bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P3113: Apyrase But Not Dipyridamole Improves Cardiac Function In Ovariectomized High-fat Diet Mice
Authors: Khan Adnan A , Russ Elizabeth , Sohail Ahmed , Bu Yifan , Mahmood Eitezaz , Bose Ruma , Cassavaugh Jessica , Khabbaz Kamal , Mahmood Feroze , robson simon , Matyal Robina
Published: October 2023

Objectives:
Postmenopausal women with metabolic disease are predisposed to develop cardiovascular disease. Our previous experiments have shown that these women experience purinergic/adenosinergic signaling alteration resulting in diastolic dysfunction. We hypothesize that these signaling alterations are reversible and to demonstrate we used exogenous CD39 agonist (apyrase) and an ENT-1 inhibitor (dipyridamole), in a murine model simulating postmenopausal women.

Methods:
We fed 23 C57BL/6 female mice a HFD (40% kcal) from 5 weeks of age and performed ovariectomy at 12 weeks. Intraperitoneal (IP) injections were given daily to three groups for 10 days at 28 weeks. The following groups and dosages were used: apyrase (9 mice, 200U/kg), dipyridamole (9 mice, 20mg/kg), and saline (5 mice). At 30 weeks, mice were assessed with an EchoMRI for body composition, and transthoracic echocardiography (TTE) used for evaluation of cardiac function while mice were anesthetized with 2.5% isoflurane.

Results:
Our apyrase-treated mice, had significantly lowered values in E/E’, E/A, with increased Ejection Fraction and Fraction Shortening when compared to the saline treated groups, analyzed with t-test. Apyrase also had lower body weight, lean mass, fat mass, and heart/body weight percentage, when compared to saline (p<0.05). Dipyridamole had significant increase in LV diastolic volume and IVRT when compared to our saline group.

Conclusion:
Our findings could suggest that increased ectonucleotidase activity may ameliorate diastolic dysfunction experienced in our murine model. Future studies are needed to confirm its effect in postmenopausal women.
Abstract P3115: Disruption Of Assembly By Estrogen Limits Microtubule Proliferation In Failing Heart Cells
Authors: Ogren Allison , Stark Simone , McClellan Mark , Hartweck Lynn , Prins Kurt W , Gardner Melissa
Published: October 2023

Right heart failure, resulting from high pressure in the pulmonary artery, is the leading cause of mortality in pulmonary arterial hypertension (PAH). Interestingly, females with PAH have superior right ventricular (RV) function, which can mostly explain improved survival in female patients. Microtubules are long filaments that regulate cellular contractility and transport within cardiac cells. The excess proliferation of microtubules is associated with pathological t-tubule remodeling in failing RV cardiomyocytes. Previous work suggests that the female hormone estrogen disrupts microtubule assembly. Here, we explored whether estrogen treatment could ameliorate the pathological proliferation of microtubules. By utilizing iPSC-derived cardiomyocytes with live-cell confocal imaging, we show that estrogen treatment leads to long pausing during microtubule growth, like the microtubule inhibitor colchicine. Additionally, estrogen treatment rescues microtubule overgrowth in endothelin-stressed primary cardiomyocytes (Fig. 1). We examined the molecular mechanism using purified tubulin, the building block of microtubules, and estrogen. In cell-free experiments, estrogen induced long pauses in microtubule growth. Our preliminary data suggest that estrogen, like colchicine, binds to free tubulin and co-polymerizes with it, disrupting microtubule assembly independent of estrogen receptors. We conclude that estrogen’s ability to limit microtubule proliferation could contribute to sex differences in RV function in PAH.

Figure 1: Primary cardiomyocytes. Microtubule proliferation in endothelin-treated cells was rescued with estradiol.
Abstract P3120: Persistent Cardiac Dysfunction In Ovariectomized Independent Of Metabolic Disturbance
Authors: Sohail Ahmed , Khan Adnan A , Russ Elizabeth , Mahmood Eitezaz , Bu Yifan , Mahmood Feroze , Bose Ruma , Khabbaz Kamal R , robson simon , Matyal Robina
Published: October 2023

Objectives:
Postmenopausal women are known to develop metabolic syndrome and cardiovascular disease. We hypothesize that a murine model of ovariectomy (OVX) and high-fat diet (HFD), simulating a post-menopausal milieu, will have decreased activity, changes in body composition, and impaired cardiac activity.

Methods:
From 5 weeks of age, 11 C57BL/6 mice were fed a HFD and 10 were fed a control diet (CTL). At 12 weeks, 11 mice (5 HFD, 6 CTL) were ovariectomized (OVX). At 30 weeks mice body composition was analyzed with EchoMRI. Metabolic activity was monitored in Promethion metabolic cages for 48 hours. Transthoracic echocardiography (TTE) was performed while mice were anesthetized with 2.5% isoflurane.

Results:
The OVX mice traveled the furthest distance, and HFD+OVX the shortest distance. HFD+OVX and HFD had increased energy expenditure and higher fat mass compared to CTL (Figure 1). All groups had increased LV Mass, and worse systolic function to control (Table 1).

Conclusion:
Ovariectomy could be associated in systolic dysfunction independent of development of metabolic syndrome.
Abstract P3140: Extracellular Vesicle MicroRNA Cargo Drives Ventricular Arrhythmia In Heart Failure Patients By Recapitulating Developmental Genes
Authors: Gokulnath Priyanka , Spanos Michail , Lehmann Helge I. , Sheng Quanhu , Xiao Ling , Valkov Nedyalka , Das Avash , Chatterjee Emeli , Li Guoping , Alsop Eric , Van Keuren-Jensen Kendall , Shah Ravi V , Das Saumya
Published: October 2023

Heart Failure (HF) is the leading cause of death worldwide, of which arrhythmias account for 50%. The relationship between HF and arrhythmias is closely intertwined. Since novel biomarkers associated with HF that lead to these arrhythmogenic events are an area of unmet need, we aimed to identify the specific plasma Extracellular vesicles (EV)-driven microRNA cargo that could predispose ventricular cardiomyocytes to arrhythmia during HF as well as delineate targetable pathways to rescue the arrhythmic phenotype. We treated human pluripotent stem cell-derived ventricular cardiomyocytes (hPSC-VCM) with plasma-derived EVs from HF and control samples and observed significantly prolonged action potential duration in HF-treated hPSC-VCM (94.41 ± 16.13 msec) using optical voltage mapping. Small RNA cargo of the plasma EVs were sequenced to reveal 26 downregulated and 70 upregulated differentially expressed miRNAs between HF and control. Upon deconvolution analysis, many of these plasma miRNA transcripts were found to be enriched in the brain, RBCs, monocytes and other tissues. We also sequenced the long-RNA transcriptome of the recipient cardiomyocytes. We prioritized 33 targets for qRT-PCR validation based on predicted protein-coding targets of miRNA, and 10 of these mRNAs were different between HF and control EV-treated hPSC-VCMs. Interestingly, some mRNAs (EIF4E, NEDD4, ID3, ID1, CDKN1A, HSPD1) are known to be expressed during development. Pathway enrichment analysis of the validated targets converged in TGF beta signaling and Hippo pathways, implicated in cardiac developmental arrhythmogenic abnormalities. In conclusion, circulating EV small RNA cargo of HF patients can alter the electrophysiological properties of cardiomyocytes, many of which are derived, predominantly from the brain. More importantly, the arrhythmic phenotype is triggered when there is a recapitulation of developmental genes induced by the EV-derived miRNAs. While these miRNAs could be identified as putative biomarkers for SCD, targeting these developmental genes may be a fruitful therapeutic approach to rescue electrical remodeling in HF patients.
Abstract P3142: Engineering A Genetically Encoded Enhancer Of L-type Ca
2+
Currents
Authors: Del Rivero Morfin Pedro Javier J , Jayaraman Srinidhi , Yang Lin , Kochiss Audrey , Colecraft Henry M , Marx Steven , Ben-Johny Manu
Published: October 2023

L-type calcium channels (LTCC) play a crucial role as they serve as vital portals for Ca
2+
entry into cardiac myocytes, neurons, and other physiological systems. Altered LTCC function is linked to various pathologies including cardiac arrhythmias and neurodevelopmental disorders. In particular, genetic studies have identified loss-of-function mutations in Ca
V
1.2 channels in patients with shortened QT interval and Brugada Syndrome, as well as neuropsychiatric disorders. Given the broad physiological importance of LTCC in various tissues, conventional pharmacological agonists of LTCC may yield off-target effects and toxicity. Therefore, new approaches to upregulate LTCC function in a cell-type dependent manner is sought after. To do so, we here develop a genetically encoded enhancer of calcium channels (GeeCC, “geek”) by leveraging both a cardiac specific L-type channel modulator, leucine rich repeat containing protein 10 (Lrrc10), and selective nanobodies that target the LTCC complex. Specifically, Lrrc10 co-expression markedly upregulates LTCC currents. Furthermore, mutations in Lrrc10 are linked to cardiac diseases, including cardiomyopathies. Through extensive structure-function analysis, we identified a minimal action domain within Lrrc10 that is critical for functional modulation of LTCC. However, as this segment alone has a low affinity for the channel complex, its expression alone yielded minimal changes in Ca
2+
current amplitude. However, fusion of this Lrrc10 domain to a nanobody (nb.F3) that targets the Ca
2+
channel beta subunit resulted in a significant increase in the LTCC current amplitude. In depth analysis revealed exquisite selectivity of GeeCC for Ca
V
1.2/Ca
V
1.3 channels. In mouse cardiomyocytes, deployment of GeeCC via adenovirus enhances endogenous L-type currents when compared to uninfected controls or cardiomyocytes infected with nanobodies alone. Additionally, in neurons, co-expression of GeeCC enhanced excitation-transcription coupling. In all, we have developed a genetically-encoded approach to selectively enhance L-type currents. This strategy may enable new insights into cardiovascular and neuronal physiology and pathophysiology, and may have potential therapeutic applications.
Abstract P3145: Enhancing Cardiac Cav1.2 Ion Channel Function By Targeted Deubiquitination
Authors: Shanmugam Sri Karthika , Choudhury Papiya , Colecraft Henry M
Published: October 2023

Ventricular excitation-contraction coupling relies on precise spatial arrangement of voltage-gated calcium channels CaV1.2 within T-tubular dyadic junctions proximal to ryanodine receptors (RyR2) that gate Ca2+ release from the sarcoplasmic reticulum. Impaired CaV1.2 trafficking is linked to devastating cardiovascular diseases such as arrythmias and cardiac hypertrophy. Ubiquitination is an important regulatory mechanism that controls ion channel surface trafficking and turnover. Emerging evidence hint at a prominent role for CaV1.2 ubiquitination to underlie heart failure disease progression, that suppresses CaV1.2 currents (ICa,L), resulting in harmful compensatory mechanisms. Targeted protein stabilization (TPS) is a burgeoning therapeutic approach for undruggable targets. We hypothesized that harnessing deubiquitinases using TPS can counteract pathological ubiquitination of CaV1.2, overcoming the need for hormonal remodeling and lead to novel treatment. To this end, we sought to develop engineered deubiquitinases (enDUBs) that can increase functional expression of CaV1.2 channels in the heart. The catalytic domain of ubiquitin specific protease 21 (USP21) fused to nb.F3 (F3-USP21) robustly increased CaV1.2 currents reconstituted in HEK293 cells as well as endogenous ICa,L in mammalian ventricular cardiomyocytes. This increase was within the physiological range of the impact of β-adrenergic stimulation of CaV1.2 and did not alter ventricular action potential duration. The mechanism of nbF3-USP21-induced increase in ICa,L is augmented CaV1.2 surface density. Reassuringly, this approach did not adversely interfere with the correct placement of CaV1.2 channels at dyadic junctions as cardiomyocytes expressing nb.F3-USP21 displayed normal colocalization of CaV1.2 with RyR2 at T-tubules. In conclusion, our study provides evidence that targeting deubiquitinases using TPS could be a viable therapeutic approach for rescuing CaV1.2 functional expression and these findings may pave the way for future development of TPS-based therapies for cardiovascular diseases such as arrhythmias and cardiac hypertrophy.
Abstract P3155: Cardiac Extracellular Vesicles Mediate The Neoplastic Properties Of Heart Failure
Authors: Caller Tal , Rotem Itai , Shaihov–Teper Olga , Lendengolts Daria , Schary Yeshai , Shai Ruty , Glick-Saar Efrat , Dominissini Dan , Boomgarden Alex , D’Souza-Schorey Crislyn , Naftali Shani Nili , Leor Jonathan
Published: October 2023

Background:
Heart failure (HF) is associated with an increased incidence of cancer independently of shared risk factors. The mechanism behind this link is complex and not entirely clear. We aimed to test the hypothesis that cardiac extracellular vesicles (cEVs) contribute to the link between HF and cancer.

Methods & Results:
We used a mouse model of heterotopic lung cancer and post-myocardial infarction (MI) HF. To determine the role of cEVs in tumor growth, we focused on cardiac mesenchymal stromal cells (cMSCs) derived EVs, isolated by size exclusion chromatography. cMSCs after MI secreted twice more EVs, characterized with unique proteome, compared to cMSCs from sham-MI (
Fig A, B
). cMSC-EVs from HF harbored more tumor trophic cytokines and microRNA (miR), such as Periostin, Osteopontin, IL-6, TNFα, miR 221, and miR 21. Next, lung cancer cells were inoculated into mice. While HF accelerated tumor growth, EV depletion by GW4869 attenuated this effect. We found that labeled cMSC-EVs targeted lung cancer tumors, and adoptive transfer of cMSC-EVs from failing hearts accelerated tumor growth with and without systemic EV depletion (
Fig C, D
). Finally, we found that spironolactone, a renin-angiotensin-aldosterone inhibitor, mitigated the neoplastic effects of HF, attenuated tumor growth (
Fig E
), and reduced the secretion of cMSC-EVs by 26%.

Conclusions:
Our results provide new insight into the link between heart failure and cancer. We show, for the first time, that cardiac extracellular vesicles promote tumor growth independently of other secreted factors. Moreover, spironolactone reduces the number of cardiac extracellular vesicles and the neoplastic effects of heart failure.
Abstract P3168: Identification Of Exosome MicroRNA In Association With Severe Calcification In Coronary Chronic Total Occlusion
Authors: Son Ji-Hye , Chang Hun Soo , Moon Inki , Kong Min Gyu , Park Su Yeong , Kim Dongeon , Choi Hyung Oh , Park Hyun-Woo , Cho Yoon Haeng , Lee Heon , Suh Jon
Published: October 2023

Backgrounds:
Coronary artery calcification (CAC) is prevalent in patients with coronary chronic total occlusion (CTO). We investigated the association between plasma miRNAs and coronary artery calcification in patients with CTO.

Methods:
Blood samples were collected from 18 patients who underwent percutaneous coronary intervention (PCI) of CTO. Exosomal small RNA sequencing was performed from plasma to quantify miRNA expression. Calcium volume was quantified in computed tomography (CT) in CTO. Gene ontology and functional pathway were analyzed in the miRNAs that significantly correlates with calcium volume.

Results:
Calcium volume was positively correlated with miR-1-3p and miR-708-3p (p <0.05), and was negatively correlated with 4 miRNAs -including let-7d-5p (p <0.05). Gene enrichment and pathway analysis showed that the target genes of the 2 positively correlated miRNAs were involved in regulation of osteoblast differentiation and osteopontin signaling pathway. In contrast, the target genes of the 4 negatively correlated miRNAs were enriched in acetylcholine-mediated vasodilation involved in regulation of systemic arterial blood pressure, blood vessel development and response to sterol. Multiple linear regression showed that miR-1-3p and let-7d-5p could be key predictors of the calcium volume of CTO (adjusted R
2
= 0.798 and p <0.001).

Conclusions:
We identified miR-1-3p and let-7d-5p could be related with CAC in patients with CTO.
Abstract P3173: Exposure Of Mitochondria Isolated From Left Ventricular Myocardium Of Dogs With Moderate Heart Failure To 4-hydroxy-2-nonenal (4-hne) Worsens Existing Mitochondrial Dysfunction
Authors: SINGH-GUPTA VINITA , Gupta Ramesh C , Castle Kristina , Zhang Kefei , Xu Jiang , Sabbah Hani N
Published: October 2023

Background:
Reactive oxygen species (ROS) generated by dysfunction of mitochondria (MITO) of the failing heart plays an important role in lipid peroxidation of polyunsaturated fatty acids in cell and MITO membranes resulting in the production of aldehydes, such as malondialdehyde and 4-hydroxy-2-nonenal (4-HNE). MITO aldehyde dehydrogenase-2 (mALDH2) is a key enzyme for the detoxification of endogenous aldehyde substrates through NAD dependent oxidation. We previously showed that mALDH2 expression and activity are markedly reduced in MITO of failing LV cardiomyocytes, a maladaptation that can lead to considerable accumulation of 4-HNE in MITO. It is unclear whether such an accumulation of 4-HNE can further exacerbate MITO dysfunction resulting in further limitation to ATP formation via oxidative phosphorylation.

Hypothesis:
This study tested the hypothesis that exposure of MITO isolated from failing hearts to exogenous 4-HNE can result in further deterioration of MITO function.

Methods:
Freshly isolated MITO from LV myocardium of dogs with moderate heart failure (HF, LV ejection fraction ~40%) were incubated for 1 hour in absence (baseline) and presence of 4-HNE at concentrations of 3 and 30 μM. MITO energetic parameters namely ADP-stimulated respiration (ADPresp), maximal respiratory capacity (MRC) and ATP-linked respiration (ATPresp) were evaluated using an XFe96 analyzer (Seahorse Biosciences).

Results:
Compared to baseline, exposure of MITO to 3 μM 4-HNE has no significant effects on any of the MITO energetic measures. However, exposure of MITO to 30 μM 4-HNE resulted in significant reduction of ADPresp (490 ± 37 vs. 179 ± 7 OCR pmols/O
2
/min, p<0.05), significant reduction of MRC (334 ± 56 vs. 124 ± 18 OCR pmols/O
2
/min, p<0.05), and significant reduction of ATPresp (48 ± 10 vs. 20 ± 12 OCR pmols/O
2
/min, p<0.05).

Conclusions:
Exposure of MITO from failing myocardium to elevated levels of 4-HNE can lead to marked deterioration of MITO function that can result in a further reduction of ATP leading to progression of LV dysfunction. Limiting the accumulation of 4-HNE through pharmacologic normalization of ALDH2 activity can potentially represent a therapeutic target for retarding the progression of LV dysfunction toward intractable HF.
Abstract P3187: Deletion Of SARM1 NAD Hydrolase Ameliorates Diabetic Cardiomyopathy By Regulating Mitochondrial Metabolism And Mitophagy
Authors: Nizami Hina Lateef , Minor Keaton , Gorecki Ignacy , Light Christine , Chiao Ying Ann , Gu Haiwei , Lee Chi Fung
Published: October 2023

Diabetes is a major risk factor of heart disease. Decline of NAD, a redox cofactor in cellmetabolism, is a hallmark of cardiometabolic disease. Here, we test if inhibiting NAD consumptionmay be therapeutic in diabetic cardiomyopathy. SARM1 is an intracellular NAD hydrolase thatpromotes neuronal death. However, its role in diabetic hearts has never been reported. Wehypothesized that SARM1 deficiency attenuates diabetic cardiomyopathy and aimed to determineunderlying molecular mechanisms.C57BL/6N wild-type (WT) and SARM1-knockout (KO) male mice were injected with streptozotocin(STZ) induce type 1 diabetes (T1D). 16-week T1D stress caused progressive systolic (fractionalshortening) and diastolic dysfunction (E’/A’, e/E’) in WT mice. T1D-KO mice had attenuatedsystolic and diastolic dysfunction, despite similar elevation of fasting glucose and no significantdifferences in plasma metabolites (243 aqueous and lipid species) from T1D-WT and T1D-KOmice. T1D-WT hearts had reduced NAD pool compared to non-diabetic (ND-WT), which waselevated by SARM1 deletion. T1D-WT hearts had upregulated cardiomyopathy gene markers(Nppb, Myh7/Myh6 ratio) that were normalized in T1D-KO hearts. Chronic T1D induced cardiacfibrosis and upregulation of profibrotic genes (Ctgf, Inhbb), both of which were attenuated in T1D-KO hearts. RNA-seq analysis identified 1948 differentially expressed genes in T1D-WT hearts,compared to non-diabetic WT hearts. Gene Module Network Analysis identified suppressedmitochondrial processes in T1D-WT hearts. Expressions of a majority of genes from complexes Ito V were lowered in T1D-WT hearts and partially reversed in T1D-KO, suggesting that SARM1promotes mitochondrial dysfunction in diabetic hearts.Mitochondria of T1D-WT hearts had 50% reduction in ADP-driven respiration compared to ND-WT, which was reversed in T1D-KO mitochondria. T1D-WT hearts had elevated expression ofBNIP3 and mitochondrial recruitment of LC3B, which were attenuated in T1D-KO hearts. Insummary, our data suggest that SARM1 regulates mitochondrial metabolism and mitophagy indiabetic hearts. However, underlying pathogenic mechanisms of SARM1 in diabetic heart andtranslational potential of SARM1 inhibition require further investigation.
Abstract P3202: The Branched Chain α-Ketoacid Dehydrogenase Kinase (BCKDK) Inhibitor BT2 Is A Mitochondrial Uncoupler
Authors: Acevedo Aracely , Jones Anthony , Divakaruni Ajit
Published: October 2023

Elevated levels of branched-chain amino acids (BCAAs) are associated with cardiovascular and metabolic disease including heart failure, diabetes, and obesity. BCAAs are first transaminated into their respective branched-chain α-ketoacids (BCKAs) by the mitochondrial branched-chain amino-transaminase (BCAT
m
). The pharmacological agent BT2 (dichloropheno[b]thiophene-2-carboxylic-acid) was designed to induce catabolism of BCAAs by inhibiting the branched-chain α-ketoacid dehydrogenase kinase (BCKDK). The function of BCKDK is to phosphorylate and therefore deactivate the branched-chain α-ketoacid dehydrogenase (BCKDH), an enzymatic complex that converts the BCKAs into their respective R-CoAs. Although it has been shown that BT2 protects from heart failure and metabolic disease in animal models, recent studies have suggested that its protective effects may originate from a mechanism independent of targeting BCAA oxidation. The objective of this study was to investigate alternative molecular mechanisms by which BT2 may confer cardioprotection and protect from metabolic disease. We hypothesized that BT2 is a mitochondrial uncoupler based on its chemical structure as a lipophilic weak acid. We demonstrate BT2 is a mitochondrial uncoupler using a combination of respirometry, membrane potential, and patch-clamp electrophysiology. BT2 has 20% of the potency of the chemical uncoupler 2,4-dinitrophenol (DNP). The data suggest BT2 may exert some of its cardioprotective effects and protection from metabolic disease via mitochondrial uncoupling.
“Physical Time within Human Time” and “Bridging the Neuroscience and Physics of Time”
Authors: Dolev Yuval
Published: October 2023

The commentary discusses whether AI devices can have an experience of time as passing. The papers commented on suggest the answer is “Yes”. However, I claim that the metaphysical view of time this answer presupposes, namely, eternalism, or the block universe, is untenable, and that a sound understanding of time must acknowledge time’s normative significance. This raises new and substantial questions regarding the possibility of representing time, and of equipping devices with “gadgets” that would facilitate as-of flow experiences for them. More generally, the commentary critically evaluates the role science may have in the context of philosophical debates.
Begonia noraaunorae (section Petermannia, Begoniaceae) a new species endemic to Surigao del Sur, Mindanao Island, Philippines
Authors: BLASCO FREDDIE A. , TANDANG DANILO N. , ALEJANDRO GRECEBIO JONATHAN D. , BUCAY MARK ANGELO C. , CORTES JUNELITO C. , RUBITE ROSARIO R.
Published: October 2023

Begonia noraaunorae is described as a new species endemic to the Philippines from the limestone forest of Surigao del Sur. It grows on limestone rocks in semi-shaded broadleaf forest along a national highway. B. noraaunorae resembles B. negrosensis in having erect stems and obovately oblong leaves with sparse hairs and an acuminate apex, but differs in having shorter stems, larger leaves with light green patches, and capsules longer than wide (vs. wider than long), without large bracteoles directly beneath (vs. with), on longer peduncles. The new species is named after Nora Aunor, National Artist for Film and Broadcast Arts. Based on IUCN criteria, B. noraaunorae is considered Vulnerable.
Larval morphology and natural history in two Minervarya species from Andaman Islands, with comments on a new phytotelmonous larval morphotype for the genus
Authors: GOPIKA C. , GARG SONALI , SIVAPERUMAN CHANDRAKASAN , GOKULAKRISHNAN G. , BIJU S. D.
Published: October 2023

We studied the larval morphology and natural history of two species of Minervarya from the Andaman Islands of India. A recent assignment of Charles Darwin’s frog to the genus Minervarya opened up new questions on the systematic affinities and natural history of its enigmatic tadpoles. Originally described as Rana charlesdarwini Das, 1998, and long considered as Ingerana charlesdarwini, the tadpoles of this species were poorly understood and incomparable to those of other presumed close relatives based on an original brief description of its phytotelmonous tadpoles. Here we present a detailed redescription of the larval morphology of M. charlesdarwini based on genetically confirmed tadpoles. At the same time, we compared the external morphology of M. charlesdarwini tadpoles to that of its closest phylogenetic and sympatric congener, M. andamanensis, consequently reporting the first-ever larval description for M. andamanensis. For the first time also for minervaryan frogs, we record that M. charlesdarwini lays eggs on the inner walls of tree holes, and the tadpoles possess morphological adaptations for a phytotelmonous life. Their unique features, such as tail-to-body ratio >2.2, reduced labial tooth rows (LTRF 1/1), acutely pointed serrations in the jaw sheath, and the medial portion of the upper sheath broadly arched and that of the lower sheath U-shaped, justify adding a new larval morphotype to the genus Minervarya. In contrast, M. andamanensis breeds and undergoes development in ground water puddles and ponds, a common trait for other known minervaryan species. Furthermore, our study generates new knowledge on the amplexus, oviposition site, and early embryonic development in these species. The deeper understanding of the biology and habitat requirements contributes additional traits for future systematic and evolutionary studies, and helps guide conservation assessments for these two species endemic to a handful of islands in the Andaman Archipelago.
CFL Optimized Forward–Backward Runge–Kutta Schemes for the Shallow-Water Equations
Authors: Lilly Jeremy R. , Engwirda Darren , Capodaglio Giacomo , Higdon Robert L. , Petersen Mark R.
Published: October 2023

We present the formulation and optimization of a Runge–Kutta-type time-stepping scheme for solving the shallow-water equations, aimed at substantially increasing the effective allowable time step over that of comparable methods. This scheme, called FB-RK(3,2), uses weighted forward–backward averaging of thickness data to advance the momentum equation. The weights for this averaging are chosen with an optimization process that employs a von Neumann–type analysis, ensuring that the weights maximize the admittable Courant number. Through a simplified local truncation error analysis and numerical experiments, we show that the method is at least second-order in time for any choice of weights and exhibits low dispersion and dissipation errors for well-resolved waves. Further, we show that an optimized FB-RK(3,2) can take time steps up to 2.8 times as large as a popular three-stage, third-order strong stability-preserving Runge–Kutta method in a quasi-linear test case. In fully nonlinear shallow-water test cases relevant to oceanic and atmospheric flows, FB-RK(3,2) outperforms SSPRK3 in admittable time step by factors roughly between 1.6 and 2.2, making the scheme approximately twice as computationally efficient with little to no effect on solution quality.

Significance Statement

The purpose of this work is to develop and optimize time-stepping schemes for models relevant to oceanic and atmospheric flows. Specifically, for the shallow-water equations we optimize for schemes that can take time steps as large as possible while retaining solution quality. We find that our optimized schemes can take time steps between 1.6 and 2.2 times larger than schemes that cost the same number of floating point operations, translating directly to a corresponding speedup. Our ultimate goal is to use these schemes in climate-scale simulations.
Accuracy of the ACS NSQIP Surgical Risk Calculator for Predicting Postoperative Complications in Gastric Cancer Following Open Gastrectomy
Authors: Hatipoglu Engin , Erginoz Ergin , Askar Ahmet , Erguney Sabri
Published: October 2023

Introduction

The prediction of complications before gastric surgery is of utmost importance in shared decision making and proper counseling of the patient in order to minimize postoperative complications. Our aim was to evaluate the predictive validity of American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) risk calculator in gastric cancer patients who underwent gastrectomy.

Methods

Preoperative assessment data of 432 patients were retrospectively reviewed and manually entered into the calculator. The accuracy of the calculator was evaluated using Pearson’s chi-squared test, C-statistic, Brier score, and Hosmer-Lemeshow test.

Results

The lowest Brier scores were observed in urinary tract infection, renal failure, venous thromboembolism, pneumonia, and cardiac complications. Best results were obtained for predicting sepsis, discharge to rehabilitation facility, and death (low Brier scores, C-statistic >.7, and Hosmer-Lemeshow P > .05).

Conclusion

The calculator had a strong performance in predicting sepsis, discharge to the rehabilitation facility, and death. However, it performed poor in predicting the most commonly observed events (any or serious complication and surgical site infection).
“I’m Not a Refugee Girl, Call Me Bella”: Professional Refugee Women, Agency, Recognition, and Emancipation
Authors: Groutsis Dimitria , Collins Jock , Reid Carol
Published: October 2023

The notion of refugees as a viable source of labor to address skill shortages in the destination country’s labor market has rarely been the dominant discourse on refugee entrants. Bella’s1 lived experience as a professional woman who arrived as a Syrian conflict refugee to Australia in 2017 presents an outlier in refugee research and challenges conventional scholarly wisdom and public discourse. A combination of human capital, a purposeful use of networks, supported by her desire for recognition and a deep sense of self-worth allowed her to navigate the formalized and structured Australian business landscape. Accordingly, she was able to overcome the stigma of being a refugee: Less worthy of employment status in a position representative of her overseas skills and qualifications. In drawing on an outlier methodology and critical theory, we develop a more nuanced understanding of the agency of skilled and qualified refugee women drawing attention to lessons for business which typically takes a “one size fits all” approach to labor integration.
Thinking About Sum Scores Yet Again, Maybe the Last Time, We Don’t Know, Oh No . . .: A Comment on
Authors: Widaman Keith F. , Revelle William
Published: October 2023

The relative advantages and disadvantages of sum scores and estimated factor scores are issues of concern for substantive research in psychology. Recently, while championing estimated factor scores over sum scores, McNeish offered a trenchant rejoinder to an article by Widaman and Revelle, which had critiqued an earlier paper by McNeish and Wolf. In the recent contribution, McNeish misrepresented a number of claims by Widaman and Revelle, rendering moot his criticisms of Widaman and Revelle. Notably, McNeish chose to avoid confronting a key strength of sum scores stressed by Widaman and Revelle—the greater comparability of results across studies if sum scores are used. Instead, McNeish pivoted to present a host of simulation studies to identify relative strengths of estimated factor scores. Here, we review our prior claims and, in the process, deflect purported criticisms by McNeish. We discuss briefly issues related to simulated data and empirical data that provide evidence of strengths of each type of score. In doing so, we identified a second strength of sum scores: superior cross-validation of results across independent samples of empirical data, at least for samples of moderate size. We close with consideration of four general issues concerning sum scores and estimated factor scores that highlight the contrasts between positions offered by McNeish and by us, issues of importance when pursuing applied research in our field.
miRNAs from Inflamed Gingiva Link Gene Signaling to Increased MET Expression
Authors: Zheng L. , Chopra A. , Weiner J. , Beule D. , Dommisch H. , Schaefer A. S.
Published: October 2023

Several array-based microRNA (miRNA) expression studies independently showed increased expression of miRNAs hsa-miR-130a-3p, -142-3p, -144-3p, -144-5p, -223-3p, -17-5p, and -30e-5p in gingiva affected by periodontal inflammation. We aimed to determine direct target genes and signaling pathways regulated by these miRNAs to identify processes relevant to gingival inflammatory responses and tissue homeostasis. We transfected miRNA mimics (mirVana) for each of the 7 miRNAs separately into human primary gingival fibroblasts cultured from 3 different donors. Following RNA sequencing, differential gene expression and second-generation gene set enrichment analyses were performed. miRNA inhibition and upregulation was validated at the transcript and protein levels using quantitative reverse transcriptase polymerase chain reaction, Western blotting, and reporter gene assays. All 7 miRNAs significantly increased expression of the gene MET proto-oncogene, receptor tyrosine kinase ( MET). Expression of known periodontitis risk genes CPEB1, ABCA1, and ATP6V1C1 was significantly repressed by hsa-miR-130a-3p, -144-3p, and -144-5p, respectively. The genes WASL, ENPP5, ARL6IP1, and IDH1 showed the most significant and strongest downregulation after hsa-miR-142-3p, -17-5p, -223-3p, and -30e-5p transfection, respectively. The most significantly regulated gene set of each miRNA related to cell cycle (hsa-miRNA-144-3p and -5p [ Padj = 4 × 10−40 and Padj = 4 × 10−6], -miR-17-5p [ Padj = 9.5 × 10−23], -miR-30e-5p [ Padj = 8.2 × 10−18], -miR-130a-3p [ Padj = 5 × 10−15]), integrin cell surface interaction (-miR-223-3p [ Padj = 2.4 × 10−7]), and interferon signaling (-miR-142-3p [ Padj = 5 × 10−11]). At the end of acute inflammation, gingival miRNAs bring together complex regulatory networks that lead to increased expression of the gene MET. This underscores the importance of mesenchymal cell migration and invasion during gingival tissue remodeling and proliferation in restoring periodontal tissue homeostasis after active inflammation. MET, a receptor of the mitogenic hepatocyte growth factor fibroblast secreted, is a core gene of this process.
On the Path to Decolonizing Health Care Services: The Role of Marketing
Authors: George Reece , D’Alessandro Steven , Mehmet Mehmet Ibrahim , Nikidehaghani Mona , Evans Michelle M. , Laud Gaurangi , Tedmanson Deirdre
Published: October 2023

Despite considerable investment, health outcomes for First Nations people are well below those of the rest of the population in several countries, including Canada, the United States, and Australia. In this article, the authors draw on actor-network theory and the case of Birthing on Country, a successful policy initiative led by First Nations Australians, to explore the decolonization of health services. Using publicly available archival data and the theoretical guidance of actor-network theory, the analysis offers insight into how marketing techniques and technologies can be deployed to achieve improved health outcomes and implement decolonized approaches. The insights provided have theoretical implications for marketing scholarship, social implications for understanding and implementing an agenda of decolonization, and practical implications for health care marketing.
Applicability of the six-phase method for auricular age estimation in an Indian population: A CT-based study
Authors: Warrier Varsha , Shedge Rutwik , Garg Pawan Kumar , Dixit Shilpi Gupta , Krishan Kewal , Kanchan Tanuj
Published: October 2023

Age estimation plays a crucial role in human identification. Amongst numerous age markers located throughout the skeletal framework, the auricular surface of the ilium presents as a resilient structure, with different methods for auricular age estimation currently in practice. Amongst these methods, the Osborne method is believed to permit accurate age estimation through its use of robust age categories and discrete phase descriptors. The present study aimed to assess the applicability of the Osborne method in an Indian population through a computed tomographic (CT) examination of the auricular surface, an aspect presently unreported. In order to do so, CT scans of 380 individuals were collected and evaluated using the Osborne method. A CT-based examination indicated that surface texture described by Osborne is difficult to appreciate through 3D CT images. Indistinct definitions associated with certain features, and the mosaic display of features within each phase further prevents applying the method effectively. Overall accuracy percentages of 99.47% and 98.90% were obtained using the method in males and females, respectively, with corresponding inaccuracy values of 10.10 years and 9.04 years. Significantly reduced accuracy percentages were obtained with alternate, more robust age brackets presented within the original study, demonstrating the limited reliability associated with the method. Inaccuracy and bias values computed for each decade indicate the relative utility of the method in aging 40–59-year-old individuals. Low accuracy percentages, high error rates and different methodological hindrances encountered within the present study illustrate the limited applicability of the Osborne method in aging an Indian population.
Party–Interest Group Ties and Patterns of Political Influence
Authors: Røed Maiken , Allern Elin Haugsgjerd , Hansen Vibeke Wøien
Published: October 2023

Organizational ties between political parties and interest groups are common in contemporary democracies, but little is known about the political effects of such ties. This article examines whether the strength of organizational ties between parties and interest groups affects the probability of (1) interest group influence on parties, (2) party influence on interest groups, and (3) mutual party–interest group influence in decision-making. Using novel interest group survey data from six democracies, we are the first to systematically examine the relationship between organizational ties and perceived and attributed influence across multiple policy areas. The findings indicate that one-sided influence is more likely when the actors have stronger ties but that such ties also increase the likelihood of influence going both ways. Close party–interest group relationships hence likely involve give-and-take across policy issues. These findings shed important new light on the role of parties and interest groups as intermediaries in democracies.
Current Classical Pentecostal Bible Reading Methods: A Critical Perspective
Authors: Nel Marius
Published: October 2023

The prevailing trend among members of the Apostolic Faith Mission of South Africa (AFM of SA) is to interpret the Bible in a biblicist and literalist way, which conflicts with how early Pentecostals read the Bible. Empirical research completed in 2020 supports the observation. In contrast, early Pentecostals read the Bible with the expectation of meeting God. Their precritical, canonical, and text-centered interpretation focused on the text inductively before they deductively compared it with related texts in a straightforward manner to formulate their teaching. The new generation of Pentecostals applied conservative Evangelical hermeneutics to focus on the world behind the text, using the historical-grammatical method to arrive objectively at the author's intended meaning. It was rooted in the Scottish Common-Sense school of philosophy in a synthesis with the Baconian method. Their new hermeneutic was based on a theory of inspiration that accepted that divine revelation terminated at the end of the first century, resulting in a discrepancy that conflicts with Pentecostals’ expectation for extrabiblical revelations, miracles, and wonders to continue. The article aims to suggest an alternative hermeneutical approach that can constructively address the discrepancy, based on the recently developed scholarly hermeneutic that employs post-critical and postmodern approaches such as literary, reader-response, and advocacy hermeneutics. It utilizes quantitative research and a comparative literature study to realize the aim.
The structural transformation of the scientific public sphere: Constitution and consequences of the path towards open access
Authors: Dobusch Leonhard , Heimstädt Maximilian
Published: October 2023

We are currently witnessing a fundamental structural transformation of the scientific public sphere, characterized by processes of specialization, metrification, internationalization, platformization and visibilization. In contrast to explanations of this structural transformation that invoke a technological determinism, we demonstrate its historical contingency by drawing on analytic concepts from organization theory and the case of the Open Access transformation in Germany. The digitization of academic journals has not broadened access to scientific output but narrowed it down even further in the course of the ‘serials crisis’. For a long time, research institutions were not able to convince large academic publishers to adopt less restrictive forms of access to academic journals. It was only through the emergence of new and in part illegal actors (shadow libraries and preprint servers) that the existing path could be broken, and an Open Access path constituted. Following this analysis, we discuss consequences of the Open Access transformation for the public spheres of science and democracy. We conclude that Open Access publishing can only help to transform both communicative spaces towards the normative ideal of a public sphere when complemented by systematic support for non-profit publication infrastructures.
Social media use for offline political action (OPA) and corruption in Africa: Impacts and transmission channels
Authors: Ngassam Sylvain B. , Asongu Simplice A. , Ngueuleweu Gildas T.
Published: October 2023

Despite a growing literature on the determinants of corruption, existing studies are sparse on the channels through which social media curbs corruption using panel data. Social media is captured by the percentages of the population and elites that use social media for offline political actions (OPA). This research uses annual data from a panel of 47 African countries over the period 2000–2018. Results show that social media used by the population for OPA directly curbs executive, judicial and legislative corruption. The use of social media by elites for OPA boosts corruption in the judicial sector. Moreover, social media indirectly curbs corruption through their effects on civil society participation. Reducing corruption in Africa requires inter alia, policies aimed at promoting the use of social media for OPA, the emergence of dynamic and effective civil society participation and the improvement of the quality of democracy.
Latent sibling violence
Authors: Rypi Anna , Burcar Alm Veronika
Published: October 2023

This article analyses latent violence to highlight important aspects of our empirical data: qualitative interviews with women who have been subjected to violence by their siblings. The concept points to the fear experienced by victims in close relationships, and the adaptations they make to avoid violence. Although the concept has been applied to family and intimate partner violence, it is also useful to describe sibling violence. Latent violence occurs when violence is not openly acknowledged; indeed, sibling violence often goes unnoticed. This invisibility can be associated with experiences of powerlessness and unpredictability for victims, who may have difficulty defining their experiences. While we emphasize the vulnerability described in the interviews, we also highlight and explore the interviewees’ strategies of resistance. Our interviewees describe how they created alternative safe spaces in spite of the violent context in which they lived, including the use of hideouts and secret refuges, outdoor places as well as fantasy spaces or escape plans. Their strategies show that children subject to latent sibling violence should be understood not as passive victims, but as actively strategizing to cope with situations that many cannot escape due to their age and lack of parental understanding.
The neural and cardiovascular effects of exposure of gram-positive bacterial inflammation in preterm fetal sheep
Authors: Dhillon Simerdeep K , Lear Christopher A , Davidson Joanne O , Magawa Shoichi , Gunn Alistair J , Bennet Laura
Published: October 2023

Perinatal infection or inflammation are associated with adverse neurodevelopmental effects and cardiovascular impairments in preterm infants. Most preclinical studies have examined the effects of gram-negative bacterial inflammation on the developing brain, although gram-positive bacterial infections are a major contributor to adverse outcomes. Killed Su-strain group 3 A streptococcus pyogenes (Picibanil, OK-432) is being used for pleurodesis in fetal hydrothorax/chylothorax. We therefore examined the neural and cardiovascular effects of clinically relevant intra-plural infusions of Picibanil. Chronically instrumented preterm (0.7 gestation) fetal sheep received an intra-pleural injection of low-dose (0.1 mg, n = 8) or high-dose (1 mg, n = 8) Picibanil or saline-vehicle (n = 8). Fetal brains were collected for histology one-week after injection. Picibanil exposure was associated with sustained diffuse white matter inflammation and loss of immature and mature oligodendrocytes and subcortical neurons, and associated loss of EEG power. These neural effects were not dose-dependent. Picibanil was also associated with acute changes in heart rate and attenuation of the maturational increase in mean arterial pressure. Even a single exposure to a low-dose gram-positive bacterial-mediated inflammation during the antenatal period is associated with prolonged changes in vascular and neural function.