bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does zinc with and without iron co-supplementation have effect on motor and mental development of children? A systematic review and meta-analysis
Authors: Sajedi Firoozeh , Shahshahani Soheila , Ghiasvand Hesam , Mosallanezhad Zahra , Fatollahierad Shiva 
Published: September 2020

AbstractBackgroundEffects of zinc with and without iron co-supplementation on child development are uncertain therefore the aims of this systematic review were to explore whether supplementation with zinc alone and zinc with iron in children aged 0–5 years old have beneficial or adverse effects on their mental and motor development.MethodWe searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL, Web of Science and Scopus until July 2020 and included randomized controlled trials, which assessed effects of zinc supplementation with and without iron in children less than 5 years old on mental and motor development. Data were pooled by random effects model and the Standardized Mean Differences (SMDs) with 95% confidence interval were estimated. The heterogeneity was assessed by I2.ResultsTwenty-five studies with 11,559 participants were eligible to be included in this systematic review. Meta-analysis was conducted with eight articles that used Bayley Scales of Infant and Toddler Development II. We concluded that zinc alone and zinc with iron co-supplementation do not have beneficial or adverse effect on child mental and motor development at 6 and 12 months of age with low to moderate quality of the evidence. Furthermore, Zinc supplementation does not have any long term effect on child development in preschool and school age children.ConclusionMost included studies did not show the efficacy of zinc with and without iron co-supplementation on child mental and motor development up to 9 years old age. Further Randomized Controlled Trials (RCTs) need to be taken into considerations the context-based differences between countries with special focus on socio-economic differences.
Herbal pair Huangqin-Baishao: mechanisms underlying inflammatory bowel disease by combined system pharmacology and cell experiment approach
Authors: Huang Xiaoqi , Chen Zhiwei , Li Minyao , Zhang Yaomin , Xu Shijie , Huang Haiyang , Wu Xiaoli , Zheng Xuebao 
Published: September 2020

AbstractBackgroundInflammatory bowel disease (IBD) is a severe digestive system condition, characterized by chronic and relapsing inflammation of the gastrointestinal tract. Scutellaria baicalensis Georgi (Huangqin, HQ) andPaeonia lactifloraPall (Baishao, BS) from a typical herbal synergic pair in traditional Chinese medicine (TCM) for IBD treatments. However, the mechanisms of action for the synergy are still unclear. Therefore, this paper aimed to predict the anti-IBD targets and the main active ingredients of the HQ-BS herbal pair.MethodsA systems pharmacology approach was used to identify the bioactive compounds and to delineate the molecular targets and potential pathways of HQ-BS herbal pair. Then, the characteristics of the candidates were analyzed according to their oral bioavailability and drug-likeness indices. Finally, gene enrichment analysis with DAVID Bioinformatics Resources was performed to identify the potential pathways associated with the candidate targets.ResultsThe results showed that, a total of 38 active compounds were obtained from HQ-BS herbal pair, and 54 targets associated with IBD were identified. Gene Ontology and pathway enrichment analysis yielded the top 20 significant results with 54 targets. Furthermore, the integrated IBD pathway revealed that the HQ-BS herbal pair probably acted in patients with IBD through multiple mechanisms of regulation of the nitric oxide biosynthetic process and anti-inflammatory effects. In addition, cell experiments were carried out to verify that the HQ-BS herbal pair and their Q-markers could attenuate the levels of nitric oxide (NO), prostaglandin E2(PGE2), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated THP-1-derived macrophage inflammation. In particular, the crude materials exerted a much better anti-inflammatory effect than their Q-markers, which might be due to their synergistic effect.ConclusionThis study provides novel insight into the molecular pathways involved in the mechanisms of the HQ-BS herbal pair acting on IBD.
Effective accreditation in postgraduate medical education: from process to outcomes and back
Authors: Bandiera Glen , Frank Jason , Scheele Fedde , Karpinski Jolanta , Philibert Ingrid 
Published: September 2020

Abstract
Background
The accreditation of medical educational programs is thought to be important in supporting program improvement, ensuring the quality of the education, and promoting diversity, equity, and population health. It has long been recognized that accreditation systems will need to shift their focus from processes to outcomes, particularly those related to the end goals of medical education: the creation of broadly competent, confident professionals and the improvement of health for individuals and populations. An international group of experts in accreditation convened in 2013 to discuss this shift.

Main text
Participants unequivocally supported the inclusion of more outcomes-based criteria in medical education accreditation, specifically those related to the societal accountability of the institutions in which the education occurs. Meaningful and feasible outcome metrics, however, are hard to identify. They are regionally variable, often temporally remote from the educational program, difficult to measure, and susceptible to confounding factors. The group identified the importance of health outcomes of the clinical milieu in which education takes place in influencing outcomes of its graduates. The ability to link clinical data with individual practice over time is becoming feasible with large repositories of assessment data linked to patient outcomes. This was seen as a key opportunity to provide more continuous oversight and monitoring of program impact. The discussants identified several risks that might arise should outcomes measures completely replace process issues. Some outcomes can be measured only by proxy process elements, and some learner experience issues may best be measured by such process elements: in brief, the “how” still matters.

Conclusions
Accrediting bodies are beginning to view the use of practice outcome measures as an important step toward better continuous educational quality improvement. The use of outcomes will present challenges in data collection, aggregation, and interpretation. Large datasets that capture clinical outcomes, experience of care, and health system performance may enable the assessment of multiple dimensions of program quality, assure the public that the social contract is being upheld, and allow identification of exemplary programs such that all may improve. There remains a need to retain some focus on process, particularly those related to the learner experience.
The trace aminergic system: a gender-sensitive therapeutic target for IBS?
Authors: Pretorius Lesha , Smith Carine 
Published: September 2020

AbstractDue to a lack of specific or sensitive biomarkers, drug discovery advances have been limited for individuals suffering from irritable bowel syndrome (IBS). While current therapies provide symptomatic relief, inflammation itself is relatively neglected, despite the presence of chronic immune activation and innate immune system dysfunction. Moreover, considering the microgenderome concept, gender is a significant aetiological risk factor. We believe that we have pinpointed a “missing link” that connects gender, dysbiosis, diet, and inflammation in the context of IBS, which may be manipulated as therapeutic target. The trace aminergic system is conveniently positioned at the interface of the gut microbiome, dietary nutrients and by-products, and mucosal immunity. Almost all leukocyte populations express trace amine associated receptors and significant amounts of trace amines originate from both food and the gut microbiota. Additionally, although IBS-specific data are sparse, existing data supports an interpretation in favour of a gender dependence in trace aminergic signalling. As such, trace aminergic signalling may be altered by fluctuations of especially female reproductive hormones. Utilizing a multidisciplinary approach, this review discusses potential mechanisms of actions, which include hyperreactivity of the immune system and aberrant serotonin signalling, and links outcomes to the symptomology clinically prevalent in IBS. Taken together, it is feasible that the additional level of regulation by the trace aminergic system in IBS has been overlooked, until now. As such, we suggest that components of the trace aminergic system be considered targets for future therapeutic action, with the specific focus of reducing oxidative stress and inflammation.
Habitual dietary intake of flavonoids and all-cause and cause-specific mortality: Golestan cohort study
Authors: Hejazi Jalal , Ghanavati Matin , Hejazi Ehsan , Poustchi Hossein , Sepanlou Sadaf G. , Khoshnia Masoud , Gharavi Abdolsamad , Sohrabpour Amir Ali , Sotoudeh Masoud , Dawsey Sanford M. , Boffetta Paolo , Abnet Christian C. , Kamangar Farin , Etemadi Arash , Pourshams Akram , FazeltabarMalekshah Akbar , Brennan Paul , Malekzadeh Reza , Hekmatdoost Azita 
Published: September 2020

Abstract
Background and objectives
Flavonoids are the most important group of polyphenols with well-known beneficial effects on health. However; the association of intake of total flavonoid or their subclasses with all-cause or cause-specific mortality is not fully understood. The present study aims to evaluate the association between intake of total flavonoid, flavonoid subclasses, and total and cause-specific mortality in a developing country.

Methods
A total number of 49,173 participants from the Golestan cohort study, who completed a validated food frequency questionnaire at recruitment, were followed from 2004 till 2018. Phenol-Explorer database was applied to estimate dietary intakes of total flavonoid and different flavonoid subclasses. Associations were examined using adjusted Cox proportional hazards models.

Results
During a mean follow-up of 10.63 years, 5104 deaths were reported. After adjusting for several potential confounders, the hazard ratios (HRs) of all-cause mortality for the highest versus the lowest quintile of dietary flavanones, flavones, isoflavonoids, and dihydrochalcones were 0.81 (95% confidence interval = 0.73–0.89), 0.83(0.76–0.92), 0.88(0.80–0.96) and 0.83(0.77–0.90), respectively. However, there was no association between total flavonoid intake or other flavonoid subclasses with all-cause mortality. In cause-specific mortality analyses, flavanones and flavones intakes were inversely associated with CVD mortality [HRs: 0.86(0.73–1.00) and 0.85(0.72–1.00)] and isoflavonoids and dihydrochalcones were the only flavonoid subclasses that showed a protective association against cancer mortality [HR: 0.82(0.68–0.98)].

Conclusion
The results of our study suggest that certain subclasses of flavonoids can reduce all-cause mortality and mortality rate from CVD and cancer.
Expression of angiopoietin-like protein 2 in ovarian tissue of rat polycystic ovarian syndrome model and its correlation study
Authors: Wang Dandan , Guo Yihong , Chai Shujuan , Shen Ke , Li Yanchun , Zhao Ruiqin 
Published: September 2020

Abstract
Background
This study investigated the expression of angiopoietin-like protein 2 (ANGPTL2) in the tissues of rat models of polycystic ovary syndrome (PCOS) and its correlation with PCOS.

Methods
Six-weeks-old female specific pathogen-free rats (n = 60) were divided into blank control, PCOS model, and metformin groups (n = 20/group). After 21 days of metformin intervention, the serum sex hormones, fasting blood glucose, fasting insulin, and insulin resistance (IR) of rats in each group were measured. The mRNA levels of ANGPTL2, Foxol, and Akt in the ovarian tissues were monitored by real-time fluorescence quantitative PCR.

Results
Compared with the control group, the levels of serum sex hormones, fasting blood glucose, fasting insulin, and IR in the model group showed significant increases, and the levels of ANGPTL2, Foxol, and Akt in the ovarian tissue also showed significant increases. Compared with the PCOS group, the serum sex hormones, fasting blood glucose, fasting insulin, and IR of rats in the metformin group were significantly decreased, and the levels of ANGPTL2, Foxol, and Akt in ovarian tissues also showed significant decreases.

Conclusions
These findings suggest that ANGPTL2 might participate in the development of PCOS through the PI3K/Akt signaling pathway. Metformin improves IR by reducing the expression of ANGPTL2, thus improving the endocrine environment of PCOS and might change the disease outcome.
Tissue-specific usage of transposable element-derived promoters in mouse development
Authors: Miao Benpeng , Fu Shuhua , Lyu Cheng , Gontarz Paul , Wang Ting , Zhang Bo 
Published: September 2020

Abstract
Background
Transposable elements (TEs) are a significant component of eukaryotic genomes and play essential roles in genome evolution. Mounting evidence indicates that TEs are highly transcribed in early embryo development and contribute to distinct biological functions and tissue morphology.

Results
We examine the epigenetic dynamics of mouse TEs during the development of five tissues: intestine, liver, lung, stomach, and kidney. We found that TEs are associated with over 20% of open chromatin regions during development. Close to half of these accessible TEs are only activated in a single tissue and a specific developmental stage. Most accessible TEs are rodent-specific. Across these five tissues, 453 accessible TEs are found to create the transcription start sites of downstream genes in mouse, including 117 protein-coding genes and 144 lincRNA genes, 93.7% of which are mouse-specific. Species-specific TE-derived transcription start sites are found to drive the expression of tissue-specific genes and change their tissue-specific expression patterns during evolution.

Conclusion
Our results suggest that TE insertions increase the regulatory potential of the genome, and some TEs have been domesticated to become a crucial component of gene and regulate tissue-specific expression during mouse tissue development.
Identification of new driver and passenger mutations within APOBEC-induced hotspot mutations in bladder cancer
Authors: Shi Ming-Jun , Meng Xiang-Yu , Fontugne Jacqueline , Chen Chun-Long , Radvanyi François , Bernard-Pierrot Isabelle 
Published: September 2020

AbstractBackgroundAPOBEC-driven mutagenesis and functional positive selection of mutated genes may synergistically drive the higher frequency of some hotspot driver mutations compared to other mutations within the same gene, as we reported forFGFR3S249C. Only a few APOBEC-associated driver hotspot mutations have been identified in bladder cancer (BCa). Here, we systematically looked for and characterised APOBEC-associated hotspots in BCa.MethodsWe analysed 602 published exome-sequenced BCas, for part of which gene expression data were also available. APOBEC-associated hotspots were identified by motif-mapping, mutation signature fitting and APOBEC-mediated mutagenesis comparison. Joint analysis of DNA hairpin stability and gene expression was performed to predict driver or passenger hotspots. Aryl hydrocarbon receptor (AhR) activity was calculated based on its target genes expression. Effects of AhR knockout/inhibition on BCa cell viability were analysed.ResultsWe established a panel of 44 APOBEC-associated hotspot mutations in BCa, which accounted for about half of the hotspot mutations. Fourteen of them overlapped with the hotspots found in other cancer types with high APOBEC activity. They mostly occurred in the DNA lagging-strand templates and the loop of DNA hairpins. APOBEC-associated hotspots presented systematically a higher prevalence than the other mutations within each APOBEC-target gene, independently of their functional impact. A combined analysis of DNA loop stability and gene expression allowed to distinguish known passenger from known driver hotspot mutations in BCa, including loss-of-function mutations affecting tumour suppressor genes, and to predict new candidate drivers, such asAHRQ383H. We further characterisedAHRQ383H as an activating driver mutation associated with high AhR activity in luminal tumours. High AhR activity was also found in tumours presenting amplifications ofAHRand its co-receptorARNT. We finally showed that BCa cells presenting those different genetic alterations were sensitive to AhR inhibition.ConclusionsOur study identified novel potential drivers within APOBEC-associated hotspot mutations in BCa reinforcing the importance of APOBEC mutagenesis in BCa. It could allow a better understanding of BCa biology and aetiology and have clinical implications such as AhR as a potential therapeutic target. Our results also challenge the dogma that all hotspot mutations are drivers and mostly gain-of-function mutations affecting oncogenes.
Understanding the impact of antibiotic perturbation on the human microbiome
Authors: Schwartz Drew J. , Langdon Amy E. , Dantas Gautam 
Published: September 2020

AbstractThe human gut microbiome is a dynamic collection of bacteria, archaea, fungi, and viruses that performs essential functions for immune development, pathogen colonization resistance, and food metabolism. Perturbation of the gut microbiome’s ecological balance, commonly by antibiotics, can cause and exacerbate diseases. To predict and successfully rescue such perturbations, first, we must understand the underlying taxonomic and functional dynamics of the microbiome as it changes throughout infancy, childhood, and adulthood. We offer an overview of the healthy gut bacterial architecture over these life stages and comment on vulnerability to short and long courses of antibiotics. Second, the resilience of the microbiome after antibiotic perturbation depends on key characteristics, such as the nature, timing, duration, and spectrum of a course of antibiotics, as well as microbiome modulatory factors such as age, travel, underlying illness, antibiotic resistance pattern, and diet. In this review, we discuss acute and chronic antibiotic perturbations to the microbiome and resistome in the context of microbiome stability and dynamics. We specifically discuss key taxonomic and resistance gene changes that accompany antibiotic treatment of neonates, children, and adults. Restoration of a healthy gut microbial ecosystem after routine antibiotics will require rationally managed exposure to specific antibiotics and microbes. To that end, we review the use of fecal microbiota transplantation and probiotics to direct recolonization of the gut ecosystem. We conclude with our perspectives on how best to assess, predict, and aid recovery of the microbiome after antibiotic perturbation.
From invention to industry from a social movement perspective: the emergence of the 3D printing industry
Authors: Lechner Christian , Pervaiz Abeer 
Published: September 2020

AbstractIn the entrepreneurship literature, the phenomenon of industry emergence has been largely investigated from an institutional perspective. Appropriate institutions would allow then a group of individual entrepreneurs (“the heroes”) to create an industry through innovative ventures. New ventures create new industries and firm entry, survival, and exit drive industry evolution. Our research, however, explores what creates the favorable set of circumstances for new ventures to emerge and focuses on the pre-emergence phase and we propose that the patterns of emergence resemble those of social movements. Through an actor perspective, this research highlights the existence of diverse actors, not necessarily entrepreneurs, who are necessary to trigger a collective action during the pre-emergence phase of industries. This research is also distinct from entrepreneurial ecosystems as its development already requires some successful entrepreneurial action. The 3D printing industry was chosen as a single longitudinal case study, where the actors are the embedded units of analysis. The findings of the study lead to the identification of three aggregate dimensions—“Social Movement Composition,” Temporal Engagement,” and “Coalitions Development”—that were prevalent during the pre-emergence phase of the 3D printing industry. Our propositions emphasize the importance of large collective action and the role of multiple actors in order to create the conditions for, first, firm emergence and, the second, to the process of industry emergence.
FibroBox: a novel noninvasive tool for predicting significant liver fibrosis and cirrhosis in HBV infected patients
Authors: Lu Xiao-Jie , Yang Xiao-Jun , Sun Jing-Yu , Zhang Xin , Yuan Zhao-Xin , Li Xiu-Hui 
Published: September 2020

Abstract
Background
China is a highly endemic area of chronic hepatitis B (CHB). The accuracy of existed noninvasive biomarkers including TE, APRI and FIB-4 for staging fibrosis is not high enough in Chinese cohort.

Methods
Using liver biopsy as a gold standard, a novel noninvasive indicator was developed using laboratory tests, ultrasound measurements and liver stiffness measurements with machine learning techniques to predict significant fibrosis and cirrhosis in CHB patients in north and east part of China. We retrospectively evaluated the diagnostic performance of the novel indicator named FibroBox, Fibroscan, aspartate transaminase-to-platelet ratio index (APRI), and fibrosis-4 index (FIB-4) in CHB patients from Jilin and Huai’an (training sets) and also in Anhui and Beijing cohorts (validation sets).

Results
Of 1289 eligible HBV patients who had liver histological data, 63.2% had significant fibrosis and 22.5% had cirrhosis. In LASSO logistic regression and filter methods, fibroscan results, platelet count, alanine transaminase (ALT), prothrombin time (PT), type III procollagen aminoterminal peptide (PIIINP), type IV collagen, laminin, hyaluronic acid (HA) and diameter of spleen vein were finally selected as input variables in FibroBox. Consequently, FibroBox was developed of which the area under the receiver operating characteristic curve (AUROC) was significantly higher than that of TE, APRI and FIB-4 to predicting significant fibrosis and cirrhosis. In the Anhui and Beijing cohort, the AUROC of FibroBox was 0.88 (95% CI, 0.72–0.82) and 0.87 (95% CI, 0.83–0.91) for significant fibrosis and 0.87 (95% CI, 0.82–0.92) and 0.90 (95% CI, 0.85–0.94) for cirrhosis. In the validation cohorts, FibroBox accurately diagnosed 81% of significant fibrosis and 84% of cirrhosis.

Conclusions
FibroBox has a better performance in predicting liver fibrosis in Chinese cohorts with CHB, which may serve as a feasible alternative to liver biopsy.