bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global analysis of expression, maturation and subcellular localization of mouse liver transcriptome identifies novel sex-biased and TCPOBOP-responsive long non-coding RNAs
Authors: Goldfarb Christine N. , Waxman David J. 
Published: March 2021

Abstract
Background
While nuclear transcription and RNA processing and localization are well established for protein coding genes (PCGs), these processes are poorly understood for long non-coding (lnc)RNAs. Here, we characterize global patterns of transcript expression, maturation and localization for mouse liver RNA, including more than 15,000 lncRNAs. PolyA-selected liver RNA was isolated and sequenced from four subcellular fractions (chromatin, nucleoplasm, total nucleus, and cytoplasm), and from the chromatin-bound fraction without polyA selection.

Results
Transcript processing, determined from normalized intronic to exonic sequence read density ratios, progressively increased for PCG transcripts in going from the chromatin-bound fraction to the nucleoplasm and then on to the cytoplasm. Transcript maturation was similar for lncRNAs in the chromatin fraction, but was significantly lower in the nucleoplasm and cytoplasm. LncRNA transcripts were 11-fold more likely to be significantly enriched in the nucleus than cytoplasm, and 100-fold more likely to be significantly chromatin-bound than nucleoplasmic. Sequencing chromatin-bound RNA greatly increased the sensitivity for detecting lowly expressed lncRNAs and enabled us to discover and localize hundreds of novel regulated liver lncRNAs, including lncRNAs showing sex-biased expression or responsiveness to TCPOBOP a xenobiotic agonist ligand of constitutive androstane receptor (Nr1i3).

Conclusions
Integration of our findings with prior studies and lncRNA annotations identified candidate regulatory lncRNAs for a variety of hepatic functions based on gene co-localization within topologically associating domains or transcription divergent or antisense to PCGs associated with pathways linked to hepatic physiology and disease.
Deep learning assisted multi-omics integration for survival and drug-response prediction in breast cancer
Authors: Malik Vidhi , Kalakoti Yogesh , Sundar Durai 
Published: March 2021

Abstract
Background
Survival and drug response are two highly emphasized clinical outcomes in cancer research that directs the prognosis of a cancer patient. Here, we have proposed a late multi omics integrative framework that robustly quantifies survival and drug response for breast cancer patients with a focus on the relative predictive ability of available omics datatypes. Neighborhood component analysis (NCA), a supervised feature selection algorithm selected relevant features from multi-omics datasets retrieved from The Cancer Genome Atlas (TCGA) and Genomics of Drug Sensitivity in Cancer (GDSC) databases. A Neural network framework, fed with NCA selected features, was used to develop survival and drug response prediction models for breast cancer patients. The drug response framework used regression and unsupervised clustering (K-means) to segregate samples into responders and non-responders based on their predicted IC50 values (Z-score).

Results
The survival prediction framework was highly effective in categorizing patients into risk subtypes with an accuracy of 94%. Compared to single-omics and early integration approaches, our drug response prediction models performed significantly better and were able to predict IC50 values (Z-score) with a mean square error (MSE) of 1.154 and an overall regression value of 0.92, showing a linear relationship between predicted and actual IC50 values.

Conclusion
The proposed omics integration strategy provides an effective way of extracting critical information from diverse omics data types enabling estimation of prognostic indicators. Such integrative models with high predictive power would have a significant impact and utility in precision oncology.
Whole-genome analysis of probiotic product isolates reveals the presence of genes related to antimicrobial resistance, virulence factors, and toxic metabolites, posing potential health risks
Authors: Wang Ying , Liang Qian , Lu Bian , Shen Hong , Liu Shuyan , Shi Ya , Leptihn Sebastian , Li Hong , Wei Jin , Liu Chengzhi , Xiao Hailong , Zheng Xiaoling , Liu Chao , Chen Huan 
Published: March 2021

Abstract
Background
Safety issues of probiotic products have been reported frequently in recent years. Ten bacterial strains isolated from seven commercial probiotic products on market were evaluated for their safety, by whole-genome analysis.

Results
We found that the bacterial species of three probiotic products were incorrectly labeled. Furthermore, six probiotic product isolates (PPS) contained genes for the production of toxic metabolites, while another three strains contained virulence genes, which might pose a potential health risk. In addition, three of them have drug-resistance genes, among which two strains potentially displayed multidrug resistance. One isolate has in silico predicted transferable genes responsible for toxic metabolite production, and they could potentially transfer to human gut microflora or environmental bacteria. Isolates of Lactobacillus rhamnosus and Bifidobacterium animalis subsp. lactis are associated with low risk for human consumption. Based on a comparative genome analysis, we found that the isolated Enterococcus faecium TK-P5D clustered with a well-defined probiotic strain, while E. faecalis TK-P4B clustered with a pathogenic strain.

Conclusions
Our work clearly illustrates that whole-genome analysis is a useful method to evaluate the quality and safety of probiotic products. Regulatory quality control and stringent regulations on probiotic products are needed to ensure safe consumption and protect human health.
Effect of ultrasound-guided transversus abdominis plane block with rectus sheath block on patients undergoing laparoscopy-assisted radical resection of rectal cancer: a randomized, double-blind, placebo-controlled trial
Authors: Liang Min , Xv Xia , Ren Chunguang , Yao Yongxing , Gao Xiujuan 
Published: March 2021

AbstractBackgroundMany patients complain of pain following laparoscopic surgery. Clinicians have used ultrasound-guided posterior transversus abdominis plane block (TAPB) and rectus sheath block (RSB) for multimodal analgesia after surgery. We investigated the analgesic effects of US-guided posterior TAPB with RSB on postoperative pain following laparoscopy-assisted radical resection of early-stage rectal cancer.MethodsSeventy-eight adults scheduled for laparoscopy-assisted radical resection of rectal cancer were enrolled in this double-blind placebo-controlled trial. Patients were randomized into 3 groups: the TR Group underwent US-guided bilateral posterior TAPB (40 mL 0.33% ropivacaine) with RSB (20 mL 0.33% ropivacaine); the T Group underwent US-guided bilateral posterior TAPB alone; and the Control Group received saline alone. All patients also had access to patient-controlled intravenous analgesia (PCIA) with sufentanil. The primary outcome was postoperative sufentanil consumption at 0–24, 24–48, and 48–72 h. The secondary outcomes were postoperative pain intensity and functional activity score at rest and while coughing for the same three time periods, intraoperative medication dosage, use of rescue analgesia, recovery parameters, and adverse effects.ResultsThe three groups had no significant differences in baseline demographic and perioperative data, use of intraoperative medications, recovery parameters, and adverse effects. The TR group had significantly lower postoperative use of PCIA and rescue analgesic than in the other two groups (P < 0.05), but the Control Group and T Group had no significant differences in these outcomes.ConclusionsPostoperative US-guided posterior TAPB with RSB reduced postoperative opioid use in patients following laparoscopy-assisted radical resection of rectal cancer.Trial registrationThe trial was registered withchictr.org(ChiCTR2000029326) on January 25, 2020.
A 2 miRNAs-based signature for the diagnosis of atherosclerosis
Authors: Han Xiujiang , Wang Huimin , Li Yongjian , Liu Lina , Gao Sheng 
Published: March 2021

Abstract
Background
Atherosclerosis (AS) is a leading cause of vascular disease worldwide. MicroRNAs (miRNAs) play an essential role in the development of AS. However, the miRNAs-based biomarkers for the diagnosis of AS are still limited. Here, we aimed to identify the miRNAs significantly related to AS and construct the predicting model based on these miRNAs for distinguishing the AS patients from healthy cases.

Methods
The miRNA and mRNA expression microarray data of blood samples from patients with AS and healthy cases were obtained from the GSE59421 and GSE20129 of Gene Expression Omnibus (GEO) database, respectively. Weighted Gene Co-expression Network Analysis (WGCNA) was performed to evaluate the correlation of the miRNAs and mRNAs with AS and identify the miRNAs and mRNAs significantly associated with AS. The potentially critical miRNAs were further optimized by functional enrichment analysis. The logistic regression models were constructed based on these optimized miRNAs and validated by threefold cross-validation method.

Results
WGCNA revealed 42 miRNAs and 532 genes significantly correlated with AS. Functional enrichment analysis identified 12 crucial miRNAs in patients with AS. Moreover, 6 miRNAs among the identified 12 miRNAs, were selected using a stepwise regression model, in which four miRNAs, including hsa-miR-654-5p, hsa-miR-409-3p, hsa-miR-485-5p and hsa-miR-654-3p, were further identified through multivariate regression analysis. The threefold cross-validation method showed that the AUC of logistic regression model based on the four miRNAs was 0.7308, 0.8258, and 0.7483, respectively, with an average AUC of 0.7683.

Conclusion
We identified a total of four miRNAs, including hsa-miR-654-5p and hsa-miR-409-3p, are identified as the potentially critical biomarkers for AS. The logistic regression model based on the identified 2 miRNAs could reliably distinguish the patients with AS from normal cases.
A retrospective study of alectinib versus ceritinib in patients with advanced non–small-cell lung cancer of anaplastic lymphoma kinase fusion in whom crizotinib treatment failed
Authors: Kuo Chih-Hsi Scott , Tung Pi-Hung , Huang Allen Chung-Cheng , Wang Chin-Chou , Chang John Wen-Cheng , Liu Chien-Ying , Chung Fu-Tsai , Fang Yueh-Fu , Guo Yi-Ke , Yang Cheng-Ta 
Published: March 2021

Abstract
Background
Crizotinib is the approved treatment for advanced non-small cell lung cancers (NSCLCs) of anaplastic lymphoma kinase (ALK) fusion. Failure of crizotinib treatment frequently involves drug intolerance or resistance. Comparison of using second-generation ALK inhibitors in this setting remains lacking.

Methods
Sixty-five ALK-positive advanced NSCLC patients receiving second-generation ALK inhibitors following treatment failure of crizotinib were retrospectively analyzed for the therapeutic efficacy.

Results
Forty-three (66.2%) and 22 (33.8%) patients received alectinib and ceritinib, respectively. Comparing alectinib to ceritinib treatment: the 12-month progression-free survival (PFS) rate (61.0% [95% confidence interval, 47.1 to 78.9%] vs. 54.5% [95% CI, 37.3 to 79.9%]); the hazard ratio (HR) for disease progression or death, 0.61 (95% CI, 0.31–1.17; p = 0.135). Multivariate Cox regression showed ECOG PS (0–1 vs. 2–3 HR 0.09 [95% CI, 0.02–0.33]; p < 0.001) and cause of crizotinib treatment failure (resistance vs. intolerance HR 2.75 [95% CI, 1.26–5.99]; p = 0.011) were the independent predictors for the PFS of second-generation ALK inhibitors. Treatment of alectinib, compared to ceritinib, was associated with a lower incidence of CNS progression (cause-specific HR, 0.10; 95% CI 0.01–0.78; p = 0.029) and a higher efficacy in patients whose cause of crizotinib treatment failure was intolerance (HR 0.29 [95% CI, 0.08–1.06]; p = 0.050). The most commonly noted adverse events were elevated AST/ALT in 10 (23.3%) patients treated with alectinib and diarrhea in 8 (36.4%) patients treated with ceritinib.

Conclusion
Second-generation ALK inhibitors in crizotinib-treated patients showed a satifactory efficacy. Alectinib treatment demonstrated a CNS protection activity and a higher PFS in selected patients failing crizotinib treatment.
Protocol for implementation of an evidence based parentally administered intervention for preterm infants
Authors: White-Traut Rosemary , Brandon Debra , Kavanaugh Karen , Gralton Karen , Pan Wei , Myers Evan R. , Andrews Bree , Msall Michael , Norr Kathleen F. 
Published: March 2021

Abstract
Background
Multi-sensory behavioral interventions for preterm infants have the potential to accelerate feeding, growth, and optimize developmental trajectories and increase parents’ interactive engagement with their infants. However, few neonatal intensive care units (NICUs) provide evidence-based standardized early behavioral interventions as routine care. Lack of implementation is a major gap between research and clinical practice. H-HOPE, is a standardized behavioral intervention with an infant- directed component (Massage+) and a parent-directed component (four participatory guidance sessions that focus on preterm infants’ behaviors and appropriate responses). H-HOPE has well documented efficacy. The purpose of this implementation study is to establish H-HOPE as the standard of care in 5 NICUs.

Methods
The study employs a Type 3 Hybrid design to simultaneously examine the implementation process and effectiveness in five NICUs. To stagger implementation across the clinical sites, we use an incomplete stepped wedge design. The five participating NICUs were purposively selected to represent different acuity levels, number of beds, locations and populations served. Our implementation strategy integrates our experience conducting H-HOPE and a well-established implementation model, the Consolidated Framework for Implementation Research (CFIR). The CFIR identifies influences (facilitators and barriers) that affect successful implementation within five domains: intervention characteristics, outer setting (the hospital and external events and stakeholders), inner setting (NICU), implementers’ individual characteristics, and the implementation process. NICUs will use the CFIR process, which includes three phases: Planning and Engaging, Executing, and Reflecting and Evaluating. Because sustaining is a critical goal of implementation, we modify the CFIR implementation process by adding a final phase of Sustaining.

Discussion
This study builds on the CFIR, adding Sustaining H-HOPE to observe what happens when sites begin to maintain implementation without outside support, and extends its use to the NICU acute care setting. Our mixed methods analysis systematically identifies key facilitators and barriers of implementation success and effectiveness across the five domains of the CFIR. Long term benefits have not yet been studied but may include substantial health and developmental outcomes for infants, more optimal parent-child relationships, reduced stress and costs for families, and substantial indirect societal benefits including reduced health care and special education costs.

Trial registration
ClinicalTrials.gov registration number NCT04555590, Registered on 8/19/2020.
Prevalence of negative emotional eating and its associated psychosocial factors among urban Chinese undergraduates in Hong Kong: a cross-sectional study
Authors: Sze Katherine Y. P. , Lee Eric K. P. , Chan Rufina H. W. , Kim Jean H. 
Published: March 2021

Abstract
Background
Emotional eating (EE), defined as eating in response to a range of emotions, has been previously associated with poor diet and obesity. Since there are limited data from non-Western populations, this study aims to examine the prevalence and factors associated with EE among urban Chinese university students.

Methods
A cross-sectional study was conducted on 424 university students (aged 18–24 years) from two large universities in Hong Kong in 2019. Respondents completed an anonymous online questionnaire that contained background questions, an emotional eating subscale of the Dutch Eating Behaviour Questionnaire (DEBQ), and Depression Anxiety and Stress Scales (DASS-21). Two-sample independent t-test and multiple regression analyses were conducted to test the association of study variables with negative emotional eating.

Results
There was over a three-fold higher likelihood of negative EE among females (14.8%) when compared with their male counterparts (4.5%) (OR = 3.7, p < 0.05). Having at least mild depressive symptoms was the only independent factor associated with negative EE among males (OR = 10.1) while for females, negative EE was independently associated with not having a romantic partner (OR = 3.45), having depressive symptoms (OR = 44.5), and having at least mild stress (OR = 5.65). Anxiety levels were not independently associated with negative EE for either gender. Both male and female students with negative EE had significantly lower self-perceived health scores, higher body mass index, and lower life satisfaction scores.

Conclusions
This study revealed that negative EE is prevalent among female Chinese university students and not uncommon among male students. Management of negative EE should be included as a component of university mental health promotion programmes in the region.
Bottom-up innovation for health management capacity development: a qualitative case study in a South African health district
Authors: Orgill Marsha , Marchal Bruno , Shung-King Maylene , Sikuza Lwazikazi , Gilson Lucy 
Published: March 2021

AbstractBackgroundAs part of health system strengthening in South Africa (2012–2017) a new district health manager, taking a bottom-up approach, developed a suite of innovations to improve the processes of monthly district management team meetings, and the practices of managers and NGO partners attending them. Understanding capacity as a property of the health system rather than only of individuals, the research explored the mechanisms triggered in context to produce outputs, including the initial sensemaking by the district manager, the subsequent sensegiving and sensemaking in the team and how these homegrown innovations interacted with existing social processes and norms within the system.MethodsWe conducted a realist evaluation, adopting the case study design, over a two-year period (2013–2015) in the district of focus. The initial programme theory was developed from 10 senior manager interviews and a literature review. To understand the processes and mechanisms triggered in the local context and identify outputs, we conducted 15 interviews with managers in the management team and seven with non-state actors. These were supplemented by researcher notes based on time spent in the district. Thematic analysis was conducted using the Context-Mechanism-Outcome configuration alongside theoretical constructs.ResultsThe new district manager drew on systems thinking, tacit and experiential knowledge to design bottom-up innovations. Capacity was triggered through micro-practices of sensemaking and sensegiving which included using sticks (positional authority, enforcement of policies, over-coding), intentionally providing justifications for change and setting the scene (a new agenda, distributed leadership). These micro-practices in themselves, and by managers engaging with them, triggered a generative process of buy-in and motivation which influenced managers and partners to participate in new practices within a routine meeting.ConclusionDistrict managers are well placed to design local capacity development innovations and must draw on systems thinking, tacit and experiential knowledge to enable relevant ‘bottom-up’ capacity development in district health systems. By drawing on soft skills and the policy resources (hardware) of the system they can influence motivation and buy-in to improve management practices. From a systems perspective, we argue that capacity development can be conceived of as part of the daily activity of managing within routine spaces.
Time spent in prior hospital stay and outcomes for ventilator patients in long-term acute care hospitals
Authors: Demiralp Berna , Koenig Lane , Xu Jing , Soltoff Samuel , Votto John 
Published: March 2021

Abstract
Background
Long-term acute care hospitals (LTACHs) treat mechanical ventilator patients who are difficult to wean and expected to be on mechanical ventilator for a prolonged period. However, there are varying views on who should be transferred to LTACHs and when they should be transferred. The purpose of this study is to assess the relationship between length of stay in a short-term acute care hospital (STACH) after endotracheal intubation (time to LTACH) and weaning success and mortality for ventilated patients discharged to an LTACH.

Methods
Using 2014–2015 Medicare claims and assessment data, we identified patients who had an endotracheal intubation in STACH and transferred to an LTACH with prolonged mechanical ventilation (defined as 96 or more consecutive hours on a ventilator). We controlled for age, gender, STACH stay procedures and diagnoses, Elixhauser comorbid conditions, and LTACH quality characteristics. We used instrumental variable estimation to account for unobserved patient and provider characteristics.

Results
The study cohort included 13,622 LTACH cases with median time to LTACH of 18 days. The unadjusted ventilator weaning rate at LTACH was 51.7%, and unadjusted 90-day mortality rate was 43.7%. An additional day spent in STACH after intubation is associated with 11.6% reduction in the odds of weaning, representing a 2.5 percentage point reduction in weaning rate at 18 days post endotracheal intubation. We found no statistically significant relationship between time to LTACH and the odds of 90-day mortality.

Conclusions
Discharging ventilated patients earlier from STACH to LTACH is associated with higher weaning probability for LTACH patients on prolonged mechanical ventilation. Our findings suggest that delaying ventilated patients’ discharge to LTACH may negatively influence the patients’ chances of being weaned from the ventilator.