bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wochenende — modular and flexible alignment-based shotgun metagenome analysis
Authors: Rosenboom Ilona , Scheithauer Tobias , Friedrich Fabian C. , Pörtner Sophia , Hollstein Lisa , Pust Marie-Madlen , Sifakis Konstantinos , Wehrbein Tom , Rosenhahn Bodo , Wiehlmann Lutz , Chhatwal Patrick , Tümmler Burkhard , Davenport Colin F. 
Published: November 2022

Abstract
Background
Shotgun metagenome analysis provides a robust and verifiable method for comprehensive microbiome analysis of fungal, viral, archaeal and bacterial taxonomy, particularly with regard to visualization of read mapping location, normalization options, growth dynamics and functional gene repertoires. Current read classification tools use non-standard output formats, or do not fully show information on mapping location. As reference datasets are not perfect, portrayal of mapping information is critical for judging results effectively.

Results
Our alignment-based pipeline, Wochenende, incorporates flexible quality control, trimming, mapping, various filters and normalization. Results are completely transparent and filters can be adjusted by the user. We observe stringent filtering of mismatches and use of mapping quality sharply reduces the number of false positives. Further modules allow genomic visualization and the calculation of growth rates, as well as integration and subsequent plotting of pipeline results as heatmaps or heat trees. Our novel normalization approach additionally allows calculation of absolute abundance profiles by comparison with reads assigned to the human host genome.

Conclusion
Wochenende has the ability to find and filter alignments to all kingdoms of life using both short and long reads, and requires only good quality reference genomes. Wochenende automatically combines multiple available modules ranging from quality control and normalization to taxonomic visualization. Wochenende is available at https://github.com/MHH-RCUG/nf_wochenende.
Evaluating methodological approaches to assess the severity of infection with SARS-CoV-2 variants: scoping review and applications on Belgian COVID-19 data
Authors: Meurisse Marjan , Van Oyen Herman , Blot Koen , Catteau Lucy , Serrien Ben , Klamer Sofieke , Cauët Emilie , Robert Annie , Van Goethem Nina 
Published: November 2022

Abstract
Background
Differences in the genetic material of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants may result in altered virulence characteristics. Assessing the disease severity caused by newly emerging variants is essential to estimate their impact on public health. However, causally inferring the intrinsic severity of infection with variants using observational data is a challenging process on which guidance is still limited. We describe potential limitations and biases that researchers are confronted with and evaluate different methodological approaches to study the severity of infection with SARS-CoV-2 variants.

Methods
We reviewed the literature to identify limitations and potential biases in methods used to study the severity of infection with a particular variant. The impact of different methodological choices is illustrated by using real-world data of Belgian hospitalized COVID-19 patients.

Results
We observed different ways of defining coronavirus disease 2019 (COVID-19) disease severity (e.g., admission to the hospital or intensive care unit versus the occurrence of severe complications or death) and exposure to a variant (e.g., linkage of the sequencing or genotyping result with the patient data through a unique identifier versus categorization of patients based on time periods). Different potential selection biases (e.g., overcontrol bias, endogenous selection bias, sample truncation bias) and factors fluctuating over time (e.g., medical expertise and therapeutic strategies, vaccination coverage and natural immunity, pressure on the healthcare system, affected population groups) according to the successive waves of COVID-19, dominated by different variants, were identified. Using data of Belgian hospitalized COVID-19 patients, we were able to document (i) the robustness of the analyses when using different variant exposure ascertainment methods, (ii) indications of the presence of selection bias and (iii) how important confounding variables are fluctuating over time.

Conclusions
When estimating the unbiased marginal effect of SARS-CoV-2 variants on the severity of infection, different strategies can be used and different assumptions can be made, potentially leading to different conclusions. We propose four best practices to identify and reduce potential bias introduced by the study design, the data analysis approach, and the features of the underlying surveillance strategies and data infrastructure.
Impact of prerelease methadone on mortality among people with HIV and opioid use disorder after prison release: results from a randomized and participant choice open-label trial in Malaysia
Authors: Bazazi Alexander R. , Culbert Gabriel J. , Wegman Martin P. , Heimer Robert , Kamarulzaman Adeeba , Altice Frederick L. 
Published: November 2022

Abstract
Introduction
Mortality is elevated after prison release and may be higher in people with HIV and opioid use disorder (OUD). Maintenance with opioid agonist therapy (OAT) like methadone or buprenorphine reduces mortality in people with OUD and may confer benefits to people with OUD and HIV leaving prison. Survival benefits of OAT, however, have not been evaluated prospectively in people with OUD and HIV leaving prison.

Methods
This study prospectively evaluated mortality after prison release and whether methadone initiated before release increased survival after release in a sample of men with HIV and OUD (n = 291). We linked national death records to data from a controlled trial of prerelease methadone initiation conducted from 2010 to 2014 with men with HIV and OUD imprisoned in Malaysia. Vital statistics were collected through 2015. Allocation to prerelease methadone was by randomization (n = 64) and participant choice (n = 246). Cox proportional hazards models were used to estimate treatment effects of prerelease methadone on postrelease survival.

Results
Overall, 62 deaths occurred over 872.5 person-years (PY) of postrelease follow-up, a crude mortality rate of 71.1 deaths per 1000 PY (95% confidence interval [CI] 54.5–89.4). Most deaths were of infectious etiology, mostly related to HIV. In a modified intention-to-treat analysis, the impact of prerelease methadone on postrelease mortality was consistent with a null effect in unadjusted (hazard ratio [HR] 1.3, 95% CI 0.6–3.1) and covariate-adjusted (HR 1.2, 95% CI 0.5–2.8) models. Predictors of mortality were educational level (HR 1.4, 95% CI 1.0–1.8), pre-incarceration alcohol use (HR 2.0, 95% CI 1.1–3.9), and lower CD4+ T-lymphocyte count (HR 0.8 per 100-cell/mL increase, 95% CI 0.7–1.0).

Conclusions
Postrelease mortality in this sample of men with HIV and OUD was extraordinarily high, and most deaths were likely of infectious etiology. No effect of prerelease methadone on postrelease mortality was observed, which may be due to study limitations or an epidemiological context in which inadequately treated HIV, and not inadequately treated OUD, is the main cause of death after prison release.
Trial registration: NCT02396979. Retrospectively registered 24/03/2015
Expression changes of Tim-3 as one of supplementary indicators for monitoring prognosis of liver pathological changes in chronic HBV infection
Authors: Wu Shanshan , Du Xinfang , Lou Guohua , Yu Shuihong , Lai Kecong , Qi Jinjin , Ni Shujun , Chen Zhi , Chen Feng 
Published: November 2022

Abstract
Purpose
This study was designed to analyze the liver tissue changes among the CHB patients who received treatment for at least 6 months and follow-up for at least 1 year, together with the correlation between the different disease condition and serum markers.

Methods
One-hundred and eighty-five CHB patients underwent antiviral therapy for at least 6 months were enrolled. In the 12-month follow-up, ultrasonography-guided biopsy was performed. The patients were grouped based on the serum markers and pathological changes in liver tissues. Then we determined the serum markers, virological tests and Tim-3 expression among these groups.

Results
Antiviral therapy significantly reduced liver inflammation indicators and serum Tim-3 level. However, the fibrosis process of liver tissue was not changed, and there are still disputes on the serum marker and hepatic lesion outcomes. Under normal liver function or negative hepatitis B e antigen (HBeAg) of CHB patients, there might be consensus between Tim-3 change and liver pathological outcome. According to the liver tissue inflammation and fibrosis conditions, Tim-3 was positively correlated with liver function indices. Besides, it was also related to fibrosis stage and inflammation grade.

Conclusion
There were inconsistent changes between serum markers and liver tissue conditions after anti-viral therapy. Tim-3 expression was more suitable to indicate the changes of liver inflammatory and fibrosis response to some extent than ALT and AST. It may serve as a certain indicator to predict the CHB prognosis, which could be used as one of the monitoring indicators in liver pathological changes of chronic HBV infection, especially in monitoring liver tissue inflammation.
Time to surgery and survival in breast cancer
Authors: An Doyeon , Choi Jihye , Lee Jaebin , Kim Jong-Yeup , Kwon Seonguk , Kim Jungeun , Lee Seunghee , Jeon Seongwoo , Lee Chungchun , Lee Suehyun , Woo Hyekyung 
Published: November 2022

Abstract
Background
This study aimed to investigate the effect of the time from diagnosis to breast cancer surgery on breast cancer patients’ prognosis.

Methods
Of the 1900 patients diagnosed with invasive (stage 1–3) breast cancer who underwent surgery in KUH between 2012 and 2019, 279 patients were enrolled in this study. All patients, including those who received neoadjuvant chemotherapy, were classified as Model 1 subjects, and those who received immediate surgical treatment were classified as Model 2 subjects. We conducted a Cox regression analysis to identify prognostic factors of breast cancer associated with the time from diagnosis to surgery.

Results
The univariate results indicated a sharp drop in both groups’ survival rates when the time to surgery was delayed for more than 8 weeks (Model 1 p = 0.000; Model 2 p = 0.001). In the multivariate analysis, the hazard ratio (HR) of Model 1increased (HR = 6.84, 95% CI 1.06–44.25) in response to a delay in surgery of more than 8 weeks. Smoking and the American Joint Committee on Cancer (AJCC) staging system had a negative effect on breast cancer prognosis, while hormone therapy had a positive effect.

Conclusion
For all patients, a delay in breast cancer surgery of more than 8 weeks was inversely associated with survival.
Epidemiology of type 1 and type 2 diabetes mellitus in Kazakhstan: data from unified National Electronic Health System 2014–2019
Authors: Galiyeva Dinara , Gusmanov Arnur , Sakko Yesbolat , Issanov Alpamys , Atageldiyeva Kuralay , Kadyrzhanuly Kainar , Nurpeissova Aiymzhan , Rakhimzhanova Marzhan , Durmanova Aigul , Sarria-Santamera Antonio , Gaipov Abduzhappar 
Published: November 2022

Abstract
Background
We aimed to explore descriptive epidemiology of T1 and T2 Diabetes Mellitus (DM) and to investigate demographic factors and comorbidities associated with all-cause mortality by aggregating and utilizing large-scale administrative healthcare data from the Unified National Electronic Health System (UNEHS) of Kazakhstan for 2014–2019 years period.

Methods
A total of 475,539 individuals were included in the analyses. The median years of follow-up for Type 1 DM patients accounted for 4.7 years and 4.5 years in Type 2 DM patients. We used Kaplan-Meier and log-rank test to calculate failure function and differences in survival by age, sex, ethnicity, and comorbidities with all-cause mortality for Type 1 and Type 2 DM. Cox proportional hazards regression analysis was used to obtain crude and adjusted hazard ratios.

Results
Prevalence of Type 1 and Type 2 DM increased 1.7 times from 2014 to 2019. Mortality of Type 1 and Type 2 DM also increased 4 times and 6 times from 2014 to 2019, respectively. Male sex, older age and Kazakh ethnicity were associated with a higher risk of all-cause death compared to females, younger age and other nationalities than Kazakh in patients with Type 1 and Type 2 DM. Coronary artery disease, diabetic nephropathy, stroke, amputations and neoplasms were associated with a higher risk of all-cause death.

Conclusion
The prevalence and mortality rate of Type 1 and Type 2 DM increased during the years 2014–2019 in Kazakhstan. Male sex, older age and Kazakh ethnicity were associated with a higher risk of all-cause death compared to females, younger age and other nationalities than Kazakh. Coronary artery disease, diabetic nephropathy, stroke, amputations and neoplasms were associated with a higher risk of all-cause death.
Factors explaining men’s intentions to support their partner’s participation in cervical cancer screening
Authors: Dsouza Jyoshma Preema , Van den Broucke Stephan , Pattanshetty Sanjay , Dhoore William 
Published: November 2022

AbstractBackgroundCervical cancer represents a high burden of disease. Many women in low- and middle-income countries face opposition from their partners and families to undergo cervical cancer screening. Identifying the social, cultural, and psychological factors that underly the opposition to screening by male partners is an important step towards reducing barriers for men to support their wives’ participation in cervical screening. This study explored the role of structural and psychological factors deriving from theoretical models as determinants of Indian men’s opposition to their partners being screened for cervical cancer.MethodsA survey among 500 sexually active males was conducted between April 2020 and August 2020 to measure knowledge of cervical cancer and screening, awareness of screening possibilities, attitude towards screening, perceived barriers to screening, and health literacy. Regression analysis was performed to assess which of the potential factors contributed to the intention to support their wives’ screening.ResultsThe majority of participants had very poor knowledge and awareness about cervical cancer and screening procedures, tended towards a negative attitude towards screening, and perceived several structural barriers. Attitude towards the screening procedure and routine participation in general screening significantly predicted their intention to support their wives’ screening for cervical cancer. Education moderated the association between knowledge and awareness and the intention to support their wives’ screening.ConclusionAs women often rely on their spouses’ financial and emotional support of cervical screening, there is a need for men to be encouraged to support their wives’ screening participation. Programs to encourage men to support their wives’ cervical screening should focus on their attitude towards screening, educate about cervical cancer and screening procedures, and reduce perceived barriers.
Systematic characterization of seed overlap microRNA cotargeting associated with lupus pathogenesis
Authors: Kitai Hiroki , Kato Noritoshi , Ogami Koichi , Komatsu Shintaro , Watanabe Yu , Yoshino Seiko , Koshi Eri , Tsubota Shoma , Funahashi Yoshio , Maeda Takahiro , Furuhashi Kazuhiro , Ishimoto Takuji , Kosugi Tomoki , Maruyama Shoichi , Kadomatsu Kenji , Suzuki Hiroshi I. 
Published: November 2022

AbstractBackgroundCombinatorial gene regulation by multiple microRNAs (miRNAs) is widespread and closely spaced target sites often act cooperatively to achieve stronger repression (“neighborhood” miRNA cotargeting). While miRNA cotarget sites are suggested to be more conserved and implicated in developmental control, the pathological significance of miRNA cotargeting remains elusive.ResultsHere, we report the pathogenic impacts of combinatorial miRNA regulation on inflammation in systemic lupus erythematosus (SLE). In the SLE mouse model, we identified the downregulation of two miRNAs, miR-128 and miR-148a, by TLR7 stimulation in plasmacytoid dendritic cells. Functional analyses using human cell lines demonstrated that miR-128 and miR-148a additively target KLF4 via extensively overlapping target sites (“seed overlap” miRNA cotargeting) and suppress the inflammatory responses. At the transcriptome level, “seed overlap” miRNA cotargeting increases susceptibility to downregulation by two miRNAs, consistent with additive but not cooperative recruitment of two miRNAs. Systematic characterization further revealed that extensive “seed overlap” is a prevalent feature among broadly conserved miRNAs. Highly conserved target sites of broadly conserved miRNAs are largely divided into two classes—those conserved among eutherian mammals and from human toCoelacanth, and the latter, including KLF4-cotargeting sites, has a stronger association with both “seed overlap” and “neighborhood” miRNA cotargeting. Furthermore, a deeply conserved miRNA target class has a higher probability of haplo-insufficient genes.ConclusionsOur study collectively suggests the complexity of distinct modes of miRNA cotargeting and the importance of their perturbations in human diseases.
Intestinal gluconeogenesis is downregulated in pediatric patients with celiac disease
Authors: Karlson Olof , Arnell Henrik , Gudjonsdottir Audur H. , Agardh Daniel , Torinsson Naluai Åsa 
Published: November 2022

Abstract
Background
Untreated celiac disease (CD) patients have increased levels of blood glutamine and a lower duodenal expression of glutaminase (GLS). Intestinal gluconeogenesis (IGN) is a process through which glutamine is turned into glucose in the small intestine, for which GLS is crucial. Animal studies suggest impaired IGN may have long-term effects on metabolic control and be associated with the development of type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). The aim of this study was to thoroughly investigate IGN at the gene expression level in children with untreated celiac disease.

Methods
Quantitative polymerase chain reaction (qPCR) was used to quantify the expression of 11 target genes related to IGN using the delta-delta Ct method with three reference genes (GUSB, IPO8, and YWHAZ) in duodenal biopsies collected from 84 children with untreated celiac disease and 58 disease controls.

Results
Significantly lower expression of nine target genes involved in IGN was seen in duodenal biopsies from CD patients compared with controls: FBP1, G6PC, GLS, GPT1, PCK1, PPARGC1A, SLC2A2, SLC5A1, and SLC6A19. No significant difference in the expression was observed for G6PC3 or GOT1.

Conclusions
Children with untreated celiac disease have lower expression of genes important for IGN. Further studies are warranted to disentangle whether this is a consequence of intestinal inflammation or due to an impaired metabolic pathway shared with other chronic metabolic diseases. Impaired IGN could be a mechanism behind the increased risk of NAFLD seen in CD patients.
Thrombin induces IL-8/CXCL8 expression by DCLK1-dependent RhoA and YAP activation in human lung epithelial cells
Authors: Yuliani Fara Silvia , Chen Jing-Yun , Cheng Wen-Hao , Wen Heng-Ching , Chen Bing-Chang , Lin Chien-Huang 
Published: November 2022

Abstract
Background
Doublecortin-like kinase 1 (DCLK1) has been recognized as a marker of cancer stem cell in several malignancies. Thrombin is crucial in asthma severity as it can promote IL-8/CXCL8 production in lung epithelial cells, which is a potent chemoattractant for neutrophils. However, the pathologic role of DCLK1 in asthma and its involvement in thrombin-stimulated IL-8/CXCL8 expression remain unknown.

Methods
IL-8/CXCL8, thrombin, and DCLK1 expression were observed in the lung tissues of severe asthma patients and ovalbumin (OVA)-induced asthmatic mice model. A549 and BEAS-2B cells were either pretreated with inhibitors or small interfering RNAs (siRNAs) before being treated with thrombin. IL-8/CXCL8 expression and the molecules involved in signaling pathway were performed using ELISA, luciferase activity assay, Western blot, or ChIP assay.

Results
IL-8/CXCL8, thrombin, and DCLK1 were overexpressed in the lung tissues of severe asthma patients and ovalbumin (OVA)-induced asthmatic mice model. Our in vitro study found that DCLK siRNA or LRKK2-IN-1 (DCLK1 inhibitor) attenuated IL-8/CXCL8 release after thrombin induction in A549 and BEAS-2B cells. Thrombin activated DCLK1, RhoA, and YAP in a time-dependent manner, in which DCLK1 siRNA inhibited RhoA and YAP activation. YAP was dephosphorylated on the Ser127 site after thrombin stimulation, resulting in YAP translocation to the nucleus from the cytosol. DCLK1, RhoA and YAP activation following thrombin stimulation were inhibited by U0126 (ERK inhibitor). Moreover, DCLK1 and YAP siRNA inhibited κB-luciferase activity. Thrombin stimulated the recruitment of YAP and p65 to the NF-κB site of the IL-8/CXCL8 promoter and was inhibited by DCLK1 siRNA.

Conclusions
Thrombin activates the DCLK1/RhoA signaling pathway, which promotes YAP activation and translocation to the nucleus from the cytosol, resulting in YAP/p65 formation, and binding to the NF-κB site, which enhances IL-8/CXCL8 expression. DCLK1 might be essential in thrombin-stimulated IL-8/CXCL8 expression in asthmatic lungs and indicates a potential therapeutic strategy for severe asthma treatment.
Impact of aerial humidity on seasonal malaria: an ecological study in Zambia
Authors: Duque Carolina , Lubinda Mukuma , Matoba Japhet , Sing’anga Caison , Stevenson Jennifer , Shields Timothy , Shiff Clive J. 
Published: November 2022

Abstract
Background
Seasonal patterns of malaria cases in many parts of Africa are generally associated with rainfall, yet in the dry seasons, malaria transmission declines but does not always cease. It is important to understand what conditions support these periodic cases. Aerial moisture is thought to be important for mosquito survival and ability to forage, but its role during the dry seasons has not been well studied. During the dry season aerial moisture is minimal, but intermittent periods may arise from the transpiration of peri-domestic trees or from some other sources in the environment. These periods may provide conditions to sustain pockets of mosquitoes that become active and forage, thereby transmitting malaria. In this work, humidity along with other ecological variables that may impact malaria transmission have been examined.

Methods
Negative binomial regression models were used to explore the association between peri-domestic tree humidity and local malaria incidence. This was done using sensitive temperature and humidity loggers in the rural Southern Province of Zambia over three consecutive years. Additional variables including rainfall, temperature and elevation were also explored.

Results
A negative binomial model with no lag was found to best fit the malaria cases for the full year in the evaluated sites of the Southern Province of Zambia. Local tree and granary night-time humidity and temperature were found to be associated with local health centre-reported incidence of malaria, while rainfall and elevation did not significantly contribute to this model. A no lag and one week lag model for the dry season alone also showed a significant effect of humidity, but not temperature, elevation, or rainfall.

Conclusion
The study has shown that throughout the dry season, periodic conditions of sustained humidity occur that may permit foraging by resting mosquitoes, and these periods are associated with increased incidence of malaria cases. These results shed a light on conditions that impact the survival of the common malaria vector species, Anopheles arabiensis, in arid seasons and suggests how they emerge to forage when conditions permit.