bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of temperature, body size, and sex on the standard metabolic rates of a sexually dimorphic freshwater piscivore, walleye (Sander vitreus)
Authors: Bihun Christian J. , Murphy Megan K. , Johnson Timothy B. , Fisk Aaron T. , Guzzo Matthew M. , Madenjian Charles P. , Raby Graham D. 
Published: March 2024

Walleye ( Sander vitreus) are a sexually dimorphic freshwater piscivore that have long been studied using bioenergetics modeling, yet robust estimates of metabolic rates for use in those models have been lacking. Therefore, we quantified the effects of body mass, water temperature, and sex, on standard metabolic rate (SMR). We estimated SMR across temperatures ranging 0.5–24 °C using intermittent-flow respirometry for male ( n = 54) and female ( n = 53) walleye raised in hatchery conditions. We found a significant interaction between sex and temperature, whereby males had lower SMR below 16 °C, but increased such that SMR was ∼16% higher than females at 22 °C. The mass-scaling coefficient, b, was similar for both sexes at a value around 1. These estimates are the first to be generated using respirometry for adult walleye and differ slightly from those being used by previous bioenergetics models, which may have underestimated the energetic costs of SMR, and did not include sex-specific estimates for metabolism.
Anomaly cancellation by generalised cohomology
Authors: Patrascu Andrei T. 
Published: March 2024

AbstractSupersymmetric states in M-theory are mapped after compactification to perturbatively non-supersymmetric states in type IIA string theory, with the supersymmetric parts being encoded in the non-perturbative section of the string theory. An observer unable to recognise certain topological features of string theory will not detect supersymmetry. Such relativity of symmetry can also be derived in the context of Theorem 3 in Patrascu (Phys Rev D 90:045018, 2014). The tool of choice in this context is the universal coefficient theorem linking cohomology theories with coefficients that reveal respectively hide certain topological features. As a consequence of these observations, it is shown that the same theorem is capable of linking perturbative with non-perturbative string theoretical domains. A discussion of inflow anomaly cancellation is also included in the context of universal coefficient theorems.
Design and Implementation of Hardware-Software Architecture Based on Hashes for SPHINCS+
Authors: Lopez-Valdivieso Jonathan , Cumplido Rene 
Published: March 2024

Advances in quantum computing have posed a future threat to today’s cryptography. With the advent of these quantum computers, security could be compromised. Therefore, the National Institute of Standards and Technology (NIST) has issued a request for proposals to standardize algorithms for post-quantum cryptography (PQC), which is considered difficult to solve for both classical and quantum computers. Among the proposed technologies, the most popular choices are lattice-based (shortest vector problem) and hash-based approaches. Other important categories are public key cryptography (PKE) and digital signatures.
Within the realm of digital signatures lies SPHINCS+. However, there are few implementations of this scheme in hardware architectures. In this article, we present a hardware-software architecture for the SPHINCS+ scheme. We utilized a free RISC-V (Reduced Instruction Set Computer) processor synthesized on a Field Programmable Gate Array (FPGA), primarily integrating two accelerator modules for Keccak-1600 and the Haraka hash function. Additionally, modifications were made to the processor to accommodate the execution of these added modules. Our implementation yielded a 15-fold increase in performance with the SHAKE-256 function and nearly 90-fold improvement when using Haraka, compared to the reference software. Moreover, it is more compact compared to related works. This implementation was realized on a Xilinx FPGA Arty S7: Spartan-7.
Early and Realistic Exploitability Prediction of Just-Disclosed Software Vulnerabilities: How Reliable Can It Be?
Authors: Iannone Emanuele , Sellitto Giulia , Iaccarino Emanuele , Ferrucci Filomena , De Lucia Andrea , Palomba Fabio 
Published: March 2024

With the rate of discovered and disclosed vulnerabilities escalating, researchers have been experimenting with machine learning to predict whether a vulnerability will be exploited. Existing solutions leverage information unavailable when a CVE is created, making them unsuitable just after the disclosure. This paper experiments with
early
exploitability prediction models driven exclusively by the initial CVE record, i.e., the original description and the linked online discussions. Leveraging NVD and Exploit Database, we evaluate 72 prediction models trained using six traditional machine learning classifiers, four feature representation schemas, and three data balancing algorithms. We also experiment with five pre-trained large language models (LLMs). The models leverage seven different corpora made by combining three data sources, i.e., CVE description,
Security Focus
, and
BugTraq
. The models are evaluated in a
realistic
, time-aware fashion by removing the training and test instances that cannot be labeled
“neutral”
with sufficient confidence. The validation reveals that CVE descriptions and
Security Focus
discussions are the best data to train on. Pre-trained LLMs do not show the expected performance, requiring further pre-training in the security domain. We distill new research directions, identify possible room for improvement, and envision automated systems assisting security experts in assessing the exploitability.
m6A Modification Promotes EMT and Metastasis of Castration-Resistant Prostate Cancer by Upregulating NFIB
Authors: Shu Feng , Liu Hao , Chen Xiaohui , Liu Ye , Zhou Jiangli , Tang Lei , Cao Wanwei , Yang Shanshan , Long Yili , Li Rongna , Wang Hao , Wang Hongsheng , Jiang Guanmin 
Published: March 2024

Abstract

The widespread use of androgen receptor (AR) signaling inhibitors has led to an increased incidence of AR-negative castration-resistant prostate cancer (CRPC), limiting effective treatment and patient survival. A more comprehensive understanding of the molecular mechanisms supporting AR-negative CRPC could reveal therapeutic vulnerabilities to improve treatment. This study showed that the transcription factor nuclear factor I/B (NFIB) was upregulated in patient with AR-negative CRPC tumors and cell lines and was positively associated with an epithelial-to-mesenchymal transition (EMT) phenotype. Loss of NFIB inhibited EMT and reduced migration of CRPC cells. NFIB directly bound to gene promoters and regulated the transcription of EMT-related factors E-cadherin (CDH1) and vimentin (VIM), independent of other typical EMT-related transcriptional factors. In vivo data further supported the positive role of NFIB in the metastasis of AR-negative CRPC cells. Moreover, N6-methyladenosine (m6A) modification induced NFIB upregulation in AR-negative CRPC. Mechanistically, the m6A levels of mRNA, including NFIB and its E3 ubiquitin ligase TRIM8, were increased in AR-negative CRPC cells. Elevated m6A methylation of NFIB mRNA recruited YTHDF2 to increase mRNA stability and protein expression. Inversely, the m6A modification of TRIM8 mRNA, induced by ALKBH5 downregulation, decreased its translation and expression, which further promoted NFIB protein stability. Overall, this study reveals that upregulation of NFIB, mediated by m6A modification, triggers EMT and metastasis in AR-negative CRPC. Targeting the m6A/NFIB axis is a potential prevention and treatment strategy for AR-negative CRPC metastasis.

Significance:
NFIB upregulation mediated by increased m6A levels in AR-negative castration-resistant prostate cancer regulates transcription of EMT-related factors to promote metastasis, providing a potential therapeutic target to improve prostate cancer treatment.
A Phase I Trial of Enzalutamide Plus Selective Glucocorticoid Receptor Modulator Relacorilant in Patients with Metastatic Castration-Resistant Prostate Cancer
Authors: Desai Kunal B. , Serritella Anthony V. , Stadler Walter M. , O'Donnell Peter H. , Sweis Randy F. , Szmulewitz Russell Z. 
Published: March 2024

Abstract

Purpose:
The majority of patients with metastatic prostate cancer who receive androgen-deprivation therapy and androgen receptor (AR) signaling inhibitors (ARSI) progress. Activation of the glucocorticoid receptor (GR) is associated with ARSI resistance. This single-arm phase I trial assessed safety and pharmacokinetic (PK) feasibility of a combined AR antagonist (enzalutamide) and selective GR modulator (relacorilant) in patients with metastatic castration-resistant prostate cancer (mCRPC).

Patients and Methods:
This was a phase I trial (NCT03674814) of relacorilant and enzalutamide in patients with refractory mCRPC enrolled using a 6+3 design. The enzalutamide dose was kept constant at 120 mg/d with escalating doses of relacorilant based on safety and PK measures in cohorts of ≥6 patients. The primary objective was safety and establishment of pharmacologically active doses. Secondary objectives were related to antitumor activity.

Results:
Thirty-five patients with mCRPC were enrolled. Twenty-three were accrued across three dose cohorts in the dose-escalation phase, and 12 enrolled at the recommended phase II dose. The combination was generally well tolerated, safe, and achieved desirable enzalutamide PK. RP2D of 120 + 150 mg/d, respectively, was established. Median time on study was 2.2 months with four patients remaining on study for longer than 11 months. Four of 12 evaluable patients had a prostate-specific antigen (PSA) partial response.

Conclusions:
This is the first prospective trial combining an AR antagonist and a nonsteroidal selective GR modulator. The combination was safe and well tolerated with PSA response and prolonged disease control observed in a limited subset of patients. Further prospective trials are justified to evaluate efficacy and identify predictive biomarkers of response.
TABERNACL: Temporary Hemodynamic Stabilization In Vivo
Authors: Halaby Rim N. , Bruce Christopher G. , Yildirim D. Korel , Uzun Dogangun , Rogers Toby , Khan Jaffar M. , Jaimes Andi E. , Grant Laurie P. , Babaliaros Vasilis C. , Greenbaum Adam B. , Lederman Robert J. 
Published: March 2024

BACKGROUND:
Acute aortic regurgitation is life-threatening with few nonsurgical options for immediate stabilization. We propose Trans-Aortic Balloon to Ease Regurgitation Applying Counter-Pulsation (TABERNACL), a simple, on-table temporary valve using commercially available equipment to temporize acute severe aortic regurgitation.

METHODS:
We hypothesize that an appropriately sized commercial balloon dilatation catheter—straddling the aortic annulus and connected to a counterpulsation console—can serve as a temporizing valve to restore hemodynamic stability in acute aortic regurgitation. We performed benchtop testing of valvuloplasty, angioplasty, and sizing balloons as counterpulsation balloons. TABERNACL was assessed in vivo in a porcine model of acute aortic regurgitation (n=8). We also tested a static undersized, continuously inflated transvalvular balloon as a spacer intended physically to obstruct the regurgitant orifice.

RESULTS:

Benchtop testing identified that Tyshak II and PTS sizing (NuMed Braun) balloon catheters performed adequately as temporary valves (ie, complete inflation and deflation with each cycle) and resisted fatigue, in contrast to others. When TABERNACL was used in the acute severe regurgitation animals, there was immediate hemodynamic improvement, with a significant 35% increase in diastolic aortic pressure by 16 mm Hg ([95% CI, 7–25]
P
=0.0056), 34% reduction in left ventricular end-diastolic pressure by −7 mm Hg ([95% CI, −10 to −5]
P
=0.0006), improvement in the aortic diastolic index by 0.28 ([95% CI, 0.18–0.39]
P
=0.0009), and reversal of electrocardiographic myocardial ischemia. As an alternative, static balloon inflation across the aortic valve stabilized regurgitation hemodynamics at the expense of a new aortic gradient and caused excessive ectopy from balloon movement in the left ventricular outflow tract.

CONCLUSIONS:
TABERNACL improves hemodynamics and reduces coronary ischemia by electrocardiography in animals with acute severe aortic regurgitation. TABERNACL valves obstruct the diastolic regurgitant orifice without systolic obstruction. This may prove a lifesaving bridge to definitive valve replacement therapy.
Correlates of Plasma NT‐proBNP/Cyclic GMP Ratio in Heart Failure With Preserved Ejection Fraction: An Analysis of the RELAX Trial
Authors: Chiu Leonard , Agrawal Vineet , Armstrong David , Brittain Evan , Collins Sheila , Hemnes Anna R. , Hill Joseph A. , Lindenfeld JoAnn , Shah Sanjiv J. , Stevenson Lynne W. , Wang Thomas J. , Gupta Deepak K. 
Published: March 2024

Background
Phosphodiesterases degrade cyclic GMP (cGMP), the second messenger that mediates the cardioprotective effects of natriuretic peptides. High natriuretic peptide/cGMP ratio may reflect, in part, phosphodiesterase activity. Correlates of natriuretic peptide/cGMP in patients with heart failure with preserved ejection fraction are not well understood. Among patients with heart failure with preserved ejection fraction in the RELAX (Phosphodiesterase‐5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure With Preserved Ejection Fraction) trial, we examined (1) cross‐sectional correlates of circulating NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide)/cGMP ratio, (2) whether selective phosphodiesterase‐5 inhibition by sildenafil changed the ratio, and (3) whether the effect of sildenafil on 24‐week outcomes varied by baseline ratio.

Methods and Results

In 212 subjects, NT‐proBNP/cGMP ratio was calculated at randomization and 24 weeks. Correlates of the ratio and its change were examined in multivariable proportional odds models. Whether baseline ratio modified the sildenafil effect on outcomes was examined by interaction terms. Higher NT‐proBNP/cGMP ratio was associated with greater left ventricular mass and troponin, the presence of atrial fibrillation, and lower estimated glomerular filtration rate and peak oxygen consumption. Compared with placebo, sildenafil did not alter the ratio from baseline to 24 weeks (
P
=0.17). The effect of sildenafil on 24‐week change in peak oxygen consumption, left ventricular mass, or clinical composite outcome was not modified by baseline NT‐proBNP/cGMP ratio (
P
‐interaction >0.30 for all).

Conclusions
Among patients with heart failure with preserved ejection fraction, higher NT‐proBNP/cGMP ratio associated with an adverse cardiorenal phenotype, which was not improved by selective phosphodiesterase‐5 inhibition. Other phosphodiesterases may be greater contributors than phosphodiesterase‐5 to the adverse phenotype associated with a high natriuretic peptide/cGMP ratio in HFpEF.

Registration Information

clinicaltrials.gov
. Identifier:
NCT00763867
.
Posttraumatic Stress Disorder After Spontaneous Coronary Artery Dissection: A Report of the International Spontaneous Coronary Artery Dissection Registry
Authors: Sumner Jennifer A. , Kim Esther S. H. , Wood Malissa J. , Chi Gerald , Nolen Jessica , Grodzinsky Anna , Gornik Heather L. , Kadian‐Dodov Daniella , Wells Bryan J. , Hess Connie N. , Lewey Jennifer , Tam Lori , Henkin Stanislav , Orford James , Wells Gretchen , Kumbhani Dharam J. , Lindley Kathryn J. , Gibson C. Michael , Leon Katherine K. , Naderi Sahar 
Published: March 2024

BackgroundMyocardial infarction secondary to spontaneous coronary artery dissection (SCAD) can be traumatic and potentially trigger posttraumatic stress disorder (PTSD). In a large, multicenter, registry‐based cohort, we documented prevalence of lifetime and past‐month SCAD‐induced PTSD, as well as related treatment seeking, and examined a range of health‐relevant correlates of SCAD‐induced PTSD.Methods and ResultsPatients with SCAD were enrolled in the iSCAD (International SCAD) Registry. At baseline, site investigators completed medical report forms, and patients reported demographics, medical/SCAD history, psychosocial factors (including SCAD‐induced PTSD symptoms), health behaviors, and health status via online questionnaires. Of 1156 registry patients, 859 patients (93.9% women; mean age, 52.3 years) completed questionnaires querying SCAD‐induced PTSD. Nearly 35% (n=298) of patients met diagnostic criteria for probable SCAD‐induced PTSD in their lifetime, and 6.4% (n=55) met criteria for probable past‐month PTSD. Of 811 patients ever reporting any SCAD‐induced PTSD symptoms, 34.8% indicated seeking treatment for this distress. However, 46.0% of the 298 patients with lifetime probable SCAD‐induced PTSD diagnoses reported never receiving trauma‐related treatment. Younger age at first SCAD, fewer years since SCAD, being single, unemployed status, more lifetime trauma, and history of anxiety were associated with greater past‐month PTSD symptom severity in multivariable regression models. Greater past‐month SCAD‐induced PTSD symptoms were associated with greater past‐week sleep disturbance and worse past‐month disease‐specific health status when adjusting for various risk factors.ConclusionsGiven the high prevalence of SCAD‐induced PTSD symptoms, efforts to support screening for these symptoms and connecting patients experiencing distress with empirically supported treatments are critical next steps.RegistrationURL:https://www.clinicaltrials.gov; Unique identifier: NCT04496687.
Loss of Cardiac PFKFB2 Drives Metabolic, Functional, and Electrophysiological Remodeling in the Heart
Authors: Harold Kylene M. , Matsuzaki Satoshi , Pranay Atul , Loveland Brooke L. , Batushansky Albert , Mendez Garcia Maria F. , Eyster Craig , Stavrakis Stavros , Chiao Ying Ann , Kinter Michael , Humphries Kenneth M. 
Published: March 2024

Background
Phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase (PFK‐2) is a critical glycolytic regulator responsible for upregulation of glycolysis in response to insulin and adrenergic signaling. PFKFB2, the cardiac isoform of PFK‐2, is degraded in the heart in the absence of insulin signaling, contributing to diabetes‐induced cardiac metabolic inflexibility. However, previous studies have not examined how the loss of PFKFB2 affects global cardiac metabolism and function.

Methods and Results
To address this, we have generated a mouse model with a cardiomyocyte‐specific knockout of PFKFB2 (cKO). Using 9‐month‐old cKO and control mice, we characterized the impacts of PFKFB2 on cardiac metabolism, function, and electrophysiology. cKO mice have a shortened life span of 9 months. Metabolically, cKO mice are characterized by increased glycolytic enzyme abundance and pyruvate dehydrogenase activity, as well as decreased mitochondrial abundance and beta oxidation, suggesting a shift toward glucose metabolism. This was supported by a decrease in the ratio of palmitoyl carnitine to pyruvate‐dependent mitochondrial respiration in cKO relative to control animals. Metabolomic, proteomic, and Western blot data support the activation of ancillary glucose metabolism, including pentose phosphate and hexosamine biosynthesis pathways. Physiologically, cKO animals exhibited impaired systolic function and left ventricular dilation, represented by reduced fractional shortening and increased left ventricular internal diameter, respectively. This was accompanied by electrophysiological alterations including increased QT interval and other metrics of delayed ventricular conduction.

Conclusions
Loss of PFKFB2 results in metabolic remodeling marked by cardiac ancillary pathway activation. This could delineate an underpinning of pathologic changes to mechanical and electrical function in the heart.
Association Between Defibrillation Using LIFEPAK 15 or ZOLL X Series and Survival Outcomes in Out‐of‐Hospital Cardiac Arrest: A Nationwide Cohort Study
Authors: Meilandt Carsten , Qvortrup Mette , Bøtker Morten Thingemann , Folke Fredrik , Borup Lars , Christensen Helle Collatz , Milling Louise , Lauridsen Kasper G. , Løfgren Bo 
Published: March 2024

Background
Defibrillation is essential for achieving return of spontaneous circulation (ROSC) following out‐of‐hospital cardiac arrest (OHCA) with shockable rhythms. This study aimed to investigate if the type of defibrillator used was associated with ROSC in OHCA.

Methods and Results
This study included adult patients with OHCA from the Danish Cardiac Arrest Registry from 2016 to 2021 with at least 1 defibrillation by the emergency medical services. We used multivariable logistic regression and a difference‐in‐difference analysis, including all patients with or without emergency medical services shock to assess the causal inference of using the different defibrillator models (LIFEPAK or ZOLL) for OHCA defibrillation. Among 6516 patients, 77% were male, the median age (quartile 1; quartile 3) was 70 (59; 79), and 57% achieved ROSC. In total, 5514 patients (85%) were defibrillated using LIFEPAK (ROSC: 56%) and 1002 patients (15%) were defibrillated using ZOLL (ROSC: 63%). Patients defibrillated using ZOLL had an increased adjusted odds ratio (aOR) for ROSC compared with LIFEPAK (aOR, 1.22 [95% CI, 1.04–1.43]). There was no significant difference in 30‐day mortality (aOR, 1.11 [95% CI, 0.95–1.30]). Patients without emergency medical services defibrillation, but treated by ZOLL‐equipped emergency medical services, had a nonsignificant aOR for ROSC compared with LIFEPAK (aOR, 1.10 [95% CI, 0.99–1.23]) and the difference‐in‐difference analysis was not statistically significant (OR, 1.10 [95% CI, 0.91–1.34]).

Conclusions
Defibrillation using ZOLL X Series was associated with increased odds for ROSC compared with defibrillation using LIFEPAK 15 for patients with OHCA. However, a difference‐in‐difference analysis suggested that other factors may be responsible for the observed association.
Introducing the Concept of Sanctuary Sites in Ischemic Stroke
Authors: Thirugnanachandran Tharani , Ma Henry , Donnan Geoffrey A. , Reutens David C. , Phan Thanh G. 
Published: March 2024

BACKGROUND:
The topography of arterial territories has been defined using digital maps of supratentorial infarcts. Regions with a high probability of infarction (Pi) exist in the deep compartment due to a paucity of collaterals. However, less attention has been given to regions with a low Pi.

METHODS:

Using published digital maps, patients with cortical stroke and documented vessel occlusion were included. Infarcts from T
2
-weighted magnetic resonance images were segmented and registered onto a standard brain template (Montreal Neurological Institute 152). Segmented magnetic resonance images were averaged to yield the Pi at a voxel level. The overall Pi for the combined arterial territories was calculated to ensure that Pi was in the range of 0 to 1. Sanctuary sites were identified as regions with Pi <0.1.

RESULTS:
There were 154 patients (63% men; median age, 69 years; and interquartile range, 57–78 years). The magnetic resonance imaging scan used for segmentation was performed at a median interval of 35 (interquartile range, 3–66) days after stroke onset. Sanctuary sites were present in the frontal (gyrus rectus, the paracentral lobule, and orbitofrontal and precentral gyrus), parietal (postcentral, supramarginal, and angular gyrus, superior and inferior parietal lobule, and precuneus and posterior cingulate), and occipital cortex (cuneus, middle, and superior occipital gyrus).

CONCLUSIONS:
We propose that following vessel occlusion, there are cortical regions with a low Pi, which we termed sanctuary sites. The anatomic basis for this observation is the compensatory capacity of leptomeningeal collaterals.