bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparing intervention strategies for reducing Clostridioides difficile transmission in acute healthcare settings: an agent-based modeling study
Authors: Stephenson Brittany , Lanzas Cristina , Lenhart Suzanne , Ponce Eduardo , Bintz Jason , Dubberke Erik R. , Day Judy 
Published: October 2020

Abstract

Background
Clostridioides difficile infection (CDI) is one of the most common healthcare infections. Common strategies aiming at controlling CDI include antibiotic stewardship, environmental decontamination, and improved hand hygiene and contact precautions. Mathematical models provide a framework to evaluate control strategies. Our objective is to evaluate the effectiveness of control strategies in decreasing C. difficile colonization and infection using an agent-based model in an acute healthcare setting.

Methods
We developed an agent-based model that simulates the transmission of C. difficile in medical wards. This model explicitly incorporates healthcare workers (HCWs) as vectors of transmission, tracks individual patient antibiotic histories, incorporates varying risk levels of antibiotics with respect to CDI susceptibility, and tracks contamination levels of ward rooms by C. difficile. Interventions include two forms of antimicrobial stewardship, increased environmental decontamination through room cleaning, improved HCW compliance, and a preliminary assessment of vaccination.

Results
Increased HCW compliance with CDI patients was ranked as the most effective intervention in decreasing colonizations, with reductions up to 56%. Antibiotic stewardship practices were highly ranked after contact precaution compliance. Vaccination and reduction of high-risk antibiotics were the most effective intervention in decreasing CDI. Vaccination reduced CDI cases to up to 90%, and the reduction of high-risk antibiotics decreased CDI cases up to 23%.

Conclusions
Overall, interventions that decrease patient susceptibility to colonization by C. difficile, such as antibiotic stewardship, were the most effective interventions in reducing both colonizations and CDI cases.
Systemic lupus Erythematosus activity and Hydroxychloroquine use before and after end-stage renal disease
Authors: Salgado Guerrero Maria , Londono Jimenez Alejandra , Dobrowolski Chrisanna , Mowrey Wenzhu B. , Goilav Beatrice , Wang Shudan , Broder Anna 
Published: October 2020

AbstractBackgroundSLE manifestations after ESRD may be underdiagnosed and undertreated, contributing to increased morbidity and mortality. Whether specific symptoms persist after ESRD or a shift towards new manifestations occurs has not been extensively studied, especially in the non-Caucasian patients in the United States. In addition, hydroxychloroquine (HCQ) prescribing patterns post-ESRD have not been described. The objective of this study was to assess lupus activity and HCQ prescribing before and after ESRD development. Knowledge gained from this study may aid in the identification of SLE manifestations and improve medication management post-ESRD.MethodsWe performed a retrospective cohort study of SLE patients with incident ESRD between 2010 and 2017. SLE-related symptoms, serologic markers of disease activity, and medication use were collected from medical records before and after ESRD development.ResultsFifty-nine patients were included in the study. Twenty-five (43%) patients had at least one clinical (non-renal) SLE manifestation documented within 12 months before ESRD. Of them, 11/25 (44%) continued to experience lupus symptoms post-ESRD; 9 patients without clinical or serological activity pre-ESRD developed new symptoms of active SLE. At the last documented visit post-ESRD, 42/59 (71%) patients had one or more clinical or serological markers of lupus activity; only 17/59 (29%) patients achieved clinical and serological remission.Thirty-three of 59 (56%) patients had an active HCQ prescription at the time of ESRD. Twenty-six of the 42 (62%) patients with active SLE manifestations post-ESRD were on HCQ. Patients who continued HCQ post-ESRD were more likely to be followed by a rheumatologist (26 [87%] vs 17 [61%],p = 0.024), had a higher frequency of documented arthritis (10 [32%] vs 1 [4%],p = 0.005), CNS manifestations (6 [20%] vs 1 [4%],p = 0.055), and concurrent immunosuppressive medication use (22 [71%] vs 12 [43%],p = 0.029).ConclusionsLupus activity may persist after the development of ESRD. New onset arthritis, lupus-related rash, CNS manifestations, low complement and elevated anti-dsDNA may develop. HCQ may be underutilized in patients with evidence of active disease pre- and post ESRD. Careful clinical and serological monitoring for signs of active disease and frequent rheumatology follow up is advised in SLE patients both, pre and post-ESRD.
Kidney transplantation from living donor with monolateral renal artery fibromuscular dysplasia using a cryopreserved iliac graft for arterial reconstruction: a case report and review of the literature
Authors: Nguefouet Momo Rostand Emmanuel , Donato Paola , Ugolini Gabriele , Nacchia Francesco , Mezzetto Luca , Veraldi Gian Franco , Marletta Stefano , Cavallo Enrico , Eccher Albino , Giambanco Annamaria , Cenzi Daniela , Boschiero Luigino 
Published: October 2020

AbstractBackgroundAging and mortality of patients on waiting lists for kidney transplantation have increased, as a result of the shortage of organs available all over the world. Living donor grafts represent a significant source to maintain the donor pool, and resorting successfully to allografts with arterial disease has become a necessity. The incidence of renal artery fibromuscular dysplasia (FMD) in potential living renal donors is reported to be 2–6%, and up to 4% of them present concurrent extra-renal involvement.Case presentationWe present a case of renal transplantation using a kidney from a living donor with monolateral FMD. Resection of the affected arterial segment and its subsequent replacement with a cryopreserved iliac artery graft from a deceased donor were performed. No intraoperative nor post-operative complications were reported. The allograft function promptly resumed, with satisfying creatinine clearance, and adequate patency of the vascular anastomoses was detected by Doppler ultrasounds.ConclusionLiterature lacks clear guidelines on the eligibility of potential living renal donors with asymptomatic FMD. Preliminary assessment of the FMD living donor should always rule out any extra-renal involvement. Whenever possible, resection and reconstruction of the affected arterial segment should be taken into consideration as this condition may progress after implantation.
Integrated genomic and transcriptomic analysis revealed mutation patterns of de-differentiated liposarcoma and leiomyosarcoma
Authors: Liu Wenshuai , Tong Hanxing , Zhang Chenlu , Zhuang Rongyuan , Guo He , Lv Chentao , Yang Hua , Lin Qiaowei , Guo Xi , Wang Zhiming , Wang Yan , Shen Feng , Wang Shengzhou , Dai Chun , Wang Guan , Liu Jun , Lu Weiqi , Zhang Yong , Zhou Yuhong 
Published: October 2020

AbstractBackgroundTreating patients with advanced sarcomas is challenging due to great histologic diversity among its subtypes. Leiomyosarcoma (LMS) and de-differentiated liposarcoma (DDLPS) are two common and aggressive subtypes of soft tissue sarcoma (STS). They differ significantly in histology and clinical behaviors. However, the molecular driving force behind the difference is unclear.MethodsWe collected 20 LMS and 12 DDLPS samples and performed whole exome sequencing (WES) to obtain their somatic mutation profiles. We also performed RNA-Seq to analyze the transcriptomes of 8 each of the LMS and DDLPS samples and obtained information about differential gene expression, pathway enrichment, immune cell infiltration in tumor microenvironment, and chromosomal rearrangement including gene fusions. Selected gene fusion events from the RNA-seq prediction were checked by RT-PCR in tandem with Sanger sequencing.ResultsWe detected loss of function mutation and deletion of tumor suppressors mostly in LMS, and oncogene amplification mostly in DDLPS. A focal amplification affecting chromosome 12q13–15 region which encodesMDM2,CDK4andHMGA2is notable in DDLPS. Mutations inTP53,ATRX,PTEN, andRB1are identified in LMS but not DDLPS, while mutation of HERC2 is only identified in DDLPS but not LMS. RNA-seq revealed overexpression ofMDM2,CDK4andHMGA2in DDLPS and down-regulation ofTP53andRB1in LMS. It also detected more fusion events in DDLPS than LMS (4.5 vs. 1,p = 0.0195), and the ones involving chromosome 12 in DDLPS stand out. RT-PCR and Sanger sequencing verified the majority of the fusion events in DDLPS but only one event in LMS selected to be tested. The tumor microenvironmental signatures are highly correlated with histologic types. DDLPS has more endothelial cells and fibroblasts content than LMS.ConclusionsOur analysis revealed different recurrent genetic variations in LMS and DDLPS including simultaneous upregulation of gene expression and gene copy number amplification ofMDM2andCDK4. Up-regulation of tumor related genes is favored in DDLPS, while loss of suppressor function is favored in LMS. DDLPS harbors more frequent fusion events which can generate neoepitopes and potentially targeted by personalized immune treatment.
Increased E2F2 predicts poor prognosis in patients with HCC based on TCGA data
Authors: Zeng Zhili , Cao Zebiao , Tang Ying 
Published: October 2020

Abstract

Background
The E2F family of transcription factor 2 (E2F2) plays an important role in the development and progression of various tumors, but its association with hepatocellular carcinoma (HCC) remains unknown. Our study aimed to investigate the role and clinical significance of E2F2 in HCC.

Methods
HCC raw data were extracted from The Cancer Genome Atlas (TCGA). Wilcoxon signed-rank test, Kruskal-Wallis test and logistic regression were applied to analyze the relationship between the expression of E2F2 and clinicopathologic characteristics. Cox regression and Kaplan-Meier were employed to evaluate the correlation between clinicopathologic features and survival. The biological function of E2F2 was annotated by Gene Set Enrichment Analysis (GSEA).

Results
The expression of E2F2 was increased in HCC samples. The expression of elevated E2F2 in HCC samples was prominently correlated with histologic grade (OR = 2.62 for G3–4 vs. G1–2, p = 1.80E-05), clinical stage (OR = 1.74 for III-IV vs. I-II, p = 0.03), T (OR = 1.64 for T3–4 vs.T1–2, p = 0.04), tumor status (OR = 1.88 for with tumor vs. tumor free, p = 3.79E-03), plasma alpha fetoprotein (AFP) value (OR = 3.18 for AFP ≥ 400 vs AFP<20, p = 2.16E-04; OR = 2.50 for 20 ≤ AFP<400 vs AFP<20, p = 2.56E-03). Increased E2F2 had an unfavorable OS (p = 7.468e− 05), PFI (p = 3.183e− 05), DFI (p = 0.001), DSS (p = 4.172e− 05). Elevated E2F2 was independently bound up with OS (p = 0.004, hazard ratio [HR] = 2.4 (95% CI [1.3–4.2])), DFI (P = 0.029, hazard ratio [HR] = 2.0 (95% CI [1.1–3.7])) and PFI (P = 0.005, hazard ratio [HR] = 2.2 (95% CI [1.3–3.9])). GSEA disclosed that cell circle, RNA degradation, pyrimidine metabolism, base excision repair, aminoacyl tRNA biosynthesis, DNA replication, p53 signaling pathway, nucleotide excision repair, ubiquitin-mediated proteolysis, citrate cycle TCA cycle were notably enriched in E2F2 high expression phenotype.

Conclusions
Elevated E2F2 can be a promising independent prognostic biomarker and therapeutic target for HCC. Additionally, cell cycle, pyrimidine metabolism, DNA replication, p53 signaling pathway, ubiquitin-mediated proteolysis, the citrate cycle TCA cycle may be the key pathway by which E2F2 participates in the initial and progression of HCC.
The majority of β-catenin mutations in colorectal cancer is homozygous
Authors: Arnold Alexander , Tronser Moritz , Sers Christine , Ahadova Aysel , Endris Volker , Mamlouk Soulafa , Horst David , Möbs Markus , Bischoff Philip , Kloor Matthias , Bläker Hendrik 
Published: October 2020

Abstract
Background
β-catenin activation plays a crucial role for tumourigenesis in the large intestine but except for Lynch syndrome (LS) associated cancers stabilizing mutations of β-catenin gene (CTNNB1) are rare in colorectal cancer (CRC). Previous animal studies provide an explanation for this observation. They showed that CTNNB1 mutations induced transformation in the colon only when CTNNB1 was homozygously mutated or when membranous β-catenin binding was hampered by E-cadherin haploinsufficiency. We were interested, if these mechanisms are also found in human CTNNB1 mutated CRCs.

Results
Among 869 CRCs stabilizing CTNNB1 mutations were found in 27 cases. Homo- or hemizygous CTNNB1 mutations were detected in 74% of CTNNB1 mutated CRCs (13 microsatellite instabile (MSI-H), 7 microsatellite stabile (MSS)) but only in 3% (1/33) of extracolonic CTNNB1 mutated cancers. In contrast to MSS CRC, CTNNB1 mutations at codon 41 or 45 were highly selected in MSI-H CRC. Of the examined three CRC cell lines, β-catenin and E-cadherin expression was similar in cell lines without or with hetereozygous CTNNB1 mutations (DLD1 and HCT116), while a reduced E-cadherin expression combined with cytoplasmic accumulation of β-catenin was found in a cell line with homozygous CTNNB1 mutation (LS180). Reduced expression of E-cadherin in human MSI-H CRC tissue was identified in 60% of investigated cancers, but no association with the CTNNB1 mutational status was found.

Conclusions
In conclusion, this study shows that in contrast to extracolonic cancers stabilizing CTNNB1 mutations in CRC are commonly homo- or hemizygous indicating a higher threshold of β-catenin stabilization to be required for transformation in the colon as compared to extracolonic sites. Moreover, we found different mutational hotspots in CTNNB1 for MSI-H and MSS CRCs suggesting a selection of different effects on β-catenin stabilization according to the molecular pathway of tumourigenesis. Reduced E-cadherin expression in CRC may further contribute to higher levels of transcriptionally active β-catenin, but it is not directly linked to the CTNNB1 mutational status.
Determining the effects of trastuzumab, cetuximab and afatinib by phosphoprotein, gene expression and phenotypic analysis in gastric cancer cell lines
Authors: Ebert Karolin , Zwingenberger Gwen , Barbaria Elena , Keller Simone , Heck Corinna , Arnold Rouven , Hollerieth Vanessa , Mattes Julian , Geffers Robert , Raimúndez Elba , Hasenauer Jan , Luber Birgit 
Published: October 2020

Abstract
Background
Gastric cancer is the fifth most frequently diagnosed cancer and the third leading cause of cancer death worldwide. The molecular mechanisms of action for anti-HER-family drugs in gastric cancer cells are incompletely understood. We compared the molecular effects of trastuzumab and the other HER-family targeting drugs cetuximab and afatinib on phosphoprotein and gene expression level to gain insights into the regulated pathways. Moreover, we intended to identify genes involved in phenotypic effects of anti-HER therapies.

Methods
A time-resolved analysis of downstream intracellular kinases following EGF, cetuximab, trastuzumab and afatinib treatment was performed by Luminex analysis in the gastric cancer cell lines Hs746T, MKN1, MKN7 and NCI-N87. The changes in gene expression after treatment of the gastric cancer cell lines with EGF, cetuximab, trastuzumab or afatinib for 4 or 24 h were analyzed by RNA sequencing. Significantly enriched pathways and gene ontology terms were identified by functional enrichment analysis. Furthermore, effects of trastuzumab and afatinib on cell motility and apoptosis were analyzed by time-lapse microscopy and western blot for cleaved caspase 3.

Results
The Luminex analysis of kinase activity revealed no effects of trastuzumab, while alterations of AKT1, MAPK3, MEK1 and p70S6K1 activations were observed under cetuximab and afatinib treatment. On gene expression level, cetuximab mainly affected the signaling pathways, whereas afatinib had an effect on both signaling and cell cycle pathways. In contrast, trastuzumab had little effects on gene expression. Afatinib reduced average speed in MKN1 and MKN7 cells and induced apoptosis in NCI-N87 cells. Following treatment with afatinib, a list of 14 genes that might be involved in the decrease of cell motility and a list of 44 genes that might have a potential role in induction of apoptosis was suggested. The importance of one of these genes (HBEGF) as regulator of motility was confirmed by knockdown experiments.

Conclusions
Taken together, we described the different molecular effects of trastuzumab, cetuximab and afatinib on kinase activity and gene expression. The phenotypic changes following afatinib treatment were reflected by altered biological functions indicated by overrepresentation of gene ontology terms. The importance of identified genes for cell motility was validated in case of HBEGF.
Supporting mental health service users to stop smoking: findings from a process evaluation of the implementation of smokefree policies into two mental health trusts
Authors: Jones S. E. , Mulrine S. , Clements H. , Hamilton S. 
Published: October 2020

Abstract

Background
Life expectancy is 10–20 years lower among people with a severe mental health disorder. Most of these early deaths are due to chronic conditions, including cardiovascular and respiratory diseases. Smoking is a major risk factor for these conditions and introducing smokefree policies has been recommended to mental health service providers in England by the National Institute for Health and Care Excellence (NICE), in their Public Health Guideline 48: Smoking: acute, maternity and mental health services. This paper reports a process evaluation of introducing these policy recommendations, which were updated in 2013.

Method
Process data were collected through semi-structured interviews with staff (n = 51), members of partnering organisations (n = 5), service users (n = 7) and carers (n = 2) between November 2016 – April 2017. Normalization Process Theory (NPT) was used to design the data collection tools and analyse the data. A framework approach was taken with the analysis, using the four concepts of NPT: coherence, cognitive participation, collective action and reflexive monitoring.

Results
The policy made sense to some staff, patients and carers (coherence) who ‘bought-into’ the idea (cognitive participation) but other participants disagreed. Although smokefree policies were operationalised (collective action), sometimes they were opposed. Progress was made, especially in some units, but continued to be resisted in others. Informal appraisal of progress (reflexive monitoring) presented a varied picture.

Conclusion
Some progress has been made in terms of changing an entrenched, smoking culture into one that is smokefree on Trust sites across the region. Perseverance and resourcing over the long-term is required to establish a non-smoking culture in on-site provision of mental health services.
Adherence to recommendations for ART and targeted PrEP use among HIV serodiscordant couples in East Africa: the “PrEP as a bridge to ART” strategy
Authors:   on behalf of the Partners Demonstration Project Team, Musinguzi Nicholas , Kidoguchi Lara , Mugo Nelly R. , Ngure Kenneth , Katabira Elly , Celum Connie L. , Baeten Jared M. , Heffron Renee , Haberer Jessica E. 
Published: October 2020

Abstract

Background
PrEP use should be aligned with periods of risk for HIV acquisition. For HIV serodiscordant couples, PrEP can be used as a bridge until the partner living with HIV takes antiretroviral therapy (ART) long enough to achieve viral suppression (the “PrEP as a Bridge to ART” strategy). However, adherence to this strategy is unknown.

Methods
In a demonstration project in Kenya and Uganda, HIV-uninfected partners of serodiscordant couples were advised to take PrEP until the partner living with HIV took ART for ≥ 6 months. PrEP discontinuation was then recommended unless there were concerns about ART adherence, immediate fertility intentions, or outside partners with unknown HIV/ART status. Electronic adherence monitoring and socio-behavioral questionnaire data were used in logistic regression models to explore completion of this strategy and continuation of PrEP beyond recommendations to stop its use.

Results
Among 833 serodiscordant couples, 436 (52%) HIV-uninfected partners completed ≥ 6 months of PrEP as a bridge to ART. Strategy completion was associated with older age (aOR per 5 years = 1.1; p = 0.008) and having fewer children (aOR = 0.9; p = 0.019). Of the 230 participants encouraged to stop PrEP according to strategy recommendations, 170 (74%) did so. PrEP continuation among the remaining 60 participants was associated with more education (aOR = 1.1; p = 0.029), a preference for PrEP over ART (aOR = 3.6; p = 0.026), comfort with managing their serodiscordant relationship (aOR = 0.6; p = 0.046), and believing PrEP makes sex safe (aOR = 0.5; p = 0.026).

Conclusion
Half of participants completed the PrEP as a bridge to ART strategy and the majority stopped PrEP as recommended. These findings suggest that targeting PrEP to periods of risk is a promising approach; however, tailoring counseling around aligning PrEP use and HIV risk will be important for optimal strategy implementation.
Sleep duration and mortality in Korean adults: a population-based prospective cohort study
Authors: Kwon Sohyeon , Lee Hyeyoung , Lee Jong-Tae , Shin Min-Jeong , Choi Sangbum , Oh Hannah 
Published: October 2020

Abstract

Background
Increasing evidence suggests that sleep duration is associated with risks of various diseases including type 2 diabetes, cardiovascular disease (CVD), and certain types of cancer. However, the relationship with mortality is not clear, particularly in non-European populations. In this study, we investigated the association between sleep duration and mortality in a population-based prospective cohort of Korean adults.

Methods
This analysis included 34,264 participants (14,704 men and 19,560 women) of the Korea National Health and Nutrition Examination Survey (KNHANES) 2007–2013 who agreed to mortality follow-up through December 31, 2016. Sleep duration was self-reported at baseline and was categorized into four groups: ≤4, 5–6, 7–8, and ≥ 9 h/day. Cox proportional hazards models were performed to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the associations with mortality (all-cause as well as CVD- and cancer-specific), adjusting for potential confounders.

Results
During up to 9.5 years of follow-up, we identified a total of 1028 deaths. We observed the lowest mortality at 5–6 h/day sleep. Compared with 7–8 h/day of sleep, short (≤4 h/day) and long (≥9 h/day) sleep were associated with a 1.05-fold (95% CI = 0.79–1.39) and 1.47-fold (95% CI = 1.15–1.87) higher all-cause mortality, respectively. After additional adjustment for self-rated health, the positive association with short sleep disappeared (HR = 0.99, 95% CI = 0.75–1.32) and the association with long sleep was slightly attenuated (HR = 1.38, 95% CI = 1.08–1.76). Long sleep was also nonsignificantly positively associated with both cancer-mortality (HR = 1.30, 95% CI = 0.86–1.98) and CVD-mortality (HR = 1.27, 95% CI = 0.73–2.21). There was no statistically significant evidence for nonlinearity in the relationships between sleep duration and mortality (all-cause as well as CVD- and cancer-specific). Effect modification by age, sex, education, and occupation were not statistically significant.

Conclusions
Our findings suggest that long sleep duration is associated with an increased all-cause mortality in Korean adults.