bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multimodal imaging shows fibrosis architecture and action potential dispersion are predictors of arrhythmic risk in spontaneous hypertensive rats
Authors: Khwaounjoo Prashanna , Sands Gregory B. , LeGrice Ian J. , Ramulgun Girish , Ashton Jesse L. , Montgomery Johanna M. , Gillis Anne M. , Smaill Bruce H. , Trew Mark L. 
Published: August 2022

AbstractHypertensive heart disease (HHD) increases risk of ventricular tachycardia (VT) and ventricular fibrillation (VF). The roles of structural vs. electrophysiological remodelling and age vs. disease progression are not fully understood. This cross‐sectional study of cardiac alterations through HHD investigates mechanistic contributions to VT/VF risk. Risk was electrically assessed in Langendorff‐perfused, spontaneously hypertensive rat hearts at 6, 12 and 18 months, and paced optical membrane voltage maps were acquired from the left ventricular (LV) free wall epicardium. Distributions of LV patchy fibrosis and 3D cellular architecture in representative anterior LV mid‐wall regions were quantified from macroscopic and microscopic fluorescence images of optically cleared tissue. Imaging showed increased fibrosis from 6 months, particularly in the inner LV free wall. Myocyte cross‐section increased at 12 months, while inter‐myocyte connections reduced markedly with fibrosis. Conduction velocity decreased from 12 months, especially transverse to the myofibre direction, with rate‐dependent anisotropy at 12 and 18 months, but not earlier. Action potential duration (APD) increased when clustered by age, as did APD dispersion at 12 and 18 months. Among 10 structural, functional and age variables, the most reliably linked were VT/VF risk, general LV fibrosis, a measure quantifying patchy fibrosis, and non‐age clustered APD dispersion. VT/VF risk related to a quantified measure of patchy fibrosis, but age did not factor strongly. The findings are consistent with the notion that VT/VF risk is associated with rate‐dependent repolarization heterogeneity caused by structural remodelling and reduced lateral electrical coupling between LV myocytes, providing a substrate for heterogeneous intramural activation as HHD progresses.
imageKey points
There is heightened arrhythmic risk with progression of hypertensive heart disease.
Risk is related to increasing left ventricular fibrosis, but the nature of this relationship has not been quantified.
This study is a novel systematic characterization of changes in active electrical properties and fibrotic remodelling during progression of hypertensive heart disease in a well‐established animal disease model.
Arrhythmic risk is predicted by several left ventricular measures, in particular fibrosis quantity and structure, and epicardial action potential duration dispersion.
Age alone is not a good predictor of risk.
An improved understanding of links between arrhythmic risk and fibrotic architectures in progressive hypertensive heart disease aids better interpretation of late gadolinium‐enhanced cardiac magnetic resonance imaging and electrical mapping signals.
Tephrochronology of the Miocene Monterey and Modelo Formations, California
Authors: Knott Jeffrey R. , Sarna-Wojcicki Andrei M. , Barron John A. , Wan Elmira , Heizler Lynn , Martinez Priscilla 
Published: August 2022

ABSTRACT
Tuff beds (volcanic ash beds and tuffs) have been known in the Miocene Monterey and Modelo Formations since they were initially described nearly 100 yr ago. Yet, these tephra layers have remained largely ignored. The ages and correlation of the Monterey and Modelo Formations are predominantly based on associated biostratigraphy. Here, we combined tephrochronology and biostratigraphy to provide more precise numerical age control for eight sedimentary sequences of the Monterey and Modelo Formations from Monterey County to Orange County in California. We correlated 38 tephra beds in the Monterey and Modelo Formations to 26 different dated tephra layers found mainly in nonmarine sequences in Nevada, Idaho, and New Mexico. We also present geochemical data for an additional 19 tephra layers in the Monterey and Modelo Formations, for which there are no known correlative tephra layers, and geochemical data for another 11 previously uncharacterized tephra layers in other areas of western North America. Correlated tephra layers range in age from 16 to 7 Ma; 31 tephra layers erupted from volcanic centers of the Snake River Plain, northern Nevada to eastern Idaho; 13 other tephra layers erupted from the Southern Nevada volcanic field; and the eruptive source is unknown for 12 other tephra layers. These tephra layers provide new time-stratigraphic markers for the Monterey and Modelo Formations and for other marine and nonmarine sequences in western North America. We identified tephra deposits of four supereruptions as much as 1200 km from the eruptive sources: Rainier Mesa (Southern Nevada volcanic field) and Cougar Point Tuff XI, Cougar Point Tuff XIII, and McMullen Creek (all Snake River Plain).
Mechanical thrombectomy in ischemic stroke after cardiovascular procedures: a propensity-matched cohort analysis
Authors: Bay Benjamin , Gloyer Nils-Ole , Remmel Marko , Schell Maximilian , Zelenak Kamil , Seiffert Moritz , Brunner Fabian J , Clemmensen Peter , Reichenspurner Hermann , Blankenberg Stefan , Thomalla Goetz , Fiehler Jens , Conradi Lenard , Waldeyer Christoph , Flottmann Fabian 
Published: August 2022

BackgroundStroke after a cardiovascular procedure (CVP) is a devastating complication adversely affecting outcome. Mechanical thrombectomy (MT) has not been investigated systematically in this population.ObjectiveTo carry out a retrospective study in patients undergoing MT for early stroke after CVP, aiming to further characterize this cohort of patients, and to evaluate the efficacy, safety, procedural characteristics, and outcome of MT.MethodsA single-center stroke registry of patients who received MT was analyzed. Baseline and procedural parameters, mortality, functional outcome, recanalization rates, and complications were evaluated. Propensity score matching was carried out, identifying a control cohort with non-periprocedural large vessel occlusion (LVO).ResultsOverall 913 patients were included (mean age 73.0 (±13.0) years, 52.5% female, median National Institutes of Health Stroke Scale score 15 (10–19)). Eleven patients with a LVO after a recent (<30 days postoperatively) CVP were identified (n=3 transcatheter aortic valve and n=1 surgical aortic valve replacements (SAVR), n=3 coronary bypass grafting (CABG) surgeries, n=2 SAVR+CABG, and n=2 aortic surgeries). After matching, 8 patients in the CVP group were compared with 16 patients in the matched cohort. Comparable rates of reperfusion were achieved. Time from symptom onset to groin puncture (171.5 min (136.3, 178.3) vs 284.0 min (215.0, 490.5); p=0.039), as well as recanalization (195.0 min (146.0, 201.0) vs 419.0 min (274.0, 613.0); p=0.028) was faster in the CVP group. However, this was not reflected by an improved outcome (modified Rankin Scale score after 90 days: 5.5 (3.3, 6.0) vs 5.0 (4.0, 6.0), mortality after 90 days 50.0% vs 37.5%). Complications did not differ between the groups.ConclusionsUse of MT for LVO stroke in patients after a recent CVP is a safe and efficient treatment in comparison with patients with a non-periprocedural LVO undergoing MT.
Stimulation holiday rescues analgesia after habituation and loss of efficacy from 10-kilohertz dorsal column spinal cord stimulation
Authors: D'Souza Ryan S , Her Yeng F 
Published: August 2022

IntroductionHabituation and loss of efficacy from spinal cord stimulation are commonly reported. This retrospective analysis investigated rescue of analgesia from spinal cord stimulation failure after implementing a strategy called a stimulation holiday, during which spinal cord stimulation is interrupted for a defined period and subsequently restarted.MethodsA 6-year review (June 1, 2016–May 13, 2022) from a tertiary care center was conducted on patients who underwent 10 kHz frequency dorsal column spinal cord stimulation for ≥3 months, experienced loss of efficacy (≤30% pain relief or patient self-report of lack of meaningful pain relief), subsequently underwent a stimulation holiday, and then restarted spinal cord stimulation. The primary outcome was comparison of pain relief and responder rate (≥50% relief in pain intensity) before and after stimulation holiday.ResultsOf 212 patients, 40 (18.9%) experienced loss of efficacy at a mean follow-up period of 452.7±326.4 days after stimulator implantation and underwent stimulation holiday. Pain relief was significantly higher 1 month after stimulation holiday (39.4%±28.6%) compared with before stimulation holiday (8.7%±13.0%; mean difference 30.6%, 95% CI 21.9% to 39.3%, paired t-test p<0.001). A significantly higher responder rate (≥50% relief in pain intensity) was identified after stimulation holiday (57.5%) compared with before stimulation holiday (0%; Fisher’s exact test p<0.001). Associations of superior pain relief and responder rate remained significant at 3 and 6 months after stimulation holiday.DiscussionPatients who experience loss of efficacy from spinal cord stimulation habituation could attempt a stimulation holiday rather than abandon therapy. Rescue of analgesia may be achieved after implementing a stimulation holiday and restarting spinal cord stimulation.
Strategy of spawning in the tropical squid Lolliguncula diomedeae females: allocation of energy, senescence, and influence of Aggregata coccidians
Authors: Alejo-Plata María del Carmen , del Rio Portilla Miguel , González-Acosta Adrián F. , León Guzmán Sairi Sarai 
Published: August 2022

Although the squid Lolliguncula diomedeae (Hoyle, 1904) is of commercial and ecological importance in the Gulf of Tehuantepec (southeastern Mexico), this is the first study to examine female spawning strategy. Information on reproductive indicators was used to assess the impact of spawning behavior on growth rates and the condition of somatic tissue, since energy for reproduction is derived mainly from somatic tissue and consumed food. Additionally, oocyte storage patterns were examined to determine the type of spawning that characterizes this species. A total of 1347 females, ranging between 27.3 and 90.0 mm dorsal mantle length (ML) and 0.1 and 25.6 g of total weight, were examined. Statolith analysis indicates that the life cycle of L. diomedeae is 212 days. Allometric growth was observed during the female life cycle. The size at maturity was 68.54 mm ML, with synchronous ovulation (by groups) and intermittent spawning. The results showed that L. diomedeae is an energetically efficient squid species that feeds during all of its reproductive life stages, thus ensuring the occurrence of partial spawning events, and that feeding ends when senescence begins. However, its life cycle could be affected by the presence of coccidian parasites, mainly during senescence.
Subregular W-algebras of type A
Authors: Fehily Zachary 
Published: August 2022

Subregular W-algebras are an interesting and increasingly important class of quantum hamiltonian reductions of affine vertex algebras. Here, we show that the [Formula: see text] subregular W-algebra can be realized in terms of the [Formula: see text] regular W-algebra and the half lattice vertex algebra [Formula: see text]. This generalizes the realizations found for [Formula: see text] and [Formula: see text] in [D. Adamović, Realizations of simple affine vertex algebras and their modules: The cases [Formula: see text] and [Formula: see text], Comm. Math. Phys. 366 (2019) 1025–1067, arXiv:1711.11342 [math.QA]; D. Adamović, K. Kawasetsu and D. Ridout, A realization of the Bershadsky–Polyakov algebras and their relaxed modules, Lett. Math. Phys., 111 (2021) 1–30, arXiv:2007.00396 [math.QA]] and can be interpreted as an inverse quantum hamiltonian reduction in the sense of Adamović. We use this realization to explore the representation theory of [Formula: see text] subregular W-algebras. Much of the structure encountered for [Formula: see text] and [Formula: see text] is also present for [Formula: see text]. Particularly, the simple [Formula: see text] subregular W-algebra at nondegenerate admissible levels can be realized purely in terms of the [Formula: see text] minimal model vertex algebra and [Formula: see text].
Existence and asymptotic behavior of non-normal conformal metrics on ℝ4 with sign-changing Q-curvature
Authors: Bernardini Chiara 
Published: August 2022

We consider the following prescribed [Formula: see text]-curvature problem: [Formula: see text] We show that for every polynomial [Formula: see text] of degree 2 such that [Formula: see text], and for every [Formula: see text], there exists at least one solution to problem ( 1 ) which assumes the form [Formula: see text], where [Formula: see text] behaves logarithmically at infinity. Conversely, we prove that all solutions to ( 1 ) have the form [Formula: see text], where [Formula: see text] and [Formula: see text] is a polynomial of degree at most two bounded from above. Moreover, if [Formula: see text] is a solution to ( 1 ), it has the following asymptotic behavior: [Formula: see text] As a consequence, we give a geometric characterization of solutions in terms of the scalar curvature at infinity of the associated conformal metric [Formula: see text].
Public-Sector Accounting Reforms and Governmental Efficiency: A Two-Stage Approach
Authors: Cuadrado-Ballesteros Beatriz , Bisogno Marco , Vaia Giovanni 
Published: August 2022

SynopsisThe research problemWe investigated the association between public-sector accounting reforms and efficiency at a central-government level, assessing efficiency through a global perspective.MotivationThe effects of financial management reforms on efficiency have rarely been investigated. We contribute to the academic debate concerning both public-sector accounting reforms (implementation of international accounting standards and accrual-accounting systems) and governmental efficiency, merging two streams of literature that have not been investigated thoroughly.The test hypothesesH1: Countries that have implemented IPSAS are more efficient.H2: Countries that have implemented accrual-accounting systems are more efficient.Target populationWe used a sample of 22 European countries in the period 2010–2018.Adopted methodologyWe adopted a two-step approach: first, we created several efficiency indicators using different techniques; second, we implemented a model to test our hypotheses.AnalysesData Envelopment Analysis (DEA) technique, DEA with application of the bootstrap technique, and Order-m modelFindingsAccrual accounting was positively associated with efficiency while findings did not totally support an association with IPSAS.
EXPLORING CONSUMER PREFERENCES FOR NET-ZERO POLICIES: WILLINGNESS TO PAY AMONG UK CITIZENS FOR NATIONAL GREENHOUSE GAS REDUCTION TARGETS UNDER DIFFERENT FUTURE DISCOUNTING ASSUMPTIONS
Authors: LAWTON RICKY N. , FUJIWARA DANIEL 
Published: August 2022

Following the UK’s hosting of the United Nations Convention of the Parties Climate Summit in 2021, political targets for reducing greenhouse gas emissions — “Net-Zero” — have gained momentum. We address the gap in how public preferences are accounted for in climate decision-making by applying Contingent-Valuation techniques which ask people to state their Willingness-to-Pay (WTP) for the UK’s 2050 Net-Zero target. Mean WTP is £37.57/household to support Net-Zero (median £11.25), with a present-value of £2.3 billion across UK households. While younger people are more likely to experience the long-term impacts of climate change, older generations are willing to pay more to support it, suggesting that public support for Net-Zero is largely based on “nonuse” benefits, rather than direct “use” benefits to oneself. The COVID-19 epidemic affected WTP bids in a quarter of respondents. Finally, we explore how choice of positive or normative discount rate affects policy conclusions when monetizing consumer preferences.
Menstrual Factors, Reproductive History and Liver Cancer Risk: Findings from a Prospective Cohort Study in Chinese Women
Authors: Tuo Jia-Yi , Li Hong-Lan , Wang Jing , Fang Jie , Tan Yu-Ting , Xiang Yong-Bing 
Published: August 2022

Abstract

Background:
Many studies suggested that menstrual and reproductive factors affected the gender disparity in liver carcinogenesis, but the results were inconsistent. Moreover, there are few studies in Asian populations. Therefore, our study was to explore the association of menstrual and reproductive factors on liver cancer risk in Chinese women.

Methods:
72,807 women were recruited in 1996 to 2000 and followed until the end of 2016 in Shanghai, China. Cox regression models were used to estimate HRs and 95% confidence intervals (CIs) for the association of menstrual and reproductive factors with liver cancer.

Results:
258 liver cancer cases were identified during 1,269,531 person-years of follow-up. In premenopausal and postmenopausal women, hormone replacement therapy (HRT) and injective contraceptives were positively associated with liver cancer risk respectively (HR, 1.23, 95% CI, 1.15–1.30; HR, 1.23, 95% CI, 1.17–1.30; HR, 1.07, 95% CI, 1.05–1.10; HR, 1.08, 95% CI, 1.05–1.11), while older age at menopause, longer reproductive period and fewer live births were associated with reduced risk, especially among postmenopausal women (Ptrend &lt; 0.05). In addition, liver cancer risk was elevated in postmenopausal women who received hysterectomy (HR, 1.07; 95% CI, 1.04–1.11), oophorectomy (HR, 1.05; 95% CI, 1.01–1.10) or oral contraceptives (HR, 1.06; 95% CI, 1.03–1.08). No association was found between age at menarche and liver cancer risk. Similar results were observed when excluding participants with less than 2 follow-up years.

Conclusions:
The findings suggested that female sex hormones could play significant roles in liver carcinogenesis.

Impact:
Our study was the first population-based cohort to provide epidemiology evidence of menstrual and reproductive factors on liver cancer risk in Chinese women.
The Timing, the Treatment, the Question: Comparison of Epidemiologic Approaches to Minimize Immortal Time Bias in Real-World Data Using a Surgical Oncology Example
Authors: Duchesneau Emilie D. , Jackson Bradford E. , Webster-Clark Michael , Lund Jennifer L. , Reeder-Hayes Katherine E. , Nápoles Anna M. , Strassle Paula D. 
Published: August 2022

Abstract

Background:
Studies evaluating the effects of cancer treatments are prone to immortal time bias that, if unaddressed, can lead to treatments appearing more beneficial than they are.

Methods:
To demonstrate the impact of immortal time bias, we compared results across several analytic approaches (dichotomous exposure, dichotomous exposure excluding immortal time, time-varying exposure, landmark analysis, clone-censor-weight method), using surgical resection among women with metastatic breast cancer as an example. All adult women diagnosed with incident metastatic breast cancer from 2013–2016 in the National Cancer Database were included. To quantify immortal time bias, we also conducted a simulation study where the “true” relationship between surgical resection and mortality was known.

Results:
24,329 women (median age 61, IQR 51–71) were included, and 24% underwent surgical resection. The largest association between resection and mortality was observed when using a dichotomized exposure [HR, 0.54; 95% confidence interval (CI), 0.51–0.57], followed by dichotomous with exclusion of immortal time (HR, 0.62; 95% CI, 0.59–0.65). Results from the time-varying exposure, landmark, and clone-censor-weight method analyses were closer to the null (HR, 0.67–0.84). Results from the plasmode simulation found that the time-varying exposure, landmark, and clone-censor-weight method models all produced unbiased HRs (bias −0.003 to 0.016). Both standard dichotomous exposure (HR, 0.84; bias, −0.177) and dichotomous with exclusion of immortal time (HR, 0.93; bias, −0.074) produced meaningfully biased estimates.

Conclusions:
Researchers should use time-varying exposures with a treatment assessment window or the clone-censor-weight method when immortal time is present.

Impact:
Using methods that appropriately account for immortal time will improve evidence and decision-making from research using real-world data.
A Phase I Trial of CT900, a Novel α-Folate Receptor–Mediated Thymidylate Synthase Inhibitor, in Patients with Solid Tumors with Expansion Cohorts in Patients with High-Grade Serous Ovarian Cancer
Authors: Banerjee Susana , Michalarea Vasiliki , Ang Joo Ern , Ingles Garces Alvaro , Biondo Andrea , Funingana Ionut-Gabriel , Little Martin , Ruddle Ruth , Raynaud Florence , Riisnaes Ruth , Gurel Bora , Chua Sue , Tunariu Nina , Porter Joanna C. , Prout Toby , Parmar Mona , Zachariou Anna , Turner Alison , Jenkins Ben , McIntosh Stuart , Ainscow Ed , Minchom Anna , Lopez Juanita , de Bono Johann , Jones Robert , Hall Emma , Cook Natalie , Basu Bristi , Banerji Udai 
Published: August 2022

Abstract

Purpose:
CT900 is a novel small molecule thymidylate synthase inhibitor that binds to α-folate receptor (α-FR) and thus is selectively taken up by α-FR–overexpressing tumors.

Patients and Methods:
A 3+3 dose escalation design was used. During dose escalation, CT900 doses of 1–6 mg/m2 weekly and 2–12 mg/m2 every 2 weeks (q2Wk) intravenously were evaluated. Patients with high-grade serous ovarian cancer were enrolled in the expansion cohorts.

Results:
109 patients were enrolled: 42 patients in the dose escalation and 67 patients in the expansion cohorts. At the dose/schedule of 12 mg/m2/q2Wk (with and without dexamethasone, n = 40), the most common treatment-related adverse events were fatigue, nausea, diarrhea, cough, anemia, and pneumonitis, which were predominantly grade 1 and grade 2. Levels of CT900 more than 600 nmol/L needed for growth inhibition in preclinical models were achieved for &gt;65 hours at a dose of 12 mg/m2. In the expansion cohorts, the overall response rate (ORR), was 14/64 (21.9%). Thirty-eight response-evaluable patients in the expansion cohorts receiving 12 mg/m2/q2Wk had tumor evaluable for quantification of α-FR. Patients with high or medium expression had an objective response rate of 9/25 (36%) compared with 1/13 (7.7%) in patients with negative/very low or low expression of α-FR.

Conclusions:
The dose of 12 mg/m2/q2Wk was declared the recommended phase II dose/schedule. At this dose/schedule, CT900 exhibited an acceptable side effect profile with clinical benefit in patients with high/medium α-FR expression and warrants further investigation.
The role of spirituality and resilience among Yemeni refugee students in the Kingdom of Saudi Arabia
Authors: Ahmed Garoon Manal Ali , Hashim Shahabuddin , Yaacob Nik Rosila Nik 
Published: August 2022

<span lang="EN-US">The purpose of this article was to explore the role of spirituality and resilience in coping and adaptation among Yemeni refugee students. This qualitative study aimed to explore the themes of spirituality and resilience that emerged among Yemeni refugee students who have experienced from conditions of war after the war that began in Yemen in 2015. This study applied in-depth, semi-structured interviews to explore the themes through qualitative interviews with Yemeni refugee students in Saudi Arabia. Thematic analysis was used to determine the role of spirituality and resilience in coping and adaptation. The study showed that Yemeni refugee students commonly use five main coping and adaptation methods to improve their lives in the host country. </span>