bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA12: Preventing melanoma progression through a genomic approach
Authors: Berwick Marianne ,   InterMEL
Published: June 2022

Abstract
The InterMEL Program Project has been designed to fill a gap in our knowledge about the biology and clinical course of Stage II and Stage III melanoma. This program, Integration of Clinical and Molecular Biomarkers for Melanoma Survival, is work from a consortium of 12 institutions, using primary melanomas, and differs from the TCGA, which was 80% metastatic melanoma. We are attempting to use genomics (next-gen sequencing, methylation analyses, miRNA, and expression analyses) to form an integrated signature for survival among those diagnosed with Stages II and III melanoma. Such a signature could assist clinicians in determining whether to treat the patient, prior to metastases, with newer therapies or to less aggressively follow those patients unlikely to die of their disease. To do this, we are evaluating 1,000 tumors—500 from those who died from melanoma within 5 years, and 500 from those who lived more than 5 years without progression. Expert pathologists review each lesion for eligibility and classification of clinical characteristics. These tumors have not been treated with immunotherapy or targeted therapies. Full clinical information is available for each tumor, including age, sex, race/ethnicity, anatomic site, histologic subtype, AJCC8 stage, sentinel lymph node status, Breslow thickness, ulceration, mitotic index, TILs, regression, satellites, tumor purity, date of progression (if progressed), vital status, follow-up time to death or last contact. To date, we have clinical and pathologic data on more than 500 of the 1,000 tumors and genomic data on more than 100 of these. We find better survival among those with higher mutation burden, poorer survival among those with a CIMP methylation phenotype, and a number of miRNAs associated with survival.
Citation Format: Marianne Berwick, InterMEL. Preventing melanoma progression through a genomic approach [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr IA12.
Abstract PR06: The glutaminase inhibitor CB-839 potentiates antimelanoma activity of standard-of-care targeted therapies and immunotherapies
Authors: Varghese Sruthy , Pramanik Snigdha , Prasad Rishika , Hodges Hannah , Williams Leila , Peng Weiyi , Tawbi Hussein , Nanda Vashisht Yennu 
Published: June 2022

Abstract
Nearly all metastatic melanoma patients who respond to targeted therapies will relapse with the disease within a year. Although more durable responses are seen with immune therapies, about half of the melanoma patients do not respond to them, and a significant number of responders eventually relapse. Most relapsed melanomas also exhibit post-treatment resistance to these treatments. Hence, there is a clear and present need to develop therapeutics that counteract resistance associated with relapse. We and others earlier showed that melanomas with elevated mitochondrial activity possess improved cellular rigor and are intrinsically resistant to the antitumor effects of BRAF and MEK inhibitors. In many other instances, melanomas that initially respond to these inhibitors acquire resistance by elevating mitochondrial activity. Mitochondrial activity is elevated in part by increased cellular uptake of glutamine, and its conversion to alpha-ketoglutarate in the TCA cycle, with glutaminase enzyme playing a rate-limiting role. In this study, we show that BRAFV600E-mutant melanomas with intrinsic or acquired resistance to MAPK pathway inhibitors have lower glucose uptake and increased glutamine uptake compared to those that are sensitive. Treatment of these resistant melanomas with single-agent glutaminase inhibitor, CB-839, moderately inhibited their growth. However, a more robust inhibition of their growth was achieved when CB-839 was combined with BRAF and MEK inhibitors. In addition, CB-839 increased the in vivo activity of tumor-infiltrating lymphocytes (TILs) in a mouse vaccine model and also enhanced the proapoptotic effect of human autologous patient-derived TILs on their cognate melanoma cells. Seahorse bioenergetics stress tests showed that CB-839 inhibited mitochondrial OxPhos in tumor cells to a greater extent than in activated TILs. Additional molecular studies are currently in progress. A recent clinical trial in melanoma patients showed that combination treatment with CB-839 and the immune checkpoint blocker, nivolumab, caused an objective response in three melanoma patients who had earlier progressed on treatment with immune checkpoint blockade. Our preclinical results complement this clinical finding and suggest that CB-839 combination could potentiate the efficacy of targeted and immune therapies in refractory melanomas.
Citation Format: Sruthy Varghese, Snigdha Pramanik, Rishika Prasad, Hannah Hodges, Leila Williams, Weiyi Peng, Hussein Tawbi, Vashisht Yennu Nanda. The glutaminase inhibitor CB-839 potentiates antimelanoma activity of standard-of-care targeted therapies and immunotherapies [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr PR06.
Genetically‐Proxied Levels of Vitamin D and Risk of Intracerebral Hemorrhage
Authors: Szejko Natalia , Acosta Julian N. , Both Cameron P. , Leasure Audrey , Matouk Charles , Sansing Lauren , Gill Thomas M. , Hongyu Zhao , Sheth Kevin , Falcone Guido J. 
Published: June 2022

Background
The evidence linking vitamin D (VitD) levels and spontaneous intracerebral hemorrhage (ICH) remains inconclusive. We tested the hypothesis that lower genetically determined VitD levels are associated with higher risk of ICH.

Methods and Results

We conducted a 2 sample Mendelian Randomization (MR) study using publicly available summary statistics from published genome‐wide association studies of VitD levels (417 580 study participants) and ICH (1545 ICH cases and 1481 matched controls). We used the inverse‐variance weighted approach to generate causal estimates and the MR Pleiotropy Residual Sum and Outlier and MR‐Egger approaches to assess for horizontal pleiotropy. To account for known differences in their underlying mechanism, we implemented stratified analysis based on the location of the hemorrhage within the brain (lobar or nonlobar). Our primary analysis indicated that each SD decrease in genetically instrumented VitD levels was associated with a 60% increased risk of ICH (odds ratio [OR], 1.60; [95% CI, 1.05–2.43];
P
=0.029). We found no evidence of horizontal pleiotropy (MR‐Egger intercept and MR Pleiotropy Residual Sum and Outlier global test with
P
>0.05). Stratified analyses indicated that the association was stronger for nonlobar ICH (OR, 1.87; [95% CI, 1.18–2.97];
P
=0.007) compared with lobar ICH (OR, 1.43; [95% CI, 0.86–2.38];
P
=0.17).

Conclusions
Lower levels of genetically proxied VitD levels are associated with higher ICH risk. These results provide evidence for a causal role of VitD metabolism in ICH.
Aspirin Therapy on Prophylactic Anticoagulation for Patients Hospitalized With COVID‐19: A Propensity Score‐Matched Cohort Analysis of the HOPE‐COVID‐19 Registry
Authors: Santoro Francesco , Núñez‐Gil Ivan J. , Vitale Enrica , Viana‐Llamas María C. , Romero Rodolfo , Maroun Eid Charbel , Feltes Guzman Gisela , Becerra‐Muñoz Victor Manuel , Fernández Rozas Inmaculada , Uribarri Aitor , Alfonso‐Rodriguez Emilio , García Aguado Marcos , Huang Jia , Castro Mejía Alex Fernando , Garcia Prieto Juan Fortunato , Elola Javier , Ugo Fabrizio , Cerrato Enrico , Signes‐Costa Jaime , Raposeiras Roubin Sergio , Jativa Mendez Jorge Luis , Espejo Paeres Carolina , López Masjuan Alvaro , Marin Francisco , Guerra Federico , El‐Battrawy Ibrahim , Cortese Bernardo , Ramakrishna Harish , Perez‐Villacastín Julian , Fernandez‐Ortiz Antonio , Brunetti Natale Daniele 
Published: June 2022

Background
COVID‐19 is an infectious illness, featured by an increased risk of thromboembolism. However, no standard antithrombotic therapy is currently recommended for patients hospitalized with COVID‐19. The aim of this study was to evaluate safety and efficacy of additional therapy with aspirin over prophylactic anticoagulation (PAC) in patients hospitalized with COVID‐19 and its impact on survival.

Methods and Results

A total of 8168 patients hospitalized for COVID‐19 were enrolled in a multicenter‐international prospective registry (HOPE COVID‐19). Clinical data and in‐hospital complications, including mortality, were recorded. Study population included patients treated with PAC or with PAC and aspirin. A comparison of clinical outcomes between patients treated with PAC versus PAC and aspirin was performed using an adjusted analysis with propensity score matching. Of 7824 patients with complete data, 360 (4.6%) received PAC and aspirin and 2949 (37.6%) PAC. Propensity‐score matching yielded 298 patients from each group. In the propensity score‐matched population, cumulative incidence of in‐hospital mortality was lower in patients treated with PAC and aspirin versus PAC (15% versus 21%, Log Rank
P
=0.01). At multivariable analysis in propensity matched population of patients with COVID‐19, including age, sex, hypertension, diabetes, kidney failure, and invasive ventilation, aspirin treatment was associated with lower risk of in‐hospital mortality (hazard ratio [HR], 0.62; [95% CI 0.42–0.92],
P
=0.018).

Conclusions
Combination PAC and aspirin was associated with lower mortality risk among patients hospitalized with COVID‐19 in a propensity score matched population compared to PAC alone.
Increases in Circulating and Fecal Butyrate are Associated With Reduced Blood Pressure and Hypertension: Results From the SPIRIT Trial
Authors: Tilves Curtis , Yeh Hsin‐Chieh , Maruthur Nisa , Juraschek Stephen P. , Miller Edgar , White Karen , Appel Lawrence J. , Mueller Noel T. 
Published: June 2022

BackgroundShort chain fatty acids (SCFAs) are microbially derived end products of dietary fiber fermentation. The SCFA butyrate reduces blood pressure (BP) in mouse models. The association of SCFAs, including butyrate, with BP in humans is unclear, due in part to predominantly cross‐sectional analyses and different biospecimens (blood versus fecal) for SCFA measurement. Longitudinal studies including both circulating and fecal SCFAs are lacking.Methods and ResultsWe leveraged existing data from the SPIRIT (Survivorship Promotion In Reducing IGF‐1 Trial), which randomized 121 adult cancer survivors with overweight/obesity to a behavioral weight‐loss intervention, metformin, or self‐directed weight‐loss. Of participants with baseline serum and fecal SCFAs measured (n=111), a subset had serum (n=93) and fecal (n=89) SCFA measurements 12 months later. We used Poisson regression with robust error variance to estimate baseline associations of SCFAs with hypertension, and we assessed the percent change in SCFAs from baseline with corresponding 12‐month changes in BP using multiple linear regression. Baseline fecal butyrate was inversely associated with prevalent hypertension (standardized PR [95%CI]: 0.71 [0.54, 0.92]). A 10% increase in fecal butyrate from baseline was associated with decreased systolic BP (β [95%CI]: −0.56 [−1.01, −0.10] mm Hg), and a 10% increase in serum butyrate was associated with decreased systolic (β [95%CI]: −1.39 [−2.15, −0.63] mm Hg) and diastolic (β [95%CI]: −0.55 [−1.03, −0.08] mm Hg) BPs. Butyrate associations with systolic BP were linear and not modified by sex, race, or intervention arm.ConclusionsIncreased serum or fecal butyrate is associated with lowered BP. Butyrate may be a target for SCFA‐centered BP‐lowering interventions.RegistrationURL:https://www.clinicaltrials.gov; Unique identifier: NCT02431676.
Racial and Ethnic Differences in Cardiac Rehabilitation Participation: Effect Modification by Household Income
Authors: Garfein Joshua , Guhl Emily N. , Swabe Gretchen , Sekikawa Akira , Barinas‐Mitchell Emma , Forman Daniel E. , Magnani Jared W. 
Published: June 2022

Background
Cardiac rehabilitation (CR) is associated with improved cardiovascular outcomes. Racial and ethnic differences in CR have been identified, but whether income may attenuate these disparities remains unknown. We evaluated (1) racial/ethnic differences in CR participation in a contemporary sample of insured US adults, and (2) assessed how household income modifies associations between race or ethnicity and CR participation.

Methods and Results

We identified 107 199 individuals with a CR‐qualifying diagnosis between January 1, 2016 and December 31, 2018 in Optum’s de‐identified Clinformatics database. We evaluated associations between race or ethnicity and participation in CR, and assessed interaction between race or ethnicity and annual household income. The mean±SD age of all participants was 70.4±11.6 years; 37.4% were female and 76.0% were White race. Overall, 28 443 (26.5%) attended ≥1 CR sessions. After adjustment, compared with White individuals, the probability of attending CR was 31% lower for Asian individuals (95% CI, 27%–36%), 19% lower for Black individuals (95% CI, 16%–22%), and 43% lower for Hispanic individuals (95% CI, 40%–45%), all
P
<0.0001. The time to CR attendance was also significantly longer for Asian, Black, and Hispanic individuals. Associations between race or ethnicity and attendance at CR differed significantly across household income categories (
P
interaction=0.0005); however, Asian, Black, and Hispanic individuals were less likely to attend CR at all incomes.

Conclusions
In a geographically and racially diverse cohort, participation in CR was low overall, and was lowest among Asian, Black, and Hispanic candidates. Household income may impact the link between race or ethnicity and attendance at CR, but substantial racial and ethnic disparities exist across incomes.
Exploring the prevalence, impact and experience of cardiac cachexia in patients with advanced heart failure and their caregivers: A sequential phased study
Authors: Carson Matthew A , Reid Joanne , Hill Loreena , Dixon Lana , Donnelly Patrick , Slater Paul , Hill Alyson , Piper Susan E , McDonagh Theresa A , Fitzsimons Donna 
Published: June 2022

Background: Cardiac Cachexia is a wasting syndrome that has a significant impact on patient mortality and quality of life world-wide, although it is poorly understood in clinical practice. Aim: Identify the prevalence of cardiac cachexia in patients with advanced New York Heart Association (NYHA) functional class and explore its impact on patients and caregivers. Design: An exploratory cross-sectional study. The sequential approach had two phases, with phase 1 including 200 patients with NYHA III-IV heart failure assessed for characteristics of cardiac cachexia. Phase 2 focussed on semi-structured interviews with eight cachectic patients and five caregivers to ascertain the impact of the syndrome. Setting/participants: Two healthcare trusts within the United Kingdom. Results: Cardiac Cachexia was identified in 30 out of 200 participants, giving a prevalence rate of 15%. People with cachexia had a significantly reduced average weight and anthropometric measures ( p < 0.05). Furthermore, individuals with cachexia experienced significantly more fatigue, had greater issues with diet and appetite, reduced physical wellbeing and overall reduced quality of life. C-reactive protein was significantly increased, whilst albumin and red blood cell count were significantly decreased in the cachectic group ( p < 0.05). From qualitative data, four key themes were identified: (1) ‘Changed relationship with food and eating’, (2) ‘Not me in the mirror’, (3) ‘Lack of understanding regarding cachexia’ and (4) ‘Uncertainty regarding the future’. Conclusions: Cardiac cachexia has a debilitating effect on patients and caregivers. Future work should focus on establishing a specific definition and clinical pathway to enhance patient and caregiver support.
Is there a correlation between urolithiasis in horseshoe kidneys and isthmus thickness or renal angulation?
Authors: Kozan Andrei Adrian , Khan Atif , Adiotomre Ese , Burbidge Simon , Kimuli Michael , Biyani Chandra Shekhar , Lee Nicola 
Published: June 2022

Background: Stone disease is a common complication of horseshoe kidneys (HSK). There are currently limited studies that examine the relationship between HSK anatomy and stone formation. We aim to determine if there is such an association by measuring the isthmus size and renal angulation in both stone and non-stone forming HSK using computed tomography (CT). Method: This is a retrospective study performed at a single tertiary centre. Using the radiological information system, all CT reports between 01 January 2010 and 31 December 2015 were searched for the keyword ‘horseshoe’ on the radiological information system. This produced a list of 285 reports. Each report and image packet of these 285 studies were reviewed to confirm the presence of an HSK and duplicate patients from multiple examinations were highlighted. One hundred and thirty-eight unique HSK patients were obtained and the studies were assessed for the presence or absence of stones. A total of 112 HSK were found; 88 of which contained no stone and 24 with stone. Angle measurements and isthmus size were measured on these kidneys. As axial images are obtained as standard in all cases, these measurements were all obtained in the axial plane. All parameters were measured and recorded manually by one person so as to reduce inter-observer variability. Results: Isthmus size varied widely, measuring from 2 to 39 mm. Right renal angle ranged from 51 to 158°, left 38 to 152°. Conclusion: The isthmus size and renal angle measurements were not found to be significant determinants for stone disease in our patient population.
Formononetin regulates endothelial nitric oxide synthase to protect vascular endothelium in deep vein thrombosis rats
Authors: Zhou Zhongxiao , Zhou Haimeng , Zou Xin , Wang Xiaowei , Yan Mengjun 
Published: June 2022

Objective Formononetin is a bioactive isoflavone that has numerous medicinal benefits. We explored the feasibility and its mechanism of formononetin on treating acute deep vein thrombosis (DVT) in rats. Materials and methods Inferior vena cava (IVC) stenosis was performed to establish the DVT rat model. First, different doses of formononetin were used to observe the feasibility of formononetin on treating DVT. In sham and DVT groups, rats were orally treated with vehicle. In the remaining groups, formononetin (10 mg/kg, 20 mg/kg, and 40 mg/kg) was orally treated once a day for 7 days at 24 h after IVC. After 7 days, the levels of thrombosis and inflammation related factors in plasma were measured. The expression of endothelial nitric oxide synthase (eNOS) was analyzed by western blot and immunofluorescence. Molecular docking was used to evaluate the interaction between the formononetin and eNOS. Further, the NOS inhibitor (L-NAME) was used to explore the mechanism of formononetin for DVT. Result After treatment with formononetin, the average weights of thrombosis were decreased, and the levels of thrombosis and inflammation related factors were also significantly decreased. Additionally, phosphorylation of eNOS was increased with the formononetin administration. There is a good activity of formononetin to eNOS (total score = −6.8). However, the effects of 40 mg/kg formononetin were concealed by the NOS inhibitor (L-NAME). Conclusion Formononetin reduces vascular endothelium injury induced by DVT through increasing eNOS in rats, which provides a potential drug for treatment of venous thrombosis.
What Do We Really Know about Productivity Differentials across Countries?
Authors: Ghosh Jayati 
Published: June 2022

This article examines and critiques the most widely used measure of productivity (output per worker employed) and argues that this is a flawed, inadequate, and even misleading measure of economic progress. In terms of cross-country comparisons and assessing trends over time, both the numerator (GDP or value added) and the denominator (number of workers or hours worked) have significant conceptual and measurement problems. These issues are considered both in general and regarding how they affect analyses of productivity differentials in the United States and India in the recent period. JEL Classification: B5, O47, E24
The Net Social Wage in Turkey, 1980–2019
Authors: Karabacak Yakup , Tonak E. Ahmet 
Published: June 2022

This essay conceptualizes the capitalist state’s taxation and expenditure activities in Marx’s circuit of capital. It also empirically shows how the net social wage has evolved in Turkey in the period 1980–2019 and in what direction it has influenced the rate of surplus value. The essay’s empirical findings demonstrate the utter failure of the pseudo-welfare state of Turkey to ameliorate income distribution. Hence, the article contributes to demolishing the myth that the Islamist party AKP, in power since 2003, is pro-poor and pro-labor, and that its fiscal policies have been consistent with its glorified Islamic values and its self-ascribed image of an antipoverty stance. JEL Classification: H2, H5, I30
Initiation of Antipsychotic Treatment for Amphetamine Induced Psychosis and Its Impact on Length of Stay
Authors: Herbst Claire , O’Connell Megan , Melton Brittany L. , Moeller Karen E. 
Published: June 2022

Introduction: A risk of amphetamine use is amphetamine-induced psychosis (AIP). Symptoms of AIP include hallucinations, delusions, and agitation. While AIP may resolve with abstinence from amphetamines, antipsychotics are commonly used despite not being FDA approved. The primary objective of this study was to compare length of stay (LOS) for patients with AIP treated with antipsychotics vs untreated. Secondary aims were to determine antipsychotic prescribed, proportion of patients utilizing as needed doses, time to initiation, and readmissions. Methods: A retrospective chart review conducted at an academic medical center identified adult participants who were diagnosed with AIP, admitted to inpatient psychiatry service, and had a urine drug screen (UDS) positive for amphetamines. Patients were excluded if they were already taking an antipsychotic, had active prescriptions for amphetamine salts, or were in the emergency department for more than 48 hours. Demographics were assessed with descriptive statistics. Length of stay was compared between treatment groups using Kruskal-Wallis. Secondary aims were assessed using chi-square, Mann-Whitney U, and Kruskal-Wallis. Results: Sixty-nine patients were included. Median LOS for patients treated with antipsychotics (n = 35) was longer than untreated patients (n = 34), (5 days vs 2.5 days, P = .001). Type of antipsychotic used and time to initiation of antipsychotic were not found to affect LOS. There was no difference in readmissions rates and positive UDS on readmission between groups. Conclusion: This study found patients with scheduled antipsychotics for AIP had a longer LOS than patients who did not receive scheduled antipsychotics. Future studies are needed to evaluate antipsychotic use in AIP.