bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of therapeutic effects of crocin in attenuating the progression of diabetic nephropathy: a preliminary randomized triple-blind placebo-controlled trial
Authors: Jaafarinia Asma , Kafami Behzad , Sahebnasagh Adeleh , Saghafi Fatemeh 
Published: October 2022

Abstract
Background
Diabetic nephropathy (DN) is one of the most important complications of type 2 diabetes (T2DM). Oxidative stress and inflammatory cytokines play an essential role in the development and progression of DN. Despite adopting appropriate therapies, many patients with DN progress to end-stage renal disease (ESRD). Therefore, exploring innovative strategies for better management of DN is crucial. Crocin, a natural compound found in saffron, has profound antioxidant, antifibrotic and anti-inflammatory properties. This study aimed to evaluate the therapeutic effects of crocin in attenuation of the progression of DN.

Methods
In this randomized, triple-blind, placebo-controlled clinical trial, 44 patients with T2DM and microalbuminuria were randomly assigned to receive either crocin (15 mg/day) or a placebo for 90 days. Eventually, 40 patients completed the study: 21 patients in the crocin group and 19 in the placebo group. The primary outcome was a change in urine Albumin-to-Creatinine Ratio (uACR) from baseline to the end of the treatment period. We also evaluated metabolic, anthropometric, and biochemical parameters as the secondary outcomes.

Results
The results of the present study showed that uACR increased in both groups, but the increment was not significantly higher in the crocin group compared with the placebo. Serum levels of transforming growth factor-β (TGF-β) decreased in the crocin group and increased in the placebo group, but none of these changes was significant. Crocin significantly reduced triglyceride (TG) as an important metabolic parameter (P-Value = 0.03).

Conclusion
This study has shown that crocin may be a safe and potential adjunct to conventional therapies for DN patients but because of our limitations such as short duration of the treatment period, and prescribing low doses of crocin, we could not achieve the significant level.
Near-peers effectively teach clinical documentation skills to early medical students
Authors: Kusnoor Anita Vijay , Balchandani Rajeev , Pillow Malford Tyson , Sherman Stephanie , Ismail Nadia 
Published: October 2022

Abstract
Background
Composing the History of Present Illness (HPI), a key component of medical communication, requires critical thinking. Small group learning strategies have demonstrated superior effectiveness at developing critical thinking skills. Finding sufficient faculty facilitators for small groups remains a major gap in implementing these sessions. We hypothesized that “near-peer” teachers could effectively teach HPI documentation skills and fill the gap of small group facilitators. Here, we present a head-to-head comparison of near-peer and faculty teaching outcomes.

Methods
Second-year medical students in a single institution participated in an HPI Workshop as a clinical skills course requirement. Students were randomly assigned a near-peer or faculty facilitator for the workshop. We compared mean facilitator evaluation scores and performance assessments of students assigned to either type of facilitator.

Results
Three hundred sixty-five students, 29 residents (near-peers) and 16 faculty participated. On post-session evaluations (5-point Likert scale), students ranked near-peer facilitators higher than faculty facilitators on encouraging participation and achieving the goals of the session (residents 4.9, faculty 4.8), demonstrating small, statistically significant differences between groups. Mean scores on written assessments after the workshop did not differ between the groups (29.3/30 for a written H&P and 9/10 for an HPI exam question).

Conclusions
Near-peer facilitators were as effective as faculty facilitators for the HPI Workshop. Utilizing near-peers to teach HPI documentation skills provided teaching experiences for residents and increased the pool of available facilitators.
Understanding how and under what circumstances decision coaching works for people making healthcare decisions: a realist review
Authors: Zhao Junqiang , Jull Janet , Finderup Jeanette , Smith Maureen , Kienlin Simone Maria , Rahn Anne Christin , Dunn Sandra , Aoki Yumi , Brown Leanne , Harvey Gillian , Stacey Dawn 
Published: October 2022

Abstract
Background
Decision coaching is non-directive support delivered by a trained healthcare provider to help people prepare to actively participate in making healthcare decisions. This study aimed to understand how and under what circumstances decision coaching works for people making healthcare decisions.

Methods
We followed the realist review methodology for this study. This study was built on a Cochrane systematic review of the effectiveness of decision coaching interventions for people facing healthcare decisions. It involved six iterative steps: (1) develop the initial program theory; (2) search for evidence; (3) select, appraise, and prioritize studies; (4) extract and organize data; (5) synthesize evidence; and (6) consult stakeholders and draw conclusions.

Results
We developed an initial program theory based on decision coaching theories and stakeholder feedback. Of the 2594 citations screened, we prioritized 27 papers for synthesis based on their relevance rating. To refine the program theory, we identified 12 context-mechanism-outcome (CMO) configurations. Essential mechanisms for decision coaching to be initiated include decision coaches’, patients’, and clinicians’ commitments to patients’ involvement in decision making and decision coaches’ knowledge and skills (four CMOs). CMOs during decision coaching are related to the patient (i.e., willing to confide, perceiving their decisional needs are recognized, acquiring knowledge, feeling supported), and the patient-decision coach interaction (i.e., exchanging information, sharing a common understanding of patient’s values) (five CMOs). After decision coaching, the patient’s progress in making or implementing a values-based preferred decision can be facilitated by the decision coach’s advocacy for the patient, and the patient’s deliberation upon options (two CMOs). Leadership support enables decision coaches to have access to essential resources to fulfill their role (one CMOs).

Discussion
In the refined program theory, decision coaching works when there is strong leadership support and commitment from decision coaches, clinicians, and patients. Decision coaches need to be capable in coaching, encourage patients’ participation, build a trusting relationship with patients, and act as a liaison between patients and clinicians to facilitate patients’ progress in making or implementing an informed values-based preferred option. More empirical studies, especially qualitative and process evaluation studies, are needed to further refine the program theory.
Toward efficient and high-fidelity metagenomic data from sub-nanogram DNA: evaluation of library preparation and decontamination methods
Authors: Wang Chun , Zhang Li , Jiang Xuan , Ma Wentai , Geng Hui , Wang Xue , Li Mingkun 
Published: October 2022

AbstractBackgroundShotgun metagenomic sequencing has greatly expanded the understanding of microbial communities in various biological niches. However, it is still challenging to efficiently convert sub-nanogram DNA to high-quality metagenomic libraries and obtain high-fidelity data, hindering the exploration of niches with low microbial biomass.ResultsTo cope with this challenge comprehensively, we evaluated the performance of various library preparation methods on 0.5 pg–5 ng synthetic microbial community DNA, characterized contaminants, and further applied different in silico decontamination methods. First, we discovered that whole genome amplification prior to library construction led to worse outcomes than preparing libraries directly. Among different non-WGA-based library preparation methods, we found the endonuclease-based method being generally good for different amounts of template and the tagmentation-based method showing specific advantages with 0.5 pg template, based on evaluation metrics including fidelity, proportion of designated reads, and reproducibility. The load of contaminating DNA introduced by library preparation varied from 0.01 to 15.59 pg for different kits and accounted for 0.05 to 45.97% of total reads. A considerable fraction of the contaminating reads were mapped to human commensal and pathogenic microbes, thus potentially leading to erroneous conclusions in human microbiome studies. Furthermore, the best performing in silico decontamination method in our evaluation, Decontam-either, was capable of recovering the real microbial community from libraries where contaminants accounted for less than 10% of total reads, but not from libraries with heavy and highly varied contaminants.ConclusionsThis study demonstrates that high-quality metagenomic data can be obtained from samples with sub-nanogram microbial DNA by combining appropriate library preparation and in silico decontamination methods and provides a general reference for method selection for samples with varying microbial biomass.
Identification and functional analysis of variants of MYH6 gene promoter in isolated ventricular septal defects
Authors: Zuo Ji-Yang , Chen Huan-Xin , Liu Zhi-Gang , Yang Qin , He Guo-Wei 
Published: October 2022

Abstract
Background
Ventricular septal defect is the most common form of congenital heart diseases. MYH6 gene has a critical effect on the growth and development of the heart but the variants in the promoter of MYH6 is unknown.

Patients and methods
In 604 of the subjects (311 isolated and sporadic ventricular septal defect patients and 293 healthy controls), DNA was extracted from blood samples and MYH6 gene promoter region variants were analyzed by sequencing. Further functional verification was performed by cellular experiments using dual luciferase reporter gene analysis, electrophoretic mobility shift assays, and bioinformatics analysis.

Results
Nine variants were identified in the MYH6 gene promoter and two of those variants [g.4085G>C(rs1222539675) and g.4716G>A(rs377648095)] were only found in the ventricular septal defect patients. Cellular function experiments showed that these two variants reduced the transcriptional activity of the MYH6 gene promoter (p < 0.001). Further analysis with online JASPAR database suggests that these variants may alter a set of putative transcription factor binding sites that possibly lead to changes in myosin subunit expression and ventricular septal defect formation.

Conclusions
Our study for the first time identifies variants in the promoter region of the MYH6 gene in Chinese patients with isolated and sporadic ventricular septal defect. These variants significantly reduced MYH6 gene expression and affected transcription factor binding sites and therefore are pathogenic. The present study provides new insights in the role of the MYH6 gene promoter region to better understand the genetic basis of VSD formation.
Co-modulation of T cells and B cells enhances the inhibition of inflammation in experimental hypersensitivity pneumonitis
Authors: Courtemanche Olivier , Huppé Carole-Ann , Blais Lecours Pascale , Lerdu Ophélie , Roy Joanny , Lauzon-Joset Jean-François , Blanchet Marie-Renée , Morissette Mathieu C. , Marsolais David 
Published: October 2022

AbstractBackgroundHypersensitivity pneumonitis (HP) is an interstitial lung disease characterized by antigen-triggered neutrophilic exacerbations. Although CD4+T cells are sufficient for HP pathogenesis, this never translated into efficient T cell-specific therapies. Increasing evidence shows that B cells also play decisive roles in HP. Here, we aimed to further define the respective contributions of B and T cells in subacute experimental HP.MethodsMice were subjected to a protocol of subacute exposure to the archaeonMethanosphaera stadmanaeto induce experimental HP. Using models of adoptive transfers of B cells and T cells in Rag1-deficient mice and of B cell-specific S1P1deletion, we assessed the importance of B cells in the development of HP by evaluating inflammation in bronchoalveolar lavage fluid. We also aimed to determine if injected antibodies targeting B and/or T cells could alleviate HP exacerbations using a therapeutic course of intervention.ResultsEven though B cells are not sufficient to induce HP, they strongly potentiate CD4+T cell-induced HP‑associated neutrophilic inflammation in the airways. However, the reduction of 85% of lung B cells in mice with a CD19-driven S1P1deletion does not dampen HP inflammation, suggesting that lung B cells are not necessary in large numbers to sustain local inflammation. Finally, we found that injecting antibodies targeting B cells after experimental HP was induced does not dampen neutrophilic exacerbation. Yet, injection of antibodies directed against B cells and T cells yielded a potent 76% inhibition of neutrophilic accumulation in the lungs. This inhibition occurred despite partial, sometimes mild, depletion of B cells and T cells subsets.ConclusionsAlthough B cells are required for maximal inflammation in subacute experimental HP, partial reduction of B cells fails to reduce HP-associated inflammation by itself. However, co-modulation of T cells and B cells yields enhanced inhibition of HP exacerbation caused by an antigenic rechallenge.
Optical genome mapping identifies clinically relevant genomic rearrangements in prostate cancer biopsy sample
Authors: Shim Yeeun , Lee Jongsoo , Seo Jieun , Park Cheol Keun , Shin Saeam , Han Hyunho , Lee Seung-Tae , Choi Jong Rak , Chung Byung Ha , Choi Young Deuk 
Published: October 2022

Abstract
Background
Prostate cancer (PCa) is characterized by complex genomic rearrangements such as the ETS oncogene family fusions, yet the clinical relevance is not well established. While paneled genetic tests of DNA repair genes are recommended in advanced PCa, conventional genomic or cytogenetic tools are not ideal for genome-wide screening of structural variations (SVs) such as balanced translocation due to cost and/or resolution issues.

Methods
In this study, we tested the feasibility of whole-genome optical genomic mapping (OGM), a newly developed platform for genome-wide SV analysis to detect complex genomic rearrangements in consecutive unselected PCa samples from MRI/US-fusion targeted biopsy.

Results
We tested ten samples, and nine (90%) passed quality check. Average mapping rate and coverage depth were 58.1 ± 23.7% and 157.3 ± 97.7×, respectively (mean ± SD). OGM detected copy number alterations such as chr6q13 loss and chr8q12-24 gain. Two adjacent tumor samples were distinguished by inter/intra-chromosomal translocations, revealing that they’re from the same ancestor. Furthermore, OGM detected large deletion of chr13q13.1 accompanied by inter-chromosomal translocation t(13;20)(q13.1;p13) occurring within BRCA2 gene, suggesting complete loss of function.

Conclusion
In conclusion, clinically relevant genomic SVs were successfully detected in PCa samples by OGM. We suggest that OGM can complement panel sequencing of DNA repair genes BRCA1/2 or ATM in high-risk PCa.
An overview on nanoparticle-based strategies to fight viral infections with a focus on COVID-19
Authors: Yasamineh Saman , Kalajahi Hesam Ghafouri , Yasamineh Pooneh , Yazdani Yalda , Gholizadeh Omid , Tabatabaie Raheleh , Afkhami Hamed , Davodabadi Fatemeh , farkhad Alireza Khanalipour , Pahlevan Daryoush , Firouzi-Amandi Akram , Nejati-Koshki Kazem , Dadashpour Mehdi 
Published: October 2022

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to COVID-19 and has become a pandemic worldwide with mortality of millions. Nanotechnology can be used to deliver antiviral medicines or other types of viral reproduction-inhibiting medications. At various steps of viral infection, nanotechnology could suggest practical solutions for usage in the fight against viral infection. Nanotechnology-based approaches can help in the fight against SARS-CoV-2 infection. Nanoparticles can play an essential role in progressing SARS-CoV-2 treatment and vaccine production in efficacy and safety. Nanocarriers have increased the speed of vaccine development and the efficiency of vaccines. As a result, the increased investigation into nanoparticles as nano-delivery systems and nanotherapeutics in viral infection, and the development of new and effective methods are essential for inhibiting SARS-CoV-2 infection. In this article, we compare the attributes of several nanoparticles and evaluate their capability to create novel vaccines and treatment methods against different types of viral diseases, especially the SARS-CoV-2 disease.Graphical Abstract
Recent developments in the probiotics as live biotherapeutic products (LBPs) as modulators of gut brain axis related neurological conditions
Authors: Ağagündüz Duygu , Gençer Bingöl Feray , Çelik Elif , Cemali Özge , Özenir Çiler , Özoğul Fatih , Capasso Raffaele 
Published: October 2022

AbstractProbiotics have been defined as “living microorganisms that create health benefits in the host when taken in sufficient amounts. Recent developments in the understanding of the relationship between the microbiom and its host have shown evidence about the promising potential of probiotics to improve certain health problems. However, today, there are some confusions about traditional and new generation foods containing probiotics, naming and classifications of them in scientific studies and also their marketing. To clarify this confusion, the Food and Drug Administration (FDA) declared that it has made a new category definition called "live biotherapeutic products" (LBPs). Accordingly, the FDA has designated LBPs as “a biological product that: i)contains live organisms, such as bacteria; ii)is applicable to the prevention, treatment, or cure of a disease/condition of human beings; and iii) is not a vaccine”. The accumulated literature focused on LBPs to determine effective strains in health and disease, and often focused on obesity, diabetes, and certain diseases like inflammatory bowel disease (IBD).However, microbiome also play an important role in the pathogenesis of diseases that age day by day in the modern world via gut-brain axis. Herein, we discuss the novel roles of LBPs in some gut-brain axis related conditions in the light of recent studies. This article may be of interest to a broad readership including those interested in probiotics as LBPs, their health effects and safety, also gut-brain axis.
Inflammatory plasma proteins predict short-term mortality in patients with an acute myocardial infarction
Authors: Schmitz T. , Harmel E. , Heier M. , Peters A. , Linseisen J. , Meisinger C. 
Published: October 2022

Abstract
Background
The aim of this study was to investigate the association between inflammatory markers and 28-day mortality in patients with ST-elevation myocardial infarction (STEMI).

Methods
In 398 STEMI patients recorded between 2009 and 2013 by the population-based Myocardial Infarction Registry Augsburg, 92 protein biomarkers were measured in admission arterial blood samples using the OLINK inflammatory panel. In multivariable-adjusted logistic regression models, the association between each marker and 28-day mortality was investigated. The values of the biomarkers most significantly associated with mortality were standardized and summarized to obtain a prediction score for 28-day mortality. The predictive ability of this biomarker score was compared to the established GRACE score using ROC analysis. Finally, a combined total score was generated by adding the standardized biomarker score to the standardized GRACE score.

Results
The markers IL-6, IL-8, IL-10, FGF-21, FGF-23, ST1A1, MCP-1, 4E-BP1, and CST5 were most significantly associated with 28-day mortality, each with FDR-adjusted (false discovery rate adjusted) p-values of < 0.01 in the multivariable logistic regression model. In a ROC analysis, the biomarker score and the GRACE score showed comparable predictive ability for 28-day mortality (biomarker score AUC: 0.7859 [CI: 0.6735–0.89], GRACE score AUC: 0.7961 [CI: 0.6965–0.8802]). By combining the biomarker score and the Grace score, the predictive ability improved with an AUC of 0.8305 [CI: 0.7269–0.9187]. A continuous Net Reclassification Improvement (cNRI) of 0.566 (CI: 0.192–0.94, p-value: 0.003) and an Integrated Discrimination Improvement (IDI) of 0.083 ((CI: 0.016–0.149, p-value: 0.015) confirmed the superiority of the combined score over the GARCE score.

Conclusions
Inflammatory biomarkers may play a significant role in the pathophysiology of acute myocardial infarction (AMI) and AMI-related mortality and might be a promising starting point for personalized medicine, which aims to provide each patient with tailored therapy.
Alpha-ketoglutarate ameliorates abdominal aortic aneurysm via inhibiting PXDN/HOCL/ERK signaling pathways
Authors: Liu Junjun , Liu Mingyuan , Feng Jiaxuan , Zhu Hongqiao , Wu Jianlie , Zhang Heng , Xiao Shun , Jing Zaiping , Zhou Jian , Niu Haitao , Guo Mingjin 
Published: October 2022

AbstractAbdominal aortic aneurysm (AAA) represents the serious vascular degenerative disorder, which causes high incidence and mortality. Alpha-ketoglutarate (AKG), a crucial metabolite in the tricarboxylic acid (TCA) cycle, has been reported to exert significant actions on the oxidative stress and inflammation. However, its role in AAA still remains elusive. Herein, we examined the effects of AKG on the formation of AAA. The study established an elastase-induced mouse abdominal aortic aneurysms model as well as a TNF-α-mediated vascular smooth muscle cells (VSMCs) model, respectively. We displayed that AKG pre-treatment remarkably prevented aneurysmal dilation assessed by diameter and volume and reduced aortic rupture. In addition, it was also observed that AKG treatment suppressed the development of AAA by attenuating the macrophage infiltration, elastin degradation and collagen fibers remodeling. In vitro, AKG potently decreased TNF-α-induced inflammatory cytokines overproduction, more apoptotic cells and excessive superoxide. Mechanistically, we discovered that upregulation of vpo1 in AAA was significantly suppressed by AKG treatment. By exploring the RNA-seq data, we found that AKG ameliorates AAA mostly though inhibiting oxidative stress and the inflammatory response. PXDN overexpression neutralized the inhibitory effects of AKG on ROS generation and inflammatory reaction in MOVAS. Furthermore, AKG treatment suppressed the expression of p-ERK1/2, 3-Cl Tyr in vivo and in vitro. ERK activator disrupted the protective of AKG on TNF-α-induced VSMCs phenotypic switch. Conclusively, AKG can serve as a beneficial therapy for AAA through regulating PXDN/HOCL/ERK signaling pathways.