bluuebunny/crossref_metadata_2025_split huggingface dataset:
Speckle tracking strain and ECG heterogeneity correlate in transcatheter aortic valve replacement-induced left bundle branch blocks and right ventricular paced rhythms
Authors: Burke Gordon M , Araujo Silva Bruna , Marum Alexandre A , Bortolotto Alexandre L , Nearing Bruce D , Chen Michael J , Fostello Sarah , Popma Jeffrey J , Verrier Richard L , Chang James D 
Published: October 2021

ObjectiveTranscatheter aortic valve replacement (TAVR) complications include left bundle branch block (LBBB) and right ventricular paced rhythm (RVP). We hypothesised that changes in electrocardiographic heterogeneity would correlate better with speckle tracking strain measures than with left ventricular ejection fraction (LVEF) on transthoracic echocardiogram (TTE) among patients with TAVR-induced conduction abnormalities.MethodsWe reviewed medical records of 446 consecutive patients who underwent TAVR at our institution. Of the 238 patients with 12-lead electrocardiograms (ECGs) that met our inclusion criteria, 58 had pre-TAVR and post-TAVR TTEs adequate for strain assessment. We compared patients who did not have an LBBB or RVP pre-TAVR and post-TAVR (controls, n=11) with patients who developed LBBBs (n=11) and who required RVPs (n=10) post-TAVR. In our study population (n=32, 41% female, mean age 85.8 years), we evaluated QRS complex duration, R-wave heterogeneity (RWH), T-wave heterogeneity (TWH), LVEF, global longitudinal strain (GLS) and mechanical dispersion (MD).ResultsTAVR-induced changes on ECG did not correlate with LVEF. TAVR-induced changes in MD and QRS complex duration correlated among all patients (r=0.4, p=0.04). GLS and RWH correlated among RVP patients (r=0.7, p=0.00003). MD and TWH correlated among LBBB patients (r=0.7, p=0.00004).ConclusionsIn this convenience sample of patients with TAVR-induced conduction abnormalities, RWH and TWH correlated with strain measures but not with LVEF. Strain measures, RWH and TWH may offer additional insights for pre-TAVR evaluation and post-TAVR clinical management.
Combined anticoagulant and antiplatelet therapy is associated with an improved outcome in hospitalised patients with COVID-19: a propensity matched cohort study
Authors: Matli Kamal , Chamoun Nibal , Fares Aya , Zibara Victor , Al-Osta Soad , Nasrallah Rabih , Salameh Pascale , Mokhbat Jacques , Ghanem Georges 
Published: October 2021

BackgroundCOVID-19 is a respiratory disease that results in a prothrombotic state manifesting as thrombotic, microthrombotic and thromboembolic events. As a result, several antithrombotic modalities have been implicated in the treatment of this disease. This study aimed to identify if therapeutic anticoagulation (TAC) or concurrent use of antiplatelet and anticoagulants was associated with an improved outcome in this patient population.MethodsA retrospective observational cohort study of adult patients admitted to a single university hospital for COVID-19 infection was performed. The primary outcome was a composite of in-hospital mortality, intensive care unit (ICU) admission or the need for mechanical ventilation. The secondary outcomes were each of the components of the primary outcome, in-hospital mortality, ICU admission, or the need for mechanical ventilation.Results242 patients were included in the study and divided into four subgroups: Therapeutic anticoagulation (TAC), prophylactic anticoagulation+antiplatelet (PACAP), TAC+antiplatelet (TACAP) and prophylactic anticoagulation (PAC) which was the reference for comparison. Multivariable Cox regression analysis and propensity matching were done and showed when compared with PAC, TACAP and TAC were associated with less in-hospital all-cause mortality with an adjusted HR (aHR) of 0.113 (95% CI 0.028 to 0.449) and 0.126 (95% CI 0.028 to 0.528), respectively. The number needed to treat in both subgroups was 11. Furthermore, PACAP was associated with a reduced risk of invasive mechanical ventilation with an aHR of 0.07 (95% CI 0.014 to 0.351). However, the was no statistically significant difference in the occurrence of major or minor bleeds, ICU admission or the composite outcome of in-hospital mortality, ICU admission or the need for mechanical ventilation.ConclusionThe use of combined anticoagulant and antiplatelet agents or TAC alone in hospitalised patients with COVID-19 was associated with a better outcome in comparison to PAC alone without an increase in the risk of major and minor bleeds. Sufficiently powered randomised controlled trials are needed to further evaluate the safety and efficacy of combining antiplatelet and anticoagulants agents or using TAC in the management of patients with COVID-19 infection.
Averaging generalized scalar-field cosmologies III: Kantowski–Sachs and closed Friedmann–Lemaître–Robertson–Walker models
Authors: Leon Genly , González Esteban , Lepe Samuel , Michea Claudio , Millano Alfredo D. 
Published: October 2021

AbstractScalar-field cosmologies with a generalized harmonic potential and matter with energy density $$\rho _m$$

ρ
m

, pressure $$p_m$$

p
m

, and barotropic equation of state (EoS) $$p_m=(\gamma -1)\rho _m, \; \gamma \in [0,2]$$

p
m

=

(
γ
-
1
)

ρ
m

,

γ
∈

[
0
,
2
]

in Kantowski–Sachs (KS) and closed Friedmann–Lemaître–Robertson–Walker (FLRW) metrics are investigated. We use methods from non-linear dynamical systems theory and averaging theory considering a time-dependent perturbation function D. We define a regular dynamical system over a compact phase space, obtaining global results. That is, for KS metric the global late-time attractors of full and time-averaged systems are two anisotropic contracting solutions, which are non-flat locally rotationally symmetric (LRS) Kasner and Taub (flat LRS Kasner) for $$0\le \gamma \le 2$$

0
≤
γ
≤
2

, and flat FLRW matter-dominated universe if $$0\le \gamma \le \frac{2}{3}$$

0
≤
γ
≤

2
3

. For closed FLRW metric late-time attractors of full and averaged systems are a flat matter-dominated FLRW universe for $$0\le \gamma \le \frac{2}{3}$$

0
≤
γ
≤

2
3

as in KS and Einstein–de Sitter solution for $$0\le \gamma <1$$

0
≤
γ
<
1

. Therefore, a time-averaged system determines future asymptotics of the full system. Also, oscillations entering the system through Klein–Gordon (KG) equation can be controlled and smoothed out when D goes monotonically to zero, and incidentally for the whole D-range for KS and closed FLRW (if $$0\le \gamma < 1$$

0
≤
γ
<
1

) too. However, for $$\gamma \ge 1$$

γ
≥
1

closed FLRW solutions of the full system depart from the solutions of the averaged system as D is large. Our results are supported by numerical simulations.
Topological sampling through windings
Authors: Albandea David , Hernández Pilar , Ramos Alberto , Romero-López Fernando 
Published: October 2021

AbstractWe propose a modification of the Hybrid Monte Carlo (HMC) algorithm that overcomes the topological freezing of a two-dimensional U(1) gauge theory with and without fermion content. This algorithm includes reversible jumps between topological sectors – winding steps – combined with standard HMC steps. The full algorithm is referred to as winding HMC (wHMC), and it shows an improved behaviour of the autocorrelation time towards the continuum limit. We find excellent agreement between the wHMC estimates of the plaquette and topological susceptibility and the analytical predictions in the U(1) pure gauge theory, which are known even at finite $$\beta $$
β
. We also study the expectation values in fixed topological sectors using both HMC and wHMC, with and without fermions. Even when topology is frozen in HMC – leading to significant deviations in topological as well as non-topological quantities – the two algorithms agree on the fixed-topology averages. Finally, we briefly compare the wHMC algorithm results to those obtained with master-field simulations of size $$L\sim 8 \times 10^3$$

L
∼
8
×

10
3

.
Quantum gravity corrections to the mean field theory of nucleons
Authors: Naqash Abrar Ahmed , Majumder Barun , Mitra Soumodeep , Bangle Moomin Mushtaq , Faizal Mir 
Published: October 2021

AbstractIn this paper, we analyze the correction to the mean field theory potential for a system of nucleons. It will be argued that these corrections can be obtained by deforming the Schrödinger’s equation describing a system of nucleons by a minimal length in the background geometry of space-time. This is because such a minimal length occurs due to quantum gravitational effects, and modifies the low energy quantum mechanical systems. In fact, as the mean field potential for the nucleons is represented by the Woods–Saxon potential, we will explicitly analyze such corrections to this potential. We will obtain the corrections to the energy eigenvalues of the deformed Schrödinger’s equation for the Woods–Saxon potential. We will also construct the wave function for the deformed Schrödinger’s equation.
The Complexity of the Ideal Membership Problem for Constrained Problems Over the Boolean Domain
Authors: Mastrolilli Monaldo 
Published: October 2021

Given an ideal
I
and a polynomial
f
the Ideal Membership Problem (IMP) is to test if
f ϵ I
. This problem is a fundamental algorithmic problem with important applications and notoriously intractable.

We study the complexity of the IMP for combinatorial ideals that arise from constrained problems over the Boolean domain. As our main result, we identify the borderline of tractability. By using Gröbner bases techniques, we extend Schaefer’s dichotomy theorem [STOC, 1978] which classifies all Constraint Satisfaction Problems (CSPs) over the Boolean domain to be either in P or NP-hard. Moreover, our result implies necessary and sufficient conditions for the efficient computation of Theta Body Semi-Definite Programming (SDP) relaxations, identifying therefore the borderline of tractability for constraint language problems.
This article is motivated by the pursuit of understanding the recently raised issue of bit complexity of Sum-of-Squares (SoS) proofs [O’Donnell, ITCS, 2017]. Raghavendra and Weitz [ICALP, 2017] show how the IMP tractability for combinatorial ideals implies bounded coefficients in SoS proofs.
Genetic Polymorphisms of IFNG, IFNGR1, and Androgen Receptor and Chronic Prostatitis/Chronic Pelvic Pain Syndrome in a Chinese Han Population
Authors: Chen Lei , Chen Junyi , Mo Fan , Bian Zichen , Jin Chen , Chen Xianguo , Liang Chaozhao 
Published: October 2021

Background. Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) refers to a common disorder with unclear etiology and unsatisfactory treatment, which reduces the male’s quality of life. Objective. To examine the effects of genetic polymorphisms of IFNG, IFNGR1, and androgen receptor (AR) on CP/CPPS. Methods. The single nucleotide polymorphisms (SNPs) of IFNG, IFNGR1, and AR were genotyped with the improved multiplex ligation detection reaction. The GTEx, RegulomeDB, HaploReg, and 3DSNP databases were adopted to predict the regulatory functions of the genotyped SNPs. The correlation between SNPs and CP/CPPS was analyzed with the

χ

2

test, logistic regression, and two genetic models (codominant and log-additive models). The nomogram was built to predict the risk of CP/CPPS occurrence. Results. On the whole, 130 CP/CPPS patients and 125 healthy controls were recruited in the study, and 18 SNPs of IFNG, IFNGR1, and AR were genotyped. The results of functional annotation indicated that the 18 genotyped SNPs might have regulatory effects in the whole blood. The rs144488434 was correlated with the elevated CP/CPPS risk (odds ratio (OR): 2.40, 95% confidence interval (CI): 1.12-5.13,

χ

2

=
5.37

, and

P
=
0.021

) by the

χ

2

test. In the built genetic models, rs10457655 was correlated with the elevated National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) scores (codominant model: GA/GG:

crude

mean

difference

MD

=
0.98

, 95% CI: -1.71-3.67 and AA/GG:

crude

MD
=
9.10

, 95% CI: 0.58-17.62,

P
=
0.10

). In subgroup analysis, rs2069718 was correlated with the elevated CP/CPPS risk (log-additive model:

crude

OR
=
2.18

, 95% CI: 1.03-4.64, and

P
=
0.034

) in

patients
≥
35

years. The nomogram integrating age, rs2069718, rs10457655, and rs144488434 showed good performance to predict the risk of CP/CPPS. Conclusions. Genetic polymorphisms of IFNG, IFNGR1, and AR might act as the genetic factors for CP/CPPS susceptibility, which deserved further explorations.
DCLK1-Short Splice Variant Promotes Esophageal Squamous Cell Carcinoma Progression via the MAPK/ERK/MMP2 Pathway
Authors: Ge Yang , Fan Xiaona , Huang Xuying , Weygant Nathaniel , Xiao Zeru , Yan Rui , Liu Heshu , Liu Jian , An Guangyu , Yao Jiannan 
Published: October 2021

Abstract

Cancer stem cell (CSC) marker doublecortin-like kinase 1 (DCLK1) contributes greatly to the malignancy of gastrointestinal cancers, and DCLK1-targeted agents have potential therapeutic value. However, the molecular pathways regulated by DCLK1-S (DCLK1 isoform 4), a shortened splice variant of DCLK1, still remain obscure. Here we found that the expression of DCLK1-S is significantly increased in human esophageal squamous cell carcinoma (ESCC) tissues and associated with malignant progression and poor prognosis. Functional studies indicated that silencing total of DCLK1 mediated by CRISPR/Cas9 inhibited ESCC cell proliferation, migration, and invasion. Conversely, these changes were largely reversed after DCLK1-S rescue or overexpression. More importantly, DCLK1-S significantly enhanced primary tumor formation and metastatic lung colonization in vivo. The Cancer Genome Atlas database and molecular analysis showed that DCLK1-S was closely related to the epithelial–mesenchymal transition (EMT) process in patients with ESCC. Further RNA sequencing and Kyoto Encyclopedia of Genes and Genomes analysis demonstrated that MAPK signaling pathway was significantly enriched. Our in vitro study proclaimed that DCLK1-S induced MMP2 expression in ESCC cells via MAPK/ERK signaling, leading to the activation of EMT. In addition, administration of ERK1/2 blocker SCH772984 attenuated the proliferative and migratory phenotype induced by DCLK1-S. In conclusion, these findings suggest that DCLK1-S may be a key molecule in MAPK/ERK/MMP2 pathway–mediated progression of ESCC, and that it has potential as a biomarker or therapeutic target to improve outcomes in patients with ESCC.

Implications
: DCLK1-S induces ESCC progression by activating the MAPK/ERK/MMP2 axis and may serve as a prognostic biomarker or therapeutic target for patients with ESCC.
Epigenetic Silencing of BMP6 by the SIN3A–HDAC1/2 Repressor Complex Drives Melanoma Metastasis via FAM83G/PAWS1
Authors: Min Dongkook , Byun Jaemin , Lee Eun-Joon , Khan Abdul A. , Liu Christina , Loudig Oliver , Hu Wei , Zhao Yong , Herlyn Meenhard , Tycko Benjamin , Cole Phillip A. , Ryu Byungwoo 
Published: October 2021

AbstractAberrant epigenetic transcriptional regulation is linked to metastasis, a primary cause of cancer-related death. Dissecting the epigenetic mechanisms controlling metastatic progression may uncover important insights to tumor biology and potential therapeutic targets. Here, we investigated the role of the SIN3A histone deacetylase 1 and 2 (SIN3A–HDAC1/2) complex in cancer metastasis. Using a mouse model of melanoma metastasis, we found that the SIN3A–HDAC1/2 transcription repressor complex silences BMP6 expression, causing increased metastatic dissemination and tumor growth via suppression of BMP6-activated SMAD5 signaling. We further discovered that FAM83G/PAWS1, a downstream effector of BMP6–SMAD5 signaling, contributes critically to metastatic progression by promoting actin-dependent cytoskeletal dynamics and cell migration. Pharmacologic inhibition of the SIN3A–HDAC1/2 complex reduced the numbers of melanoma cells in the circulation and inhibited metastatic tumor growth by inducing disseminated cell dormancy, highlighting the SIN3A–HDAC1/2 repressor complex as a potential therapeutic target for blocking cancer metastasis.Implications:This study identifies the novel molecular links in the metastatic progression to target cytoskeletal dynamics in melanoma and identifies the SIN3A–HDAC1/2 complex and FAM83G/PAWS1 as potential targets for melanoma adjuvant therapy.
Reduction in Vaccine HPV Type Infections in a Young Women Group (18–25 Years) Five Years after HPV Vaccine Introduction in Colombia
Authors: Combita Alba L. , Reyes Viviana , Puerto Devi , Murillo Raúl , Sánchez Ricardo , Nuñez Marcela , Hernandez-Suarez Gustavo A. , Wiesner Carolina 
Published: October 2021

Abstract

In Colombia, the human papillomavirus (HPV) vaccine was launched in 2012 in the context of a school-based national vaccination program targeting girls ages 9 to 14 and offering catch-up vaccination for girls ages 14 to 17. In this study, we evaluated the program's impact on type-specific HPV infection by comparing HPV cervical prevalence among vaccinated and nonvaccinated women. This is a comparative cross-sectional study conducted 5 years after the quadrivalent HPV vaccination implementation in a sentinel Colombian City. This study included young women (18–25 years old) who had been vaccinated in the catch-up group and were attending universities and technical institutions, and women who attended primary health care facilities for Pap smear screening. The HPV prevalence of 1,287 unvaccinated women was compared with the prevalence of 1,986 vaccinated women. The prevalence of HPV16/18 infections was significantly lower in vaccinated compared with unvaccinated women (6.5% vs. 15.4%; P &lt; 0.001), whereas for HPV6/11 infections, a decrease of 63.7% in vaccinated women (1.02% vs. 2.81%) was observed. The adjusted effectiveness to HPV16/18 was 61.4%; 95% CI, 54.3%–67.6%. However, the effectiveness against HPV16/18 was significantly higher among women vaccinated before their sexual debut 91.5%; 95% CI, 86.8–94.5, compared with effectiveness for vaccination after their sexual debut, 36.2%; 95% CI, 23.6–46.7. Five years after the introduction of HPV vaccines in Colombia, high effectiveness of HPV to prevent HPV16/18 infections is observed in the catch-up cohorts including virgin and sexually active women.

Prevention Relevance:
Monitoring HPV vaccines post-licensure plays an important role in assessing the progress of immunization programs, demonstrating the impact of vaccines on the population, and providing data for policy needs. In Colombia, HPV vaccines showed effectiveness when administered before start of sexual activity, and two doses are sufficient to achieve good protection.
Celecoxib Colorectal Bioavailability and Chemopreventive Response in Patients with Familial Adenomatous Polyposis
Authors: Yang Peiying , Zuo Xiangsheng , Advani Shailesh , Wei Bo , Malek Jessica , Day Rena Sue , Shureiqi Imad 
Published: October 2021

AbstractWhy celecoxib exerts chemopreventive activity in only some familial adenomatous polyposis (FAP) patients remains poorly understood. We conducted a phase II clinical study to identify potential predictive biomarkers for celecoxib chemopreventive activity in FAP. Twenty-seven patients with FAP completed a 6-month oral course of 400 mg of celecoxib twice a day; they underwent colonoscopies before and after celecoxib treatment to assess colorectal polyp tumor burden and to obtain normal and polyp colorectal biopsies to measure celecoxib, 13-S-hydroxyoctadecadienoic acid (13-HODE), 15-HETE, 12-HETE, and LTB4 levels by LC/MS-MS. Celecoxib levels in sera from those patients were also measured before treatment and after 2, 4, and 6 months of treatment. Nineteen of the 27 patients experienced a response to celecoxib, with a ≥ 28% reduction of colonic polyp burden on the basis of a reproducible quantitative assessment of colonoscopy results. Celecoxib levels were significantly lower in polyp tissues than in normal colorectal tissues. Celecoxib levels in sera and normal colorectal tissues were correlated in patients who experienced a response to celecoxib but not in those who did not. Among the measured lipoxygenase products, only 13-HODE levels were significantly lower in polyp tissues than in normal tissues. Our findings demonstrate the differential bioavailability of celecoxib between normal and polyp tissues and its potential effects on clinical response in patients with FAP.Prevention Relevance:This study evaluated potential predictive biomarkers for celecoxib chemopreventive activity in patients with FAP. Our findings demonstrated the differential bioavailability of celecoxib between normal and polyp tissues and its potential effects on clinical chemopreventive response in patients with FAP.See related Spotlight, p. 205
Characterization of the Genomic and Immunologic Diversity of Malignant Brain Tumors through Multisector Analysis
Authors: Schaettler Maximilian O. , Richters Megan M. , Wang Anthony Z. , Skidmore Zachary L. , Fisk Bryan , Miller Katherine E. , Vickery Tammi L. , Kim Albert H. , Chicoine Michael R. , Osbun Joshua W. , Leuthardt Eric C. , Dowling Joshua L. , Zipfel Gregory J. , Dacey Ralph G. , Lu Hsiang-Chih , Johanns Tanner M. , Griffith Obi L. , Mardis Elaine R. , Griffith Malachi , Dunn Gavin P. 
Published: October 2021

Abstract

Despite some success in secondary brain metastases, targeted or immune-based therapies have shown limited efficacy against primary brain malignancies such as glioblastoma (GBM). Although the intratumoral heterogeneity of GBM is implicated in treatment resistance, it remains unclear whether this diversity is observed within brain metastases and to what extent cancer cell–intrinsic heterogeneity sculpts the local immune microenvironment. Here, we profiled the immunogenomic state of 93 spatially distinct regions from 30 malignant brain tumors through whole-exome, RNA, and T-cell receptor sequencing. Our analyses identified differences between primary and secondary malignancies, with gliomas displaying more spatial heterogeneity at the genomic and neoantigen levels. In addition, this spatial diversity was recapitulated in the distribution of T-cell clones in which some gliomas harbored highly expanded but spatially restricted clonotypes. This study defines the immunogenomic landscape across a cohort of malignant brain tumors and contains implications for the design of targeted and immune-based therapies against intracranial malignancies.

Significance:
This study describes the impact of spatial heterogeneity on genomic and immunologic characteristics of gliomas and brain metastases. The results suggest that gliomas harbor significantly greater intratumoral heterogeneity of genomic alterations, neoantigens, and T-cell clones than brain metastases, indicating the importance of multisector analysis for clinical or translational studies.
This article is highlighted in the In This Issue feature, p. 1