bluuebunny/crossref_metadata_2025_split huggingface dataset:
Calcaneal tendon stiffness is not associated with dynamic time-dependent contractile output
Authors: Kulkarni Sohum V. , Paris Michael T. , Rice Charles L. 
Published: February 2023

The ability to rapidly generate muscular torque and velocity is important in specialized activities and daily tasks of living. Tendon stiffness is one factor in the neuromuscular system that influences musculoskeletal torque transmission. Previous studies have reported weak-to-moderate correlations between tendon stiffness and rate of torque development (RTD). However, these correlations have been reported only for isometric contractions, which may not be relevant to contractions involving joint rotation (i.e., dynamic). The purpose was to investigate the effect of calcaneal tendon stiffness on the dynamic RTD and rate of velocity development (RVD) in plantar flexor muscles. Young adult males ( n = 13) and females ( n = 2) performed prone isometric- and isotonic-mode maximal voluntary plantar flexion contractions (MVC). Ultrasound imaging was used to quantify tendon morphological characteristics to estimate Young's elastic modulus (YM). Maximal voluntary and electrically evoked (300 Hz) isometric- and isotonic-mode (at 10% and 40% MVC loads) contractions were evaluated for RTD and RVD through a 25° ankle joint range of motion. YM was correlated with isometric RTD, but only for evoked contractions (RTD0–50 ms: r = 0.54, p = 0.02, RTD0–200 ms: r = 0.62, p = 0.01). Conversely, YM was not correlated with dynamic RTD (voluntary: r = −0.07–0.41, p = 0.06–0.40, evoked: r = −0.2–0.3, p = 0.14–0.24) nor RVD (voluntary: r = −0.08–0.24, p = 0.27–0.40, evoked: r = 0.12–0.3, p = 0.14–0.34). These correlations would indicate that calcaneal tendon stiffness is an important factor for rapid isometric torque development, but less so for isotonic contractions. The determinants of dynamic contractile rates are more complex and warrant further study.
On parity-odd sector in metric-affine theories
Authors: Beltrán Jiménez Jose , Jiménez-Cano Alejandro , Obukhov Yuri N. 
Published: February 2023

AbstractWe undertake the construction of quadratic parity-violating terms involving the curvature in the four-dimensional metric-affine gravity. We demonstrate that there are only 12 linearly independent scalars, plus an additional one that can be removed by using the Pontryagin invariant. Several convenient bases for this sector are provided in both components and differential form notation. We also particularize our general findings to some constrained geometries like Weyl–Cartan and metric-compatible connections.
On differences between even and odd anisotropic-flow harmonics in non-equilibrated systems
Authors: Bachmann Benedikt , Borghini Nicolas , Feld Nina , Roch Hendrik 
Published: February 2023

AbstractTo assess how anisotropic transverse flow is created in a system out of equilibrium, we compare several kinetic-theoretical models in the few-rescatterings regime. We compare the flow harmonics $$v_n$$

v
n

from three types of transport simulations, with either $$2\rightarrow 2$$

2
→
2

or $$2\rightarrow 0$$

2
→
0

collision kernels and in the former case allowing the particles to rescatter several times or not, and from analytical calculations neglecting the gain term of the Boltzmann equation. We find that the even flow harmonics are similar in all approaches, while the odd ones differ significantly. This suggests that while even $$v_n$$

v
n

harmonics may to a large extent be due to the anisotropic escape probability of particles, this is not the predominant mechanism underlying the odd $$v_n$$

v
n

coefficients.
Socially disruptive periods and topics from information-theoretical analysis of judicial decisions
Authors: Font-Pomarol Lluc , Piga Angelo , Garcia-Teruel Rosa Maria , Nasarre-Aznar Sergio , Sales-Pardo Marta , Guimerà Roger 
Published: February 2023

AbstractLaws and legal decision-making regulate how societies function. Therefore, they evolve and adapt to new social paradigms and reflect changes in culture and social norms, and are a good proxy for the evolution of socially sensitive issues. Here, we use an information-theoretic methodology to quantitatively track trends and shifts in the evolution of large corpora of judicial decisions, and thus to detect periods in which disruptive topics arise. When applied to a large database containing the full text of over 100,000 judicial decisions from Spanish courts, we are able to identify an abrupt change in housing-related decisions around 2016. Because our information-theoretic approach pinpoints the specific content that drives change, we are also able to interpret the results in terms of the role played by legislative changes, landmark decisions, and the influence of social movements.
FERNET: An Integrated Hybrid DCNN Model for Driver Stress Monitoring via Facial Expressions
Authors: Gupta Chinmay , Kumar Mohit , Yadav Arun Kumar , Yadav Divakar 
Published: February 2023

Drivers undergo a lot of stress that might cause distraction and might lead to an unfortunate incident. Emotional recognition via facial expressions is one of the most important field in the human–machine interface. The goal of this paper is to analyze the drivers’ facial expressions in order to monitor their stress levels. In this paper, we propose FERNET — a hybrid deep convolutional neural network model for driver stress recognition through facial emotion recognition. FERNET is an integration of two DCNNs, pre-trained ResNet101V2 CNN and a custom CNN, ConvNet4. The experiments were carried out on the widely used public datasets CK[Formula: see text], FER2013 and AffectNet, achieving the accuracies of 99.70%, 74.86% and 70.46%, respectively, for facial emotion recognition. These results outperform the recent state-of-the-art methods. Furthermore, since a few specific isolated emotions lead to higher stress levels, we analyze the results for stress- and nonstress-related emotions for each individual dataset. FERNET achieves stress prediction accuracies of 98.17%, 90.16% and 84.49% for CK[Formula: see text], FER2013 and AffectNet datasets, respectively.
The alteration of the Schwinger effect on radiatively corrected Higgs inflationary magneto-genesis by axial coupling
Authors: Kamarpour Mehran 
Published: February 2023

We study the alteration of the Schwinger effect on radiatively corrected Higgs inflationary magneto-genesis by axial coupling function. The conformal invariance of Maxwell action should be broken by axial coupling with the inflaton field. We use the potential of [M. Kamarpour, Gen. Relativ. Gravit. 53 (2021) 53, doi:10.1007/s10714-021-02824-0; M. Kamarpour, Gen. Relativ. Gravit. 54 (2022) 32, doi:10.1007/s10714-022-02920-9] with the simplest coupling function [Formula: see text] in which [Formula: see text] is a dimensionless coupling parameter.In comparison to our previous work (in which we used curvature-based coupling or so-called nonminimal coupling function to gravity to break conformal invariance of action) of [M. Kamarpour, Gen. Relativ. Gravit. 54 (2022) 32, doi:10.1007/s10714-022-02920-9] we find that the Schwinger effect does alter magneto-genesis and is considerable. In fact, in comparison to our previous work of [M. Kamarpour, Gen. Relativ. Gravit. 54 (2022) 32, doi:10.1007/s10714-022-02920-9] we obtain that for some certain values of coupling parameter [Formula: see text] the Schwinger effect does alter magneto-genesis (see [M. Kamarpour, Gen. Relativ. Gravit. 53 (2021) 53, doi:10.1007/s10714-021-02824-0]) and the energy density of created charged particles during the Schwinger effect becomes considerable and of course comparable to the energy density of inflaton field. Therefore, the Schwinger effect decreases the value of the electric field, so that it helps to finish the inflation stage. Then the universe enters the stage of preheating.The Schwinger effect produces charged particles, imposing the Schwinger reheating framework even before the ending of last oscillations of the inflaton field.
A Pro-Regenerative Environment Triggers Premalignant to Malignant Transformation of Senescent Hepatocytes
Authors: Wuestefeld Anna , Iakovleva Viktoriia , Yap Shirlyn Xue Ling , Ong Agnes Bee Leng , Huang Daniel Q. , Shuen Timothy Wai Ho , Toh Han Chong , Dan Yock Young , Zender Lars , Wuestefeld Torsten 
Published: February 2023

Abstract

Unfortunately, available liver cancer treatments are associated with modest survival advantage. The biggest factor improving survival is early detection, but the current understanding of early transformation events is limited. Therefore, we set up a model to study these early events and investigated the relationship of premalignant, senescent hepatocytes, a regenerative environment, and the influence of secreted factors on liver tumorigenesis. Oncogene-induced senescence (OIS) was triggered in a subset of mouse hepatocytes, which under normal conditions, are eliminated by immunosurveillance. Inducing liver damage and regeneration was sufficient to trigger immunosurveillance escape of OIS hepatocytes, resulting in premalignant to malignant transformation and hepatocellular tumor development. Trefoil factor 3 (TFF3) was found to be overexpressed in OIS hepatocytes and in hepatocellular carcinoma. TFF3 deficiency strongly attenuated malignant transformation by increasing insulin-like growth factor binding protein 5 (IGFBP5) expression, which consequently dampened IGF receptor signaling. Furthermore, analysis of precancerous liver tissue validated TFF3 as an early liver cancer biomarker. Altogether, these findings provide mechanistic insights into early transformation and immunosurveillance escape in liver cancer, revealing TFF3 and IGFBP5 to be important players with opposite roles in tumorigenesis.

Significance:
Liver damage induces a compensatory regenerative response that can drive premalignant to malignant transformation of senescent hepatocytes.
Bone Marrow Mesenchymal Stem Cells Induce Metabolic Plasticity in Estrogen Receptor–Positive Breast Cancer
Authors: Buschhaus Johanna M. , Rajendran Shrila , Chen Siyi , Wharram Bryan L. , Bevoor Avinash S. , Cutter Alyssa C. , Humphries Brock A. , Robison Tanner H. , Farfel Alex P. , Luker Gary D. 
Published: February 2023

AbstractCancer cells reprogram energy metabolism through metabolic plasticity, adapting ATP-generating pathways in response to treatment or microenvironmental changes. Such adaptations enable cancer cells to resist standard therapy. We employed a coculture model of estrogen receptor–positive (ER+) breast cancer and mesenchymal stem cells (MSC) to model interactions of cancer cells with stromal microenvironments. Using single-cell endogenous and engineered biosensors for cellular metabolism, coculture with MSCs increased oxidative phosphorylation, intracellular ATP, and resistance of cancer cells to standard therapies. Cocultured cancer cells had increased MCT4, a lactate transporter, and were sensitive to the MCT1/4 inhibitor syrosingopine. Combining syrosingopine with fulvestrant, a selective estrogen receptor degrading drug, overcame resistance of ER+ breast cancer cells in coculture with MSCs. Treatment with antiestrogenic therapy increased metabolic plasticity and maintained intracellular ATP levels, while MCT1/4 inhibition successfully limited metabolic transitions and decreased ATP levels. Furthermore, MCT1/4 inhibition decreased heterogenous metabolic treatment responses versus antiestrogenic therapy. These data establish MSCs as a mediator of cancer cell metabolic plasticity and suggest metabolic interventions as a promising strategy to treat ER+ breast cancer and overcome resistance to standard clinical therapies.Implications:This study reveals how MSCs reprogram metabolism of ER+ breast cancer cells and point to MCT4 as potential therapeutic target to overcome resistance to antiestrogen drugs.
Targeted MDM2 Degradation Reveals a New Vulnerability for p53-Inactivated Triple-Negative Breast Cancer
Authors: Adams Clare M. , Mitra Ramkrishna , Xiao Youcai , Michener Peter , Palazzo Juan , Chao Allen , Gour Jitendra , Cassel Joel , Salvino Joseph M. , Eischen Christine M. 
Published: February 2023

AbstractTriple-negative breast cancers (TNBC) frequently inactivate p53, increasing their aggressiveness and therapy resistance. We identified an unexpected protein vulnerability in p53-inactivated TNBC and designed a new PROteolysis TArgeting Chimera (PROTAC) to target it. Our PROTAC selectively targets MDM2 for proteasome-mediated degradation with high-affinity binding and VHL recruitment. MDM2 loss in p53 mutant/deleted TNBC cells in two-dimensional/three-dimensional culture and TNBC patient explants, including relapsed tumors, causes apoptosis while sparing normal cells. Our MDM2-PROTAC is stable in vivo, and treatment of TNBC xenograft-bearing mice demonstrates tumor on-target efficacy with no toxicity to normal cells, significantly extending survival. Transcriptomic analyses revealed upregulation of p53 family target genes. Investigations showed activation and a required role for TAp73 to mediate MDM2-PROTAC–induced apoptosis. Our data, challenging the current MDM2/p53 paradigm, show MDM2 is required for p53-inactivated TNBC cell survival, and PROTAC-targeted MDM2 degradation is an innovative potential therapeutic strategy for TNBC and superior to existing MDM2 inhibitors.Significance:p53-inactivated TNBC is an aggressive, therapy-resistant, and lethal breast cancer subtype. We designed a new compound targeting an unexpected vulnerability we identified in TNBC. Our MDM2-targeted degrader kills p53-inactivated TNBC cells, highlighting the requirement for MDM2 in TNBC cell survival and as a new therapeutic target for this disease.See related commentary by Peuget and Selivanova, p. 1043.This article is highlighted in the In This Issue feature, p. 1027
Como as experiências europeia e estadunidense podem contribuir com o diálogo competitivo brasileiro?
Authors: Moreira Filho Getúlio Velasco 
Published: February 2023

Na década de 1990, o Estado brasileiro transferiu atividades econômicas, até então sob a égide do setor público, para a iniciativa privada. Nesse contexto, surgem as agências reguladoras no Brasil. Nesse artigo, inicia-se com um breve histórico sobre a criação das agências reguladoras, com destaque para o modelo americano. Segue-se com a abordagem acerca dos motivos que levaram à sua estruturação no Brasil para, então, analisar nuances da Lei Geral das Agências Reguladoras em âmbito federal, sempre sob a perspectiva da tutela dos direitos consumeristas. Trazem-se exemplos, como do setor de energia elétrica, para demonstrar que, mesmo em período pandêmico, a “manutenção do equilíbrio” das relações de consumo, quando o assunto é tarifário, pende para um único lado. Aborda-se o recente regramento do setor de saneamento, refletindo sobre a necessidade de expansão dos serviços, porém, sem que isso onere mais o consumidor. Enfim, procura-se analisar criteriosamente se a atividade regulatória do Estado tem espelhado os anseios da coletividade ou tem privilegiado setores econômicos e políticos. Pondera-se, por fim, ser fundamental a harmonização dos interesses e a observância dos ditames constitucionais acerca dos direitos dos consumidores para que o modelo regulatório brasileiro atenda os fins para os quais se destina.
Paroxysmal Atrial Fibrillation Ablation Using a Novel Variable-Loop Biphasic Pulsed Field Ablation Catheter Integrated With a 3-Dimensional Mapping System: 1-Year Outcomes of the Multicenter inspIRE Study
Authors: Duytschaever Mattias , De Potter Tom , Grimaldi Massimo , Anic Ante , Vijgen Johan , Neuzil Petr , Van Herendael Hugo , Verma Atul , Skanes Allan , Scherr Daniel , Pürerfellner Helmut , Rackauskas Gediminas , Jaïs Pierre , Reddy Vivek Y. , Natale Andrea , Di Biase Luigi , Knecht Sebastien , Petru Jan , Kollias Georgios , Lukac Peter , Hansen Jim , Phlips Thomas 
Published: February 2023

Background:
The inspIRE study (Study for Treatment of Paroxysmal Atrial Fibrillation [PAF] by Pulsed Field Ablation [PFA] System With Irreversible Electroporation [IRE]) evaluated safety and effectiveness of a fully integrated biphasic pulsed field ablation (PFA) system with a variable-loop circular catheter for the treatment of drug-refractory paroxysmal atrial fibrillation.

Methods:
Subjects underwent pulmonary vein (PV) isolation with the PFA system, using at least 12 applications per vein; adenosine/isoproterenol was administered to confirm entrance block. Wave I assessed initial safety, including for esophageal lesions, silent cerebral lesions, and PV stenosis. Wave II (pivotal phase) tested (1) primary safety, incidence of early-onset primary adverse events, and (2) primary effectiveness, confirmed PV isolation with freedom from documented atrial arrhythmia at 12 months. The study design specified an interim analysis to determine early success once 30 subjects reached the 12-month follow-up and all subjects reached 3-month follow-up.

Results:
Across 13 centers in Europe/Canada, 226 subjects were enrolled, met criteria for safety and effectiveness evaluations, and received PFA (Wave I, 40; Wave II, 186). Wave I demonstrated no esophageal thermal lesions or PV stenosis. Among 39 subjects with cerebral magnetic resonance imaging, silent cerebral lesions were detected in 4 of the first 6 subjects, after which workflow enhancements, including a 10-second pause between PFA applications, were implemented; subsequently, only 4 of 33 subjects had silent cerebral lesions. In the Wave II phase, no primary adverse events were reported. Upon declaring early success, 83 subjects reached 12-month follow-up. With 100% entrance block, PV isolation without acute reconnection was achieved in 97.1% of targeted veins. For Wave II, the primary effectiveness end point per Kaplan-Meier at the time of interim analysis was 70.9%; 12-month freedom from symptomatic atrial fibrillation/atrial flutter/atrial tachycardia recurrence and repeat ablation was 78.9% and 92.3%, respectively. Total procedure and transpired PFA times were 70.1±27.7 and 26.7±14.0 minutes, respectively.

Conclusions:
The inspIRE trial confirmed the safety and effectiveness of the novel mapping-integrated PFA system.

Registration:

URL:
https://www.clinicaltrials.gov
; unique identifier: NCT04524364.
GLP−1 Promotes Cortical and Medullary Perfusion in the Human Kidney and Maintains Renal Oxygenation During NaCl Loading
Authors: Haddock Bryan , Kristensen Kasper B. , Tayyab Mahvish , Larsson Henrik B. W. , Lindberg Ulrich , Vestergaard Mark , Francis Susan , Jensen Boye L. , Andersen Ulrik B. , Asmar Ali 
Published: February 2023

Background
GLP‐1 (glucagon‐like peptide‐1) receptor agonists exert beneficial long‐term effects on cardiovascular and renal outcomes. In humans, the natriuretic effect of GLP‐1 depends on GLP‐1 receptor interaction, is accompanied by suppression of angiotensin II, and is independent of changes in renal plasma flow. In rodents, angiotensin II constricts vasa recta and lowers medullary perfusion. The current randomized, controlled, crossover study was designed to test the hypothesis that GLP‐1 increases renal medullary perfusion in healthy humans.

Methods and Results

Healthy male participants (n=10, aged 27±4 years) ingested a fixed sodium intake for 4 days and were examined twice during a 1‐hour infusion of either GLP‐1 (1.5 pmol/kg per minute) or placebo together with infusion of 0.9% NaCl (750 mL/h). Interleaved measurements of renal arterial blood flow, oxygenation (R
2
*), and perfusion were acquired in the renal cortex and medulla during infusions, using magnetic resonance imaging. GLP‐1 infusion increased medullary perfusion (32±7%,
P
<0.001) and cortical perfusion (13±4%,
P
<0.001) compared with placebo. Here, NaCl infusion decreased medullary perfusion (−5±2%,
P
=0.007), whereas cortical perfusion remained unchanged. R
2
* values increased by 3±2% (
P
=0.025) in the medulla and 4±1% (
P
=0.008) in the cortex during placebo, indicative of decreased oxygenation, but remained unchanged during GLP‐1. Blood flow in the renal artery was not altered significantly by either intervention.

Conclusions
GLP‐1 increases predominantly medullary but also cortical perfusion in the healthy human kidney and maintains renal oxygenation during NaCl loading. In perspective, suppression of angiotensin II by GLP‐1 may account for the increase in regional perfusion.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04337268.
Dual Antiplatelet Therapy With Cilostazol for Secondary Prevention in Lacunar Stroke: Subanalysis of the CSPS.com Trial
Authors: Nishiyama Yasuhiro , Kimura Kazumi , Otsuka Toshiaki , Toyoda Kazunori , Uchiyama Shinichiro , Hoshino Haruhiko , Sakai Nobuyuki , Okada Yasushi , Origasa Hideki , Naritomi Hiroaki , Houkin Kiyohiro , Yamaguchi Keiji , Minematsu Kazuo , Matsumoto Masayasu , Tominaga Teiji , Tomimoto Hidekazu , Terayama Yasuo , Yasuda Satoshi , Yamaguchi Takenori ,   for the CSPS.com Trial Investigators
Published: February 2023

Background:
The effectiveness of long-term dual antiplatelet therapy (DAPT) to prevent recurrent strokes in patients with lacunar stroke remains unclarified. Therefore, this study aimed to compare and to elucidate the safety and effectiveness of DAPT and single antiplatelet therapy (SAPT) in preventing recurrence in chronic lacunar stroke.

Methods:
CSPS.com (Cilostazol Stroke Prevention Study for Antiplatelet Combination) was a prospective, multicenter, randomized controlled trial. In this prespecified subanalysis, 925 patients (mean age, 69.5 years; 69.4% men) with lacunar stroke were selected from 1884 patients with high-risk noncardioembolic stroke, enrolled in the CSPS.com trial after 8 to 180 days following stroke. Patients were randomly assigned to receive either SAPT or DAPT using cilostazol and were followed for 0.5 to 3.5 years. The primary efficacy outcome was the first recurrence of ischemic stroke. The safety outcomes were severe or life-threatening bleeding.

Results:
The DAPT group receiving cilostazol and either aspirin or clopidogrel and SAPT group receiving aspirin or clopidogrel alone comprised 464 (50.2%) and 461 (49.8%) patients, respectively. Ischemic stroke occurred in 12 of 464 patients (1.84 per 100 patient-years) in the DAPT group and 31 of 461 patients (4.42 per 100 patient-years) in the SAPT group, during follow-up. After adjusting for multiple potential confounding factors, ischemic stroke risk was significantly lower in the DAPT group than in the SAPT group (hazard ratio, 0.43 [95% CI, 0.22–0.84]). The rate of severe or life-threatening hemorrhage did not differ significantly between the groups (2 patients [0.31 per 100 patient-years] versus 6 patients [0.86 per 100 patient-years] in the DAPT and SAPT groups, respectively; hazard ratio, 0.36 [95% CI, 0.07–1.81]).

Conclusions:
In patients with lacunar stroke, DAPT using cilostazol had significant benefits in reducing recurrent ischemic stroke incidence compared with SAPT without increasing the risk of severe or life-threatening bleeding.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01995370. URL:
https://www.umin.ac.jp/ctr
; Unique identifier: UMIN000012180.