bluuebunny/crossref_metadata_2025_split huggingface dataset:
A scaling-free minimum enclosing ball method to detect differentially expressed genes for RNA-seq data
Authors: Zhou Yan , Yang Bin , Wang Junhui , Zhu Jiadi , Tian Guoliang 
Published: June 2021

Abstract
Background
Identifying differentially expressed genes between the same or different species is an urgent demand for biological and medical research. For RNA-seq data, systematic technical effects and different sequencing depths are usually encountered when conducting experiments. Normalization is regarded as an essential step in the discovery of biologically important changes in expression. The present methods usually involve normalization of the data with a scaling factor, followed by detection of significant genes. However, more than one scaling factor may exist because of the complexity of real data. Consequently, methods that normalize data by a single scaling factor may deliver suboptimal performance or may not even work.The development of modern machine learning techniques has provided a new perspective regarding discrimination between differentially expressed (DE) and non-DE genes. However, in reality, the non-DE genes comprise only a small set and may contain housekeeping genes (in same species) or conserved orthologous genes (in different species). Therefore, the process of detecting DE genes can be formulated as a one-class classification problem, where only non-DE genes are observed, while DE genes are completely absent from the training data.

Results
In this study, we transform the problem to an outlier detection problem by treating DE genes as outliers, and we propose a scaling-free minimum enclosing ball (SFMEB) method to construct a smallest possible ball to contain the known non-DE genes in a feature space. The genes outside the minimum enclosing ball can then be naturally considered to be DE genes. Compared with the existing methods, the proposed SFMEB method does not require data normalization, which is particularly attractive when the RNA-seq data include more than one scaling factor. Furthermore, the SFMEB method could be easily extended to different species without normalization.

Conclusions
Simulation studies demonstrate that the SFMEB method works well in a wide range of settings, especially when the data are heterogeneous or biological replicates. Analysis of the real data also supports the conclusion that the SFMEB method outperforms other existing competitors. The R package of the proposed method is available at https://bioconductor.org/packages/MEB.
Comparison of six statistical methods for interrupted time series studies: empirical evaluation of 190 published series
Authors: Turner Simon L. , Karahalios Amalia , Forbes Andrew B. , Taljaard Monica , Grimshaw Jeremy M. , McKenzie Joanne E. 
Published: June 2021

AbstractBackgroundThe Interrupted Time Series (ITS) is a quasi-experimental design commonly used in public health to evaluate the impact of interventions or exposures. Multiple statistical methods are available to analyse data from ITS studies, but no empirical investigation has examined how the different methods compare when applied to real-world datasets.MethodsA random sample of 200 ITS studies identified in a previous methods review were included. Time series data from each of these studies was sought. Each dataset was re-analysed using six statistical methods. Point and confidence interval estimates for level and slope changes, standard errors,p-values and estimates of autocorrelation were compared between methods.ResultsFrom the 200 ITS studies, including 230 time series, 190 datasets were obtained. We found that the choice of statistical method can importantly affect the level and slope change point estimates, their standard errors, width of confidence intervals andp-values. Statistical significance (categorised at the 5% level) often differed across the pairwise comparisons of methods, ranging from 4 to 25% disagreement. Estimates of autocorrelation differed depending on the method used and the length of the series.ConclusionsThe choice of statistical method in ITS studies can lead to substantially different conclusions about the impact of the interruption. Pre-specification of the statistical method is encouraged, and naive conclusions based on statistical significance should be avoided.
Strengthening methods for tracking adaptations and modifications to implementation strategies
Authors: Haley Amber D. , Powell Byron J. , Walsh-Bailey Callie , Krancari Molly , Gruß Inga , Shea Christopher M. , Bunce Arwen , Marino Miguel , Frerichs Leah , Lich Kristen Hassmiller , Gold Rachel 
Published: June 2021

Abstract
Background
Developing effective implementation strategies requires adequate tracking and reporting on their application. Guidelines exist for defining and reporting on implementation strategy characteristics, but not for describing how strategies are adapted and modified in practice. We built on existing implementation science methods to provide novel methods for tracking strategy modifications.

Methods
These methods were developed within a stepped-wedge trial of an implementation strategy package designed to help community clinics adopt social determinants of health-related activities: in brief, an ‘Implementation Support Team’ supports clinics through a multi-step process. These methods involve five components: 1) describe planned strategy; 2) track its use; 3) monitor barriers; 4) describe modifications; and 5) identify / describe new strategies. We used the Expert Recommendations for Implementing Change taxonomy to categorize strategies, Proctor et al.’s reporting framework to describe them, the Consolidated Framework for Implementation Research to code barriers / contextual factors necessitating modifications, and elements of the Framework for Reporting Adaptations and Modifications-Enhanced to describe strategy modifications.

Results
We present three examples of the use of these methods: 1) modifications made to a facilitation-focused strategy (clinics reported that certain meetings were too frequent, so their frequency was reduced in subsequent wedges); 2) a clinic-level strategy addition which involved connecting one study clinic seeking help with community health worker-related workflows to another that already had such a workflow in place; 3) a study-level strategy addition which involved providing assistance in overcoming previously encountered (rather than de novo) challenges.

Conclusions
These methods for tracking modifications made to implementation strategies build on existing methods, frameworks, and guidelines; however, as none of these were a perfect fit, we made additions to several frameworks as indicated, and used certain frameworks’ components selectively. While these methods are time-intensive, and more work is needed to streamline them, they are among the first such methods presented to implementation science. As such, they may be used in research on assessing effective strategy modifications and for replication and scale-up of effective strategies. We present these methods to guide others seeking to document implementation strategies and modifications to their studies.

Trial registration
clinicaltrials.gov ID: NCT03607617 (first posted 31/07/2018).
General practitioners’ perceived indicators of vulnerability in pregnancy- A qualitative interview study
Authors: Brygger Venø L , Jarbøl DE. , Pedersen LB. , Søndergaard J , Ertmann RK 
Published: June 2021

Abstract
Objective
To explore general practitioners’ (GPs’) perceived indicators of vulnerability among pregnant women in primary care.

Design
A qualitative study with semi-structured in-depth focus group interviews.

Setting
General practices located in a mixture of urban, semi-urban and rural practices throughout the Region of Southern Denmark

Subjects
Twenty GPs.

Main outcome measures
Through qualitative analysis with systematic text condensation of the interview data, the following themes emerged: (1) obvious indicators of vulnerability—i.e. somatic or psychological illnesses, or complex social problems and 2) intangible indicators of vulnerability – i.e. identification depended on the GPs’ gut-feeling.
From the GPs’ perspective, the concept of vulnerability in pregnancy were perceived as the net result of risk factors and available individual and social resources, with a psychosocial etiology as the dominant framework.

Conclusions
The GPs demonstrated a broad variety of perceived indicators of vulnerability in pregnancy; most importantly, the GPs were aware of a group of pregnant women with intangible vulnerability mainly representing low resilience. Despite not fitting into the GPs' perceived concept of vulnerability, the GPs had a strong gut feeling that these women might be vulnerable. Misjudging the resources of pregnant women due to their physical appearance could delay the GPs’ identification of vulnerability. Future studies should explore the challenges GPs experiences when assessing vulnerability among pregnant women.
Hepatitis B virus (HBV) viral load, liver and renal function in adults treated with tenofovir disoproxil fumarate (TDF) vs. untreated: a retrospective longitudinal UK cohort study
Authors: Wang Tingyan , Smith David A. , Campbell Cori , Mokaya Jolynne , Freeman Oliver , Salih Hizni , McNaughton Anna L. , Cripps Sarah , Várnai Kinga A. , Noble Theresa , Woods Kerrie , Collier Jane , Jeffery Katie , Davies Jim , Barnes Eleanor , Matthews Philippa C. 
Published: June 2021

AbstractBackgroundCurrent clinical guidelines recommend treating chronic hepatitis B virus (HBV) infection in a minority of cases, but there are relatively scarce data on evolution or progression of liver inflammation and fibrosis in cases of chronic HBV (CHB) that do not meet treatment criteria. We aimed to assess the impact of TDF on liver disease, and the risk of renal impairment in treated CHB patients in comparison to untreated patients.MethodsWe studied a longitudinal ethnically diverse CHB cohort in the UK attending out-patient clinics between 2005 and 2018. We examined TDF treatment (vs. untreated) as the main exposure, with HBV DNA viral load (VL), ALT, elastography scores and eGFR as the main outcomes, using paired tests and mixed effects model for longitudinal measurements. Additionally, decline of eGFR during follow-up was quantified within individuals by thresholds based on clinical guidelines. Baseline was defined as treatment initiation for TDF group and the beginning of clinical follow-up for untreated group respectively.ResultsWe included 206 adults (60 on TDF, 146 untreated), with a median ± IQR follow-up duration of 3.3 ± 2.8 years. The TDF group was significantly older (median age 39 vs. 35 years,p = 0.004) and more likely to be male (63% vs. 47%,p = 0.04) compared to the untreated group. Baseline difference between TDF and untreated groups reflected treatment eligibility criteria. As expected, VL and ALT declined significantly over time in TDF-treated patients. Elastography scores normalised during treatment in the TDF group reflecting regression of inflammation and/or fibrosis. However, 6/81 (7.4%) of untreated patients had a progression of fibrosis stage from F0-F1 to F2 or F3. There was no evidence of difference in rates or incidence of renal impairment during follow-up in the TDF vs. untreated group.ConclusionsRisk of liver inflammation and fibrosis may be raised in untreated patients compared to those receiving TDF, and TDF may benefit a larger percentage of the CHB population.
Presence of gustatory and olfactory dysfunction in the time of the COVID-19 pandemic
Authors: Kusnik Alexander , Weiss Christel , Neubauer Melanie , Huber Bianca , Gerigk Marlis , Miethke Thomas , Hunter Nicole , Rotter Nicole , Ludwig Sonja , Schell Angela , Ebert Matthias P. , Teufel Andreas 
Published: June 2021

Abstract
Background
The unexpected outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused more than 49 million cases and an estimated 2,000,000 associated deaths worldwide. In Germany, there are currently more than 2,000,000 laboratory-confirmed coronavirus disease 2019 (COVID-19) cases including 51,800 deaths. However, regional differences also became apparent and with the second wave of infections, the detailed characterization of COVID-19 patients is crucial to early diagnosis and disruption of chains of infections.

Methods
Handing out detailed questionnaires to all individuals tested for COVID-19, we evaluated the clinical characteristics of negative and positive tested individuals.
Expression of symptoms, symptom duration and association between predictor variables (i.e. age, gender) and a binary outcome (olfactory and gustatory dysfunction) were assessed.

Results
Overall, the most common symptoms among individuals who tested positive for SARS-CoV-2 were fatigue, headache, and cough. Olfactory and gustatory dysfunction were also reported by many SARS-CoV-2 negative individuals, more than 20% of SARS-CoV-2 negative tested individuals in our study reported olfactory and gustatory dysfunction. Independent of SARS-CoV-2 status, more females displayed symptoms of gustatory (29.8%, p = 0.0041) and olfactory dysfunction (22.9%, p = 0.0174) compared to men.

Conclusions
Bringing early SARS-CoV-2 tests to the populations at risk must be a main focus for the upcoming months. The reliability of olfactory and gustatory dysfunction in COVID-19 negative tested individuals requires deeper investigation in the future.
Clinicopathologic features of TDO2 overexpression in renal cell carcinoma
Authors: Pham Quoc Thang , Taniyama Daiki , Sekino Yohei , Akabane Shintaro , Babasaki Takashi , Kobayashi Go , Sakamoto Naoya , Sentani Kazuhiro , Oue Naohide , Yasui Wataru 
Published: June 2021

Abstract
Background
Tryptophan 2,3-dioxygenase (TDO2) is the primary enzyme catabolizing tryptophan. Several lines of evidence revealed that overexpression of TDO2 is involved in anoikis resistance, spheroid formation, proliferation, and invasion and correlates with poor prognosis in some cancers. The aim of this research was to uncover the expression and biofunction of TDO2 in renal cell carcinoma (RCC).

Methods
To show the expression of TDO2 in RCC, we performed qRT-PCR and immunohistochemistry in integration with TCGA data analysis. The interaction of TDO2 with PD-L1, CD44, PTEN, and TDO2 expression was evaluated. We explored proliferation, colony formation, and invasion in RCC cells line affected by knockdown of TDO2.

Results
RNA-Seq and immunohistochemical analysis showed that TDO2 expression was upregulated in RCC tissues and was associated with advanced disease and poor survival of RCC patients. Furthermore, TDO2 was co-expressed with PD-L1 and CD44. In silico analysis and in vitro knockout of PTEN in RCC cell lines revealed the ability of PTEN to regulate the expression of TDO2. Knockdown of TDO2 suppressed the proliferation and invasion of RCC cells.

Conclusion
Our results suggest that TDO2 might have an important role in disease progression and could be a promising marker for targeted therapy in RCC.
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Cardiovascular events and mortality in a population-based cohort initially diagnosed with ductal carcinoma in situ
Authors: Yoo Tae-Kyung , Park Sang Hyun , Do Han Kyung , Chae Byung Joo 
Published: June 2021

Abstract
Background
Ductal carcinoma in situ (DCIS) patients are usually diagnosed through cancer screening programs, suggesting a healthy user effect. In this population-based cohort, we assessed the risk of cardiovascular events and mortality in DCIS patients.

Methods
Using the Korean National Health Insurance Service database, 13,740 women, who were initially diagnosed with DCIS between 2007 and 2013, were analyzed. A control group was matched according to age and the year of diagnosis at a 3:1 ratio (n = 41,220). Follow-up was performed until 2016. Subgroup analysis was performed according to the subsequent diagnosis of invasive breast cancer within 1 year: pure DCIS and DCIS+Invasive group.

Results
DCIS patients were more likely to have underlying diseases, higher incomes, and to live in urban districts compared to the control group. Women diagnosed of DCIS had lower myocardial infarct risk (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.46–0.90) and lower stroke risk (HR 0.77; 95% CI 0.60–0.98) compared to the control group. This trend of lower risk was sustained after adjusting for age, income, residence and comorbidities. The mortality rate was similar between the control group and pure DCIS patients but was higher in the DCIS+Invasive group (HR 1.63; 95% CI 1.34–1.98). However, after adjusting for age, income, residence and comorbidities, mortality did not differ between the control group and DCIS+Invasive group (HR 0.99; 95% CI 0.78–1.24).

Conclusions
DCIS patients were at lower risk for MI and stroke compared to a control group despite a higher rate of comorbidities, which may reflect changes in health behaviour. The importance of managing pre-existing comorbidities along with DCIS treatment should be emphasized.
Prevalence of acute diarrhea and associated factors among children under five in semi-urban areas of northeastern Ethiopia
Authors: Natnael Tarikuwa , Lingerew Mistir , Adane Metadel 
Published: June 2021

AbstractBackgroundDiarrheal disease is still one of the most common causes of mortality and morbidity in children under five in developing countries, including Ethiopia. Lack of specific data on the prevalence of acute diarrhea and associated factors among under-five children in the semi-urban areas of Gelsha, found in northeastern Ethiopia’s South Wollo zone, remains a major gap. Therefore, this study was designed to provide data that is important for proper planning of intervention measures to reduce the problem in this area.MethodsA community-based cross-sectional study was conducted among 340 systematically selected children under five in semi-urban areas of Gelsha from January to March 2019. The data was collected using a structured questionnaire and an observational checklist. Bivariable (crude odds ratio [COR]) and multivariable analysis (adjusted odds ratio [AOR]) were employed using binary logistic regression model with 95% CI (confidence interval). Variables with ap-value < 0.05 from the multivariable analysis were declared as factors significantly associated with acute diarrhea.ResultThe prevalence of acute diarrhea among children under five in the study area was 11% (95%CI: 7.8–14.3%). About two-thirds (63.60%) of study participants used water from improved sources. About half (54.90%) of study participants practiced poor handwashing and 45.10% practiced good handwashing. We found that factors significantly associated with acute diarrhea were a child’s age of 12–23 months (AOR = 4.68, 95% CI: 1.45–1.50), the presence of two or more under-five children in the house (AOR = 2.84, 95% CI: 1.19–6.81), unimproved water sources (AOR = 2.97, 95% CI: 1.28–6.87) and presence of feces around the pit hole/slab/floor of the latrine (AOR = 3.34, 95% CI: 1.34–8.31).ConclusionThe prevalence of acute diarrhea among children under five was relatively high. To reduce the problem, various prevention strategies are essential, such as the provision of health education to mothers/caregivers that focuses on keeping sanitation facilities clean and child care, and construction of improved water sources. Furthermore, implementing a strong health extension program, advocating an open defecation-free environment, and practicing a community-led total sanitation and hygiene approach might be helpful to sustainably reduce childhood diarrhea.
Development and assessment of a hospital admissions-based syndromic surveillance system for COVID-19 in Ontario, Canada: ACES Pandemic Tracker
Authors: Papadomanolakis-Pakis Nicholas , Maier Allison , van Dijk Adam , VanStone Nancy , Moore Kieran Michael 
Published: June 2021

AbstractBackgroundThe COVID-19 pandemic has continued to pose a major global public health risk. The importance of public health surveillance systems to monitor the spread and impact of COVID-19 has been well demonstrated. The purpose of this study was to describe the development and effectiveness of a real-time public health syndromic surveillance system (ACES Pandemic Tracker) as an early warning system and to provide situational awareness in response to the COVID-19 pandemic in Ontario, Canada.MethodsWe used hospital admissions data from the Acute Care Enhanced Surveillance (ACES) system to collect data on pre-defined groupings of symptoms (syndromes of interest; SOI) that may be related to COVID-19 from 131 hospitals across Ontario. To evaluate which SOI for suspected COVID-19 admissions were best correlated with laboratory confirmed admissions, laboratory confirmed COVID-19 hospital admissions data were collected from the Ontario Ministry of Health. Correlations and time-series lag analysis between suspected and confirmed COVID-19 hospital admissions were calculated. Data used for analyses covered the period between March 1, 2020 and September 21, 2020.ResultsBetween March 1, 2020 and September 21, 2020, ACES Pandemic Tracker identified 22,075 suspected COVID-19 hospital admissions (150 per 100,000 population) in Ontario. After correlation analysis, we found laboratory-confirmed hospital admissions for COVID-19 were strongly and significantly correlated with suspected COVID-19 hospital admissions when SOI were included (Spearman’s rho = 0.617) and suspected COVID-19 admissions when SOI were excluded (Spearman’s rho = 0.867). Weak to moderate significant correlations were found among individual SOI. Laboratory confirmed COVID-19 hospital admissions lagged in reporting by 3 days compared with suspected COVID-19 admissions when SOI were excluded.ConclusionsOur results demonstrate the utility of a hospital admissions syndromic surveillance system to monitor and identify potential surges in severe COVID-19 infection within the community in a timely manner and provide situational awareness to inform preventive and preparatory health interventions.
Comparison of gluteus medius strength between individuals with obesity and normal-weight individuals: a cross-sectional study
Authors: Fenato Rafael Ratti , Araujo Allan Cezar Faria , Guimarães Ana Tereza Bittencourt 
Published: June 2021

AbstractBackgroundThe hip abductor muscles, primarily the gluteus medius, play an important role in stabilizing the pelvis during gait. Gluteus medius weakness is associated with biomechanical changes and musculoskeletal disorders. Individuals with obesity can have great difficulty maintaining abductor muscular function due to being overweight and possibly experiencing a decrease in muscle mass. However, it is still unclear whether the musculature of person with obesity can compensate for these changes. Therefore, the aim of this study was to compare gluteus medius strength between individuals with obesity and normal-weight individuals using a digital hand-held dynamometer.MethodsTwenty-five participants with obesity (BMI > 35 kg/m2) were matched for sex, age, and height with normal-weight individuals. Gluteus medius strength was measured by a single examiner using a belt-stabilized hand-held digital dynamometer placed on the knee of the individuals positioned in lateral decubitus. Three measurements were recorded with rest intervals, and only the highest value measured for each limb was used for analysis. The differences between pairs were calculated, and the normality of the data was assessed using the Shapiro-Wilk test (p < 0.05). The matrices of the variables were standardized and analysed using principal component analysis (PCA).ResultsFor the strength variables (Newtons) on both sides, no significant differences were detected between the groups (p > 0.05). However, significant differences were detected in these variables between the groups (p < 0.05) when the measurements were normalized to body weight (Newtons/kilograms). PCA indicated that both the absolute and normalized values of strength are lower in participants with obesity than in normal-weight.ConclusionsThese findings suggest that people with obesity could have the same or less strength (PCA) to move more mass, which may imply a relative weakness that induces functional limitations.