis (CMA). However, a prospective back-to-back comparison evaluating accuracy, efficacy, and incremental yield of CNV-seq compared with CMA is warranted. Methods: A total of 72 mosaicism cases identified by karyotyping or CMA were recruited in this study, and 67 samples (40 sex chromosome aneuploidy, 22 autosomal aneuploidy and 5 submicroscopic CNVs) were eventually analyzed by CNV-seq. Results: CNV-seq not only identified all 43 chromsomal aneuploidies or submicroscopic CNVs detected by CMA, but also provided a 34.88% (15/43) increased yield compared with CMA. Besides, the level of mosaicism defined by CNV-seq range from 6% to 92%. Conclusion: In the context of prenatal diagnosis, CNV-seq identified additional and clinically significant information with enhanced resolution and increased sensitivity of detecting mosaicism as compared with the CMA platform we used. This study provides strong evidence for applying CNV-seq as an alternative prenatal diagnostic test.