bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anisotropic neutron stars modelling: constraints in Krori–Barua spacetime
Authors: Roupas Zacharias , Nashed Gamal G. L. 
Published: September 2020

AbstractDense nuclear matter is expected to be anisotropic due to effects such as solidification, superfluidity, strong magnetic fields, hyperons, pion-condensation. Therefore an anisotropic neutron star core seems more realistic than an ideally isotropic one. We model anisotropic neutron stars working in the Krori–Barua (KB) ansatz without preassuming an equation of state. We show that the physics of general KB solutions is encapsulated in the compactness. Imposing physical and stability requirements yields a maximum allowed compactness $$2GM/Rc^2 < 0.71$$

2
G
M
/
R

c
2

<
0.71

for a KB-spacetime. We further input observational data from numerous pulsars and calculate the boundary density. We focus especially on data from the LIGO/Virgo collaboration as well as recent independent measurements of mass and radius of miilisecond pulsars with white dwarf companions by the Neutron Star Interior Composition Explorer (NICER). For these data the KB-spacetime gives the same boundary density which surprisingly equals the nuclear saturation density within the data precision. Since this value designates the boundary of a neutron core, the KB-spacetime applies naturally to neutron stars. For this boundary condition we calculate a maximum mass of 4.1 solar masses.
On Existential MSO and Its Relation to ETH
Authors: Ganian Robert , Haan Ronald de , Kanj Iyad , Szeider Stefan 
Published: October 2020

Impagliazzo et al. proposed a framework, based on the logic fragment defining the complexity class SNP, to identify problems that are equivalent to
k
-CNF-
Sat
modulo subexponential-time reducibility (serf-reducibility). The subexponential-time solvability of any of these problems implies the failure of the Exponential Time Hypothesis (ETH). In this article, we extend the framework of Impagliazzo et al. and identify a larger set of problems that are equivalent to
k
-CNF-
Sat
modulo serf-reducibility. We propose a complexity class, referred to as Linear Monadic NP, that consists of all problems expressible in existential monadic second-order logic whose expressions have a linear
measure
in terms of a complexity parameter, which is usually the universe size of the problem.

This research direction can be traced back to Fagin’s celebrated theorem stating that NP coincides with the class of problems expressible in existential second-order logic. Monadic NP, a well-studied class in the literature, is the restriction of the aforementioned logic fragment to existential
monadic
second-order logic. The proposed class Linear Monadic NP is then the restriction of Monadic NP to problems whose expressions have linear measure in the complexity parameter.

We show that Linear Monadic NP includes many natural complete problems such as the satisfiability of linear-size circuits, dominating set, independent dominating set, and perfect code. Therefore, for any of these problems, its subexponential-time solvability is equivalent to the failure of ETH. We prove, using logic games, that the aforementioned problems are inexpressible in the monadic fragment of SNP, and hence, are not captured by the framework of Impagliazzo et al. Finally, we show that
Feedback Vertex Set
is inexpressible in existential monadic second-order logic, and hence is not in Linear Monadic NP, and investigate the existence of certain reductions between
Feedback Vertex Set
(and variants of it) and
3-CNF-Sat
.
Splenic Hematopoietic and Stromal Cells in Cancer Progression
Authors: Steenbrugge Jonas , De Jaeghere Emiel A. , Meyer Evelyne , Denys Hannelore , De Wever Olivier 
Published: September 2020

Abstract
Tumor-derived secretory factors orchestrate splenic hematopoietic and stromal cells to fuel metastasis. The spleen acts as a reservoir site for hematopoietic stem and progenitor cells, which are rapidly exploited as myeloid-derived suppressor cells at the cost of tumor-reactive lymphoid cells. Splenic erythroid progenitor cells and mesenchymal stromal cells contribute directly and indirectly to both tumor immune escape and the metastatic cascade. Animal models provide valuable mechanistic insights, but their translation to a clinical setting highlights specific challenges and open issues. In this review, we envision the exploitation of the spleen as a source for novel biomarkers and therapeutic approaches.
Development of Helicobacter pylori Whole-Proteome Arrays and Identification of Serologic Biomarkers for Noncardia Gastric Cancer in the MCC-Spain Study
Authors: Jeske Rima , Reininger Dennis , Turgu Busra , Brauer Amber , Harmel Christoph , Fernández de Larrea-Baz Nerea , Martín Vicente , Moreno Victor , Kogevinas Manolis , Pollán Marina , Hoheisel Jörg D. , Waterboer Tim , Butt Julia , Aragonés Nuria , Hufnagel Katrin 
Published: September 2020

Abstract

Background:
Helicobacter pylori (H. pylori) is a bacterial carcinogen and the leading risk factor for noncardia gastric cancer (NCGC). Detecting antibodies against specific H. pylori proteins in peripheral blood can be applied to characterize infection and determine disease associations. Most studies analyzing the association between H. pylori infection and gastric cancer have focused on previously identified antigens, predominantly the virulence factor cytotoxin-associated gene A (CagA). Selecting antigens in an unbiased approach may, however, allow the identification of novel biomarkers.

Methods:
Using a combination of multiple spotting technique and cell-free, on-chip protein expression, we displayed the H. pylori genome (strain 26695) on high-density microarrays. Immunogenic proteins were identified by serum pool incubations and henceforth analyzed in individual samples. To test its applicability, we used sera from a multicase–control (MCC)-Spain study. Serologic responses between NCGC cases and controls were assessed by conditional logistic regression estimating ORs and 95% confidence intervals.

Results:
We successfully expressed 93% of the 1,440 H. pylori open reading frames in situ. Of these, 231 (17%) were found to be immunogenic. By comparing 58 NCGC cases with 58 matched controls, we confirmed a higher seroprevalence of CagA among cases (66%) than controls (31%). We further identified a potential novel marker, the Helicobacter outer membrane protein A (HopA).

Conclusions:
In this study, we provide evidence that our H. pylori whole-proteome microarray offers a platform for unbiased de novo identification of serologic biomarkers.

Impact:
Given its versatile workflow, antibody responses against other H. pylori strains and possible associations with diverse H. pylori–related outcomes can be systematically analyzed.
The Steroid Metabolome and Breast Cancer Risk in Women with a Family History of Breast Cancer: The Novel Role of Adrenal Androgens and Glucocorticoids
Authors: Houghton Lauren C. , Howland Renata E. , Wei Ying , Ma Xinran , Kehm Rebecca D. , Chung Wendy K. , Genkinger Jeanine M. , Santella Regina M. , Hartmann Michaela F. , Wudy Stefan A. , Terry Mary Beth 
Published: September 2020

Abstract

Background:
No study has comprehensively examined how the steroid metabolome is associated with breast cancer risk in women with familial risk.

Methods:
We examined 36 steroid metabolites across the spectrum of familial risk (5-year risk ranged from 0.14% to 23.8%) in pre- and postmenopausal women participating in the New York site of the Breast Cancer Family Registry (BCFR). We conducted a nested case–control study with 62 cases/124 controls individually matched on menopausal status, age, and race. We measured metabolites using GC-MS in urine samples collected at baseline before the onset of prospectively ascertained cases. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) per doubling in hormone levels.

Results:
The average proportion of total steroid metabolites in the study sample were glucocorticoids (61%), androgens (26%), progestogens (11%), and estrogens (2%). A doubling in glucocorticoids (aOR = 2.7; 95% CI = 1.3–5.3) and androgens (aOR = 1.6; 95% CI = 1.0–2.7) was associated with increased breast cancer risk. Specific glucocorticoids (THE, THF αTHF, 6β-OH-F, THA, and α-THB) were associated with 49% to 161% increased risk. Two androgen metabolites (AN and 11-OH-AN) were associated with 70% (aOR = 1.7; 95% CI = 1.1–2.7) and 90% (aOR = 1.9; 95% CI = 1.2–3.1) increased risk, respectively. One intermediate metabolite of a cortisol precursor (THS) was associated with 65% (OR = 1.65; 95% CI = 1.0–2.7) increased risk. E1 and E2 estrogens were associated with 20% and 27% decreased risk, respectively.

Conclusions:
Results suggest that glucocorticoids and 11-oxygenated androgens are positively associated with breast cancer risk across the familial risk spectrum.

Impact:
If replicated, our findings suggest great potential of including steroids into existing breast cancer risk assessment tools.
Phase I Study of Alvocidib Followed by 7+3 (Cytarabine + Daunorubicin) in Newly Diagnosed Acute Myeloid Leukemia
Authors: Zeidner Joshua F. , Lee Daniel J. , Frattini Mark , Fine Gil D. , Costas Judy , Kolibaba Kathryn , Anthony Stephen P. , Bearss David , Smith B. Douglas 
Published: September 2020

Abstract

Purpose:
Alvocidib is a cyclin-dependent kinase 9 inhibitor leading to downregulation of the antiapoptotic BCL-2 family member, MCL-1. Alvocidib has shown clinical activity in a timed sequential regimen with cytarabine and mitoxantrone in relapsed/refractory and newly diagnosed acute myeloid leukemia (AML) but has not been studied in combination with traditional 7+3 induction therapy.

Patients and Methods:
A multiinstitutional phase I dose-escalation study of alvocidib on days 1–3 followed by 7+3 (cytarabine 100 mg/m2/day i.v. infusion days 5–12 and daunorubicin 60 mg/m2 i.v. days 5–7) was performed in newly diagnosed AML ≤65 years. Core-binding factor AML was excluded.

Results:
There was no MTD on this study; the recommended phase II dose of alvocidib was 30 mg/m2 i.v. over 30 minutes followed by 60 mg/m2 i.v. infusion over 4 hours. There was one dose-limiting toxicity of cytokine release syndrome. The most common grade ≥3 nonhematologic toxicities were diarrhea (44%) and tumor lysis syndrome (34%). Overall, 69% (22/32) of patients achieved complete remission (CR). In an exploratory cohort, eight of nine (89%) patients in complete remission had no measurable residual disease, as determined by a centralized flow cytometric assay. Clinical activity was seen in patients with secondary AML, AML with myelodysplastic syndrome–related changes, and a genomic signature of secondary AML (50%, 50%, and 92% CR rates, respectively).

Conclusions:
Alvocidib can be safely administered prior to 7+3 induction with encouraging clinical activity. These findings warrant further investigation of alvocidib combinations in newly diagnosed AML. This study was registered at clinicaltrials.gov identifier NCT03298984.
Survival Implications of the Relationship between Tissue versus Circulating Tumor DNA TP53 Mutations—A Perspective from a Real-World Precision Medicine Cohort
Authors: Rosenberg Shai , Okamura Ryosuke , Kato Shumei , Soussi Thierry , Kurzrock Razelle 
Published: September 2020

Abstract
Interrogating the genomics of circulating tumor DNA (ctDNA; the liquid biopsy) has advantages in patients in whom tissue biopsy is difficult. However, the reported concordance between genomic analysis of tissue DNA and ctDNA is variable among studies. Herein, we characterized the clinical implications of the relationship between mutations in TP53 genes in tissue DNA versus ctDNA. The molecular profiles of both liquid (Guardant Health) and tissue (Foundation Medicine) biopsies from 433 patients were analyzed (pan-cancer setting). In 71/433 (16%) cases, all same TP53 mutations were detected in both tissue DNA and ctDNA; in 18/433 (4%), same mutation plus additional mutation/mutations; and in 27/433 (6%), different TP53 mutations were detected. In 99/433 (23%) cases, TP53 mutations were detected only in tissue DNA; in 43/433 (10%), only in ctDNA; and in 175/433 (40%), no TP53 mutations were detected in either test. When TP53 mutations were identical in tissue and ctDNA, the alterations were enriched for nonsense mutations, and survival was significantly shorter in multivariate analysis (as compared with different mutations in ctDNA vs. tissue or no mutations); this finding was independent of tumor type, time interval between tests, and the %ctDNA for TP53 mutations. In summary, in 16% of 433 patients with diverse cancers, TP53 mutations were identical in tissue DNA and ctDNA. In these individuals, the alterations were enriched for stop–gain (nonsense) mutations (results in a premature termination codon). Though unknown confounders cannot be ruled out, these patients fared significantly worse than those whose ctDNA and tissue DNA harbored different TP53 mutation portfolios or no TP53 mutations.
PROgesterone Therapy for Endometrial Cancer Prevention in Obese Women (PROTEC) Trial: A Feasibility Study
Authors: Derbyshire Abigail E. , Allen Jennifer L. , Gittins Matthew , Lakhiani Bhavna , Bolton James , Shaw Joseph , Pemberton Philip W. , Needham Michelle , MacKintosh Michelle L. , Edmondson Richard J. , Kitchener Henry C. , Crosbie Emma J. 
Published: September 2020

Abstract
Obesity is the major etiologic driver for endometrial cancer. The levonorgestrel intrauterine system (LNG-IUS) reduces the risk of endometrial cancer and its precursor, atypical hyperplasia. We assessed feasibility and uptake of the LNG-IUS for primary prevention of endometrial cancer in high-risk women and its impact on endometrial tissue biomarkers. Women with class-III obesity [body mass index (BMI) &gt; 40 kg/m2] and histologically normal endometrium were invited to participate in a clinical trial of the LNG-IUS for endometrial protection. Recruitment, successful LNG-IUS insertion, and adherence to trial procedures were recorded. We measured impact of the LNG-IUS on circulating biomarkers of endometrial cancer risk, endometrial proliferation (Ki-67, pAKT, PTEN), endometrial hormone receptor status [estrogen receptor and progesterone receptor (PR)], mental wellbeing, and menstrual function. At 6 months, women chose to keep their LNG-IUS or have it removed. In total, 103 women were approached, 54 were offered a participant information sheet, 35 agreed to participate, and 25 received a LNG-IUS. Their median age and BMI were 54 years [interquartile range (IQR) 52–57] and 47 kg/m2 (IQR 44–51), respectively. Three women (3/35, 9%) were ineligible due to atypical hyperplasia/endometrial cancer on their baseline biopsy. The LNG-IUS was well tolerated and had a positive overall effect on bleeding patterns and mental wellbeing. The LNG-IUS was associated with endometrial morphologic change, reduced Ki-67, and PR expression, but circulating biomarkers of endometrial cancer risk were unchanged. All but one woman (96%) kept her LNG-IUS. The LNG-IUS appears to be acceptable to some women with class-III obesity for primary prevention of endometrial cancer, which could provide a strategy for a prevention trial.
Prevention Relevance: Novel strategies are urgently needed to prevent the rise in endometrial cancer diagnoses predicted by escalating obesity rates. Here, we show that women with class III obesity are willing to engage in risk reduction with a levonorgestrel intrauterine system, which could provide a strategy for an endometrial cancer prevention trial.
Risk Model for Decline in Activities of Daily Living Among Older Adults Hospitalized With Acute Myocardial Infarction: The SILVER‐AMI Study
Authors: Hajduk Alexandra M. , Dodson John A. , Murphy Terrence E. , Tsang Sui , Geda Mary , Ouellet Gregory M. , Gill Thomas M. , Brush John E. , Chaudhry Sarwat I. 
Published: October 2020

Background
Functional decline (ie, a decrement in ability to perform everyday activities necessary to live independently) is common after acute myocardial infarction (AMI) and associated with poor long‐term outcomes; yet, we do not have a tool to identify older AMI survivors at risk for this important patient‐centered outcome.

Methods and Results
We used data from the prospective SILVER‐AMI (Comprehensive Evaluation of Risk Factors in Older Patients With Acute Myocardial Infarction) study of 3041 patients with AMI, aged ≥75 years, recruited from 94 US hospitals. Participants were assessed during hospitalization and at 6 months to collect data on demographics, geriatric impairments, psychosocial factors, and activities of daily living. Clinical variables were abstracted from the medical record. Functional decline was defined as a decrement in ability to independently perform essential activities of daily living (ie, bathing, dressing, transferring, and ambulation) from baseline to 6 months postdischarge. The mean age of the sample was 82±5 years; 57% were men, 90% were White, and 13% reported activity of daily living decline at 6 months postdischarge. The model identified older age, longer hospital stay, mobility impairment during hospitalization, preadmission physical activity, and depression as risk factors for decline. Revascularization during AMI hospitalization and ability to walk a quarter mile before AMI were associated with decreased risk. Model discrimination (c=0.78) and calibration were good.

Conclusions
We identified a parsimonious model that predicts risk of activity of daily living decline among older patients with AMI. This tool may aid in identifying older patients with AMI who may benefit from restorative therapies to optimize function after AMI.
Relation of Different Fruit and Vegetable Sources With Incident Cardiovascular Outcomes: A Systematic Review and Meta‐Analysis of Prospective Cohort Studies
Authors: Zurbau Andreea , Au‐Yeung Fei , Blanco Mejia Sonia , Khan Tauseef A. , Vuksan Vladimir , Jovanovski Elena , Leiter Lawrence A. , Kendall Cyril W. C. , Jenkins David J. A. , Sievenpiper John L. 
Published: October 2020

Background
Public health policies reflect concerns that certain fruit sources may not have the intended benefits and that vegetables should be preferred to fruit. We assessed the relation of fruit and vegetable sources with cardiovascular outcomes using a systematic review and meta‐analysis of prospective cohort studies.

Methods and Results

MEDLINE, EMBASE, and Cochrane were searched through June 3, 2019. Two independent reviewers extracted data and assessed study quality (Newcastle‐Ottawa Scale). Data were pooled (fixed effects), and heterogeneity (Cochrane‐Q and I
2
) and certainty of the evidence (Grading of Recommendations Assessment, Development, and Evaluation) were assessed. Eighty‐one cohorts involving 4 031 896 individuals and 125 112 cardiovascular events were included. Total fruit and vegetables, fruit, and vegetables were associated with decreased cardiovascular disease (risk ratio, 0.93 [95% CI, 0.89–0.96]; 0.91 [0.88–0.95]; and 0.94 [0.90–0.97], respectively), coronary heart disease (0.88 [0.83–0.92]; 0.88 [0.84–0.92]; and 0.92 [0.87–0.96], respectively), and stroke (0.82 [0.77–0.88], 0.82 [0.79–0.85]; and 0.88 [0.83–0.93], respectively) incidence. Total fruit and vegetables, fruit, and vegetables were associated with decreased cardiovascular disease (0.89 [0.85–0.93]; 0.88 [0.86–0.91]; and 0.87 [0.85–0.90], respectively), coronary heart disease (0.81 [0.72–0.92]; 0.86 [0.82–0.90]; and 0.86 [0.83–0.89], respectively), and stroke (0.73 [0.65–0.81]; 0.87 [0.84–0.91]; and 0.94 [0.90–0.99], respectively) mortality. There were greater benefits for citrus, 100% fruit juice, and pommes among fruit sources and allium, carrots, cruciferous, and green leafy among vegetable sources. No sources showed an adverse association. The certainty of the evidence was “very low” to “moderate,” with the highest for total fruit and/or vegetables, pommes fruit, and green leafy vegetables.

Conclusions
Fruits and vegetables are associated with cardiovascular benefit, with some sources associated with greater benefit and none showing an adverse association.

Registration

URL:
https://www.clini​caltr​ials.gov
; Unique identifier: NCT03394339.
Association of Isolated Diastolic Hypertension Based on the Cutoff Value in the 2017 American College of Cardiology/American Heart Association Blood Pressure Guidelines With Subsequent Cardiovascular Events in the General Population
Authors: Kaneko Hidehiro , Itoh Hidetaka , Yotsumoto Haruki , Kiriyama Hiroyuki , Kamon Tatsuya , Fujiu Katsuhito , Morita Kojiro , Michihata Nobuaki , Jo Taisuke , Takeda Norifumi , Morita Hiroyuki , Yasunaga Hideo , Komuro Issei 
Published: September 2020

Background
The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines lowered the threshold of blood pressure (BP) for hypertension to 130/80 mm Hg. However, the clinical significance of isolated diastolic hypertension (IDH) according to the cutoff value of the 2017 ACC/AHA guidelines was uncertain.

Methods and Results
We analyzed the claims database of Japan Medical Data Center (a nationwide epidemiological database). We excluded individuals who were aged <20 years, had systolic hypertension, were taking antihypertensive medication, or had prevalent cardiovascular disease, and studied 1 746 493 individuals (mean age, 42.9±10.7 years; 961 097 men [55.0%]). The average observational period was 1107±855 days. Stage 1 IDH, defined as diastolic BP 80 to 89 mm Hg, and stage 2 IDH, defined as diastolic BP ≥90 mm Hg, were found in 230 513 (13.2%) and 16 159 (0.9%) individuals, respectively. Compared with individuals with normal diastolic BP, individuals with stage 1 and stage 2 IDH were older and more likely to be men. Prevalence of classic risk factors was higher in patients with IDH. Kaplan–Meier curves showed that stage 1 and stage 2 IDH were associated with a higher incidence of cardiovascular events, defined as myocardial infarction, angina pectoris, and stroke. Multivariable analysis showed that stage 1 (hazard ratio [HR], 1.17) and stage 2 (HR, 1.28) IDH were independently associated with a higher incidence of cardiovascular events. Subgroup analyses showed that the association of IDH with cardiovascular events was seen irrespective of age and sex.

Conclusions
The analysis of a nationwide epidemiological database showed that IDH based on the cutoff value in the 2017 ACC/AHA BP guidelines was associated with an elevated risk of subsequent cardiovascular events.
Molecular identification, phylogeny and phylogeography of the entomopathogenic nematodes of the genus Heterorhabditis Poinar, 1976: a multigene approach
Authors: Dhakal Manoj , Nguyen Khuong B. , Hunt David J. , Ehlers Ralf-Udo , Spiridonov Sergei E. , Subbotin Sergei A. 
Published: October 2020

Summary
Presently, the genus Heterorhabditis contains 16 valid entomopathogenic nematode species. In this study we used samples from 11 species: H. amazonensis, H. bacteriophora, H. baujardi, H. beicherriana, H. downesi, H. floridensis, H. georgiana, H. indica, H. megidis, H. noenieputensis, and H. zealandica to amplify and sequence five gene fragments: the D2-D3 expansion segments of 28S rRNA, ITS rRNA, COI mtDNA genes and unc-87 and cmd-1 genes encoding thin filament (F-actin)-associated protein and calmodulin, respectively. Fifty new sequences for 11 species were generated. More than 980 sequences of five genes were analysed. Phylogenetic and sequence analysis of these genes using Bayesian inference, maximum likelihood and statistical parsimony confirmed a division of the genus into three clades (groups): ‘Indica’, ‘Bacteriophora’ and ‘Megidis’. The analysis of gene sequences downloaded from GenBank and identified as Heterorhabditis revealed many cases of species misidentifications and presence of reading mistakes in some sequences. Synonymisation of H. somsookae with H. baujardi, H. gerrardi, H. pakistanensis with H. indica, and H. sonorensis with H. taysearae, are confirmed by sequence and phylogenetic analysis. The ITS rRNA and COI genes could be considered as informative markers for species identification, barcoding and phylogeographical studies of Heterorhabditis.