bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of positive surgical margin location and perineural invasion on biochemical recurrence in patients undergoing radical prostatectomy
Authors: Lian Zhenpeng , Zhang Hongtuan , He Zhaowei , Ma Shenfei , Wang Xiaoming , Liu Ranlu 
Published: August 2020

AbstractObjectiveTo estimate the prognostic value of positive surgical margins (PSM) location and perineural invasion (PNI) for biochemical recurrence (BCR) in patients undergoing radical prostatectomy (RP).MethodsAll men with prostate cancer (PCa) who received RP in the second hospital of Tianjin Medical University from 2014 to 2018 were retrospectively identified. All patients met the following criteria: no neoadjuvant or adjuvant treatment, absence of lymph node invasion, or distant metastasis confirmed by surgery or imaging. Comparisons were made between cases with only apex positive (AM), isolated nonapical positive (OM), multiple positive (MM), and negative surgical margins (NSM). Patients were also subdivided according to the Gleason score and pathological tumor stage for analysis.ResultsA total of 416 patients available for analysis, of which 132 (31.7%) were PSM, 43 were AM, 37 were OM, and 52 were MM at a median follow-up of 27 months. The PNI was in 30.5% of patients. BCR occurred in 22.6% of patients during follow-up. Both AM and MM were noticed to be independent predictors of BCR with a hazard ratio of 4.192 (95% CI 2.185–8.042;p< 0.001) and 2.758 (95% CI 1.559–4.880;p< 0.001), respectively, when compared to NSM. Though the correlation was significant in univariate analysis, PNI was not an independent risk factor for BCR (p= 0.369). Subgroup analyses suggested that MM was not particularly predictive for BCR in the Gleason score < 8. The hole Cox regression model for the C-index was 0.843ConclusionsPSM location was a significant independent predictor of BCR in PCa, especially in patients with AM or MM, while PNI is a non-independent risk factor. Compared with other locations, AM has a higher BCR risk.
Nadir CA-125 serum levels during neoadjuvant chemotherapy and no residual tumor at interval debulking surgery predict prognosis in advanced stage ovarian cancer
Authors: Nakamura Kazuto , Kitahara Yoshikazu , Nishimura Toshio , Yamashita Soichi , Kigure Keiko , Ito Ikuro , Kanuma Tatsuya 
Published: August 2020

AbstractBackgroundRecent phase III randomized trials have suggested that neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) is a treatment option for patients with advanced epithelial ovarian cancer. This study aimed to use CA-125 and computed tomography (CT) scanning to generate a simple and clinically applicable model of predicting complete cytoreduction by interval debulking surgery (IDS) and the overall survival in patients who receive taxane/platinum-based chemotherapy as neoadjuvant chemotherapy (NACT).MethodsPatients with stage IIIc or IV epithelial ovarian cancer who underwent taxane/platinum-based NACT followed by IDS in Gunma Prefectural Cancer Center, Takasaki General Medical Center, and Gunma University from April 2009 to March 2015 were included. Patients underwent a CT scan to confirm confirm tumors unresectable by standard surgery before NACT. CA-125 levels were measured pre-NACT, after each cycle of NACT, and before IDS. CT was also performed before IDS to evaluate tumor metastasis. Data were collected retrospectively and analyzed to determine the predictive factors of complete resection and overall survival.ResultsAmong 63 patients who received NACT-IDS, 43 and 20 patients had stages IIIc and IV epithelial ovarian cancer at diagnosis, respectively. CT predictors of residual tumors after IDS such as extra-ovarian implants (P= 0.009) and omental cakes (P= 0.038) were not present. Univariate analysis revealed that the independent factors for overall survival were no residual tumor by IDS (P= 0.0016) and CA125 ≤ 20 U/ml before IDS (P= 0.0011).ConclusionsAlthough this study had a small sample size, NACT-IDS used to completely remove macroscopic disease which significantly improved the prognosis of patients with preoperative CA-125 ≤ 20 U/ml. Results from this study provide useful information for future studies on the management of patients with advanced epithelial ovarian cancer.
Temporal trends in leisure-time sedentary behavior among adolescents aged 12-15 years from 26 countries in Asia, Africa, and the Americas
Authors: Felez-Nobrega Mireia , Raine Lauren B. , Haro Josep Maria , Wijndaele Katrien , Koyanagi Ai 
Published: August 2020

AbstractBackgroundMulti-country studies examining trends in sedentary behaviors among adolescents have mainly focused on high-income or Western countries, and almost no data exists for the rest of the world. Thus, this study aims to examine temporal trends in adolescents’ leisure time sedentary behavior (LTSB) employing nationally representative datasets from 26 countries from five WHO-defined geographical regions.MethodsData from the Global School-based Student Health Survey 2003–2017 were analyzed in 17,734 adolescents [mean (SD) age: 13.7 (1.0) years; 49.0% boys]. LTSB was self-reported and included all types of sedentary behaviors, excluding time spent at school or doing homework. The prevalence and 95%CI of high LTSB (i.e., ≥3 h/day) was calculated for the overall sample and by sex for each survey. Crude linear trends in high LTSB were assessed by linear regression models. Interaction analyses were conducted to examine differing trends among boys and girls.ResultsTemporal variations in LTSB substantially diverged across countries, with results showing increasing (6/26 countries), decreasing (4/26) and stable trends. The sharpest increases in LTSB occurred in United Arab Emirates, Kuwait, and Thailand. Some countries did not show an increase in LTSB prevalence over time but had very high levels of LTSB (i.e., > 40%) across multiple years. Most countries showed no differences in LTSB trends between boys and girls.ConclusionsData from our study may serve as an important platform for policymakers, as well as local and national stakeholders, to establish country-specific and tailored strategies for reducing LTSB.
Determinants of comprehensive knowledge of HIV/AIDS among reproductive age (15–49 years) women in Ethiopia: further analysis of 2016 Ethiopian demographic and health survey
Authors: Agegnehu Chilot Desta , Geremew Bisrat Misganaw , Sisay Malede Mequanent , Muchie Kindie Fentahun , Engida Zinash Teferu , Gudayu Temesgen Worku , Weldetsadik Daniel Sisay , Liyew Alemneh Mekuriaw 
Published: August 2020

Abstract
Background
The key cause of HIV transmission is failure to provide adequate information about HIV/AIDS which is a substantial public health issue in low and middle-income countries. While global health coverage continues, there is still little understanding of HIV/AIDS among women of reproductive age (15–49 years) in Ethiopia. Therefore, the purpose of this study was to identify the determinants of comprehensive knowledge of HIV/AIDS among women of reproductive age in Ethiopia.

Methods
A secondary data analysis was employed using the 2016 Ethiopian demographic and health survey data. Data were extracted about comprehensive knowledge of HIV/AIDS among women of reproductive age. We used multi-variable mixed-effect binary logistic regression to identify factors associated with comprehensive knowledge of HIV/AIDS among women of reproductive age. The adjusted odds ratio with 95% confidence interval was used to declare statistical significance.

Results
We found that having primary (AOR = 1.75, 95% CI 1.56–1.97),secondary (AOR = 2.74, 95% CI 2.33–3.22), and higher (AOR = 4.07, 95% CI 3.32–4.99) educational statuses, being in highest wealth quintiles; richer (AOR = 1.20, 95% CI 1.01–1.43) and richest (AOR = 1.51, 95% CI 1.22–1.87), knowing the place for HIV test (AOR = 2.13, 95% CI 1.88–2.42), use of traditional contraceptive method (AOR = 1.93,95% CI 1.12–3.35), female household head (AOR = 1.18, 95% CI 1.07–1.31), watching television (AOR = 1.22, 95% CI 1.06–1.41) and own mobile phone (AOR = 1.18, 95% CI 1.05–1.33) were positively associated with comprehensive knowledge of HIV/AIDS among women of reproductive age in Ethiopia.

Conclusion
Women with higher education and higher wealth quintiles, knowing the place of HIV test, watching television, a traditional contraceptive method use, having a mobile phone and being in female headed household were positively associated with comprehensive knowledge of HIV/AIDS among women of reproductive age in Ethiopia. Programs working on HIV/AIDS should target women based on the identified factors so as to scale up their comprehensive knowledge towards HIV/AIDS. In this context, the media should actively contribute to raising awareness of HIV/AIDS.
Biomarkers in critical care nutrition
Authors: Stoppe Christian , Wendt Sebastian , Mehta Nilesh M. , Compher Charlene , Preiser Jean-Charles , Heyland Daren K. , Kristof Arnold S. 
Published: August 2020

AbstractThe goal of nutrition support is to provide the substrates required to match the bioenergetic needs of the patient and promote the net synthesis of macromolecules required for the preservation of lean mass, organ function, and immunity. Contemporary observational studies have exposed the pervasive undernutrition of critically ill patients and its association with adverse clinical outcomes. The intuitive hypothesis is that optimization of nutrition delivery should improve ICU clinical outcomes. It is therefore surprising that multiple large randomized controlled trials have failed to demonstrate the clinical benefit of restoring or maximizing nutrient intake. This may be in part due to the absence of biological markers that identify patients who are most likely to benefit from nutrition interventions and that monitor the effects of nutrition support. Here, we discuss the need for practical risk stratification tools in critical care nutrition, a proposed rationale for targeted biomarker development, and potential approaches that can be adopted for biomarker identification and validation in the field.
Unspecific post-mortem findings despite multiorgan viral spread in COVID-19 patients
Authors: Remmelink Myriam , De Mendonça Ricardo , D’Haene Nicky , De Clercq Sarah , Verocq Camille , Lebrun Laetitia , Lavis Philomène , Racu Marie-Lucie , Trépant Anne-Laure , Maris Calliope , Rorive Sandrine , Goffard Jean-Christophe , De Witte Olivier , Peluso Lorenzo , Vincent Jean-Louis , Decaestecker Christine , Taccone Fabio Silvio , Salmon Isabelle 
Published: August 2020

Abstract
Background
Post-mortem studies can provide important information for understanding new diseases and small autopsy case series have already reported different findings in COVID-19 patients.

Methods
We evaluated whether some specific post-mortem features are observed in these patients and if these changes are related to the presence of the virus in different organs. Complete macroscopic and microscopic autopsies were performed on different organs in 17 COVID-19 non-survivors. Presence of SARS-CoV-2 was evaluated with immunohistochemistry (IHC) in lung samples and with real-time reverse-transcription polymerase chain reaction (RT-PCR) test in the lung and other organs.

Results
Pulmonary findings revealed early-stage diffuse alveolar damage (DAD) in 15 out of 17 patients and microthrombi in small lung arteries in 11 patients. Late-stage DAD, atypical pneumocytes, and/or acute pneumonia were also observed. Four lung infarcts, two acute myocardial infarctions, and one ischemic enteritis were observed. There was no evidence of myocarditis, hepatitis, or encephalitis. Kidney evaluation revealed the presence of hemosiderin in tubules or pigmented casts in most patients. Spongiosis and vascular congestion were the most frequently encountered brain lesions. No specific SARS-CoV-2 lesions were observed in any organ. IHC revealed positive cells with a heterogeneous distribution in the lungs of 11 of the 17 (65%) patients; RT-PCR yielded a wide distribution of SARS-CoV-2 in different tissues, with 8 patients showing viral presence in all tested organs (i.e., lung, heart, spleen, liver, colon, kidney, and brain).

Conclusions
In conclusion, autopsies revealed a great heterogeneity of COVID-19-associated organ injury and the remarkable absence of any specific viral lesions, even when RT-PCR identified the presence of the virus in many organs.
MDM2 inhibition in combination with endocrine therapy and CDK4/6 inhibition for the treatment of ER-positive breast cancer
Authors: Portman Neil , Milioli Heloisa H. , Alexandrou Sarah , Coulson Rhiannon , Yong Aliza , Fernandez Kristine J. , Chia Kee Ming , Halilovic Ensar , Segara Davendra , Parker Andrew , Haupt Sue , Haupt Ygal , Tilley Wayne D. , Swarbrick Alex , Caldon C. Elizabeth , Lim Elgene 
Published: August 2020

AbstractBackgroundResistance to endocrine therapy is a major clinical challenge in the management of oestrogen receptor (ER)-positive breast cancer. In this setting, p53 is frequently wildtype and its activity may be suppressed via upregulation of its key regulator MDM2. This underlies our rationale to evaluate MDM2 inhibition as a therapeutic strategy in treatment-resistant ER-positive breast cancer.MethodsWe used the MDM2 inhibitor NVP-CGM097 to treat in vitro and in vivo models alone and in combination with fulvestrant or palbociclib. We perform cell viability, cell cycle, apoptosis and senescence assays to evaluate anti-tumour effects in p53 wildtype and p53 mutant ER-positive cell lines (MCF-7, ZR75-1, T-47D) and MCF-7 lines resistant to endocrine therapy and to CDK4/6 inhibition. We further assess the drug effects in patient-derived xenograft (PDX) models of endocrine-sensitive and endocrine-resistant ER-positive breast cancer.ResultsWe demonstrate that MDM2 inhibition results in cell cycle arrest and increased apoptosis in p53-wildtype in vitro and in vivo breast cancer models, leading to potent anti-tumour activity. We find that endocrine therapy or CDK4/6 inhibition synergises with MDM2 inhibition but does not further enhance apoptosis. Instead, combination treatments result in profound regulation of cell cycle-related transcriptional programmes, with synergy achieved through increased antagonism of cell cycle progression. Combination therapy pushes cell lines resistant to fulvestrant or palbociclib to become senescent and significantly reduces tumour growth in a fulvestrant-resistant patient-derived xenograft model.ConclusionsWe conclude that MDM2 inhibitors in combination with ER degraders or CDK4/6 inhibitors represent a rational strategy for treating advanced, endocrine-resistant ER-positive breast cancer, operating through synergistic activation of cell cycle co-regulatory programmes.
Strain-level epidemiology of microbial communities and the human microbiome
Authors: Yan Yan , Nguyen Long H. , Franzosa Eric A. , Huttenhower Curtis 
Published: August 2020

AbstractThe biological importance and varied metabolic capabilities of specific microbial strains have long been established in the scientific community. Strains have, in the past, been largely defined and characterized based on microbial isolates. However, the emergence of new technologies and techniques has enabled assessments of their ecology and phenotypes within microbial communities and the human microbiome. While it is now more obvious how pathogenic strain variants are detrimental to human health, the consequences of subtle genetic variation in the microbiome have only recently been exposed. Here, we review the operational definitions of strains (e.g., genetic and structural variants) as they can now be identified from microbial communities using different high-throughput, often culture-independent techniques. We summarize the distribution and diversity of strains across the human body and their emerging links to health maintenance, disease risk and progression, and biochemical responses to perturbations, such as diet or drugs. We list methods for identifying, quantifying, and tracking strains, utilizing high-throughput sequencing along with other molecular and “culturomics” technologies. Finally, we discuss implications of population studies in bridging experimental gaps and leading to a better understanding of the health effects of strains in the human microbiome.
Computational homogenization of transient chemo-mechanical processes based on a variational minimization principle
Authors: Polukhov Elten , Keip Marc-André 
Published: August 2020

AbstractWe present a variational framework for the computational homogenization of chemo-mechanical processes of soft porous materials. The multiscale variational framework is based on a minimization principle with deformation map and solvent flux acting as independent variables. At the microscopic scale we assume the existence of periodic representative volume elements (RVEs) that are linked to the macroscopic scale via first-order scale transition. In this context, the macroscopic problem is considered to be homogeneous in nature and is thus solved at a single macroscopic material point. The microscopic problem is however assumed to be heterogeneous in nature and thus calls for spatial discretization of the underlying RVE. Here, we employ Raviart–Thomas finite elements and thus arrive at a conforming finite-element formulation of the problem. We present a sequence of numerical examples to demonstrate the capabilities of the multiscale formulation and to discuss a number of fundamental effects.
Culturally and developmentally adapting group interpersonal therapy for adolescents with depression in rural Nepal
Authors: Rose-Clarke Kelly , Pradhan Indira , Shrestha Pragya , B.K. Prakash , Magar Jananee , Luitel Nagendra P. , Devakumar Delan , Rafaeli Alexandra Klein , Clougherty Kathleen , Kohrt Brandon A. , Jordans Mark J. D. , Verdeli Helen 
Published: August 2020

Abstract
Background
Evidence-based interventions are needed to reduce depression among adolescents in low- and middle-income countries (LMICs). One approach could be cultural adaptation of psychological therapies developed in high-income countries. We aimed to adapt the World Health Organization’s Group Interpersonal Therapy (IPT) Manual for adolescents with depression in rural Nepal.

Methods
We used a participatory, multi-stage adaptation process involving: translation and clinical review of the WHO Manual; desk reviews of adaptations of IPT in LMICs, and literature on child and adolescent mental health interventions and interpersonal problems in Nepal; a qualitative study to understand experiences of adolescent depression and preferences for a community-based psychological intervention including 25 interviews with adolescent boys and girls aged 13–18 with depression, four focus group discussions with adolescents, four with parents/caregivers and two with teachers, six interviews with community health workers and one with a representative from a local non-governmental organisation (total of 126 participants); training of IPT trainers and facilitators and practice IPT groups; and consultation with a youth mental health advisory board. We used the Ecological Validity Framework to guide the adaptation process.

Results
We made adaptations to optimise treatment delivery and emphasise developmental and cultural aspects of depression. Key adaptations were: integrating therapy into secondary schools for delivery by school nurses and lay community members; adding components to promote parental engagement including a pre-group session with the adolescent and parent to mobilise parental support; using locally acceptable terms for mental illness such as udas-chinta (sadness and worry) and man ko samasya (heart-mind problem); framing the intervention as a training programme to de-stigmatise treatment; and including activities to strengthen relationships between group members. We did not adapt the therapeutic goals of IPT and conserved IPT-specific strategies and techniques, making edits only to the way these were described in the Manual.

Conclusions
Group IPT can be adapted for adolescents in Nepal and delivered through the education system. A randomised controlled trial is needed to assess the impact and costs of the intervention in this setting. Future research in LMICs to adapt IPT for adolescents could use this adapted intervention as a starting point.
Development of a highly sensitive method for detection of FLT3D835Y
Authors: Guo Yao , Sun Honghua , Zhang Dengyang , Zhao Yuming , Shi Mingxia , Yang Ming , Xing Shu , Fu Xueqi , Bin Ting , Lu Bo , Wu Shunjie , Xu Xiaojun , Xu Xuesong , Chen Yun , Zhao Zhizhuang Joe 
Published: August 2020

Abstract
Background
Acute myeloid leukemia (AML) is a malignant hematological neoplasm of myeloid progenitor cells. Mutations of FLT3 in its tyrosine kinase domain (FLT3-TKD) are found in ~ 8% of patients with AML, with D835Y as the most common substitution. This mutation activates survival signals that drives the disease and is resistant to the first generation FLT3 inhibitors. Development of a highly sensitive method to detect FLT3D835Y is important to direct therapeutic options, predict prognosis, and monitor minimal residual disease in patients with AML.

Methods and results
In the present study, we developed a highly sensitive FLT3D835Y detection method by using the restriction fragment nested allele-specific PCR technique. The method consists of three steps: 1) initial amplification of DNA samples with PCR primers surrounding the FLT3D835Y mutation site, 2) digestion of the PCR products with restriction enzyme EcoRV that only cleaves the wild type allele, and 3) detection of FLT3D835Y by allele-specific PCR with nested primers. We were able to detect FLT3D835Y with a sensitivity of 0.001% by using purified plasmid DNAs and blood cell DNAs containing known proportions of FLT3D835Y. We analyzed blood cell DNA samples from 64 patients with AML and found six FLT3D835Y-positive cases, two of which could not be detected by conventional DNA sequencing methods. Importantly, the method was able to detect FLT3D835Y in a sample collected from a relapsed patient while the patient was in complete remission with negative MRD determined by flow cytometry. Therefore, our RFN-AS-PCR detected MRD after treatment that was missed by flow cytometry and Sanger DNA sequencing, by conventional methods.

Conclusions
We have developed a simple and highly sensitive method that will allow for detection of FLT3D835Y at a very low level. This method may have major clinical implications for treatment of AML.