bluuebunny/crossref_metadata_2025_split huggingface dataset:
Independent and synergistic effects of pain, insomnia, and depression on falls among older adults: a longitudinal study
Authors: Li Yuxiao , Liu Minhui , Sun Xiaocao , Hou Tianxue , Tang Siyuan , Szanton Sarah L. 
Published: November 2020

Abstract
Background
Few studies have examined the relationship between falls and pain, insomnia and depressive symptoms which are common and risk factors in older adults. We aimed to examine the independent and synergistic effects of these risk factors on future falls among older adults.

Methods
We used data of 2558 community-dwelling older adults from 2011 (Y1) to 2015 (Y5) of the National Health and Aging Trends Study (NHATS). Pain was determined by whether participants reported bothersome pain in the last month. Insomnia was assessed by two questions about how often the participants had trouble falling asleep and maintaining sleep. Depressive symptoms were assessed by Patient Health Questionnaire-2. Generalized estimation equation (GEE) models were used to examine the independent effects of pain, insomnia and depressive symptoms at prior-wave (period y-1) on falls at current wave (period y) adjusting for covariates (age, sex, education, race/ethnicity, living arrangement, BMI, smoking, vigorous activities, number of chronic illnesses and hospitalization). The significance of the three-way interaction of these factors (pain*insomnia*depression) was tested using the aforementioned GEE models to determine their synergistic effects on falls.

Results
Overall, the participants were mainly 65–79 years old (68%), female (57%) and non-Hispanic White (70%). At Y1, 50.0% of the participants reported pain, 22.6% reported insomnia and 9.9% reported depressive symptoms. The incidence of falls from Y2 to Y5 was 22.4, 26.0, 28.3, and 28.9%, respectively. Participants with pain (Odds ratio [OR], 95% confidence interval [CI] = 1.36, 1.23–1.50) and depressive symptoms (OR, 95% CI = 1.43, 1.23–1.67) had high rates of falling adjusting for covariates. After further adjustment for insomnia and depressive symptoms, pain independently predicted falls (OR, 95% CI = 1.36, 1.22–1.51). Depressive symptoms also independently predicted falls after further adjusting for pain and insomnia (OR, 95% CI = 1.40, 1.20–1.63). After adjusting for pain and depression, the independent effects of insomnia were not significant. None of the interaction terms of the three risk factors were significant, suggesting an absence of their synergistic effects.

Conclusions
Pain and depressive symptoms independently predict falls, but synergistic effects seem absent. Further research is needed to develop effective strategies for reducing falls in older adults, particularly with pain and depressive symptoms.
Factors influencing self-management of adults living with HIV on antiretroviral therapy in Northwest Ethiopia: a cross-sectional study
Authors: Areri Habtamu , Marshall Amy , Harvey Gillian 
Published: November 2020

AbstractBackgroundEffective self-management is an important consideration for adults living with HIV on therapy to enable people to maintain their health and well-being whilst living with chronic HIV. Although numerous attempts have been made to implement and improve HIV self-management practice, there is limited evidence on effective self-management strategies, particularly in sub-Saharan Africa. This study aimed to identify the level and factors influencing the self-management practice of adults living with HIV on antiretroviral therapy.MethodsA cross-sectional survey was conducted on a sample of 415 adults living with HIV on antiretroviral therapy at a major referral hospital in Northwest Ethiopia using convenience sampling. A theory of self-management – the Individual and Family Self-Management Theory - guided the study design, analysis and presentation of the data. A face-to-face survey tool was administered for data collection, and the data were entered and analyzed using SPSS version 25.0.ResultsOver half (58.1%) of the respondents were female. Many of the respondents did not know their HIV stage (76.9%) but reported adequate knowledge of their treatment (79.5%). The mean self-management score was 1.94+ 0.22 out of a total score of 3. Female gender was associated with decreased self-management. Contextual factors (gender, educational level, job status, income, living in a rural area, and awareness of HIV stage) explained 8.2% of the variance in self-management. The explanatory power increased by 9.2% when self-management process variables (self-efficacy, setting a goal, knowledge of antiretroviral therapy, HIV disclosure, and use of reminders) were added. Intervention-focused variables (encouraging disclosure and adherence support) increased the proportion of explained variance by 2.3%.ConclusionsThe findings of the study indicate that the level of self-management practice amongst the population studied was low compared to international literature. Our study findings support the theoretical model and previously identified factors influencing HIV self-management. The most important predictors of lower self-management practice in Ethiopia were female gender, illiteracy, lack of awareness of HIV stage, low self-efficacy, absence of reminders, lack of encouragement to disclose and absence of adherence support. HIV care providers should seek ways to empower and support adults living with HIV to self-manage, particularly through enhancing self-efficacy and encouraging the use of reminders.
Hepatocellular carcinoma: Intratumoral EpCAM-positive cancer stem cell heterogeneity identifies high-risk tumor subtype
Authors: Krause Jenny , von Felden Johann , Casar Christian , Fründt Thorben W. , Galaski Johanna , Schmidt Constantin , Jung Caroline , Ittrich Harald , Weidemann Sören A. , Krech Till , Heumann Asmus , Li Jun , Fischer Lutz , Sauter Guido , Lohse Ansgar W. , Wege Henning , Schulze Kornelius 
Published: November 2020

Abstract
Background
The translational interest in the intratumoral heterogeneity of hepatocellular carcinoma (HCC) has been increasing. The dismal prognosis of this pathology is linked to the features of the HCC harbouring cancer stem cells (CSC), represented by EpCAM-expression. However, the extent of the impact of intratumoral distribution of CSC-features, both on the recurrence after curative resection and on clinical outcome, remains unknown. To address this, we investigated the spatial heterogeneity of CSC-features with the aim of identifying the unique HCC patient subgroups amenable to adjuvant treatment.

Methods
We designed a tissue microarray (TMA) from patients who had received liver resection between 2011 and 2017. Tumor specimens were sampled at multiple locations (n = 3–8). EpCAM-positivity was assessed for intensity and proportion by applying a score dividing three groups: (i) negative (E−/−); (ii) heterogeneous (E−/+); and (iii) homogeneous (E+/+). The groups were further analysed with regard to time-to-recurrence (TTR) and recurrence-free-survival (RFS).

Results
We included 314 tumor spots from 69 patients (76.8% male, median age 66, liver cirrhosis/fibrosis 75.8%). The risk factors were alcohol abuse (26.2%), NASH (13.1%), HBV (15.5%), HCV (17.9%) and others (27.4%), representative of a typical Western cohort. E+/+ patients experienced significantly shorter TTR and RFS compared to E+/− and E−/− patients (TTR 5 vs. 19 months, p = 0.022; RFS 5 vs. 14 vs. 21 months, p = 0.016). Only homogeneous EpCAM-positivity correlated with higher AFP levels (> 400 ng/ml, p = 0.031).

Conclusions
Spatial heterogeneity of EpCAM-expression was markedly present in the cohort. Of note, only homogeneous EpCAM-expression correlated significantly with early recurrence, whereas heterogeneous EpCAM-expression was associated with clinical endpoints comparable to EpCAM-negativity. We identified a unique HCC subtype associated with a high risk of tumor recurrence.
Evaluating the impact of stay-at-home orders on the time to reach the peak burden of Covid-19 cases and deaths: does timing matter?
Authors: Medline Alexandra , Hayes Lamar , Valdez Katia , Hayashi Ami , Vahedi Farnoosh , Capell Will , Sonnenberg Jake , Glick Zoe , Klausner Jeffrey D. 
Published: November 2020

Abstract
Background
The economic, psychological, and social impact of pandemics and social distancing measures prompt the urgent need to determine the efficacy of non-pharmaceutical interventions (NPIs), especially those considered most stringent such as stay-at-home and self-isolation mandates. This study focuses specifically on the impact of stay-at-home orders, both nationally and internationally, on the control of COVID-19.

Methods
We conducted an observational analysis from April to May 2020 and included both countries and US states with known stay-at-home orders. Our primary exposure was the time between the date of the first reported case of COVID-19 to an implemented stay-at-home mandate for each region. Our primary outcomes were the time from the first reported case to the highest number of daily cases and daily deaths. We conducted linear regression analyses, controlling for the case rate of the outbreak in each respective region.

Results
For countries and US states, a longer period of time between the first reported case and stay-at-home mandates was associated with a longer time to reach both the peak daily case and death counts. The largest effect was among regions classified as the latest 10% to implement a mandate, which in the US, predicted an extra 35.3 days (95% CI: 18.2, 52.5) to the peak number of cases, and 38.3 days (95% CI: 23.6, 53.0) to the peak number of deaths.

Conclusions
Our study supports the association between the timing of stay-at-home orders and the time to peak case and death counts for both countries and US states. Regions in which mandates were implemented late experienced a prolonged duration to reaching both peak daily case and death counts.
Steroid metabolites for diagnosing and predicting clinicopathological features in cortisol-producing adrenocortical carcinoma
Authors: Suzuki Sawako , Minamidate Tomoki , Shiga Akina , Ruike Yutarou , Ishiwata Kazuki , Naito Kumiko , Ishida Akiko , Deguchi Hanna , Fujimoto Masanori , Koide Hisashi , Tatsuno Ichiro , Ikeda Jun-ichiro , Yamazaki Yuto , Sasano Hironobu , Yokote Koutaro 
Published: November 2020

Abstract
Background
Approximately 60% of adrenocortical carcinomas (ACC) are functional, and Cushing’s syndrome is the most frequent diagnosis that has been revealed to have a particularly poor prognosis. Since 30% of ACC present steroid hormone-producing disorganization, measurement of steroid metabolites in suspected ACC is recommended. Previous reports demonstrated that steroid hormone precursors or their urine metabolites, which can be assessed using liquid chromatography tandem mass spectrometry (LC-MS/MS) or gas chromatography mass spectrometry (GC-MS) respectively, are useful for distinguishing ACC from cortisol-producing adenomas (CPA); however, despite high precision, LC-MS/MS and GC-MS require a highly trained team, are expensive and have limited capacity.

Methods
Here, we examined 12 serum steroid metabolites using an immunoassay, which is a more rapid and less costly method than LC-MS/MS, in cortisol-producing ACC and CPA. Further, the correlation of each steroid metabolite to the classification stage and pathological status in ACC was analyzed.

Results
Reflecting disorganized steroidogenesis, the immunoassay revealed that all basal levels of steroid precursors were significantly increased in cortisol-producing ACC compared to CPA; in particular, 17-hydroxypregnenolone (glucocorticoid and androgen precursor) and 11-deoxycorticosterone (mineralocorticoid precursor) showed a large area under the ROC curve with high sensitivity and specificity when setting the cut-off at 1.78 ng/ml and 0.4 mg/ml, respectively. Additionally, a combination of androstenedione and DHEAS also showed high specificity with high accuracy. In cortisol-producing ACC, 11-deoxycortisol (glucocorticoid precursor) showed significant positive correlations with predictive prognostic factors used in ENSAT classification, while testosterone showed significant positive correlations to the Ki67-index in both men and women.

Conclusion
Less expensive and more widely available RIA and ECLIA may also biochemically distinguish ACC from CPA and may predict the clinicopathological features of ACC.
Impact of periodontitis on quality of life among subjects with rheumatoid arthritis: a cross sectional study
Authors: Han Philip Sheng Hui , Saub Roslan , Baharuddin Nor Adinar , Sockalingam Sargunan , Bartold Peter Mark , Vaithilingam Rathna Devi 
Published: November 2020

AbstractBackgroundThis study aimed to assess the impact of periodontitis (PD) on the health related quality of life (HRQoL) and oral health related QoL (OHRQoL) of subjects with rheumatoid arthritis (RA) and PD.MethodsSubjects from dental and RA clinics were screened. Complete periodontal examinations were performed. Subjects were divided into 4 groups: RA-PD, RA, PD and healthy controls (HC). Questionnaires on characteristics and Malaysian versions of Oral Health Impact Profile (OHIP-14(M)) and Health Assessment Questionnaire (HAQ-DI)) were answered.ResultsA total of 187 subjects were included (29 RA-PD, 58 RA, 43 PD and 57 HC). OHIP-14(M) severity score was highest in the PD group (17.23 ± 10.36) but only significantly higher than the HC group (p < 0.05). The HAQ-DI scores of the RA group was significantly higher than the PD and HC groups (p < 0.05). The interaction between the effects of PD and RA on the OHRQoL and HRQoL was statistically significant (p < 0.05).ConclusionPD and RA subjects both suffer impacts on their OHRQoL and HRQoL respectively. The interaction effect of both diseases significantly conferred impacts on their OHRQoL and HRQoL as measured by the OHIP-14(M) and HAQ-DI.
Impact of ISO/IEC 17025 laboratory accreditation in sub-Saharan Africa: a case study
Authors: Okezue Mercy A. , Adeyeye Mojisola C. , Byrn Steve J. , Abiola Victor O. , Clase Kari L. 
Published: November 2020

Abstract
Background
The number and severity of nonconformities generated during an audit of a medicine testing laboratory indicates its level of quality compliance. Quality standards are established and maintained to ensure the reliability of laboratory test reports. The National Medicines Regulatory Authority (NMRA) Quality Control laboratories assess the quality of medicines used by the populace as part of their regulatory function. Although countries desire to have reliable medicine testing facilities, accrediting a national laboratory to international standards poses financial and technical challenges for many low-income countries. Sharing the benefits of laboratory accreditation could help more countries within sub-Saharan Africa overcome existing challenges to achieve accreditation and robust quality systems. This study investigated the impact of ISO/IEC 17025 accreditation on the performance of an NMRA Quality Control laboratory to provide evidence of improved quality compliance within a low-resource setting.

Methods
Pre- and post- accreditation audits of nonconformities for management and technical requirements of the ISO/IEC17025:2005 standards were evaluated from a Quality Control laboratory in the National Agency for Food and Drug Administration and Control (NAFDAC), located in Nigeria, West Africa. The following research questions were addressed: “does accreditation impact the adherence to quality standards?” and “does accreditation decrease the severity of nonconformities in Quality Control laboratory audits?”

Results
Statistical analysis of the pre- to post- accreditation audits from the years 2013 through 2017 revealed a significant decrease in the total number of nonconformities (χ2 = 74, p-value = 9.99e-05, r = 0.67). Further examination of audits from the years 2013 through 2018 audits also revealed a reduction in the number of nonconformities (χ2 = 53, p-value = 9.99e-05, r = 0.62). A reduction in the number of major observations and a decrease in the severity of nonconformities was also observed.

Conclusions
A higher level of quality compliance was exhibited for the laboratory during the post-accreditation years. Overall, ISO/IEC 17025 accreditation of the NMRA Quality Control laboratory resulted in improved reliability of test reports and enhancement of the laboratory quality system.
Genome-scale CRISPR screening at high sensitivity with an empirically designed sgRNA library
Authors: Henkel Luisa , Rauscher Benedikt , Schmitt Barbara , Winter Jan , Boutros Michael 
Published: November 2020

AbstractBackgroundIn recent years, large-scale genetic screens using the CRISPR/Cas9 system have emerged as scalable approaches able to interrogate gene function with unprecedented efficiency and specificity in various biological contexts. By this means, functional dependencies on both the protein-coding and noncoding genome of numerous cell types in different organisms have been interrogated. However, screening designs vary greatly and criteria for optimal experimental implementation and library composition are still emerging. Given their broad utility in functionally annotating genomes, the application and interpretation of genome-scale CRISPR screens would greatly benefit from consistent and optimal design criteria.ResultsWe report advantages of conducting viability screens in selected Cas9 single-cell clones in contrast to Cas9 bulk populations. We further systematically analyzed published CRISPR screens in human cells to identify single-guide (sg) RNAs with consistent high on-target and low off-target activity. Selected guides were collected in a novel genome-scale sgRNA library, which efficiently identifies core and context-dependent essential genes.ConclusionWe show how empirically designed libraries in combination with an optimized experimental design increase the dynamic range in gene essentiality screens at reduced library coverage.
Ovarian teratoma in a woodchuck (Marmota monax) with hepatocellular carcinoma: radiologic and pathologic features
Authors: Zeng Johnathan , Starost Matthew F. , Mauda-Havakuk Michal , Mikhail Andrew S. , Partanen Ari , Wood Bradford J. , Karanian John W. , Pritchard William F. 
Published: November 2020

Abstract
Background
Teratomas are germ cell neoplasms composed of a wide variety of tissues. In the woodchuck, only one testicular teratoma has been described in the literature. The objective of this report was to describe the radiologic and pathologic findings in a female woodchuck (Marmota monax) with an ovarian teratoma consisting of mature tissues originating from all three germ layers.

Case presentation
A 2-year-old female woodchuck that had been infected at birth with woodchuck hepatitis virus and subsequently developed hepatocellular carcinoma was incidentally discovered to have a mobile 6.6 × 4.8 × 4.7 cm abdominal mass on computed tomography (CT) imaging. The tumor was predominantly solid and heterogenous on CT with soft tissue, fat, and areas of dense calcification. The teratoma did not enhance with intravenous contrast administration. On ultrasound, the tumor was solid with heterogeneous echogenicity, reflecting the fat content and areas of calcification. Sonolucent areas were present that may have represented cysts. There was heterogeneously increased signal on T1-weighted magnetic resonance imaging (MRI) and heterogeneous hyperintensity in T2-weighted imaging. Fat was evident within the tumor. At necropsy, the tumor was attached to the distal end of the right uterine horn. Histopathology showed mature tissue types representing all three germ layers.

Conclusions
Ovarian teratoma should be considered in the differential diagnosis of ovarian or abdominal masses in woodchucks. The tumor displayed mature tissue derived from all three germ layers. CT, ultrasound, and MRI findings were presented in detail and matched the typical imaging appearance of teratomas.
A random forest based biomarker discovery and power analysis framework for diagnostics research
Authors: Acharjee Animesh , Larkman Joseph , Xu Yuanwei , Cardoso Victor Roth , Gkoutos Georgios V. 
Published: November 2020

AbstractBackgroundBiomarker identification is one of the major and important goal of functional genomics and translational medicine studies. Large scale –omics data are increasingly being accumulated and can provide vital means for the identification of biomarkers for the early diagnosis of complex disease and/or for advanced patient/diseases stratification. These tasks are clearly interlinked, and it is essential that an unbiased and stable methodology is applied in order to address them. Although, recently, many, primarily machine learning based, biomarker identification approaches have been developed, the exploration of potential associations between biomarker identification and the design of future experiments remains a challenge.MethodsIn this study, using both simulated and published experimentally derived datasets, we assessed the performance of several state-of-the-art Random Forest (RF) based decision approaches, namely the Boruta method, the permutation based feature selection without correction method, the permutation based feature selection with correction method, and the backward elimination based feature selection method. Moreover, we conducted a power analysis to estimate the number of samples required for potential future studies.ResultsWe present a number of different RF based stable feature selection methods and compare their performances using simulated, as well as published, experimentally derived, datasets. Across all of the scenarios considered, we found the Boruta method to be the most stable methodology, whilst the Permutation (Raw) approach offered the largest number of relevant features, when allowed to stabilise over a number of iterations. Finally, we developed and made available a web interface (https://joelarkman.shinyapps.io/PowerTools/) to streamline power calculations thereby aiding the design of potential future studies within a translational medicine context.ConclusionsWe developed a RF-based biomarker discovery framework and provide a web interface for our framework, termed PowerTools, that caters the design of appropriate and cost-effective subsequent future omics study.