bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incident Cancer Risk and Signatures Among Older MUTYH Carriers: Analysis of Population-Based and Genomic Cohorts
Authors: Downie Jonathan M. , Riaz Moeen , Xie Jing , Lee Minyi , Chan Andrew T. , Gibbs Peter , Orchard Suzanne G. , Mahady Suzanne E. , Sebra Robert P. , Murray Anne M. , Macrae Finlay , Schadt Eric , Woods Robyn L. , McNeil John J. , Lacaze Paul , Gala Manish 
Published: July 2022

Abstract

MUTYH carriers have an increased colorectal cancer risk in case–control studies, with loss of heterozygosity (LOH) as the presumed mechanism. We evaluated cancer risk among carriers in a prospective, population-based cohort of older adults. In addition, we assessed if cancers from carriers demonstrated mutational signatures (G:C&gt;T:A transversions) associated with early LOH. We calculated incident risk of cancer and colorectal cancer among 13,131 sequenced study participants of the ASPirin in Reducing Events in the Elderly cohort, stratified by sex and adjusting for age, smoking, alcohol use, BMI, polyp history, history of cancer, and aspirin use. MUTYH carriers were identified among 13,033 participants in The Cancer Genome Atlas and International Cancer Genome Consortium, and somatic signatures of cancers were analyzed. Male MUTYH carriers demonstrated an increased risk for overall cancer incidence [multivariable HR, 1.66; 95% confidence interval (CI), 1.03–2.68; P = 0.038] driven by increased colorectal cancer incidence (multivariable HR, 3.55; 95% CI, 1.42–8.78; P = 0.007), as opposed to extracolonic cancer incidence (multivariable HR, 1.40; 95% CI, 0.81–2.44; P = 0.229). Female carriers did not demonstrate increased risk of cancer, colorectal cancer, or extracolonic cancers. Analysis of mutation signatures from cancers of MUTYH carriers revealed no significant contribution toward early mutagenesis from widespread G:C&gt;T:A transversions among gastrointestinal epithelial cancers. Among cancers from carriers, somatic transversions associated with base-excision repair deficiency are uncommon, suggestive of diverse mechanisms of carcinogenesis in carriers compared with those who inherit biallelic MUTYH mutations.

Prevention Relevance:
Despite absence of loss of heterozygosity in colorectal cancers, elderly male MUTYH carriers appeared to be at increased of colorectal cancer.
GLS1 is a Protective Factor in Patients with Ovarian Clear Cell Carcinoma and its Expression Does Not Correlate with ARID1A-mutated Tumors
Authors: Clemente Valentino , Hoshino Asumi , Shetty Mihir , Nelson Andrew , Erickson Britt K. , Baker Ruth , Rubin Nathan , Khalifa Mahmoud , Weroha S. John , Lou Emil , Bazzaro Martina 
Published: July 2022

Targeting glutamine metabolism has emerged as a novel therapeutic strategy for several human cancers, including ovarian cancer. The primary target of this approach is the kidney isoform of glutaminase, glutaminase 1 (GLS1), a key enzyme in glutamine metabolism that is overexpressed in several human cancers. A first-in-class inhibitor of GLS1, called CB839 (Telaglenastat), has been investigated in several clinical trials, with promising results. The first clinical trial of CB839 in platinum-resistant patients with ovarian cancer is forthcoming. ARID1A-mutated ovarian clear cell carcinoma (OCCC) is a relatively indolent and chemoresistant ovarian cancer histotype. In OCCC-derived cells ARID1A simultaneously drives GLS1 expression and metabolism reprograming. In ARID1A-mutated OCCC-derived mouse models, loss of ARID1A corresponds to GLS1 upregulation and increases sensitivity to GLS1 inhibition. Thus, targeting of GLS1 with CB839 has been suggested as a targeted approach for patients with OCCC with tumors harboring ARID1A mutations. Here, we investigated whether GLS1 is differentially expressed between patients with OCCC whose tumors are ARID1A positive and patients whose tumors are ARID1A negative. In clinical specimens of OCCC, we found that GLS1 overexpression was not correlated with ARID1A loss. In addition, GLS1 overexpression was associated with better clinical outcomes. Our findings have implications for human trials using experimental therapeutics targeting GLS1.Significance:GLS1 differential expression in patients with OCCC with or without ARID1A mutations is significant because a clinical trial with a GLS1 inhibitor is forthcoming. Tumors without ARID1A have low levels of GLS1 and GLS1 expression is associated to better outcome. Thus, blockade of GLS1 could be counterproductive for patients with OCCC.
Socioeconomic Deprivation: An Important, Largely Unrecognized Risk Factor in Primary Prevention of Cardiovascular Disease
Authors: Kimenai Dorien M. , Pirondini Leah , Gregson John , Prieto David , Pocock Stuart J. , Perel Pablo , Hamilton Tilly , Welsh Paul , Campbell Archie , Porteous David J. , Hayward Caroline , Sattar Naveed , Mills Nicholas L. , Shah Anoop S.V. 
Published: July 2022

Background:
Socioeconomic deprivation is associated with higher cardiovascular morbidity and mortality. Whether deprivation status should be incorporated in more cardiovascular risk estimation scores remains unclear. This study evaluates how socioeconomic deprivation status affects the performance of 3 primary prevention cardiovascular risk scores.

Methods:
The Generation Scotland Scottish Family Health Study was used to evaluate the performance of 3 cardiovascular risk scores with (ASSIGN [Assessing cardiovascular risk using SIGN (Scottish Intercollegiate Guidelines Network) guidelines to ASSIGN preventive treatment]) and without (SCORE2 [Systematic Coronary Risk Evaluation 2 algorithm], Pooled Cohort Equations) socioeconomic deprivation as a covariate in the risk prediction model. Deprivation was defined by Scottish Index of Multiple Deprivation score. The predicted 10-year risk was evaluated against the observed event rate for the cardiovascular outcome of each risk score. The comparison was made across 3 groups defined by the deprivation index score consisting of group 1 defined as most deprived, group 3 defined as least deprived, and group 2, which consisted of individuals in the middle deprivation categories.

Results:

The study population consisted of 15 506 individuals (60.0% female, median age of 51). Across the population, 1808 (12%) individuals were assigned to group 1 (most deprived), 8119 (52%) to group 2, and 4708 (30%) to group 3 (least deprived), and 871 (6%) individuals had a missing deprivation score. Risk scores based on models that did not include deprivation status significantly under predicted risk in the most deprived (6.43% observed versus 4.63% predicted for SCORE2 [
P
=0.001] and 6.69% observed versus 4.66% predicted for Pooled Cohort Equations [
P
<0.001]). Both risk scores also significantly overpredicted the risk in the least deprived group (3.97% observed versus 4.72% predicted for SCORE2 [
P
=0.007] and 4.22% observed versus 4.85% predicted for Pooled Cohort Equations [
P
=0.028]). In contrast, no significant difference was demonstrated in the observed versus predicted risk when using the ASSIGN risk score, which included socioeconomic deprivation status in the risk model.

Conclusions:
Socioeconomic status is a largely unrecognized risk factor in primary prevention of cardiovascular disease. Risk scores that exclude socioeconomic deprivation as a covariate under- and overestimate the risk in the most and least deprived individuals, respectively. This study highlights the importance of incorporating socioeconomic deprivation status in risk estimation systems to ultimately reduce inequalities in health care provision for cardiovascular disease.
Association of Extreme Heat and Cardiovascular Mortality in the United States: A County-Level Longitudinal Analysis From 2008 to 2017
Authors: Khatana Sameed Ahmed M. , Werner Rachel M. , Groeneveld Peter W. 
Published: July 2022

Background:
Extreme-heat events are increasing as a result of climate change. Prior studies, typically limited to urban settings, suggest an association between extreme heat and cardiovascular mortality. However, the extent of the burden of cardiovascular deaths associated with extreme heat across the United States and in different age, sex, or race and ethnicity subgroups is unclear.

Methods:
County-level daily maximum heat index levels for all counties in the contiguous United States in summer months (May–September) and monthly cardiovascular mortality rates for adults ≥20 years of age were obtained. For each county, an extreme-heat day was identified if the maximum heat index was ≥90 °F (32.2 °C) and in the 99th percentile of the maximum heat index in the baseline period (1979–2007) for that day. Spatial empirical Bayes smoothed monthly cardiovascular mortality rates from 2008 to 2017 were the primary outcome. A Poisson fixed-effects regression model was estimated with the monthly number of extreme-heat days as the independent variable of interest. The model included time-fixed effects and time-varying environmental, economic, demographic, and health care–related variables.

Results:

Across 3108 counties, from 2008 to 2017, each additional extreme-heat day was associated with a 0.12% (95% CI, 0.04%–0.21%;
P
=0.004) higher monthly cardiovascular mortality rate. Extreme heat was associated with an estimated 5958 (95% CI, 1847–10 069) additional deaths resulting from cardiovascular disease over the study period. In subgroup analyses, extreme heat was associated with a greater relative increase in mortality rates among men compared with women (0.20% [95% CI, 0.07%–0.33%]) and non-Hispanic Black compared with non-Hispanic White adults (0.19% [95% CI, 0.01%–0.37%]). There was a greater absolute increase among elderly adults compared with nonelderly adults (16.6 [95% CI, 14.6–31.8] additional deaths per 10 million individuals per month).

Conclusions:
Extreme-heat days were associated with higher adult cardiovascular mortality rates in the contiguous United States between 2008 and 2017. This association was heterogeneous among age, sex, race, and ethnicity subgroups. As extreme-heat events increase, the burden of cardiovascular mortality may continue to increase, and the disparities between demographic subgroups may widen.
Cost Comparison: Evaluating Transfemoral and Transradial Access for Diagnostic Cerebral Angiography
Authors: Dodd William S. , Small Coulter N. , Goutnik Michael , Laurent Dimitri , Crossman James , Motwani Kartik , Lucke‐Wold Brandon , Polifka Adam J. , Koch Matthew , Brzezicki Grzegorz , Hoh Brian L. , Chalouhi Nohra 
Published: July 2022

Background
Modern medicine necessitates the delivery of increasingly complex health care while minimizing cost. Transradial access (TRA) for neuroendovascular procedures is becoming more common as accumulating data demonstrate fewer complications, improved patient satisfaction, and high rates of treatment success compared with the transfemoral access (TFA) approach; however, disparities in cost between these approaches remain unclear. We compared supply and equipment costs between TRA and TFA for diagnostic cerebral angiography and evaluate the specific items that account for these differences.

Methods
We reviewed all adult patients who underwent diagnostic cerebral angiography from July 1, 2019 to December 31, 2019. Data related to patient demographics, vascular access site, catheters used, cost of catheters, arterial access sheath use, cost of sheaths, closure devices used, and cost of closure devices were collected.

Results
The transradial approach resulted in higher price of radial access sheath; however, the overall cost of closure devices was much lower in TRA group than in the TFA cohort. There was no significant difference in the cost of catheters. Overall, the total supply costs for TRA cerebral angiography were significantly lower than those of TFA cerebral angiography. The relative materials cost difference of using TRA was 20.9%.

Conclusion
This study is the first itemized materials cost analysis of TRA versus TFA cerebral angiography. TRA necessitates the use of a more expensive access sheath device; however, this cost is offset by the increased cost of devices used for femoral arteriotomy closure. Overall, the supply and equipment costs were significantly lower for TRA than TFA.
A Primer on Phased Array Radar Technology for the Atmospheric Sciences
Authors: Palmer Robert , Bodine David , Kollias Pavlos , Schvartzman David , Zrnić Dusan , Kirstetter Pierre , Zhang Guifu , Yu Tian-You , Kumjian Matthew , Cheong Boonleng , Collis Scott , Frasier Stephen , Fulton Caleb , Hondl Kurt , Kurdzo James , Ushio Tomoo , Rowe Angela , Salazar-Cerrenˉo Jorge , Torres Sebastián , Weber Mark , Yeary Mark 
Published: July 2022

Abstract
The scientific community has expressed interest in the potential of phased array radars (PARs) to observe the atmosphere with finer spatial and temporal scales. Although convergence has occurred between the meteorological and engineering communities, the need exists to increase access of PAR to meteorologists. Here, we facilitate these interdisciplinary efforts in the field of ground-based PARs for atmospheric studies. We cover high-level technical concepts and terminology for PARs as applied to studies of the atmosphere. A historical perspective is provided as context along with an overview of PAR system architectures, technical challenges, and opportunities. Envisioned scan strategies are summarized because they are distinct from traditional mechanically scanned radars and are the most advantageous for high-resolution studies of the atmosphere. Open access to PAR data is emphasized as a mechanism to educate the future generation of atmospheric scientists. Finally, a vision for the future of operational networks, research facilities, and expansion into complementary radar wavelengths is provided.
Mixing driven by critical reflection of near-inertial waves over the Texas-Louisiana shelf
Authors: Qu Lixin , Thomas Leif N. , Hetland Robert D. , Kobashi Daĳiro 
Published: July 2022

Abstract
Studies of internal wave-driven mixing in the coastal ocean have been mainly focused on internal tides, while wind-driven near-inertial waves (NIWs) have received less attention in this regard. This study demonstrates a scenario of NIW-driven mixing over the Texas-Louisiana shelf. Supported by a high-resolution simulation over the shelf, the NIWs driven by land-sea breeze radiate downward at a sharp front and enhance the mixing in the bottom boundary layer where the NIWs are focused due to slantwise critical reflection. The criterion for slantwise critical reflection of NIWs is (where ω is the wave frequency, Sbot is the bottom slope, and Sp is the isopycnal slope) under the assumption that the mean flow is in a thermal wind balance and only varies in the slope-normal direction. The mechanism driving the enhanced mixing is explored in an idealized simulation. During slantwise critical reflection, NIWs are amplified with enhanced shear and periodically destratify a bottom boundary layer via differential buoyancy advection, leading to periodically enhanced mixing. Turbulent transport of tracers is also enhanced during slantwise critical reflection of NIWs, which has implications for bottom hypoxia over the Texas-Louisiana shelf.
Russia-Ukraine War and WTO’s National Security Exception
Authors: Ranjan Prabhash 
Published: July 2022

The Russian invasion of Ukraine is one of the most flagrant violations of international law in recent times. The Russian action has received global condemnation with various countries imposing sanctions on Russia. This article argues that concerning imposing trade sanctions against Russia, countries can rely on the national security exception in the World Trade Organization (WTO). The relevant legal provision in this regard is Article XXI of the General Agreements on Tariffs and Trade (GATT). The article undertakes a doctrinal analysis of GATT’s Article XXI. This analysis is conducted in the light of two WTO disputes—the Russia: Transit case and the Saudi Arabia: Intellectual Property case—that have interpreted the national security exception. The article argues that while the national security exception given in GATT’s Article XXI is not self-judging, countries will enjoy deference in determining their essential security interests. The article then applies this doctrinal understanding to the current Russia–Ukraine war. The current situation will fall under Article XXI, and countries can impose trade-restricting measures against Russia (such as suspension of the most-favoured-nation treatment) following Article XXI of GATT. JEL Codes: F13, F19, F52, F51
Left ventricular venting during extracorporeal membrane oxygenation; the effects on cardiac performance in a porcine model of critical post-cardiotomy failure
Authors: Solholm Atle , Salminen Pirjo-Riitta , Stangeland Lodve , Dahle Geir Olav , Mongstad Arve , Svenheim Bård , Zhang Liqun , Haaverstad Rune , Grong Ketil 
Published: July 2022

Introduction Left ventricular distension is a major concern with postcardiotomy veno-arterial extracorporeal membrane oxygenation (VA-ECMO) supporting a critical heart failure after cardiac surgery. This porcine study evaluates the effects of left ventricular venting on cardiac function during ECMO-supported circulation and after weaning from ECMO. Methods Twenty anaesthetised open-chest pigs were put on cardiopulmonary bypass with aortic cross-clamping and suboptimal cardioplegic arrest for 40 min. After declamping and defibrillation, the animals were supported by VA-ECMO for 180 min either with or without additional left ventricular venting. Continuous haemodynamic evaluations were performed at baseline and at cardiac arrest, during VA-ECMO and for 120 min after weaning from circulatory support. Left ventricular perfusion and function were evaluated with microspheres, pressure-volume loops and epicardial echocardiography at baseline and after 1 and 2 h with unsupported circulation. Results In vented animals both mean aortic and left ventricular peak systolic pressure increased at the end of the ECMO-supported period compared to those not vented and remained increased also after weaning. Both at 60 min and 120 min after weaning from circulatory support, left ventricular stroke work and pressure-volume area were increased in vented compared to not vented animals. At 120 min left ventricular stroke volume was increased in vented compared to not vented animals, myocardial perfusion did not differ. The left ventricular mechanical efficiency, defined as the ratio between pressure volume area and myocardial perfusion, was increased (53.2 ± 5 vs 36.2 ± 2.1 J/mL/g, p = 0.011) in vented- compared to not vented hearts. Conclusion This experimental study demonstrate that left ventricular venting during post-cardiotomy veno-arterial ECMO for 3 h attenuates deterioration of left ventricular function and haemodynamics early after weaning from circulatory support.
Postoperative Adjuvant Chemoradiotherapy Versus Chemotherapy Alone for Stage III Endometrial Cancer: A Multicenter Retrospective Study
Authors: Yoo Ji Geun , Kim Jin Hwi , Kim Chan Joo , Lee Hae Nam , Song Min Jong , Park Dong Choon , Yoon Joo Hee , Kim Sang Il , Hur Soo Young , Lee Sung Jong 
Published: July 2022

Introduction We aimed to evaluate the efficacy and toxicity of the combination of 6 cycles of chemotherapy and radiation therapy compared with chemotherapy alone as postoperative adjuvant therapy for patients with stage III endometrial cancer. Methods This retrospective cohort study included patients with stage III endometrial cancer who received postoperative chemoradiotherapy or chemotherapy alone at 6 hospitals between January 2009 and December 2019. The progression-free survival (PFS) and overall survival (OS) for each treatment group were analyzed using the Kaplan–Meier method. We also assessed differences in toxicity profiles between the treatment groups. Results A total of 133 patients met the inclusion criteria. Of these, 80 patients (60.2%) received adjuvant chemoradiotherapy and 53 (39.8%) received chemotherapy alone. The PFS and OS did not differ significantly between the groups. For patients with stage IIIC endometrioid subtype, the chemoradiotherapy group had significantly longer PFS rate than did the chemotherapy alone group (log-rank test, P = .019), although there was no significant difference in the OS (log-rank test, P = .100). CRT was identified as a favorable prognostic factor for PFS in multivariate analysis (adjusted HR, .37; 95% CI, .16-.87; P = .022). Patients treated with chemoradiotherapy more frequently suffered from grade 4 neutropenia (73.8% vs 52.8%; P = .018) and grade 3 or worse thrombocytopenia (36.3% vs 9.4%; P = .001) compared with the chemotherapy alone group. There were no differences between the 2 treatment groups in the frequency of toxicity-related treatment discontinuation or dose reduction. Conclusion We confirmed that chemoradiotherapy yields longer progression-free survival than does chemotherapy alone for patients with stage IIIC endometrioid endometrial cancer, with an acceptable toxicity profile.
Long-term changes in blood metal ion levels in patients with hip resurfacing implants: implications for patient surveillance after 10 years follow-up
Authors: Reito Aleksi , Lainiala Olli , Berryman Fiona , Dunlop David J , Eskelinen Antti , Matharu Gulraj S 
Published: July 2022

Background: Studies investigating changes in blood metal ion levels during the second decade of the implant lifetime in MoM hip resurfacing patients are scarce. Methods: Patients implanted with either Birmingham Hip Resurfacing (BHR) or Articular Surface Replacement (ASR) hip resurfacings with >10 years follow-up and repeated blood metal ion measurements were identified at 2 large specialist European arthroplasty centres. After excluding patients with initial metal ion levels >7 ppb, the proportion of patients with an increase in blood metal ion levels above previously validated implant-specific thresholds (cobalt 2.15 ppb for unilateral implants, cobalt or chromium 5.5 ppb for bilateral) was assessed. Results: We included 2743 blood metal ion measurements from 457 BHR patients (555 hips) and 216 ASR patients (263 hips). Of patients with initial metal ion levels below implant specific thresholds, increases in cobalt or chromium level, respectively, to above these thresholds during the second decade were seen as follows: unilateral BHR (cobalt = 15.6%), unilateral ASR (cobalt = 13.8%), bilateral BHR (cobalt = 8.2%, chromium = 11.8%), bilateral ASR (cobalt = 8.5%, chromium = 4.3%). Measurement-to-measurement changes exceeding +2.15 ppb or +5.5 ppb were, however, uncommon during the second decade. Subgroup results with small diameter (<50 mm) implants were similar. Conclusions: We recommend less frequent blood metal ion measurements are needed (every 3 to 5 years) for hip resurfacing patients if initial values were below 7ppb.