bluuebunny/crossref_metadata_2025_split huggingface dataset:
GeneTonic: an R/Bioconductor package for streamlining the interpretation of RNA-seq data
Authors: Marini Federico , Ludt Annekathrin , Linke Jan , Strauch Konstantin 
Published: December 2021

AbstractBackgroundThe interpretation of results from transcriptome profiling experiments via RNA sequencing (RNA-seq) can be a complex task, where the essential information is distributed among different tabular and list formats—normalized expression values, results from differential expression analysis, and results from functional enrichment analyses. A number of tools and databases are widely used for the purpose of identification of relevant functional patterns, yet often their contextualization within the data and results at hand is not straightforward, especially if these analytic components are not combined together efficiently.ResultsWe developed the software package, which serves as a comprehensive toolkit for streamlining the interpretation of functional enrichment analyses, by fully leveraging the information of expression values in a differential expression context. is implemented in R and Shiny, leveraging packages that enable HTML-based interactive visualizations for executing drilldown tasks seamlessly, viewing the data at a level of increased detail. is integrated with the core classes of existing Bioconductor workflows, and can accept the output of many widely used tools for pathway analysis, making this approach applicable to a wide range of use cases. Users can effectively navigate interlinked components (otherwise available as flat text or spreadsheet tables), bookmark features of interest during the exploration sessions, and obtain at the end a tailored HTML report, thus combining the benefits of both interactivity and reproducibility.Conclusionis distributed as an R package in the Bioconductor project (https://bioconductor.org/packages/GeneTonic/) under the MIT license. Offering both bird’s-eye views of the components of transcriptome data analysis and the detailed inspection of single genes, individual signatures, and their relationships, aims at simplifying the process of interpretation of complex and compelling RNA-seq datasets for many researchers with different expertise profiles.
Intravenous tacrolimus is a superior induction therapy for acute severe ulcerative colitis compared to oral tacrolimus
Authors: Shimizu Hiromichi , Fujii Toshimitsu , Kinoshita Kenji , Kawamoto Ami , Hibiya Shuji , Takenaka Kento , Saito Eiko , Nagahori Masakazu , Ohtsuka Kazuo , Watanabe Mamoru , Okamoto Ryuichi 
Published: December 2021

Abstract
Background
Intravenous corticosteroid is the mainstay for managing acute severe ulcerative colitis, but one-third of patients do not respond to intravenous corticosteroid. Tacrolimus, a salvage therapy before colectomy, is usually orally administered, though its bioavailability is low compared intravenous administration. The efficacy of intravenous tacrolimus has not been widely studied.

Aim
To determine the efficacy and safety of intravenous tacrolimus for the treatment of acute severe ulcerative colitis.

Methods
Eighty-seven hospitalized acute severe ulcerative colitis patients were enrolled for a prospective cohort study between 2009 and 2017. Sixty-five patients received intravenous tacrolimus and 22 received oral tacrolimus. The primary outcome was the achievement of clinical remission within 2 weeks. Relapse and colectomy incidence and adverse events were assessed at 24 weeks.

Results
Response rates of both treatments exceeded 50% but were not significantly different. The remission rate was higher in intravenous tacrolimus compared with oral tacrolimus. At 24 weeks, oral and intravenous tacrolimus showed similar relapse-free survival rates; however, colectomy-free survival rates were higher in intravenous tacrolimus compared with oral tacrolimus.

Conclusions
Patients receiving intravenous tacrolimus achieved superior remission and colectomy-free survival rates compared with patients receiving oral tacrolimus. Safety was similar between the two treatments.
Understanding the determinants of postnatal care uptake for babies: A mixed effects multilevel modelling of 2016–18 Papua New Guinea Demographic and Health Survey
Authors: Appiah Francis , Fenteng Justice Ofosu Darko , Dare Felix , Salihu Tarif , Darteh Andrews Ohene , Takyi Matthew , Ayerakwah Patience Ansomah , Ameyaw Edward Kwabena 
Published: December 2021

Abstract
Background
Papua New Guinea (PNG) recorded 22 neonatal deaths out of every 1,000 livebirths in 2019. Some of these deaths are related to complications that arise shortly after childbirth; hence, postnatal care (PNC) utilisation could serve as a surviving strategy for neonates as recommended by the World Health Organisation. National level study on determinants of PNC uptake in PNG is limited. Utilising the Bronfenbrenner’s Ecological Model of Human Development, the study aimed at assessing determinants of PNC utilisation for babies by their mothers aged 15–49 in PNG.

Methods
The study used data from the women’s file of the 2016–18 PNG Demographic and Health Survey (2016–18 PNGDHS) and a sample of 4,908 women aged 15–49 who had complete information on the variables of interest to the study. Nineteen (19) explanatory variables were selected for the study whereas PNC for babies within first two months after being discharged after birth was the main outcome variable. At 95% confidence interval (95% CI), six multilevel logistic models were built. The Akaike Information Criterion (AIC) was used to assess models’ fit. All analyses were carried out using STATA version 14.0.

Results
Generally, 31% of the women utilised PNC for their babies. Women with primary education [aOR = 1.42, CI = 1.13–1.78], those belonging to the middle wealth quintile [aOR = 1.42, CI = 1.08–1.87], working class [aOR = 1.28, CI = 1.10–1.49], women who had the four or more ANC visits [aOR = 1.23, CI = 1.05–1.43], those with twins [aOR = 1.83, CI = 1.01–3.29], women who belonged to community of medium literate class [aOR = 1.75, CI = 1.34–2.27] and those of moderate socioeconomic status [aOR = 1.60, CI = 1.16–2.21] had higher odds of seeking PNC for their babies. The odds to seek PNC services for babies reduced among the cohabiting women [aOR = 0.79, CI = 0.64–0.96], those at parity four or more [aOR = 0.77, CI = 0.63–0.93], women who gave birth to small babies [aOR = 0.80, CI = 0.67–0.98] and residents in the Highlands region [aOR = 0.47, CI = 0.36–0.62].

Conclusions
Maternal education, wealth quintile, occupation, partner’s education, ANC visits, marital status, parity, child size at birth, twin status, community literacy and socioeconomic status as well as region of residence were associated with PNC uptake for babies in PNG. Variation in PNC uptake for babies existed from one community/cluster to the other. There is the need to strengthen public health education to increase awareness about the benefits of seeking PNC services for babies among women in PNG. Such programs should consider maternal and community/cluster characteristics in their design.
History of drinking problems diminishes the protective effects of within-guideline drinking on 18-year risk of dementia and CIND
Authors: Brennan Penny L. , Holahan Charles J. , Moos Rudolf H. , Schutte Kathleen K. 
Published: December 2021

Abstract
Objective
To examine the moderating effect of older adults’ history of drinking problems on the relationship between their baseline alcohol consumption and risk of dementia and cognitive impairment, no dementia (CIND) 18 years later.

Method
A longitudinal Health and Retirement Study cohort (n = 4421) was analyzed to demonstrate how older adults’ baseline membership in one of six drinking categories (non-drinker, within-guideline drinker, and outside-guideline drinker groups, divided to reflect absence or presence of a history of drinking problems) predicts dementia and CIND 18 years later.

Results
Among participants with no history of drinking problems, 13% of non-drinkers, 5% of within-guideline drinkers, and 9% of outside-guideline drinkers were classified as having dementia 18-years later. Among those with a history of drinking problems, 14% of non-drinkers, 9% of within-guideline drinkers, and 7% of outside-guideline drinkers were classified with dementia. With Non-Drinker, No HDP as reference category, being a baseline within-guideline drinker with no history of drinking problems reduced the likelihood of dementia 18 years later by 45%, independent of baseline demographic and health characteristics; being a baseline within-guideline drinker with a history of drinking problems reduced the likelihood by only 13% (n.s.). Similar patterns obtained for the prediction of CIND.

Conclusions
For older adults, consuming alcohol at levels within validated guidelines for low-risk drinking may offer moderate long-term protection from dementia and CIND, but this effect is diminished by having a history of drinking problems. Efforts to predict and prevent dementia and CIND should focus on older adults’ history of drinking problems in addition to how much alcohol they consume.
Factors associated with antihypertensive medication use and blood pressure control in a rural area in Bangladesh: baseline data from a cluster randomised control trial
Authors: Amirul Islam Fakir M. , Lambert Elisabeth A. , Islam Sheikh Mohammed Shariful , Islam M. Ariful , Maddison Ralph , Thompson Bruce , Lambert Gavin W. 
Published: December 2021

Abstract
Background
The use of antihypertensive medications is critical for controlling high blood pressure. We aimed to investigate associations between socio-demographic factors and antihypertensive medications use, and antihypertensive medications use with different types of drugs use with levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP).

Methods
For the present report we derived data from the baseline measurements of a cluster randomised control trial on 307 participants with previously diagnosed hypertension from the rural district of Narial in Bangladesh. We measured the participant’s current blood pressure levels and recorded antihypertensive medications uses. Associated factors included socio-economic status, diabetes, antihypertensive medications use, and types of drugs and doses used for controlling blood pressure. We applied analysis of variance and logistic regression techniques to identify factors associated with blood pressure.

Results
Of the total participants, 144 (46.9%) were on antihypertensive medications. After multivariate adjustment, binary logistic regression revealed that employees (odds ratio, (95% confidence interval (CI)) (OR 3.58, 95%CI 1.38-9.28) compared to farmers, and people with diabetes (OR 2.43, 95%CI 1.13-5.26) compared to people without diabetes were associated with a higher proportion of antihypertensive medications use. Of 144 participants on antihypertensive medications, 7 (5%) had taken two doses, 114 (79%) had taken one dose per day and the rest were irregular in medication use. The mean (standard deviation) [min, max] SBP and DBP were 149 (19) mmHg [114, 217] and 90 (10) mmHg [75, 126], respectively. Overall, there was no significant difference in SBP (p = 0.10) or DBP (p = 0.67) between participants with or without antihypertensive medications or using any type of medications (p = 0.54 for SBP and 0.76 for DBP). There was no significant association between antihypertensive medications use and elevated BP levels SBP/DBP≥140/90 mmHg (p = 0.42)

Conclusion
Less than half of the people with hypertension were on medication. Irrespective of the antihypertensive medications use, most of the participant’s blood pressure was high. Further study is needed with a large sample to understand the factors and aetiology of unmanaged hypertension in rural areas of Bangladesh where the prevalence of hypertension is very high.
Development of a community orientation program (COP) as a community-based medical education method for undergraduate medical students: an experience from India
Authors: Narapureddy Bayapa Reddy , Patan Shakeer Kahn , Deepthi C. Sravana , Chaudhuri Sirshendu , John K. R. , Chittooru Chandrasekar , Babu Surendra , Nagoor Khadervali , Jeeragyal Devika , Basha Jawahar , Nell Theo , Reddy Ravi Shankar 
Published: December 2021

AbstractBackgroundIntra-regional cultural and linguistic differences are common in low- and middle-income countries. To sensitise undergraduate medical students to the social and contextual determinants of health to achieve the ‘health for all’ goal, these countries must focus on innovative teaching methods. The early introduction of a Community Orientation Program (COP) as a Community-based Medical Education (CBME) method could be a game changing strategy. In this paper the methods, evaluation, and implication of the COP in an Indian setting are described.MethodsThe curriculum of the COP was developed based on the analysis, design, development, implementation, and evaluation (ADDIE) model for educational intervention. In this learner-centric and supervised educational program, the key aim was to focus on developing students’ communication skills, observation power and enhancing their motivation for learning through collaborative learning. To meet the objectives of the COP, a situated learning model under the constructivism theory was adopted.ResultsBetween 2016 and 2019, 557 students were trained through the COP by visiting more than 1300 households in ten villages. To supplement the students’ observations in the community, more than 150 small group discussions, a health education programme for the community and summary presentations were conducted. The students’ feedback indicated the need to improve the clinical examinations demonstration quality and increase the number of instruments for clinical examinations. More than 80% of students felt that the program would assist them to improve their communication skills, their understanding of the various socio-demographic factors associated with the common diseases, and it will enable them to respect the local culture during their clinical practice.ConclusionsEarly initiation of the COP as a CBME method in the undergraduate medical curriculum in an Indian setting has shown promising results. Further evidence is required to adopt such a program routinely for under-graduate medical teaching in the low- and middle- income settings.
Kernel principal components based cascade forest towards disease identification with human microbiota
Authors: Zhou Jiayu , Ye Yanqing , Jiang Jiang 
Published: December 2021

AbstractBackgroundNumerous pieces of clinical evidence have shown that many phenotypic traits of human disease are related to their gut microbiome, i.e., inflammation, obesity, HIV, and diabetes. Through supervised classification, it is feasible to determine the human disease states by revealing the intestinal microbiota compositional information. However, the abundance matrix of microbiome data is so sparse, an interpretable deep model is crucial to further represent and mine the data for expansion, such as the deep forest model. What’s more, overfitting can still exist in the original deep forest model when dealing with such “large p, small n” biology data. Feature reduction is considered to improve the ensemble forest model especially towards the disease identification in the human microbiota.MethodsIn this work, we propose the kernel principal components based cascade forest method, so-called KPCCF, to classify the disease states of patients by using taxonomic profiles of the microbiome at the family level. In detail, the kernel principal components analysis method is first used to reduce the original dimension of human microbiota datasets. Besides, the processed data is fed into the cascade forest to preliminarily discriminate against the disease state of the samples.ResultsThe proposed KPCCF algorithm can represent the small-scale and high-dimension human microbiota datasets with the sparse feature matrix. Systematic comparison experiments demonstrate that our method consistently outperforms the state-of-the-art methods with the comparative study on 4 datasets.ConclusionDespite sharing some common characteristics, a one-size-fits-all solution does not exist in any space. The traditional depth model has limitations in the biological application of the unbalanced scale between small samples and high dimensions. KPCCF distinguishes from the standard deep forest model for its excellent performance in the microbiota field. Additionally, compared to other dimensionality reduction methods, the kernel principal components analysis method is more suitable for microbiota datasets.
Overnight variation in tidal expiratory flow limitation in COPD patients and its correction: an observational study
Authors: McKenzie J. , Nisha P. , Cannon-Bailey S. , Cain C. , Kissel M. , Stachel J. , Proscyk C. , Romano R. , Hardy B. , Calverley P. M. A. 
Published: December 2021

Abstract
Background
Tidal expiratory flow limitation (EFLT) is common among COPD patients. Whether EFLT changes during sleep and can be abolished during home ventilation is not known.

Methods
COPD patients considered for noninvasive ventilation used a ventilator which measured within-breath reactance change at 5 Hz (∆Xrs) and adjusted EPAP settings to abolish EFLT. Participants flow limited (∆Xrs > 2.8) when supine underwent polysomnography (PSG) and were offered home ventilation for 2 weeks. The EPAP pressure that abolished EFLT was measured and compared to that during supine wakefulness. Ventilator adherence and subjective patient perceptions were obtained after home use.

Results
Of 26 patients with supine EFLT, 15 completed overnight PSG and 10 the home study. In single night and 2-week home studies, EFLT within and between participants was highly variable. This was unrelated to sleep stage or body position with only 14.6% of sleep time spent within 1 cmH2O of the awake screening pressure. Over 2 weeks, mean EPAP was almost half the mean maximum EPAP (11.7 vs 6.4 cmH2O respectively). Group mean ∆Xrs was ≤ 2.8 for 77.3% of their home use with a mean time to abolish new EFLT of 5.91 min. Adherence to the ventilator varied between 71 and 100% in prior NIV users and 36–100% for naïve users with most users rating therapy as comfortable.

Conclusions
Tidal expiratory flow limitation varies significant during sleep in COPD patients. This can be controlled by auto-titrating the amount of EPAP delivered. This approach appears to be practical and well tolerated by patients.
Trial registration: The trial was retrospectively registered at CT.gov NCT04725500.
BTB and CNC homology 1 (Bach1) induces lung cancer stem cell phenotypes by stimulating CD44 expression
Authors: Jiang Pan , Li Fan , Liu Zilong , Hao Shengyu , Gao Jian , Li Shanqun 
Published: December 2021

Abstract
Background
Growing evidence suggests that cancer stem cells (CSCs) are responsible for cancer initiation in tumors. Bach1 has been identified to contribute to several tumor progression, including lung cancer. The role of Bach1 in CSCs remains poorly known. Therefore, the function of Bach1 on lung CSCs was focused currently.

Methods
The expression of Bach1, CD133, CD44, Sox2, Nanog and Oct4 mRNA was assessed using Real-Time Quantitative Reverse Transcription PCR (RT-qPCR). Protein expression of Bach1, CD133, CD44, Sox2, Nanog, Oct4, p53, BCL2, BAX, p-p38, p-AKT1, c-Fos and c-Jun protein was analyzed by western blotting. 5-ethynyl-29-deoxyuridine (EdU), colony formation, Flow cytometry analysis and transwell invasion assay were carried out to analyze lung cancer cell proliferation, apoptosis and invasion respectively. Tumor sphere formation assay was utilized to evaluate spheroid capacity. Flow cytometry analysis was carried out to isolate CD133 or CD44 positive lung cancer cells. The relationship between Bach1 and CD44 was verified using ChIP-qPCR and dual-luciferase reporter assay. Xenograft tumor tissues were collected for hematoxylin and eosin (HE) staining and IHC analysis to evaluate histology and Ki-67.

Results
The ratio of CD44 + CSCs from A549 and SPC-A1 cells were significantly enriched. Tumor growth of CD44 + CSCs was obviously suppressed in vivo compared to CD44− CSCs. Bach1 expression was obviously increased in CD44 + CSCs. Then, via using the in vitro experiment, it was observed that CSCs proliferation and invasion were greatly reduced by the down-regulation of Bach1 while cell apoptosis was triggered by knockdown of Bach1. Loss of Bach1 was able to repress tumor-sphere formation and tumor-initiating CSC markers. A repression of CSCs growth and metastasis of shRNA-Bach1 was confirmed using xenograft models and caudal vein injection. The direct interaction between Bach1 and CD44 was confirmed by ChIP-qPCR and dual-luciferase reporter assay. Furthermore, mitogen-activated protein kinases (MAPK) signaling pathway was selected and we proved the effects of Bach1 on lung CSCs were associated with the activation of the MAPK pathway. As manifested, loss of Bach1 was able to repress p-p38, p-AKT1, c-Fos, c-Jun protein levels in lung CSCs. Inhibition of MAPK signaling remarkably restrained lung CSCs growth and CSCs properties induced by Bach1 overexpression.

Conclusion
In summary, we imply that Bach1 demonstrates great potential for the treatment of lung cancer metastasis and recurrence via activating CD44 and MPAK signaling.
Multi-omics analysis defines 5-fluorouracil drug resistance in 3D HeLa carcinoma cell model
Authors: Wang Lin , Wang Xueting , Wang Tong , Zhuang Yingping , Wang Guan 
Published: December 2021

AbstractCervical cancer is a serious health problem in women around the globe. However, the use of clinical drug is seriously dampened by the development of drug resistance. Efficient in vitro tumor model is essential to improve the efficiency of drug screening and the accuracy of clinical application. Multicellular tumor spheroids (MTSs) can in a way recapitulates tumor traits in vivo, thereby representing a powerful transitional model between 2D monolayer culture and xenograft. In this study, based on the liquid overlay method, a protocol for rapid generation of the MTSs with uniform size and high reproducibility in a high-throughput manner was established. As expected, the cytotoxicity results showed that there was enhanced 5-fluorouracil (5-FU) resistance of HeLa carcinoma cells in 3D MTSs than 2D monolayer culture with a resistance index of 5.72. In order to obtain a holistic view of the molecular mechanisms that drive 5-FU resistance in 3D HeLa carcinoma cells, a multi-omics study was applied to discover hidden biological regularities. It was observed that in the 3D MTSs mitochondrial function-related proteins and the metabolites of the tricarboxylic acid cycle (TCA cycle) were significantly decreased, and the cellular metabolism was shifted towards glycolysis. The differences in the protein synthesis, processing, and transportation between 2D monolayer cultures and 3D MTSs were significant, mainly in the heat shock protein family, with the up-regulation of protein folding function in endoplasmic reticulum (ER), which promoted the maintenance of ER homeostasis in the 3D MTSs. In addition, at the transcript and protein level, the expression of extracellular matrix (ECM) proteins (e.g., laminin and collagen) were up-regulated in the 3D MTSs, which enhanced the physical barrier of drug penetration. Summarizing, this study formulates a rapid, scalable and reproducible in vitro model of 3D MTS for drug screening purposes, and the findings establish a critical role of glycolytic metabolism, ER hemostasis and ECM proteins expression profiling in tumor chemoresistance of HeLa carcinoma cells towards 5-FU.Graphical Abstract