bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promotion of ubiquitination-dependent survivin destruction contributes to xanthohumol-mediated tumor suppression and overcomes radioresistance in human oral squamous cell carcinoma
Authors: li ming , gao feng , yu xinfang , zhao qiung , zhou li , liu wenbin , li wei 
Published: May 2020

Abstract
Background: Overexpression of survivin plays a crucial role in tumorigenesis and correlates with poor prognosis in human malignancies. Thus, survivin has been proposed as an attractive target for new anti-tumor interventions. Methods: A natural product library was used for natural compound screening through MTS assay. The expression of survivin in oral squamous cell carcinoma (OSCC) and the inhibitory effect of xanthohumol (XN) on OSCC were examined by anchorage-dependent and -independent growth assays, immunoblot, immunofluorescence, immunohistochemical staining, ubiquitination analysis, co-immunoprecipitation assay, CRISPR-Cas9-based gene knockout, and xenograft experiment. Results: Survivin is highly expressed in OSCC patient-derived tissues and cell lines. Knockout of survivin reduced the tumorigenic properties of OSCC cells in vitro and in vivo . With a natural compound screening, we identified that xanthohumol inhibited OSCC cells by reducing survivin protein level and activating mitochondrial apoptotic signaling. Xanthohumol inhibited the Akt-Wee1-CDK1 signaling, which in turn decreased survivin phosphorylation on Thr34, and facilitated E3 ligase Fbxl7-mediated survivin ubiquitination and degradation. Xanthohumol alone or in combination with radiation overcame radioresistance in OSCC xenograft tumors. Conclusion: Our findings indicate that targeting survivin for degradation might a promising strategy for OSCC treatment.
Effects of reflection and immediate feedback to improve clinical reasoning of medical students in the assessment of dermatologic conditions: A randomised controlled trial
Authors: Choi Sungjun , Oh Sohee , Lee Dong-Hun , Yoon Hyun-Sun 
Published: May 2020

Abstract
BACKGROUND: There are few studies that directly compared different interventions to improve medical students’ clinical reasoning for dermatologic conditions. OBJECTIVE: To investigate the effectiveness of adding practice with reflection and immediate feedback on traditional dermatology electives in improving medical students' ability in evaluating skin lesions. METHODS: The participants were fourth-year medical students of Seoul National University College of Medicine, Korea, who were enrolled to take a 2-week dermatology elective course (n=87). Students were assigned to one of the three educational interventions: 2-hour training involving 10 written clinical cases (experimental); 1-hour lecture and 1-hour outpatient clinic (lecture); and 2-hour outpatient clinic (no intervention). Before and at the end of rotation, diagnostic accuracy was estimated using 20 written clinical cases with photographs (10 novel cases presented in diagnostic training [training set], 10 cases with diagnoses not included in training [control set]). RESULTS: There was a significant interaction effect of intervention×set×time. A post hoc analysis indicated that the students in the experimental group outperformed students in the other two groups only in the training set of the final tests; after completing the 2-week rotation, for the training set, the mean score was higher in the experimental group (7.5±1.3) than in the lecture (5.7±1.6) and no intervention (5.6±1.3) groups, producing an effect size of 1.2 standard deviation (SD) and 1.5 SD, respectively. CONCLUSION: Practicing written clinical cases with reflection and feedback is superior to a lecture-based approach and yields additional benefits to a dermatology elective, thereby enhancing medical students’ ability to accurately diagnose skin lesions. Trial registration: ClinicalTrials.gov, NCT03472001. Registered 21 March 2018, https://clinicaltrials.gov/ct2/show/NCT03472001
Left Atrial Strain and Diastolic Function Abnormalities in Obese and Type 2 Diabetic Adolescents and Young Adults.
Authors: Steele Jeremy Mark , Urbina Elaine M , Mazur Wojciech M , Khoury Philip R , Nagueh Sherif F , Tretter Justin T , Alsaied Tarek 
Published: May 2020

Abstract
Background
Adults with obesity and type 2 diabetes mellitus (T2DM) related to obesity are at increased risk of heart failure with preserved ejection fraction (HFpEF). Whether left ventricular (LV) diastolic function abnormalities related to obesity and T2DM start in adolescence and early adulthood is unknown. We non-invasively evaluated the differences seen in LV diastolic and left atrial (LA) function in adolescents and young adults with obesity and T2DM.
Methods
We analyzed echocardiographic measures of LV diastolic function in patients with structurally normal hearts which were divided into 3 groups (normal weight, obese, and T2DM). Spectral and tissue Doppler and 2-D speckle tracking measurements of diastolic function were obtained. Logistic regression was performed to compare the prevalence of abnormalities in diastolic function based on the worst 25th percentile for each measure to determine the prevalence of diastolic and LA function abnormalities in obese and T2DM patients.
Results
331 teenagers and young adults (median age 22.1 years) were analyzed (101 normal weight, 114 obese, 116 T2DM). Obese and T2DM group had lower E/A and higher E/e’. Obese and T2DM patients had significantly lower atrial reservoir, conduit, and booster strain and worse reservoir and conduit strain rate compared to normal patients (p < 0.001 for all measures). All patients had normal LA volumes. On multivariable analysis, conduit strain and reservoir and conduit strain rate were independently associated with having below the 25th percentile e’. Conduit strain rate was independently associated with having below the 25th percentile for mitral E/A ratio on multivariable analysis.
Conclusions
Abnormal indices of LV diastolic function are detected in adolescents and young adults with obesity and T2DM. LA function and strain analysis were able to detect evidence of decreased reservoir, conduit, and booster strain in these patients although LA volume was normal. The use of LA function strain may increase our ability to detect early diastolic function abnormalities in this population.
Occurrence and predictive risk factors associated with in-stent restenosis after drug-eluting stent implantation in diabetic patients: a prospective, clinical cohort study
Authors: Zhao ShengGang , Xu Jian-Jiang , Jiang Li-Qin , Chu Zhen-Liang , Tao An-Qian , Jin Lei , Han Ji-Bo , Zhang Bin , Zheng Zhan-Xiong , Shi Feng-Jie , Zhang Ran , Zhang Xiang-Yu , Jiang Fen-Fen , Han Bing-Jiang 
Published: May 2020

Abstract
Background

The incidence of in-stent restenosis (ISR) in patients with diabetes mellitus (DM) after percutaneous coronary intervention (PCI) is significantly higher than that in patients without DM, but the mechanism is not clear. We hypothesised that patients with and risk factors including dyslipidaemia, elevated inflammatory factors would be prone to induction of ISR, and that dynamic observation of the comprehensive risk factor changes before and after PCI would be helpful to identify ISR .
Methods

This prospective cohort study consecutively enrolled 360 patients who received coronary drug-eluting stent implantation. Patients who underwent coronary angiography (CAG) and received clinical follow-up were prospectively reviewed. The patients were assigned to a DM (262) or a non-DM (98) group. The patients were further assigned according to whether ISR was present to the non-DM + non-ISR, non-DM + ISR, DM + non-ISR, and DM + ISR groups. The patients were further assigned according to whether low-density lipoprotein (LDL-c) was decreased more than 50% compared with baseline, or was less than 1.80 mmol/L in the follow-up, to the LDL-c achieved or the LDL-c failure groups.
Results

DM patients were prone to develop ISR after PCI and the degree of coronary stenosis was more severe than in non-DM patients. This result was more striking in DM and LDL-c failure patients. The levels of total cholesterol (TC), triglyceride, high-density lipoprotein (HDL-c), LDL-c, apolipoprotein B100, apolipoprotein E, remnant lipoprotein, TC/HDL-c ratio and triglyceride/HDL-c ratio in the DM + non-ISR were similar to those in the DM + ISR group before PCI and CAG. .The DM + ISR group had the highest levels of haemoglobin A1c and the highest Gensini scores. The inflammatory index changes including leukocytes and neutrophils were the most striking in the DM + ISR group. In multivariate regression analysis, neutrophil changes and glycosylated haemoglobin were independent risk factors for ISR [△neutrophil, OR 1.929,95% CI 1.216–3.058; HbA1-c OR 1.559,95% CI 1.001–1.707].
Conclusion

Coronary artery disease patients with DM had a high risk for ISR if they had preoperative risk factors including dyslipidaemia, elevated inflammatory factors, and a high Gensini score. Dynamic observation of the changes of the preoperative and postoperative comprehensive risk factors was helpful to identify ISR in patients with DM.
Antimicrobial Activity Screening of Rhizosphere Soil Bacteria from Tomato and Genome-Based Analysis of their Antimicrobial Biosynthetic Potential
Authors: Zhou Lu , Song Chunxu , Li Zhibo , Kuipers Oscar P. 
Published: May 2020

Abstract
Background: Tomato plant growth is frequently hampered by a high susceptibility to pests and diseases. Traditional chemical control causes a serious impact on both the environment and human health. Therefore, seeking environment-friendly and cost-effective green methods in agricultural production becomes crucial nowadays. Plant Growth Promoting Rhizobacteria (PGPR) can promote plant growth through biological activity. Their use is considered to be a promising sustainable approach for crop growth. Moreover, a vast number of biosynthetic gene clusters (BGCs) for secondary metabolite production are being revealed in PGPR, which helps to find potential anti-microbial activities for tomato disease control.Results: We isolated 351 bacterial strains (181 of which are Bacillus sp.) from healthy tomato, rhizosphere soil, and tomato tissues. In vitro antagonistic assays revealed that 34 Bacillus strains have antimicrobial activity against Erwinia carotovora, Pseudomonas syringae; Rhizoctonia solani; Botrytis cinerea; Verticillium dahliae and Phytophthora infestans. The genomes of 10 Bacillus and Paenibacillus strains with good antagonistic activity were sequenced. Via genome mining approaches, we identified 120 BGCs encoding NRPs, PKs-NRPs, PKs, terpenes and bacteriocins, including known compounds such as fengycin, surfactin, bacillibactin, subtilin, etc. In addition, several novel BGCs were identified. We discovered that the NRPs and PKs-NRPs BGCs in Bacillus species are encoding highly conserved known compounds as well as various novel variants.Conclusions: This study highlights the great number of varieties of BGCs in Bacillus strains. These findings pave the road for future usage of Bacillus strains as biocontrol agents for tomato disease control and are a resource arsenal for novel antimicrobial discovery.
BMP4 Signaling Activates the Wnt-Lin28A-Blimp1-Wnt Positive Feedback Pathway to Promote Primordial Germ Cell Formation via Altering H3K4me2
Authors: Zuo Qisheng , Zhang Yani , Chen Guohong , Li Bichun 
Published: May 2020

Abstract
(Background) The unique developmental characteristics of bird primordial germ cells (PGC) have enabled genetic engineering–based breeding and restoration of endangered birds via transplantation in vitro. However, the limited number of PGC has limited their application. Thus, there is an urgent need to elucidate the mechanism of PGC formation in vitro to enhance its efficiency. (Results) Here, we confirmed that activation of BMP4 and Wnt signaling (Wnt5A/β-catenin/TCF7L2) is critical for PGC formation via RNA-seq (ESCs, PGC and SSCs) and in vitro induction models. Wnt signaling activated via BMP4 in turn activates transcription of Lin28A by inducing β-catenin to compete with LSD1 for binding to the transcription factor TCF7L2, causing LSD1 to dissociate from the Lin28A promoter and enhanced H3K4me2 methylation in this region. Lin28A promotes PGC formation by inhibiting gga-let7a-3p maturation to initiate Blimp1 expression. Interestingly, expression of Blimp1 helped sustain Wnt5A expression by preventing LSD1 binding to the Wnt5A promoter. We thus elucidated a positive feedback pathway involving Wnt-Lin28-Blimp1-Wnt, with BMP4 functioning as an activator that ensures PGC formation. (Conclusion) In summary, our study clarified the molecular mechanism by which BMP4 and Wnt signaling regulate PGC formation via a positive feedback system. Our data provide both a theoretical and technical basis for studies aimed at enhancing the generation of PGC in vitro.
A Survey of U.S. Medical School Full-Time Faculty Members Age 55+ One-fifth are caregivers and most report caregiving strain
Authors: Skarupski Kimberly Ann , Roth David L , Durso Samuel C 
Published: May 2020

Abstract
Background Nearly one-third of medical school faculty members are age 55+. As the global population ages, the prevalence of family caregiving is increasing, yet we know very little about the caregiving experiences of aging faculty members in academic medicine. Faculty caregiving responsibilities coupled with projected physician shortages and burnout will likely impact the workforce. We examined the prevalence of caregiving and concomitant caregiving strain and well-being differences between aging, male and female medical school faculty members.Methods We analyzed data from a survey of 2,126 full-time medical school faculty 55 + years of age conducted in 2017. We used chi-square tests of independence and independent samples t-tests to calculate statistical differences between groups.Results Of the faculty members invited to participate, 40.8% completed the survey (N = 2,126). Most were male (1,425; 67.2%), white (1,841; 88.3%), and married/partnered (1,803; 85.5%). The mean age was 62.3 years. Of this sample, 19.0% reported providing care on an on-going basis to a family member, friend, or neighbor with a chronic illness or disability (17.3% [n = 242] of the 1,425 males and 22.4% [n = 154] of female respondents). Among the 396 caregiving faculty members, 90.2% reported experiencing some or a lot of mental or emotional strain from caregiving. Compared to their female faculty caregiver counterparts, males were older (mean age 62.3 years vs. 60.0) and more likely to be married and not living alone.Conclusion These data highlight caregiving responsibilities and significant concomitant mental or emotional strain of a significant proportion of U.S. medical schools’ rapidly aging workforce. Human resource leaders in academic medicine should increase attention to these expanding needs.
Oncologic results in rectal cancer patients with a subcentimeter distal margin after laparoscopic-assisted sphincter-preserving surgery by stratified analysis
Authors: Zhang Chenghai , Yang Hong , Cui Ming , Xing Jiadi , Yao Zhendan , Tan Fei , Zhang Nan , Chen Lei , Liu Maoxing , Xu Kai , Su Xiangqian 
Published: May 2020

Abstract
Background

Distal resection margin (DRM) is closely associated with sphincter-preserving surgery and oncologic safety for patients with mid-low rectal cancers. However, the optimal DRM has not been determined. The purpose of this study to assess the impact of a DRM of ≤ 1 cm on oncologic safety.
Methods

Data of 378 patients who underwent laparoscopic-assisted sphincter-preserving surgery from 2009 to 2015 were retrospectively analyzed. Patients were divided into two groups based on DRM: ≤ 1 cm (n = 74) and > 1 cm (n = 304). Stratified analysis was performed according to neoadjuvant chemoradiotherapy.
Results

On the whole, no significant differences in 5-year disease-free survival (DFS) (92.8 vs. 81.3%; P = 0.128) and 5-year overall survival (OS) (83.7 vs. 82.2%; p = 0.892) were observed in patients with DRMs of ≤ 1 and > 1 cm, respectively. A total of 44 patients received preoperative chemoradiotherapy. In this cohort, the 5-year local recurrence (LR) rates ( p = 0.118) and the 5-year DFS rates ( p = 0.298) were not significantly different between the two groups. A total of 334 patients received surgery without neoadjuvant chemoradiotherapy. There were also no significant differences in the 5-year LR rates ( p = 0.150) and 5-year DFS rates ( p = 0.172) between the two groups.
Conclusions

No matter whether patients with rectal cancers received neoadjuvant therapy or not, sphincter-preserving surgery with a DRM ≤ 1 cm may be acceptable in low rectal cancer without jeopardizing oncologic safety.
Development and Feasibility of A Tailored Habit-based Dietary Intervention Coupled With Oral Rehabilitation On The Nutritional Status Of Older Patients
Authors: McCrum Leigh-Ann , Watson Sinead , McGowan Laura , Mcguinness Bernadette , Cardwell Chris , Clarke Mike , Woodside Jayne V , McKenna Gerry 
Published: May 2020

Abstract
BackgroundOlder adults suffering partial tooth loss may need additional intervention strategies other than oral rehabilitation alone to improve their nutritional status. This study aimed to design and develop a habit-based tailored dietary intervention and to assess the feasibility and acceptability of the intervention, in conjunction with oral rehabilitation, amongst partially dentate older adults.MethodsThe design and development of the dietary intervention (Phase 1) consisted of analysis of the target population’s dietary intake and qualitative research through focus groups with community-dwelling older adults (aged 65 years and over). Feasibility of the intervention was then tested among older adults receiving oral rehabilitation in a small non-randomised single arm study (Phase 2). The primary feasibility outcome was the usability and acceptability of the intervention which was measured using evaluation questionnaires and by conducting post-intervention semi-structured interviews. Secondary outcomes consisted of feasibility of screening procedures; recruitment strategies; and retention/ attrition rates as well as the participant’s compliance to the intervention assessed through self-monitoring tracking sheets.ResultsTwenty-one older adults (mean [SD] age 72.1 [10.4].) took part in one of four focus group discussions (Phase 1). Twelve themes related to barriers (e.g oral health, appetite) and facilitators (e.g nutritional knowledge, retirement) of healthy eating guided intervention development, as did a further five themes when asked for direct intervention feedback. Nine older adult participants (mean [SD] age 72.5[9.7]) were recruited into the feasibility study (Phase 2) where eight themes were identified from feedback interview discussions. Primary outcome measures identified intervention feasibility as participants considered the intervention acceptable and useable as both the evaluation questionnaire and qualitative interview results were overwhelmingly positive. As a secondary outcome measure, strong intervention compliance was also achieved. Screening procedures were accepted but additional recruitment strategies (e.g incorporation of home study visits or recruitment via posters advertisement) may benefit future study enrolment and retention.ConclusionPhase 1 and Phase 2 findings have allowed for an iterative, user-driven intervention to be developed and refined for a randomised control study to evaluate the intervention’s effectiveness.Trial registration: ISRCTN66118345
Efficacy of Integrative Chinese-Western Medicine Treatments for COVID-19 Patients in ICU in Yichang, Hubei, China
Authors: Yuan Ziwen , Zhang Min , Li Jingcheng , Peng Ting , Liang Chen , Lin Zhengfeng , Ming Quan , Peng Qiuping , Fang Run , Zhao Weijun , Luo Bin , Liu Hongbo , Wei Xiaojie , Huang Wusong , Shao Yanfeng , Xiong Shengnan 
Published: May 2020

Abstract
Background The prognosis of severe COVID-19 patients is poor. There are currently no definitely effective vaccines or antivirus drugs for COVID-19.Methods This prospective cohort study compared the efficacy and safety of integrative Chinese-Western medicine (ICWM) treatments with Western medicine (WM) treatments in severe or critically ill patients. The outcomes included: mortality, hospital stay in ICU, days with ventilator-assisted ventilation, etc.Results A total of 36 confirmed COVID-19 patients in ICU were included. The median age of patients was 66 years (IQR: 53-77.5), and there were 16 female patients (44.4%). There were no significant differences in laboratory tests and complications after treatments between groups. A total of 18 (50%) patients died during hospitalization, and the mortality in the ICWM group (28.6%) was significantly lower than that of the WM group (63.6%, adjusted P = 0.031). And the time of assisted ventilation was shorter in the ICWM group (adjusted P = 0.67). However, the median hospital stay was significantly longer in the ICWM group (18 vs. 14 days, adjusted P༜0.05).Conclusions ICWM treatments could significantly reduce the mortality and improve the clinical symptoms for severe or critically ill patients with COVID-19, and it was safe and cost-effective to add Chinese medicine.
Bile acids increase intestinal markers via FXR/SNAI2/miR-1 axis in the stomach
Authors: Wang Na , Chen Min , Zeng Jiaoxia , Lu Guofang , Wang Jiaojiao , Zhang Jian , Wu Siran , Shi Yongquan 
Published: May 2020

Abstract
Background

Intestinal metaplasia (IM) is a precancerous lesion that increases risk of subsequent gastric cancer (GC). However, factors governing the transformation from normal gastric epithelial cells to IM remain unclear. Previously, miR-1 turned out to play an essential role in the initiation of bile acids (BA)-induced IM. Here, we investigate the mechanism underlying miR-1 inhibition by BA in gastric cells.
Methods

We conducted IPA analysis to determine the potential molecular interacting BA with miR-1. The changes of FXR and SNAI2 after BA treatment were detected by western blot and qRT-PCR. IHC was performed to assess the expression level of FXR and SNAI2 in normal and IM tissue microarrays. The transcriptional regulation of SNAI2 or miR-1 was verified by bioinfamatics, luciferase reporter assay and chromatin immunoprecipitation PCR.
Results

BA treatment caused aberrant expression of FXR and IM markers in gastric cells. Augmented FXR led to the transcriptional activation of SNAI2 which further stimulates the expression of downstream IM markers. Bioinformatics analysis indicated that SNAI2 had miR-1 promoter binding region and we identified that SNAI2 negatively regulated miR-1 transcription. Both FXR and SNAI2 were increased in patients with IM.
Conclusions

This study demonstrated that FXR might be responsible for a series molecular changes in gastric cells after BA, and FXR/SNAI2/miR-1 axis exert a crucial role in BA-induced IM progression. Blocking the activation of the FXR-oriented axis may provide a promising approach for IM or even GC treatment.