bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive Joint Modeling of First-Line Therapeutics in Non-Small Cell Lung Cancer
Authors: Schneider Benjamin K , Benzekry Sebastien , Mochel Jonathan P 
Published: November 2020

AbstractFirst-line antiproliferatives for non-small cell lung cancer (NSCLC) have a relatively high failure rate due to high intrinsic resistance rates and acquired resistance rates to therapy. 57% patients are diagnosed in late-stage disease due to the tendency of early-stage NSCLC to be asymptomatic. For patients first diagnosed with metastatic disease the 5-year survival rate is approximately 5%. To help accelerate the development of novel therapeutics and computer-based tools for optimizing individual therapy, we have collated data from 11 different clinical trials in NSCLC and developed a semi-mechanistic, clinical model of NSCLC growth and pharmacodynamics relative to the various therapeutics represented in the study. In this study, we have produced extremely precise estimates of clinical parameters fundamental to cancer modeling such as the rate of acquired resistance to various pharmaceuticals, the relationship between drug concentration and rate of cancer cell death, as well as the fine temporal dynamics of anti-VEGF therapy. In the simulation sets documented in this study, we have used the model to make meaningful descriptions of efficacy gain in making bevacizumab-antiproliferative combination therapy sequential, over a series of days, rather than concurrent.
Effect of a multi-faceted Rapid Response System re-design on repeat calling of the Rapid Response Team
Authors: Chalwin Richard , Salter Amy , Karnon Jonathon , Eaton Victoria , Giles Lynne 
Published: November 2020

ABSTRACTBackgroundRepeat Rapid Response Team (RRT) calls are associated with increased mortality risk to patients and pose a resource burden to organisations. Use of Non-Technical Skills (NTS) at calls has the potential to reduce potentially preventable repeat calling. NTS are usually improved through training, however this consumes time and financial resources. Modifications to the Rapid Response System (RRS) that promote use of NTS are worth exploring as a cost-effective alternative.MethodsA pre-post observational study of a RRS re-design on proportion of admissions each month subject to repeat RRT calling and number of calls per admission, with univariate and multivariable interrupted time series analyses comparing outcomes between study phases.ResultsThe proportion of admissions with repeat calls each month increased across both phases of the study period, but the increase was lower in the post re-design phase (change in adjusted regression slope -0.12 (standard error 0.07) post versus pre re-design). The multivariable model showed an estimated 6.0% reduction (P=0.19) in the proportion of admissions having repeat calls at the end of the study versus that predicted had the re-design not occurred.For the number of calls per the multivariable model predicted a reduction of 0.07 calls per admission at the end of the post re-design phase (95% confidence interval -0.23 – 0.08, P=0.35), equating to one fewer repeat call per 14 patients having RRT calls.ConclusionThis study showed no observed statistically significant effect on rates of repeat calling or numbers of repeat calls per admission from the implementation of a RRS re-design. However, the results demonstrate, at an organisational level, the feasibility of a low-cost initiative to improve NTS use by the RRS.
Symptom-based prediction model of SARS-CoV-2 infection developed from self-reported symptoms of SARS-CoV-2-infected individuals in an online survey
Authors: Schulze Hansjörg , Hoffmann Daniel , Bayer Wibke 
Published: November 2020

AbstractBackgroundInfections with the newly emerged severe acute respiratory syndrome virus 2 (SARS-CoV-2) have quickly reached pandemic proportions and are causing a global health crisis. First recognized for the induction of severe disease, the virus also causes asymptomatic infections or infections with mild symptoms that can resemble common colds. Since infections with mild course are probably a major contributor to the spread of SARS-CoV-2, better detection of such cases is important. To provide better understanding of these mild SARS-CoV-2 infections and to improve information for potentially infected individuals, we performed a detailed analysis of self-reported symptoms of SARS-CoV-2 positive and SARS-CoV-2 negative individuals.MethodsIn an online-based survey, 963 individuals provided information on symptoms associated with an acute respiratory infection, 336 of the participants had tested positive for SARS-CoV-2 infection, 107 had tested negative, and 520 had not been tested for SARS-CoV-2 infection.ResultsThe symptoms reported most frequently by SARS-CoV-2 infected individuals were tiredness, loss of appetite, impairment of smell or taste and dry cough. The symptoms with the highest odds ratios between SARS-CoV-2 positive and negative individuals were loss of appetite and impairment of smell or taste. Based on the most distinguishing symptoms, we developed a Bayesian prediction model, which had a positive predictive value of 0.80 and a negative predictive value of 0.72 on the SARS-CoV-2 tested individuals. The model predicted 56 of 520 non-tested individuals to be SARS-CoV-2 positive with more than 75% probability, and another 84 to be SARS-CoV-2 positive with probability between 50% and 75%.ConclusionsA combination of symptoms can provide a good estimate of the probability of SARS-CoV-2 infection.
HPV16 and HPV18 type-specific APOBEC3 and integration profiles in different diagnostic categories of cervical samples
Authors: Lagström Sonja , Løvestad Alexander Hesselberg , Umu Sinan Uğur , Ambur Ole Herman , Nygård Mari , Rounge Trine B. , Christiansen Irene Kraus 
Published: November 2020

AbstractHuman papillomavirus 16 and 18 are the most predominant types in cervical cancer. Only a small fraction of HPV infections progress to cancer, indicating that genomic factors, such as minor nucleotide variation caused by APOBEC3 and chromosomal integration, contribute to the carcinogenesis.We analysed minor nucleotide variants (MNVs) and integration in HPV16 and HPV18 positive cervical samples with different morphology. Samples were sequenced using an HPV whole genome sequencing protocol TaME-seq. A total of 80 HPV16 and 51 HPV18 positive cervical cell samples passed the sequencing depth criteria of 300× reads, showing the following distribution: non-progressive disease (HPV16 n=21, HPV18 n=12); cervical intraepithelial neoplasia (CIN) grade 2 (HPV16 n=27, HPV18 n=9); CIN3/adenocarcinoma in situ (AIS) (HPV16 n=27, HPV18 n=30); cervical cancer (HPV16 n=5).Similar rates of MNVs in HPV16 and HPV18 samples were observed for most viral genes but for HPV16, the non-coding region (NCR) showed a trend towards increasing variation with increasing lesion severity. APOBEC3 signatures were observed in HPV16 lesions, while similar mutation patterns were not detected for HPV18. The proportion of samples with integration was 13% for HPV16 and 59% for HPV18 positive samples, with a noticeable portion located within or close to cancer-related genes.
Spatially resolved simulations of the spread of COVID-19 in European countries
Authors: Parisi Andrea , Brand Samuel P. C. , Hilton Joe , Aziza Rabia , Keeling Matt , Nokes D. James 
Published: November 2020

AbstractWe explore the spatial and temporal spread of the novel SARS-CoV-2 virus under containment measures in three European countries based on fits to data of the early outbreak. Using data from Spain and Italy, we estimate an age dependent infection fatality ratio for SARS-CoV-2, as well as risks of hospitalization and intensive care admission. We use them in a model that simulates the dynamics of the virus using an age structured, spatially detailed agent based approach, that explicitly incorporates governamental interventions, changes in mobility and contact patterns occurred during the COVID-19 outbreak in each country. Our simulations reproduce several of the features of its spatio-temporal spread in the three countries studied. They show that containment measures combined with high density are responsible for the containment of cases within densely populated areas, and that spread to less densely populated areas occurred during the late stages of the first wave. The capability to reproduce observed features of the spatio-temporal dynamics of SARS-CoV-2 makes this model a potential candidate for forecasting the dynamics of SARS-CoV-2 in other settings, and we recommend its application in low and lower-middle countries which remain understudied.
Prevalence of Mental Health Disorders among Elderly Diabetics and Associated Risk Factors in Indonesia
Authors: Azam Mahalul , Sulistiana Rina , Fibriana Arulita Ika , Savitri Soesmeyka , Al Junid Syed Mohamed 
Published: November 2020

AbstractThis cross-sectional study aimed to explore the prevalence of mental health disorders (MHD) among elderly diabetics in Indonesia and their associated risk factors. Data were extracted from the 2018 national basic health survey, Indonesia (abbreviated as the acronym of RISKESDAS). The survey involved households randomly selected from 34 provinces, 416 districts, and 98 cities in Indonesia, with 1,017,290 respondents. The number of subjects selected in this study was 2,818 elderly diabetic subjects. MHD was determined by self-reporting assessment. Secondary data acquired from the RISKESDAS 2018 data involved age, sex, urban-rural residence status, marital status, educational level, employment status, obesity, hypertension, heart disease, stroke, family history of MHD, and duration of DM. Binary logistic regression was used to analyze the risk factors related to MHD among elderly diabetics. Prevalence of MHD among elderly diabetics in Indonesia was 19.3%. Factors associated with MHD among elderly diabetics were obesity (prevalence odds ratio [POR]=4.57; 95% CI: 3.312-6.297), family history of MHD (POR=2.43; 95% CI: 1.707-3.471), lower education (POR=1.93; 95% CI: 1.464-2.533), stroke (POR=1.76; 95% CI: 1.292-2.384), hypertension (POR=1.74; 95% CI: 1.416-2.145), heart diseases (POR=1.49; 95% CI: 1.123-1.973), female (POR=1.43; 95% CI: 1.122-1.813), and urban residence (POR=0.75; 95% CI: 0.607-1.183). The prevalence of MHD among elderly diabetics in Indonesia was 19.3%, suggesting that screening for psychological problems and educating elderly diabetic patients is essential. Obesity, family history of MHD, lower education, stroke, hypertension, heart disease, female, and rural residence altogether more likely to experience MHD in elderly diabetics.
Autosomal Dominant Polycystic Kidney Disease does not significantly alter major COVID-19 outcomes among veterans
Authors: Cui Xiangqin , Gallini Julia W. , Jasien Christine L. , Mrug Michal 
Published: November 2020

AbstractChronic kidney disease (CKD), as well as its common causes (e.g., diabetes and obesity), are recognized risk factors for severe COVID-19 illness. To explore whether the most common inherited cause of CKD, autosomal dominant polycystic kidney disease (ADPKD), is also an independent risk factor, we studied data from the VA health system and the VA COVID-19-shared resources (e.g., ICD codes, demographics, pre-existing conditions, pre-testing symptoms, and post-testing outcomes). Among 61 COVID-19-positive ADPKD patients, 21 (34.4%) were hospitalized, 10 (16.4%) were admitted to ICU, 4 (6.6%) required ventilator, and 4 (6.6%) died by August 18, 2020. These rates were comparable to patients with other cystic kidney diseases and cystic liver-only diseases. ADPKD was not a significant risk factor for any of the four outcomes in multivariable logistic regression analyses when compared with other cystic kidney diseases and cystic liver-only diseases. In contrast, diabetes was a significant risk factor for hospitalization [OR 2.30 (1.61, 3.30), p<0.001], ICU admission [OR 2.23 (1.47, 3.42), p<0.001], and ventilator requirement [OR 2.20 (1.27, 3.88), p=0.005]. Black race significantly increased the risk for ventilator requirement [OR 2.00 (1.18, 3.44), p=0.011] and mortality [OR 1.60 (1.02, 2.51), p=0.040]. We also examined the outcome of starting dialysis after COVID-19 confirmation. The main risk factor for starting dialysis was CKD [OR 6.37 (2.43, 16.7)] and Black race [OR 3.47 (1.48, 8.1)]. After controlling for CKD, ADPKD did not significantly increase the risk for newly starting dialysis comparing with other cystic kidney diseases and cystic liver-only diseases. In summary, ADPKD did not significantly alter major COVID-19 outcomes among veterans when compared to other cystic kidney and liver patients.
The psychosocial impact on frontline health and social care professionals in the UK during the COVID-19 pandemic: a qualitative interview study
Authors: Aughterson Henry , McKinlay Alison , Fancourt Daisy , Burton Alexandra 
Published: November 2020

AbstractObjectivesTo explore the psychosocial well-being of health and social care professionals working during the COVID-19 pandemic.DesignThis was a qualitative study deploying in-depth, individual interviews, which were audio-recorded and transcribed verbatim. Thematic analysis was used for coding.ParticipantsThis study involved 25 participants from a range of frontline professions in health and social care.SettingInterviews were conducted over the phone or video call, depending on participant preference.ResultsFrom the analysis, we identified 5 overarching themes: communication challenges, work-related stressors, support structures, personal growth, and individual resilience. The participants expressed difficulties such as communication challenges and changing work conditions, but also positive factors such as increased team unity at work, and a greater reflection on what matters in life.ConclusionsThis study provides evidence on the support needs of health and social care professionals amid continued and future disruptions caused by the pandemic. It also elucidates some of the successful strategies (such as mindfulness, hobbies, restricting news intake, virtual socialising activities) deployed by health and social care professionals that can support their resilience and well-being and be used to guide future interventions.Strengths and limitations of this studyThis is the first study in the UK to interview both health and social care professionals working in a range of settings on their experiences working through COVID-19.This study used a strong theoretical approach to inform the topic guide, and one-to-one interviews allowed in-depth analysis of the psychosocial experiences of health and social care professionals, complementing the wider availability of quantitative evidence.We interviewed a wide range of professions, which provided breadth of experience but might limit the specificity of findings.Given the fluctuating nature of the pandemic, attitudes of health and social care professionals may change over time. This can be challenging to capture during a single interview, however we did ask questions on how their experience had progressed longitudinally.Our sample may have been biased towards people who had more free time to participate and so were coping better than others. However, our sample still described a number of stressful experiences during the pandemic, and it is also possible that workers who were frustrated or stressed wished to express their views.
Endometrial Receptivity on Assisted Reproductive Technology Cycles – a correlation between Serial Serum Estradiol levels and Serial Endometrial Volume Assessment
Authors: Silva Martins R. , Helio Oliani A. , Vaz Oliani D. , Martinez de Oliveira J. 
Published: November 2020

AbstractResearch QuestionDiagnosis of endometrial receptivity is still unclear and conflicting. Despite advances in embryo development during assisted reproductive technologies (ART) cycles, the intricate process of implantation is still matter for debate and research.DesignSerial serum estradiol levels and 3D transvaginal ultrasound performed in women on ART cycle to evaluate a pattern that better predicts implantation rates. 169 subjects on a prospective case control study were assessed. Serial biochemical and biophysical parameters were assessed during ovarian controlled stimulation and results compared in terms of pregnancy outcome.ResultsNo statistical difference was noted between the two groups in terms of demographics and ART procedures and scores. Serum estradiol was significantly higher in the positive group from day 8 after ovarian controlled stimulation. Endometrial volume and adjusted endometrial volume were significantly higher in the positive group as soon as day 6 of ovarian controlled stimulation.ConclusionsContinuous serum estradiol and 3D endometrial volume and adjusted endometrial volumes may reflect endometrial changes during ART procedures and provide a useful real time tool for clinicians in predicting endometrial receptivity.
Large-Scale Meta-Analysis of Potential Biomarkers for Treatment Response to Anti-PD-1/PD-L1 Immune Checkpoint Inhibitors
Authors: Mariam Arshiya , Kamath Suneel , Schveder Kimberly , McLeod Howard L. , Rotroff Daniel M. 
Published: November 2020

AbstractImmune checkpoint inhibitors (ICIs) blocking programmed death receptor 1 or its ligand (anti-PD-1/PD-L1) are a burgeoning class of promising cancer treatments. However, not all patients respond to these treatments. Although studies have suggested potential biomarkers to predict patients likely to respond to treatment, no consensus biomarker has been identified. Here, 95 peer-reviewed studies representing 18,978 subjects across 15 cancer types were meta-analyzed to determine biomarkers that best predicted ICI response within and across cancers. Performance was assessed using the sensitivity, specificity, area under the receiver operating characteristic curve, and others. Across all cancers, multimodal biomarkers and tumor mutational burden discriminated ICI response better than PD-L1 immunohistochemistry assays (IHC) (P=.04) with sensitivities of 0.57 and 0.70 and specificities of 0.76 and 0.53, respectively. Marginal improvements were also observed for nascent microbiome biomarkers compared to IHC (P=.06). Current ICI biomarker performances indicate that additional research is needed to develop highly accurate and precise biomarkers for widespread clinical adoption.
Regulating enzymatic reactions in Escherichia coli utilizing light-responsive cellular compartments based on liquid-liquid phase separation
Authors: Huang Zikang , Sun Lize , Lu Genzhe , Liu Hongrui , Zhai Zihan , Feng Site , Gao Ji , Chen Chunyu , Qing Chuheng , Fang Meng , Chen Bowen , Fu Jiale , Wang Xuan , Chen Guo-Qiang 
Published: November 2020

AbstractEnzymatic reactions in cells are well organized into different compartments, among which protein-based membraneless compartments formed through liquid-liquid phase separation (LLPS) are believed to play important roles1,2. Hijacking them for our own purpose has promising applications in metabolic engineering3. Yet, it is still hard to precisely and dynamically control target enzymatic reactions in those compartments4. To address those problems, we developed Photo-Activated Switch in E. coli (PhASE), based on phase separating scaffold proteins and optogenetic tools. In this system, a protein of interest (POI) can be enriched up to 15-fold by LLPS-based compartments from cytosol within only a few seconds once activated by light, and become fully dispersed again within 15 minutes. Furthermore, we explored the potentiality of the LLPS-based compartment in enriching small organic molecules directly via chemical-scaffold interaction. With enzymes and substrates co-localized under light induction, the overall reaction efficiency could be enhanced. Using luciferin and catechol oxidation as model enzymatic reactions, we found that they could accelerate 2.3-fold and 1.6-fold, respectively, when regulated by PhASE. We anticipate our system to be an extension of the synthetic biology toolkit, facilitating rapid recruitment and release of POIs, and reversible regulation of enzymatic reactions.
Precise oculocentric mapping of TMS-evoked phosphenes
Authors: Silva Andrew E. , Tsang Katelyn , Hasan Syeda Javeria , Thompson Benjamin 
Published: November 2020

ABSTRACTTranscranial Magnetic Stimulation (TMS) – evoked phosphenes are oculocentric; their perceived location depends upon eye position. We investigated the accuracy and precision of TMS-evoked phosphene oculocentric mapping and demonstrate that perceived phosphene locations map veridically to eye position, although there are considerable individual differences in the reliability of this mapping. Our results emphasize the need to carefully control eye movements when carrying out phosphene localization studies and suggest that individual differences in the reliability of the reported position of individual phosphenes must be considered.
First demonstration of the FLASH effect with ultrahigh dose-rate high-energy X-rays
Authors: Gao Feng , Yang Yiwei , Zhu Hongyu , Wang JianXin , Xiao Dexin , Zhou Zheng , Dai Tangzhi , Zhang Yu , Feng Gang , Li Jie , Lin Binwei , Xie Gang , Ke Qi , Zhou Kui , Li Peng , Shen Xuming , Wang Hanbin , Yan Longgang , Lao Chenglong , Shan Lijun , Li Ming , Lu Yanhua , Chen Menxue , Feng Song , Zhao Jianheng , Wu Dai , Du Xiaobo 
Published: November 2020

ABSTRACTUltrahigh dose-rate (FLASH) radiotherapy has attracted immense attention because of its tumor control efficiency and healthy tissue protection during preclinical experiments with electrons, kilo-voltage X-rays, and protons. Using high-energy X-rays (HEXs) in FLASH is advantageous owing to its deep penetration, small divergence, and cost-effectiveness. This is the first report on the implementation of HEXs with FLASH (HEX-FLASH) and its corresponding applicationin vivo. With a high-current and high-energy superconducting linear accelerator, FLASH with a good dose rate and high penetration was achieved. Breast cancers artificially induced in BAL b/c mice were efficiently controlled, and normal tissues surrounding the thorax/abdomen in C57BL/6 mice were protected from radiation with HEX-FLASH. Theoretical analyses of cellular responses following HEX-FLASH irradiation were performed to interpret the experimental results and design further experiments. Thus, this study highlights the generation of HEX-FLASH for the first time and its potential in future clinical applications.
Effect of RBD mutation (Y453F) in spike glycoprotein of SARS-CoV-2 on neutralizing antibody affinity
Authors: Hayashi Takuma , Yaegashi Nobuo , Konishi Ikuo 
Published: November 2020

AbstractNatural selection “adaptation” in the coronavirus can occur during coronavirus amplification in vivo in farmed minks. Natural selection in such viruses is observed by introduction of mutations in SARS- CoV-2 that are not observed during the growth process in humans. Infection with a mutant (Y453F) of SARS-CoV-2 from farmed minks is known to widely spread among humans. We investigated the virological characteristics of this SARS-CoV-2 mutant (Y453F) using three-dimensional protein structural analysis. Our experimental study suggests that virus variants with the Y453F mutation partially escaped detection by four neutralizing monoclonal antibodies. The spread of SARS-CoV-2 variants mediated by millions of infected farmed minks is uncontrolled; consequently, raising a concern that infection of SARS-CoV-2 mutants that cause serious symptoms in humans may spread globally.