bluuebunny/crossref_metadata_2025_split huggingface dataset:
On Rogers–Shephard-type inequalities for the lattice point enumerator
Authors: Alonso-Gutiérrez David , Lucas Eduardo , Yepes Nicolás Jesús 
Published: April 2022

In this paper, we study various Rogers–Shephard-type inequalities for the lattice point enumerator [Formula: see text] on [Formula: see text]. In particular, for any non-empty convex bounded sets [Formula: see text], we show that [Formula: see text] and [Formula: see text] for [Formula: see text], [Formula: see text]. Additionally, a discrete counterpart to a classical result by Berwald for concave functions, from which other discrete Rogers–Shephard-type inequalities may be derived, is shown. Furthermore, we prove that these new discrete analogues for [Formula: see text] imply the corresponding results involving the Lebesgue measure.
Biogeomorphology
Authors: Viles Heather A. 
Published: April 2022

Abstract
Biogeomorphological research blossomed during the second half of the twentieth century, partly in response to some big, unanswered questions about the role of vegetation in fluvial geomorphology, but also as technical advances allowed more detailed study of the complex interactions between biota and Earth surface processes. Formal recognition of biogeomorphology (also known as ecogeomorphology) as a subfield of geomorphology came in the late 1980s, building on several foundational pieces of research. Key foci of interest for biogeomorphological research up until the end of the twentieth century were quantifying the impact of vegetation on erosion and the geomorphological roles of individual animal species, as well as understanding the human influences on biogeomorphic systems.
Racial Disparities in Prostate Cancer: Evaluation of Diet, Lifestyle, Family History, and Screening Patterns
Authors: Hansen Megan , Hamieh Nadine M. , Markt Sarah C. , Vaselkiv Jane B. , Pernar Claire H. , Gonzalez-Feliciano Amparo G. , Peisch Samuel , Chowdhury-Paulino Ilkania M. , Rencsok Emily M. , Rebbeck Timothy R. , Platz Elizabeth A. , Giovannucci Edward L. , Wilson Kathryn M. , Mucci Lorelei A. 
Published: April 2022

Abstract

Background:
Racial disparities in prostate cancer incidence and mortality rates are considerable. We previously found in the Health Professionals Follow-up Study (HPFS) that African-American men had an 80% higher prostate cancer risk than White men. With 21 additional years of follow-up and four-fold increase in cases, we undertook a contemporary analysis of racial differences in prostate cancer incidence and mortality in HPFS.

Methods:
For 47,679 men, we estimated HRs and 95% confidence intervals (CI) for the association between race and risk of prostate cancer through 2016 using Cox proportional hazards regression. Multivariable models (mHR) were adjusted for lifestyle, diet, family history, and PSA screening collected on biennial questionnaires.

Results:
6,909 prostate cancer cases were diagnosed in White, 89 in African-American, and 90 in Asian-American men. African-Americans had higher prostate cancer incidence (mHR = 1.31; 95% CI, 1.06–1.62) and mortality (mHR = 1.67; 95% CI, 1.00–2.78), and lower PSA screening prevalence than White men. The excess risk was greater in the pre-PSA screening era (HR = 1.68; 95% CI, 1.14–2.48) than the PSA screening era (HR = 1.20; 95% CI, 0.93–1.56). Asian-Americans had lower prostate cancer risk (mHR = 0.74; 95% CI, 0.60–0.92), but similar risk of fatal disease compared with white men.

Conclusions:
Racial differences in prostate cancer incidence and mortality in HPFS are not fully explained by differences in lifestyle, diet, family history, or PSA screening.

Impact:
Additional research is necessary to address the disproportionately higher rates of prostate cancer in African-American men.
Role of Medicaid in Early Detection of Screening-Amenable Cancers
Authors: Bradley Cathy J. , Sabik Lindsay M. , Entwistle Julia , Stevens Jennifer L. , Enewold Lindsey , Warren Joan L. 
Published: April 2022

Abstract

Background:
This study examines the association between Medicaid enrollment, including through the National Breast and Cervical Cancer Early Detection Program (NBCCEDP), and distant stage for three screening-amenable cancers: breast, cervical, and colorectal.

Methods:
We use the Surveillance, Epidemiology, and End Results Cancer Registry linked with Medicaid enrollment data to compare patients who were Medicaid insured with patients who were not Medicaid insured. We estimate the likelihood of distant stage at diagnosis using logistic regression.

Results:
Medicaid enrollment following diagnosis was associated with the highest likelihood of distant stage. Medicaid enrollment through NBCCEDP did not mitigate the likelihood of distant stage disease relative to Medicaid enrollment prior to diagnosis. Non-Hispanic Black patients had a greater likelihood of distant stage breast and colorectal cancer. Residing in higher socioeconomic areas was associated with a lower likelihood of distant stage breast cancer.

Conclusions:
Medicaid enrollment prior to diagnosis is associated with a lower likelihood of distant stage in screen amenable cancers but does not fully ameliorate disparities.

Impact:
Our study highlights the importance of health insurance coverage prior to diagnosis and demonstrates that while targeted programs such as the NBCCEDP provide critical access to screening, they are not a substitute for comprehensive insurance coverage.
Association of Fruit, Vegetable, and Animal Food Intakes with Breast Cancer Risk Overall and by Molecular Subtype among Vietnamese Women
Authors: Nguyen Sang M. , Tran Huong T.T. , Nguyen Lan M. , Bui Oanh Thi , Hoang Dong V. , Shrubsole Martha J. , Cai Qiuyin , Ye Fei , Zheng Wei , Luu Hung N. , Tran Thuan V. , Shu Xiao-Ou 
Published: April 2022

Abstract

Background:
Evidence on associations between dietary intake and risk of breast cancer subtypes is limited and inconsistent. We evaluated associations of fruit, vegetable, meat, and fish consumption with risk of breast cancer overall and by molecular subtype in the Vietnamese Breast Cancer Study (VBCS).

Method:
VBCS includes 476 incident breast cancer cases and 454 age-matched controls. Dietary habits over the past 5 years were assessed by in-person interviews using a validated food frequency questionnaire. Associations of food groups with breast cancer were evaluated via logistic regression for overall and molecular subtype with adjustment for age, education, income, family history of cancer, menopausal status, body mass index, exercise, total energy intake, and other potential dietary confounders. Odds ratio (OR) was used to approximate relative risk.

Results:
High fruit intake was inversely associated with breast cancer risk, with adjusted ORs [95% confidence intervals (CI)] of 0.67 (95% CI, 0.47–0.95) and 0.41 (95% CI, 0.27–0.61) for second and third tertiles versus first tertile, respectively (Ptrend &lt; 0.001). This association was stronger for triple-negative than other subtypes (Pheterogeneity &lt; 0.001). High intake of freshwater fish was inversely associated with overall breast cancer (ORT3vsT1 = 0.63; 95% CI, 0.42–0.95; Ptrend = 0.03). An inverse association was observed between HER2-enriched subtype and red and organ meat intake (ORT3vsT1 = 0.40; 95% CI, 0.17–0.93; Ptrend = 0.04; Pheterogeneity = 0.50).

Conclusions:
High intakes of fruit and freshwater fish were associated with reduced breast cancer risk; association for the former was stronger for triple-negative subtype.

Impact:
Our findings suggest high intakes of fruit and freshwater fish may reduce breast cancer risk among Vietnamese women.
Race Differences in Telomere Length in Benign Prostate Biopsies and Subsequent Risk of Prostate Cancer
Authors: Rybicki Benjamin A. , Sadasivan Sudha M. , Chen Yalei , Loveless Ian , Gupta Nilesh S. , Chitale Dhananjay A. , Williamson Sean R. , Rundle Andrew G. , Tang Deliang L. 
Published: April 2022

AbstractBackground:Telomere shortening is linked to aging and may be associated with increased risk for cancer. Most cancer studies have used telomere length in leukocytes rather than in the target tissue of cancer origin.Methods:A case–control study of 524 case–control pairs with a benign prostate biopsy nested within a historical cohort of 10,478 men was conducted to determine whether premalignant prostate telomere length (assessed using a modified qRT-PCR) is associated with prostate cancer risk.Results:Telomere lengths in benign prostate biopsies of cases versus controls were similar (1.46 ± 0.38 vs. 1.45 ± 0.42; P = 0.49). African American (AA) men had significantly shorter telomeres compared with White men (1.51 ± 0.38 vs. 1.63 ± 0.39; P &lt; 0.0001). In race-stratified analyses, increasing telomere length was more strongly associated with prostate cancer risk in White men, wherein those with telomere length in the highest quartile had 1.9-fold greater adjusted risk of prostate cancer compared with men with prostate telomere lengths in the lowest quartile [OR = 1.90; 95% confidence interval (CI) = 1.08–3.36]. Men in the highest telomere length quartile also had a greater risk of aggressive prostate cancer compared with men with telomere lengths in the lowest quartile (OR = 2.78; 95% CI = 1.25–6.19).Conclusions:White men have longer telomeres in benign prostate tissue compared with AA men, and those with the longest telomeres may be at increased risk for prostate cancer, particularly the more aggressive form of the disease.Impact:Race-specific telomere length measures may be an early biomarker of aggressive prostate cancer.
Increasing Incidence of Gallbladder Cancer among Non-Hispanic Blacks in the United States: A Birth Cohort Phenomenon
Authors: Raza Syed Ahsan , da Costa Wilson L. , Thrift Aaron P. 
Published: April 2022

AbstractBackground:Gallbladder cancer incidence varies among racial/ethnic subgroups in the United States (US). We investigated trends in gallbladder cancer incidence rates in 50 states from 2001 to 2018.Methods:Age-adjusted incidence rates and trends in adults were calculated using data from the US Cancer Statistics registry. We used joinpoint regression to compute annual percentage of changes (APC). We analyzed incidence trends by time periods, age groups, and birth cohorts through age–period-cohort modeling.Results:Overall, age standardized incidence rates for gallbladder cancer decreased by 0.3% annually between 2001 and 2018 [95% confidence interval (CI) −0.5% to −0.1%]. However, secular trends varied by race/ethnicity. Although gallbladder cancer rates declined in other racial/ethnic groups, rates increased by 1.4% annually among non-Hispanic Blacks (NHB) between 2001 and 2018 (APC = 1.4%; 95% CI, 0.9%–2.0%). We found evidence for period and birth cohort effects with increasing rates among successive birth cohorts of NHBs. Relative to NHB cohorts born circa 1946, gallbladder cancer rates were 85% higher in NHB cohorts born circa 1971 [incidence rate ratio (IRR), 1.85; 95% CI, 1.26–2.72). The rates among NHBs in South region were higher in cohorts born circa 1971 (IRR, 2.17; 95% CI, 1.27–3.73) relative to those born circa 1946.Conclusions:The incidence of gallbladder cancer has consistently increased in the US among NHBs. A notable increase in incidence was observed among NHBs with evidence of birth cohort effects in South, Northeast, and Midwest regions.Impact:The cohort effect observed among NHBs with increasing rates in different US regions suggests that gallbladder cancer rates will continue to rise in the US in the near future.
Metabolically Defined Body Size Phenotypes and Risk of Endometrial Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)
Authors: Kliemann Nathalie , Ould Ammar Romain , Biessy Carine , Gicquiau Audrey , Katzke Verena , Kaaks Rudolf , Tjønneland Anne , Olsen Anja , Sánchez Maria-Jose , Crous-Bou Marta , Pasanisi Fabrizio , Tin Tin Sandar , Perez-Cornago Aurora , Aune Dagfinn , Christakoudi Sofia , Heath Alicia K. , Colorado-Yohar Sandra M. , Grioni Sara , Skeie Guri , Sartor Hanna , Idahl Annika , Rylander Charlotta , May Anne M. , Weiderpass Elisabete , Freisling Heinz , Playdon Mary C. , Rinaldi Sabina , Murphy Neil , Huybrechts Inge , Dossus Laure , Gunter Marc J. 
Published: April 2022

Abstract

Background:
Obesity is a risk factor for endometrial cancer but whether metabolic dysfunction is associated with endometrial cancer independent of body size is not known.

Methods:
The association of metabolically defined body size phenotypes with endometrial cancer risk was investigated in a nested case–control study (817 cases/ 817 controls) within the European Prospective Investigation into Cancer and Nutrition (EPIC). Concentrations of C-peptide were used to define metabolically healthy (MH; &lt;1st tertile) and metabolically unhealthy (MU; ≥1st tertile) status among the control participants. These metabolic health definitions were combined with normal weight (NW); body mass index (BMI)&lt;25 kg/m2 or waist circumference (WC)&lt;80 cm or waist-to-hip ratio (WHR)&lt;0.8) and overweight (OW; BMI≥25 kg/m2 or WC≥80 cm or WHR≥0.8) status, generating four phenotype groups for each anthropometric measure: (i) MH/NW, (ii) MH/OW, (iii) MU/NW, and (iv) MU/OW.

Results:
In a multivariable-adjusted conditional logistic regression model, compared with MH/NW individuals, endometrial cancer risk was higher among those classified as MU/NW [ORWC, 1.48; 95% confidence interval (CI), 1.05–2.10 and ORWHR, 1.68; 95% CI, 1.21–2.35] and MU/OW (ORBMI, 2.38; 95% CI, 1.73–3.27; ORWC, 2.69; 95% CI, 1.92–3.77 and ORWHR, 1.83; 95% CI, 1.32–2.54). MH/OW individuals were also at increased endometrial cancer risk compared with MH/NW individuals (ORWC, 1.94; 95% CI, 1.24–3.04).

Conclusions:
Women with metabolic dysfunction appear to have higher risk of endometrial cancer regardless of their body size. However, OW status raises endometrial cancer risk even among women with lower insulin levels, suggesting that obesity-related pathways are relevant for the development of this cancer beyond insulin.

Impact:
Classifying women by metabolic health may be of greater utility in identifying those at higher risk for endometrial cancer than anthropometry per se.
TOP1-DNA Trapping by Exatecan and Combination Therapy with ATR Inhibitor
Authors: Jo Ukhyun , Murai Yasuhisa , Agama Keli K. , Sun Yilun , Saha Liton Kumar , Yang Xi , Arakawa Yasuhiro , Gayle Sophia , Jones Kelli , Paralkar Vishwas , Sundaram Ranjini K. , Van Doorn Jinny , Vasquez Juan C. , Bindra Ranjit S. , Choi Woo Suk , Pommier Yves 
Published: April 2022

Abstract
Exatecan and deruxtecan are antineoplastic camptothecin derivatives in development as tumor-targeted-delivery warheads in various formulations including peptides, liposomes, polyethylene glycol nanoparticles, and antibody–drug conjugates. Here, we report the molecular pharmacology of exatecan compared with the clinically approved topoisomerase I (TOP1) inhibitors and preclinical models for validating biomarkers and the combination of exatecan with ataxia telangiectasia and Rad3-related kinase (ATR) inhibitors. Modeling exatecan binding at the interface of a TOP1 cleavage complex suggests two novel molecular interactions with the flanking DNA base and the TOP1 residue N352, in addition to the three known interactions of camptothecins with the TOP1 residues R364, D533, and N722. Accordingly, exatecan showed much stronger TOP1 trapping, higher DNA damage, and apoptotic cell death than the classical TOP1 inhibitors used clinically. We demonstrate the value of SLFN11 expression and homologous recombination (HR) deficiency (HRD) as predictive biomarkers of response to exatecan. We also show that exatecan kills cancer cells synergistically with the clinical ATR inhibitor ceralasertib (AZD6738). To establish the translational potential of this combination, we tested CBX-12, a clinically developed pH-sensitive peptide–exatecan conjugate that selectively targets cancer cells and is currently in clinical trials. The combination of CBX-12 with ceralasertib significantly suppressed tumor growth in mouse xenografts. Collectively, our results demonstrate the potency of exatecan as a TOP1 inhibitor and its clinical potential in combination with ATR inhibitors, using SLFN11 and HRD as predictive biomarkers.
Targeting WEE1/AKT Restores p53-Dependent Natural Killer–Cell Activation to Induce Immune Checkpoint Blockade Responses in “Cold” Melanoma
Authors: Dinavahi Saketh S. , Chen Yu-Chi , Punnath Kishore , Berg Arthur , Herlyn Meenhard , Foroutan Momeneh , Huntington Nicholas D. , Robertson Gavin P. 
Published: April 2022

Abstract

Immunotherapy has revolutionized cancer treatment. Unfortunately, most tumor types do not respond to immunotherapy due to a lack of immune infiltration or “cold” tumor microenvironment (TME), a contributing factor in treatment failure. Activation of the p53 pathway can increase apoptosis of cancer cells, leading to enhanced antigen presentation, and can stimulate natural killer (NK) cells through expression of stress ligands. Therefore, modulation of the p53 pathway in cancer cells with wild-type TP53 has the potential to enhance tumor immunogenicity to NK cells, produce an inflammatory TME, and ultimately lead to tumor regression. In this study, we report simultaneous targeting of the AKT/WEE1 pathways is a novel and tolerable approach to synergistically induce p53 activation to inhibit tumor development. This approach reduced the growth of melanoma cells and induced plasma membrane surface localization of the ER-resident protein calreticulin, an indicator of immunogenic cell death (ICD). Increase in ICD led to enhanced expression of stress ligands recognized by the activating NK-cell receptor NKG2D, promoting tumor lysis. WEE1/AKT inhibition resulted in recruitment and activation of immune cells, including NK cells, in the TME, triggering an inflammatory cascade that transformed the “cold” TME of B16F10 melanoma into a “hot” TME that responded to anti–programmed cell death protein 1 (anti–PD-1), resulting in complete regression of established tumors. These results suggest that AKT/WEE1 pathway inhibition is a potential approach to broaden the utility of class-leading anti–PD-1 therapies by enhancing p53-mediated, NK cell–dependent tumor inflammation and supports the translation of this novel approach to further improve response rates for metastatic melanoma.
Comprehensive Assessment of Anaplastic Lymphoma Kinase in Localized and Metastatic Prostate Cancer Reveals Targetable Alterations
Authors: Patel Radhika A. , Coleman Ilsa , Roudier Martine P. , Konnick Eric Q. , Hanratty Brian , Dumpit Ruth , Lucas Jared M. , Ang Lisa S. , Low Jin-Yih , Tretiakova Maria S. , Ha Gavin , Lee John K. , True Lawrence D. , De Marzo Angelo M. , Nelson Peter S. , Morrissey Colm , Pritchard Colin C. , Haffner Michael C. 
Published: April 2022

Anaplastic lymphoma kinase (ALK) is a tyrosine kinase with genomic and expression changes in many solid tumors. ALK inhibition is the first-line therapy for lung cancers with ALK alterations, and an effective therapy in other tumor types, but has not been well-studied in prostate cancer. Here, we aim to delineate the role of ALK genomic and expression changes in primary and metastatic prostate cancer. We determined ALK expression by IHC and RNA sequencing, and genomic alterations by NGS. We assessed functional consequences of ALK overexpression and pharmacologic ALK inhibition by cell proliferation and cell viability assays. Among 372 primary prostate cancer cases, we identified one case with uniformly high ALK protein expression. Genomic analysis revealed a novel SLC45A3-ALK fusion which promoted oncogenesis in in vitro assays. We observed ALK protein expression in 5 of 52 (9%) of metastatic prostate cancer cases, of which 4 of 5 had neuroendocrine features. ALK-expressing neuroendocrine prostate cancer had a distinct transcriptional program, and earlier disease progression. An ALK-expressing neuroendocrine prostate cancer model was sensitive to pharmacologic ALK inhibition. In summary, we found that ALK overexpression is rare in primary prostate cancer, but more frequent in metastatic prostate cancers with neuroendocrine differentiation. Furthermore, ALK fusions similar to lung cancer are an occasional driver in prostate cancer. Our data suggest that ALK-directed therapies could be an option in selected patients with advanced prostate cancer.Significance:Anaplastic lymphoma kinase (ALK) is a validated drug target in cancer. Here we delineate the spectrum of ALK alterations in prostate cancer. We show that ALK overexpression is present in advanced prostate cancers, in particular in cases with features of neuroendocrine carcinoma. Furthermore, ALK expression is associated with responses to pharmacologic ALK inhibition. Our study demonstrates that ALK-directed therapies should be considered in selected prostate cancer cases.
Strategies to Increase Racial and Ethnic Diversity in the Surgical Workforce: A State of the Art Review
Authors: Burks Ciersten A. , Russell Trinity I. , Goss Deborah , Ortega Gezzer , Randolph Gregory W. , Varvares Mark A. , Brown David J. , Gray Stacey T. , Bergmark Regan W. 
Published: April 2022

ObjectiveTo evaluate strategies to increase racial and ethnic diversity in the surgical workforce among trainees and faculty across surgical specialties.Data SourcesEmbase, OVID/Medline, and Web of Science Core Collection.Review MethodsA review of US‐based, peer‐reviewed articles examining the effect of targeted strategies on racial and ethnic diversity in the surgical workforce was conducted from 2000 to 2020 with the PRISMA checklist and STROBE tool. Studies without an outlined strategy and associated outcomes were excluded. Eleven studies met inclusion criteria and were completed in general surgery, orthopaedic surgery, and otolaryngology–head and neck surgery.ConclusionsEfforts to increase exposure to surgery through internship programs and required clerkships with efforts to improve mentorship were common (6 of 11 [54.5%] and 3 of 11 [27.3%] studies, respectively). Three (27.3%) studies aimed to diversify the recruitment and selection process for the residency match and faculty hiring, and 2 (18.2%) aimed to increase representation among trainees, faculty, and leadership through holistic review processes paired with departmental commitment. Outcome metrics included surgical residency applications for individuals underrepresented in medicine, interview and match rates, faculty hiring, measures of a successful academic surgical career, and leadership representation. All strategies were successful in increasing diversity in the surgical workforce.Implications for PracticeA convincing yet limited body of literature exists to describe strategies and outcomes that address racial and ethnic diversity in the surgical workforce. While future inquiry is needed to move this field of interest forward, the evidence presented provides a framework for surgical residency programs/departments to develop approaches to increase racial and ethnic diversity.