bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of the addition of a transversus abdominis plane block to an enhanced recovery program with opioid consumption, postoperative antiemetic use, and discharge time in patients undergoing laparoscopic bariatric surgery: a retrospective study
Authors: McCarthy Robert J , Ivankovich Katarina G , Ramirez Emily A , Adams Ashley M , Ramesh Arjun K , Omotosho Philip A , Buvanendran Asokumar 
Published: January 2020

BackgroundIncreasing numbers of laparoscopic bariatric surgeries are being performed and enhanced recovery from anesthesia and surgery (ERAS) protocols have been implemented to optimize care for these patients. We evaluated the effects of an anesthesiologist placed preoperative transversus abdominis plane block (TAP) as part of a bariatric surgery ERAS protocol. We hypothesized that an anesthesiologist placed preoperative TAP added to an ERAS protocol following laparoscopic bariatric surgery would reduce total opioid consumption.MethodsA retrospective cohort of consecutive patients between January 1, 2017 and December 31, 2018 at a single large tertiary care center studied. TAP blocks were added to the ERAS protocol beginning in the second quarter of 2017. The primary outcome was total opioid analgesia use in mg oral morphine equivalents. Secondary outcomes were antiemetics administered and length of hospitalization. Data were analyzed using a generalized linear mixed model adjusted for sociodemographic, surgical, and preoperative risk factors that have been associated with opioid and antiemetic use and length of hospitalization.ResultsFive hundred and nine cases were analyzed; TAP blocks were performed in 94/144 (65%) laparoscopic Roux-en-Y gastric bypass (LRYGB) and in 172/365 (47%) laparoscopic sleeve gastrectomy (LSG) patients. Mean (95% CI) adjusted total opioid administered was lower by 11% (1% to 19%, p=0.02), antiemetic drug administration was lower by 15% (-2% to 25%, p=0.06) and discharge time lower by 39% (26% to 48%, p<0.01) following LRYGB in the TAP group. Mean (95% CI) adjusted total opioid administered was lower by 9% (2% to 16%, p<0.01), antiemetic drug administration was lower by 11% (3% to 18%, p<0.01) and discharge time lower by 11% (2% to 18%, p=0.02) following LSG in the TAP group.ConclusionsTAP blocks added to a laparoscopic bariatric surgery ERAS protocol were associated with decreased total opioid use, number of antiemetic treatments, and length of stay; however, these changes were not likely clinically important. Our findings do not support widespread clinical benefit of TAP use in ERAS protocols for laparoscopic bariatric surgery.
Cigarette and cigar sales in Hawaii before and after implementation of a Tobacco 21 Law
Authors: Glover-Kudon Rebecca , Gammon Doris G , Rogers Todd , Coats Ellen M , Loomis Brett , Johnson Lila , Welton MaryBeth , Lavinghouze René 
Published: January 2020

IntroductionOn 1 January 2016, Hawaii raised the minimum legal age for tobacco access from 18 to 21 years (‘Tobacco 21 (T21)’) statewide, with no special population exemptions. We assessed the impact of Hawaii’s T21 policy on sales of cigarettes and large cigars/cigarillos in civilian food stores, including menthol/flavoured product sales share.MethodsCigarette and large cigar/cigarillo sales and menthol/flavoured sales share were assessed in Hawaii, California (implemented T21 in June 2016 with a military exemption), and the US mainland using the only Nielsen data consistently available for each geographical area. Approximate monthly sales data from large-scale food stores with sales greater than US$2 million/year covered June 2012 to February 2017. Segmented regression analyses estimated changes in sales from prepolicy to postpolicy implementation periods.ResultsFollowing T21 in Hawaii, average monthly cigarette unit sales dropped significantly (−4.4%, p<0.01) coupled with a significant decrease in menthol market share (−0.8, p<0.01). This combination of effects was not observed in comparison areas. Unit sales of large cigars/cigarillos decreased significantly in each region following T21 implementation. T21 policies in Hawaii and California showed no association with flavoured/menthol cigar sales share, but there was a significant increase in flavoured/menthol cigar sales share in the USA (7.1%, p<0.01) relative to Hawaii’s implementation date, suggesting T21 may have attenuated an otherwise upward trend.ConclusionsAs part of a comprehensive approach to prevent or delay tobacco use initiation, T21 laws may help to reduce sales of cigarette and large cigar products most preferred by US youth and young adults.
Developing Cognitive and Non-Cognitive Entrepreneurial Competences through Business Simulation Games
Authors: Costin Yvonne , O’Brien Michael P. , Hynes Briga 
Published: January 2020

Today, entrepreneurship is seen as a major driver for innovation, economic growth and job creation, with entrepreneurial competencies highly sought after by practitioners and policy-makers alike. Competencies considered entrepreneurial include knowledge about how entrepreneurs create value; skills in marketing, resource acquisition and opportunity identification; and attitudes such as entrepreneurial passion, self-efficacy, proactiveness and tenacity. There is widespread consensus in the literature that entrepreneurial competencies can be developed through entrepreneurship learning. This study adopts an existing framework for entrepreneurial competencies based on previous research to investigate the role and influence that simulation games can play in the development of cognitive (knowledge and skills) and non-cognitive (attitudes) entrepreneurial competencies. The paper showcases the many benefits of using business simulation as an effective mode for developing entrepreneurial competencies. Such competencies are not only beneficial for individuals working in an entrepreneurial context — but are transferable to any business context, bringing to the fore the importance of entrepreneurial learning for all students to develop such competencies.
Nanoformulated SOD1 ameliorates the combined NASH and alcohol-associated liver disease partly via regulating CYP2E1 expression in adipose tissue and liver
Authors: Gopal Thiyagarajan , Kumar Narendra , Perriotte-Olson Curtis , Casey Carol A. , Donohue Terrence M. , Harris Edward N. , Talmon Geoffrey , Kabanov Alexander V. , Saraswathi Viswanathan 
Published: January 2020

Enhanced free fatty acid (FFA) flux from adipose tissue (AT) to liver plays an important role in the development of nonalcoholic steatohepatitis (NASH) and alcohol-associated liver disease (AALD). We determined the effectiveness of nanoformulated superoxide dismutase 1 (Nano) in attenuating liver injury in a mouse model exhibiting a combination of NASH and AALD. Male C57BL6/J mice were fed a chow diet (CD) or a high-fat diet (HF) for 10 wk followed by pair feeding of the Lieber-DeCarli control (control) or ethanol (ET) diet for 4 wk. Nano was administered once every other day for the last 2 wk of ET feeding. Mice were divided into 1) CD + control diet (CD + Cont), 2) high-fat diet (HF) + control diet (HF + Cont), 3) HF + Cont + Nano, 4) HF + ET diet (HF + ET), and 5) HF + ET + Nano. The total fat mass, visceral AT mass (VAT), and VAT perilipin 1 content were significantly lower only in HF + ET-fed mice but not in HF + ET + Nano-treated mice compared with controls. The HF + ET-fed mice showed an upregulation of VAT CYP2E1 protein, and Nano abrogated this effect. We noted a significant rise in plasma FFAs, ALT, and monocyte chemoattractant protein-1 in HF + ET-fed mice, which was blunted in HF + ET + Nano-treated mice. HF + ET-induced increases in hepatic steatosis and inflammatory markers were attenuated upon Nano treatment. Nano reduced hepatic CYP2E1 and enhanced catalase levels in HF + ET-fed mice with a concomitant increase in SOD1 protein and activity in liver. Nano was effective in attenuating AT and liver injury in mice exhibiting a combination of NASH and AALD, partly via reduced CYP2E1-mediated ET metabolism in these organs.NEW & NOTEWORTHY Increased free fatty acid flux from adipose tissue (AT) to liver accompanied by oxidative stress promotes nonalcoholic steatohepatitis (NASH) and alcohol-associated liver injury (AALD). Obesity increases the severity of AALD. Using a two-hit model involving a high-fat diet and chronic ethanol feeding to mice, and treating them with nanoformulated superoxide dismutase (nanoSOD), we have shown that nanoSOD improves AT lipid storage, reduces CYP2E1 in AT and liver, and attenuates the combined NASH/AALD in mice.
Myocardin and myocardin-related transcription factor-A synergistically mediate actin cytoskeletal-dependent inhibition of liver fibrogenesis
Authors: Shi Zengdun , Ren Mudan , Rockey Don C. 
Published: January 2020

Activation of hepatic stellate cells (HSCs), characterized by development of a robust actin cytoskeleton and expression of abundant extracellular matrix (ECM) proteins, such as type 1 collagen (COL.1), is a central cellular and molecular event in liver fibrosis. It has been demonstrated that HSCs express both myocardin and myocardin-related transcription factor-A (MRTF-A). However, the biological effects of myocardin and MRTF-A on HSC activation and liver fibrosis, as well as the molecular mechanism under the process, remain unclear. Here, we report that myocardin and MRTF-A’s expression and nuclear accumulation are prominently increased during the HSC activation process, accompanied by robust activation of actin cytoskeleton dynamics. Targeting myocardin and MRTF-A binding and function with a novel small molecule, CCG-203971, led to dose-dependent inhibition of HSC actin cytoskeleton dynamics and abrogated multiple functional features of HSC activation (i.e., HSC contraction, migration and proliferation) and decreased COL.1 expression in vitro and liver fibrosis in vivo. Mechanistically, blocking the myocardin and MRTF-A nuclear translocation pathway with CCG-203971 directly inhibited myocardin/MRTF-A-mediated serum response factor (SRF), and Smad2/3 activation in the COL.1α2 promoter and indirectly abrogated actin cytoskeleton-dependent regulation of Smad2/3 and Erk1/2 phosphorylation and their nuclear accumulation. Finally, there was no effect of CCG-203971 on markers of inflammation, suggesting a direct effect of the compound on HSCs and liver fibrosis. These data reveal that myocardin and MRTF-A are two important cotranscriptional factors in HSCs and represent entirely novel therapeutic pathways that might be targeted to treat liver fibrosis. NEW & NOTEWORTHY Myocardin and myocardin-related transcription factor-A (MRTF-A) are upregulated in activated hepatic stellate cells (HSCs) in vitro and in vivo, closely associated with robustly increased actin cytoskeleton remodeling. Targeting myocardin and MRTF-A by CCG-203971 leads to actin cytoskeleton-dependent inhibition of HSC activation, reduced cell contractility, impeded cell migration and proliferation, and decreased COL.1 expression in vitro and in vivo. Dual expression of myocardin and MRTF-A in HSCs may represent novel therapeutic targets in liver fibrosis.
Lymphoma Angiogenesis Is Orchestrated by Noncanonical Signaling Pathways
Authors: Gloger Marleen , Menzel Lutz , Grau Michael , Vion Anne-Clemence , Anagnostopoulos Ioannis , Zapukhlyak Myroslav , Gerlach Kerstin , Kammertöns Thomas , Hehlgans Thomas , Zschummel Maria , Lenz Georg , Gerhardt Holger , Höpken Uta E. , Rehm Armin 
Published: January 2020

Abstract

Tumor-induced remodeling of the microenvironment relies on the formation of blood vessels, which go beyond the regulation of metabolism, shaping a maladapted survival niche for tumor cells. In high-grade B-cell lymphoma, angiogenesis correlates with poor prognosis, but attempts to target established proangiogenic pathways within the vascular niche have been inefficient. Here, we analyzed Myc-driven B-cell lymphoma–induced angiogenesis in mice. A few lymphoma cells were sufficient to activate the angiogenic switch in lymph nodes. A unique morphology of dense microvessels emerged without obvious tip cell guidance and reliance on blood endothelial cell (BEC) proliferation. The transcriptional response of BECs was inflammation independent. Conventional HIF1α or Notch signaling routes prevalent in solid tumors were not activated. Instead, a nonconventional hypersprouting morphology was orchestrated by lymphoma-provided VEGFC and lymphotoxin (LT). Interference with VEGF receptor-3 and LTβ receptor signaling pathways abrogated lymphoma angiogenesis, thus revealing targets to block lymphomagenesis.

Significance:
In lymphoma, transcriptomes and morphogenic patterns of the vasculature are distinct from processes in inflammation and solid tumors. Instead, LTβR and VEGFR3 signaling gain leading roles and are targets for lymphomagenesis blockade.
Association of Anti-Mullerian Hormone, Follicle-Stimulating Hormone, and Inhibin B with Risk of Ovarian Cancer in the Janus Serum Bank
Authors: Irvin Sarah R. , Weiderpass Elisabete , Stanczyk Frank Z. , Brinton Louise A. , Trabert Britton , Langseth Hilde , Wentzensen Nicolas 
Published: January 2020

Abstract

Background:
Reproductive factors, including parity, breastfeeding, and contraceptive use, affect lifetime ovulatory cycles and cumulative exposure to gonadotropins and are associated with ovarian cancer. To understand the role of ovulation-regulating hormones in the etiology of ovarian cancer, we prospectively analyzed the association of anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), and inhibin B with ovarian cancer risk.

Methods:
Our study included 370 women from the Janus Serum Bank, including 54 type I and 82 type II invasive epithelial ovarian cancers, 49 borderline tumors, and 185 age-matched controls. We used conditional logistic regression to assess the relationship between hormones and risk of ovarian cancer overall and by subtype (types I and II).

Results:
Inhibin B was associated with increased risk of ovarian cancer overall [OR, 1.97; 95% confidence interval (CI), 1.14–3.39; Ptrend = 0.05] and with type I ovarian (OR, 3.10; 95% CI, 1.04–9.23; Ptrend = 0.06). FSH was not associated with ovarian cancer risk overall, but higher FSH was associated with type II ovarian cancers (OR, 2.78; 95% CI, 1.05–7.38). AMH was not associated with ovarian cancer risk.

Conclusions:
FSH and inhibin B may be associated with increased risk in different ovarian cancer subtypes, suggesting that gonadotropin exposure may influence risk of ovarian cancer differently across subtypes.

Impact:
Associations between prospectively collected AMH, FSH, and inhibin B levels with risk of ovarian cancer provide novel insight on the influence of premenopausal markers of ovarian reserve and gonadotropin signaling. Heterogeneity of inhibin B and FSH effects in different tumor types may be informative of tumor etiology.
Temporal Trends in Population-Level Cure of Cancer: The Australian Context
Authors: Kou Kou , Dasgupta Paramita , Cramb Susanna M. , Yu Xue Qin , Baade Peter D. 
Published: January 2020

Abstract

Background:
With the improvements in cancer diagnosis and treatment, more patients with cancer are surviving for longer periods than before. This study aims to quantify the proportion cured and median survival time for those who are not cured for major cancers in Australia.

Methods:
Australian population-based cohort of 2,164,172 cases, ages 15 to 89 years, whose first cancer diagnosis between 1982 and 2014 was one of 22 leading cancers, were followed up to December 2014. Flexible parametric cure models were used to estimate the proportion cured and median survival time for those uncured by age, sex, and spread of disease, and temporal trends in these measures.

Results:
Cure estimates could be generated for 19 of the 22 cancer types. The unadjusted proportion cured ranged from 5.0% for pancreatic cancer to 90.0% for melanoma. Median survival time for those uncured ranged from 0.35 years for pancreatic cancer to 6.05 years for prostate cancer. Cancers were divided into four groups according to their proportion cured in the 1980s and the degree of improvement over 28 years. Esophageal, stomach, pancreatic, liver, gallbladder, lung, and brain cancer had lower proportion cured and smaller improvements over time.

Conclusions:
For cancers with poor survival in which little has changed over time either in prolonging life or achieving statistical cure, efforts should be focused on reducing the prevalence of known risk factors and earlier detection, thereby enabling more effective treatment.

Impact:
Cure models provide unique insights into whether survival improvements are due to prolonging life or through curing the disease.
Metabolic Pathway Analysis and Effectiveness of Tamoxifen in Danish Breast Cancer Patients
Authors: Ahern Thomas P. , Collin Lindsay J. , Baurley James W. , Kjærsgaard Anders , Nash Rebecca , Maliniak Maret L. , Damkier Per , Zwick Michael E. , Isett R. Benjamin , Christiansen Peer M. , Ejlertsen Bent , Lauridsen Kristina L. , Christensen Kristina B. , Silliman Rebecca A. , Toft Sørensen Henrik , Tramm Trine , Hamilton-Dutoit Stephen , Lash Timothy L. , Cronin-Fenton Deirdre 
Published: January 2020

Abstract

Background:
Tamoxifen and its metabolites compete with estrogen to occupy the estrogen receptor. The conventional dose of adjuvant tamoxifen overwhelms estrogen in this competition, reducing breast cancer recurrence risk by nearly half. Phase I metabolism generates active tamoxifen metabolites, and phase II metabolism deactivates them. No earlier pharmacogenetic study has comprehensively evaluated the metabolism and transport pathways, and no earlier study has included a large population of premenopausal women.

Methods:
We completed a cohort study of 5,959 Danish nonmetastatic premenopausal breast cancer patients, in whom 938 recurrences occurred, and a case–control study of 541 recurrent cases in a cohort of Danish predominantly postmenopausal breast cancer patients, all followed for 10 years. We collected formalin-fixed paraffin-embedded tumor blocks and genotyped 32 variants in 15 genes involved in tamoxifen metabolism or transport. We estimated conventional associations for each variant and used prior information about the tamoxifen metabolic path to evaluate the importance of metabolic and transporter pathways.

Results:
No individual variant was notably associated with risk of recurrence in either study population. Both studies showed weak evidence of the importance of phase I metabolism in the clinical response to adjuvant tamoxifen therapy.

Conclusions:
Consistent with prior knowledge, our results support the role of phase I metabolic capacity in clinical response to tamoxifen. Nonetheless, no individual variant substantially explained the modest phase I effect on tamoxifen response.

Impact:
These results are consistent with guidelines recommending against genotype-guided prescribing of tamoxifen, and for the first time provide evidence supporting these guidelines in premenopausal women.
A New Comprehensive Colorectal Cancer Risk Prediction Model Incorporating Family History, Personal Characteristics, and Environmental Factors
Authors: Zheng Yingye , Hua Xinwei , Win Aung K. , MacInnis Robert J. , Gallinger Steven , Marchand Loic Le , Lindor Noralane M. , Baron John A. , Hopper John L. , Dowty James G. , Antoniou Antonis C. , Zheng Jiayin , Jenkins Mark A. , Newcomb Polly A. 
Published: January 2020

Abstract

Purpose:
Reducing colorectal cancer incidence and mortality through early detection would improve efficacy if targeted. We developed a colorectal cancer risk prediction model incorporating personal, family, genetic, and environmental risk factors to enhance prevention.

Methods:
A familial risk profile (FRP) was calculated to summarize individuals' risk based on detailed cancer family history (FH), family structure, probabilities of mutation in major colorectal cancer susceptibility genes, and a polygenic component. We developed risk models, including individuals' FRP or binary colorectal cancer FH, and colorectal cancer risk factors collected at enrollment using population-based colorectal cancer cases (N = 4,445) and controls (N = 3,967) recruited by the Colon Cancer Family Registry Cohort (CCFRC). Model validation used CCFRC follow-up data for population-based (N = 12,052) and clinic-based (N = 5,584) relatives with no cancer history at recruitment to assess model calibration [expected/observed rate ratio (E/O)] and discrimination [area under the receiver-operating-characteristic curve (AUC)].

Results:
The E/O [95% confidence interval (CI)] for FRP models for population-based relatives were 1.04 (0.74–1.45) for men and 0.86 (0.64–1.20) for women, and for clinic-based relatives were 1.15 (0.87–1.58) for men and 1.04 (0.76–1.45) for women. The age-adjusted AUCs (95% CI) for FRP models for population-based relatives were 0.69 (0.60–0.78) for men and 0.70 (0.62–0.77) for women, and for clinic-based relatives were 0.77 (0.69–0.84) for men and 0.68 (0.60–0.76) for women. The incremental values of AUC for FRP over FH models for population-based relatives were 0.08 (0.01–0.15) for men and 0.10 (0.04–0.16) for women, and for clinic-based relatives were 0.11 (0.05–0.17) for men and 0.11 (0.06–0.17) for women.

Conclusions:
Both models calibrated well. The FRP-based model provided better risk stratification and risk discrimination than the FH-based model.

Impact:
Our findings suggest detailed FH may be useful for targeted risk-based screening and clinical management.
High Extratumoral Mast Cell Counts Are Associated with a Higher Risk of Adverse Prostate Cancer Outcomes
Authors: Hempel Sullivan Heidi , Heaphy Christopher M. , Kulac Ibrahim , Cuka Nathan , Lu Jiayun , Barber John R. , De Marzo Angelo M. , Lotan Tamara L. , Joshu Corinne E. , Sfanos Karen S. 
Published: January 2020

Abstract

Background:
Given our previous findings that low intratumoral and high extratumoral mast cell numbers are associated with higher risk of biochemical recurrence after radical prostatectomy, we now assessed this relationship with race and the development of metastases.

Methods:
We stained for mast cell tryptase via IHC and fluorescent immunolabeling in 885 men across multiple tissue microarray sets designed to assess biomarkers in association with race and prostate cancer outcomes (median follow-up, 7.0 years).

Results:
Intratumoral and extratumoral mast cell counts were significantly lower in tissues from African-American compared with European-American men, but not within strata of cancer grade. There was no association between mast cell counts and ERG positivity, PTEN loss, or TP53 missense mutation. Higher minimum extratumoral mast cells were associated with an increased risk of biochemical recurrence [comparing highest with lowest tertiles: HR, 1.61; 95% confidence interval (CI), 1.12–2.29; P trend = 0.01]; this pattern was similar among European-American and African-American men and by grade of disease. There was no significant association between minimum intratumoral mast cell count and biochemical recurrence, overall or within strata of race and grade. Finally, high minimum number of extratumoral mast cells was associated with prostate cancer metastases (comparing highest with lowest tertiles: HR, 2.12; 95% CI, 1.24–3.63; P trend = 0.01).

Conclusions:
High extratumoral mast cell numbers are associated with biochemical recurrence and the development of metastases after radical prostatectomy.

Impact:
Higher numbers of benign tissue mast cells are associated with a higher risk of adverse outcomes after radical prostatectomy, including metastatic prostate cancer.