bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pulsating strings in I-brane background
Authors: Biswas Sagar , Padhi Nibedita , Panigrahi Kamal L. 
Published: February 2024

AbstractWe study pulsating strings both on a single stack of NS5-branes and two orthogonal stacks of NS5-branes (the so called I-brane) by using the Polyakov form of the fundamental string action. For the I-brane background, by using a symmetry that decouples the two spheres from the flat geometry, we study pulsating solutions of the string when it pulsates on both the spheres independently and simultaneously. We finally derive the energy of pulsating strings as a function of adiabatic invariant oscillation number in these cases and studied some limiting cases in detail.
Building cubic gravity with healthy and viable scalar and tensor perturbations
Authors: Asimakis Petros , Basilakos Spyros , Saridakis Emmanuel N. 
Published: February 2024

AbstractWe investigate sufficient conditions under which cubic gravity is healthy and viable at the perturbation level. We perform a detailed analysis of the scalar and tensor perturbations. We impose the requirement that the two scalar potentials, whose ratio is the post-Newtonian parameter $$\gamma $$
γ
, should deviate only minimally form general relativity. Additionally, concerning tensor perturbations we impose satisfaction of the LIGO-VIRGO and Fermi Gamma-ray Burst observations, and thus we result to a gravitational-wave equation with gravitational-wave speed equal to the speed of light, and where the only deviation from general relativity appears in the dispersion relation. Furthermore, we show that cubic gravity exhibits an effective Newton’s constant that depends on the model parameter, on the background evolution, and on the wavenumber scale. Hence, by requiring its deviation from the standard Newton’s constant to be within observational bounds we extract the constraints on the single coupling parameter $$\beta $$
β
.
“Gentle Disruptions”: A Critical Reflection on Participatory Arts in Expanding the Language System for Meaningful Community Engagement Around Local Climate Adaptation
Authors: Liguori Antonia , McEwen Lindsey , Rossignol Karen Le , Kraus Sharron , Wilson Michael 
Published: February 2024

This paper proposes a critical reflection on the use of language to address the challenge of promoting and supporting civic agencies in adaptation to increasing extreme weather risk. Such reflection needs to focus on the opportunities and limitations of language, and the navigation amongst multiple or contested meanings within interdisciplinary and inter-sectorial collaborations. This commentary was inspired by the authors’ conversations on their journey in writing the paper — Liguori et al. (2023) “Exploring the uses of arts-led community spaces to build resilience: Applied storytelling for successful co-creative work” and the impact it had on their understanding of various language systems. Here writing was conceived as a form of networking, undertaking a sequence of intimate, in-depth discussions in a safe space. ‘Playing’ with words, moving out from our disciplinary homes, provided a fertile way of thinking within multi/inter-sectorial/disciplinary conversations to expand the language system for meaningful community engagement around local climate adaptation. Three key terms were at the core of these diverse — and sometimes divergent — ways of looking at social preparedness for extreme weather events: disruption, empowerment, and creative ecosystem. The meta-reflections, based on iterative conversations around these three key terms, highlight the importance of explorations of language as a generative meaning-making process that can be boundary-spanning. There is significant value in understanding the implications of language used in public engagement — its different interpretations, their loading and potential for transformed thinking when conceived creatively. Such insight can contribute to more effective approaches for participatory research and practice working with communities when addressing issues related to climate adaptation. This commentary argues that the socially engaged or participatory arts are particularly well placed to be active in such processes.
Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail
Authors: Veena Mysore S. , Gahng Jungmo J. , Alani Mustafa , Ko Albert Y. , Basak Saroj K. , Liu Isabelle Y. , Hwang Kimberly J. , Chatoff Jenna R. , Venkatesan Natarajan , Morselli Marco , Yan Weihong , Ali Ibraheem , Kaczor-Urbanowicz Karolina Elżbieta , Gowda Bhavani Shankara , Frost Patrick , Pellegrini Matteo , Moatamed Neda A. , Wilczynski Sharon P. , Bomont Pascale , Wang Marilene B. , Shin Daniel Sanghoon , Srivatsan Eri S. 
Published: February 2024

Abstract

Gigaxonin is an E3 ubiquitin ligase that plays a role in cytoskeletal stability. Its role in cancer is not yet clearly understood. Our previous studies of head and neck cancer had identified gigaxonin interacting with p16 for NFκB ubiquitination. To explore its role in cancer cell growth suppression, we analyzed normal and tumor DNA from cervical and head and neck cancers. There was a higher frequency of exon 8 SNP (c.1293 C&gt;T, rs2608555) in the tumor (46% vs. 25% normal, P = 0.011) pointing to a relationship to cancer. Comparison of primary tumor with recurrence and metastasis did not reveal a statistical significance. Two cervical cancer cell lines, ME180 and HT3 harboring exon 8 SNP and showing T allele expression correlated with higher gigaxonin expression, reduced in vitro cell growth and enhanced cisplatin sensitivity in comparison with C allele expressing cancer cell lines. Loss of gigaxonin expression in ME180 cells through CRISPR-Cas9 or siRNA led to aggressive cancer cell growth including increased migration and Matrigel invasion. The in vitro cell growth phenotypes were reversed with re-expression of gigaxonin. Suppression of cell growth correlated with reduced Snail and increased e-cadherin expression. Mouse tail vein injection studies showed increased lung metastasis of cells with low gigaxonin expression and reduced metastasis with reexpression of gigaxonin. We have found an association between C allele expression and RNA instability and absence of multimeric protein formation. From our results, we conclude that gigaxonin expression is associated with suppression of epithelial–mesenchymal transition through inhibition of Snail.

Significance:
Our results suggest that GAN gene exon 8 SNP T allele expression correlates with higher gigaxonin expression and suppression of aggressive cancer cell growth. There is downregulation of Snail and upregulation of e-cadherin through NFκB ubiquitination. We hypothesize that exon 8 T allele and gigaxonin expression could serve as diagnostic markers of suppression of aggressive growth of head and neck cancer.
Dabrafenib Alters MDSC Differentiation and Function by Activation of GCN2
Authors: Ciudad M. Teresa , Quevedo Rene , Lamorte Sara , Jin Robbie , Nzirorera Nadine , Koritzinsky Marianne , McGaha Tracy L. 
Published: February 2024

Abstract

The effect of targeted therapeutics on anticancer immune responses is poorly understood. The BRAF inhibitor dabrafenib has been reported to activate the integrated stress response (ISR) kinase GCN2, and the therapeutic effect has been partially attributed to GCN2 activation. Because ISR signaling is a key component of myeloid-derived suppressor cell (MDSC) development and function, we measured the effect of dabrafenib on MDSC differentiation and suppressive activity. Our data showed that dabrafenib attenuated MDSC ability to suppress T-cell activity, which was associated with a GCN2-dependent block of the transition from monocytic progenitor to polymorphonuclear (PMN)-MDSCs and proliferative arrest resulting in PMN-MDSC loss. Transcriptional profiling revealed that dabrafenib-driven GCN2 activation altered metabolic features in MDSCs enhancing oxidative respiration, and attenuated transcriptional programs required for PMN development. Moreover, we observed a broad downregulation of transcriptional networks associated with PMN developmental pathways, and increased activity of transcriptional regulons driven by Atf5, Mafg, and Zbtb7a. This transcriptional program alteration underlies the basis for PMN-MDSC developmental arrest, skewing immature MDSC development toward monocytic lineage cells. In vivo, we observed a pronounced reduction in PMN-MDSCs in dabrafenib-treated tumor-bearing mice suggesting that dabrafenib impacts MDSC populations systemically and locally, in the tumor immune infiltrate. Thus, our data reveal transcriptional networks that govern MDSC developmental programs, and the impact of GCN2 stress signaling on the innate immune landscape in tumors, providing novel insight into potentially beneficial off-target effects of dabrafenib.

Significance:
An important, but poorly understood, aspect of targeted therapeutics for cancer is the effect on antitumor immune responses. This article shows that off-target effects of dabrafenib activating the kinase GCN2 impact MDSC development and function reducing PMN-MDSCs in vitro and in vivo. This has important implications for our understanding of how this BRAF inhibitor impacts tumor growth and provides novel therapeutic target and combination possibilities.
Myosin Light Chain Phosphatase Plays an Important Role in Cardiac Fibrosis in a Model of Mineralocorticoid Receptor‐Associated Hypertension
Authors: Ye Zhe , Okamoto Ryuji , Ito Hiromasa , Ito Rie , Moriwaki Keishi , Ichikawa Mizuki , Kimena Lupiya , Ali Yusuf , Ito Masaaki , Gomez‐Sanchez Celso E. , Dohi Kaoru 
Published: February 2024

Background
Myosin phosphatase targeting subunit 2 (MYPT2) is an important subunit of cardiac MLC (myosin light chain) phosphatase, which plays a crucial role in regulating the phosphorylation of MLC to phospho‐MLC (p‐MLC). A recent study demonstrated mineralocorticoid receptor‐related hypertension is associated with RhoA/Rho‐associated kinase/MYPT1 signaling upregulation in smooth muscle cells. Our purpose is to investigate the effect of MYPT2 on cardiac function and fibrosis in mineralocorticoid receptor‐related hypertension.

Methods and Results

HL‐1 murine cardiomyocytes were incubated with different concentrations or durations of aldosterone. After 24‐hour stimulation, aldosterone increased CTGF (connective tissue growth factor) and MYPT2 and decreased p‐MLC in a dose‐dependent manner. MYPT2 knockdown decreased CTGF. Cardiac‐specific MYPT2‐knockout (c‐MYPT2
−/−
) mice exhibited decreased type 1 phosphatase catalytic subunit β and increased p‐MLC. A disease model of mouse was induced by subcutaneous aldosterone and 8% NaCl food for 4 weeks after uninephrectomy. Blood pressure elevation and left ventricular hypertrophy were observed in both c‐MYPT2
−/−
and MYPT2
+/+
mice, with no difference in heart weights or nuclear localization of mineralocorticoid receptor in cardiomyocytes. However, c‐MYPT2
−/−
mice had higher ejection fraction and fractional shortening on echocardiography after aldosterone treatment. Histopathology revealed less fibrosis, reduced CTGF, and increased p‐MLC in c‐MYPT2
−/−
mice. Basal global radial strain and global longitudinal strain were higher in c‐MYPT2
−/−
than in MYPT2
+/+
mice. After aldosterone treatment, both global radial strain and global longitudinal strain remained higher in c‐MYPT2
−/−
mice compared with MYPT2
+/+
mice.

Conclusions
Cardiac‐specific MYPT2 knockout leads to decreased myosin light chain phosphatase and increased p‐MLC. MYPT2 deletion prevented cardiac fibrosis and dysfunction in a model of mineralocorticoid receptor‐associated hypertension.
Association Between ECG Abnormalities and Mortality in a Low‐Risk Population
Authors: Lee Sung Ho , Lee Mi Yeon , Kang Jeonggyu , Choi Hyo‐In , Lee Seung‐Jae , Lee Jong‐Young , Kim Byung Jin , Sung Ki‐Chul , Park Kyoung‐Min 
Published: February 2024

Background
The ECG is a simple, noninvasive screening method for cardiovascular disease and arrhythmia. The impact of ECG abnormality on mortality is not certain in low‐risk populations. To address this, we evaluated the association between ECG abnormality and mortality.

Methods and Results
We retrospectively assessed baseline ECG and all‐cause mortality and cardiovascular mortality in 660 383 patients presenting for medical check‐ups. Baseline ECG abnormalities were classified according to the Minnesota Code. Among the total 660 383 participants, 23 609 (3.6%) had major and 110 038 (16.7%) had minor ECG abnormalities. All‐cause mortality occurred in 7751 patients (1.1%) and cardiovascular mortality in 1180 (0.18%) over a median follow‐up period of 8.8 years. Major ECG abnormalities were associated with all‐cause mortality (hazard ratio [HR], 1.11 [95%, 1.03–1.2]) and cardiovascular mortality (HR, 1.92 [95% CI, 1.63–2.27]) compared with no ECG abnormalities. All‐cause mortality was associated with right atrial enlargement (HR, 2.11 [95% CI, 1.1–4.07]), left atrial enlargement (HR, 1.76 [95% CI, 1.1–2.84]), sinus tachycardia (HR, 1.52 [95% CI, 1.15–2.01]), complete atrioventricular block (HR, 2.1 [95% CI, 1.05–4.2]), atrial fibrillation (HR, 1.52 [95% CI, 1.26–1.84]), and left ventricular hypertrophy (HR, 1.15 [95% CI, 1.02–1.3]). Cardiovascular mortality was associated with left atrial enlargement (HR, 4.52 [95% CI, 2.15–9.5]), atrial fibrillation (HR, 3.22 [95% CI, 2.33–4.46]), left ventricular hypertrophy (HR, 1.72 [95% CI, 1.35–2.19]), major Q‐wave abnormality (HR, 1.6 [95% CI, 1.08–2.39]), and major ST‐T abnormality (HR, 1.76 [95% CI, 1.01–3.04]).

Conclusions
ECG abnormalities, including left atrial enlargement, left ventricular hypertrophy, atrial fibrillation, and major Q‐wave and ST‐T abnormalities, were associated with cardiovascular mortality in a low‐risk population.
Use of the SONAS Ultrasound Device for the Assessment of Cerebral Perfusion in Acute Ischemic Stroke
Authors: Molaie Amir M. , Wilfling Sibylle , Kilic Mustafa , Wendl Christina , Linker Ralf A. , Schlachetzki Felix , Liebeskind David S. 
Published: February 2024

Background
Early recognition of large‐vessel occlusion in acute ischemic stroke is pivotal to ensuring timely and effective treatment. However, current prehospital evaluation strategies largely rely on stroke scales that lack sensitivity and specificity. Recently, a novel, portable, noninvasive brain perfusion ultrasound device (SONAS) was developed as a diagnostic aid and demonstrated robust correlation with magnetic resonance imaging–based brain perfusion imaging. The present study aimed to investigate the feasibility and diagnostic performance of the SONAS device in identifying alterations in cerebral blood flow in patients with acute ischemic stroke with suspected or known perfusion deficits.

Methods
We performed a phase II, single‐arm, prospective study using SONAS in a close timely relation to computed tomography perfusion imaging in subjects diagnosed with acute ischemic stroke and suspected or known large‐vessel pathology, presenting within 24 hours of symptom onset between April 2019 through December 2019. Performance end points included successful measurement of time‐to‐peak in each hemisphere and comparison of perfusion deficits measured by SONAS to the reference standard computed tomography perfusion imaging. Safety end points included frequency, severity, and outcome of adverse events.

Results
A total of 20 subjects were enrolled. Eighteen subjects (90%) had microbubble signals successfully detected on initial assessment by SONAS. The diagnostic accuracy of the SONAS device in identifying a perfusion deficit was 88.9%. The sensitivity was 14 of 15 (93.3%), and the specificity was 2 of 3 (66.7%). No adverse events were reported secondary to SONAS or the contrast agent used.

Conclusion
In this clinical study, we demonstrated that the SONAS system is a safe tool that can aid in identifying cerebral perfusion deficits in this selected population of patients with acute ischemic stroke with suspected or known perfusion deficits. Future studies should assess the efficacy and impact on clinical outcomes of using SONAS in a real‐world “in the field” setting on a large subset of patients with suspected stroke and in addition to prehospital stroke scales.
The Paradox of Creating a Cocreator
Authors: Thelle Notto J. W. , Wærstad Bernt Isak 
Published: February 2024

Abstract
With the latest developments in AI, it is becoming increasingly common to view machines as cocreators. In this article, we follow four musicians in the project Co-Creative Spaces through a six-month long collaborative process in which they created new music through improvising with each other and—subsequently—with computer-based imitations of themselves. These musical agents were trained through machine learning to generate output in the style of the musicians and were capable of both following what they “heard” and initiating new directions in the interaction, leading to the question, “What happens to musical cocreation when AI is included in the creative cycle?” The musicians involved in Co-Creative Spaces are from Norway and Kenya—two countries with fundamentally different musical traditions. This leads to a second question: “How is the collaboration affected by possible cultural biases inherent in the technology and in the musicians themselves?”
These questions were examined as part of two five-day workshops—one at the beginning and one at the end of the project period—before two final concerts. The musicians engaged in improvisation sessions and recorded ensuing discussions. For each workshop day, the musicians also had conversations in focus groups moderated by a fifth project member, who, together with one of the musicians, was also responsible for the development of the software powering the musical agents. The analysis of the data from the workshops paints a complex picture of what it is like being at the intersection between different technological, musical, and cultural paradigms. The machine becomes a cocreator only when humans permit themselves to attribute creative agency to it.
The Southern African Heat Low: Structure, Seasonal and Diurnal Variability, and Climatological Trends
Authors: Attwood Kitty , Washington Richard , Munday Callum 
Published: February 2024

Abstract
Heat lows are key features of subtropical climates and monsoon systems. In southern Africa, they are pivotal to understanding divergent climate change projections, in particular the veracity of future rainfall decline. Compared to other heat lows, including in West Africa and Australia, the southern African heat low remains poorly documented. Here, we analyze the diurnal cycle, seasonal variability, and trends of the heat low in reanalysis data. In ERA5, 462 strong heat low days are detected between September and March from 1990 to 2019, equating to 7.3% of days sampled. These events feature ascent (exceeding −0.2 Pa s−1) at low levels (strongest between 800 and 600 hPa) and subsidence aloft, generating low-level cyclonic flow with anticyclonic flow above. This flow exhibits strong diurnal variability, with peak windspeeds between 0600 and 0900 UTC and maximum ascent at ∼2300 UTC. Heat lows form preferentially over Angola in September (∼14°S) and October (15°–20°S), and in Namibia from November to March (∼20°–26°S). Strongest ascent occurs over areas of high elevation. Finally, we show a rapidly increasing frequency of strong heat low days, with a 175% increase between 1960–89 and 1990–2019. The greatest increase (459%) has occurred in the early summer months of September and October, consistent with projections of delayed rainfall onset. Strikingly, more strong heat lows are detected in the most recent 5 years of analysis (2014–19) than in the 30-yr period from 1960 to 1989. These results suggest the heat low is an important feature in determining drying trends over southern Africa and is a vital indicator of climate model accuracy.

Significance Statement
This work documents the heat low that forms in southern Africa in the lowest levels of the atmosphere. The feature is present during austral summer (from September to March) and is associated with below average rainfall across much of the subcontinent. The frequency of strong heat lows has rapidly increased in line with regional amplified warming trends. The heat low is identified as an important control on circulation and precipitation patterns and changes in the frequency or intensity of the feature in the future are likely to influence the strength of declining rainfall trends across southern Africa.
The Effects of Combined Virtual Reality Exercises and Robot Assisted Gait Training on Cognitive Functions, Daily Living Activities, and Quality of Life in High Functioning Individuals With Subacute Stroke
Authors: Akinci Murat , Burak Mustafa , Kasal Fatma Zehra , Özaslan Ezgi Aydın , Huri Meral , Kurtaran Zeynep Aydan 
Published: February 2024

Stroke is a global health concern causing significant mortality. Survivors face physical, cognitive, and emotional challenges, affecting their life satisfaction and social participation. Robot-assisted gait training with virtual reality, like Lokomat, is a promising rehabilitation tool. We investigated its impact on cognitive status, activities of daily living, and quality of life in individuals with stroke. Between September 2022 and August 2023, we exposed 34 first stroke patients (8 women, 26 men; M age = 59.15 , SD = 11.09; M height = 170.47, SD = 8.13 cm; M weight = 75.97; SD = 10.87 kg; M days since stroke = 70.44, SD = 33.65) in the subacute stage (3–6 months post-stroke) to Lokomat exercise. Participant exclusion criteria were Lokamat exercise inability, disabilities incompatible with intended measurements, and any cognitive limitations. The Control Group (CG) received conventional physiotherapy, while the Lokomat Group (LG) received both conventional physiotherapy and robot-assisted gait training with virtual reality, administered by an occupational therapist. Evaluations were conducted by a physiotherapist who was unaware of the participants’ group assignments and included assessments with the Montreal Cognitive Assessment, Lawton Brody Instrumental Activities of Daily Living Scale, and Stroke Specific Quality of Life Scale (SS-QoL). Both groups demonstrated an improved quality of life, but the LG outperformed the CG with regard to SS-QoL (p = .01) on measures of Energy ( p = .002) and Mobility ( p = .005). Both groups showed improvements in cognitive functioning ( p < .001) with no between-group difference, and in activities of daily living ( p < .05) for which the LG was superior to the CG ( p = .023). Thus, adding robot-assisted gait training with Lokomat and virtual reality improved self-reported quality of life and daily activities at levels beyond conventional physiotherapy for patients in the subacute stroke phase. An incremental impact on cognitive functions was not evident, possibly due to rapid cognitive recovery or this was undetected by limited cognitive testing.