bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unification of conformal gravity and internal interactions
Authors: Roumelioti Danai , Stefas Stelios , Zoupanos George 
Published: June 2024

AbstractBased on the observation that the dimension of the tangent space is not necessarily equal to the dimension of the corresponding curved manifold and on the known fact that gravitational theories can be formulated in a gauge theoretic way, we discuss how to describe all known interactions in a unified manner. This is achieved by enlarging the tangent group of the four-dimensional manifold to SO(2, 16), which permits the inclusion of both gauge groups, the one that describes gravity as a gauge theory as well as the SO(10) describing the internal interactions. Moreover it permits the use of both Weyl and Majorana conditions imposed on the fermions, as to avoid the duplication of fermion multiplets of SO(10) appearing in previous attempts. The gravity theory discussed in the present work is the Conformal Gravity which, after a spontaneous symmetry breaking, can lead either to Weyl Gravity or to the usual Einstein Gravity.
PREPARATION OF HIGH QUALITY NANOCOMPOSITES OF CuO/TiO2 WITH Ar+ IONS IRRADIATION WITH ENHANCED PHOTOELECTRONIC PROPERTIES
Authors: MUNEER URFA , HONEY SHEHLA , BANO NARGIS , MAZHAR MUHAMMAD EHSAN , MEHMOOD HASSAN , MAKGOPA KATLEGO , AHMAD JAVED , ASIM JAMIL , MAAZA M. , MALIK SADIA , ARIF NADEEM 
Published: June 2024

In this research work, nanocomposites of CuO/TiO2 were initially fabricated using drop casting method. Later on, these nanocomposites were irradiated for the first time by a beam of Argon ions (Ar[Formula: see text] by keeping the fluence rates of [Formula: see text] ions cm[Formula: see text], [Formula: see text] ions cm[Formula: see text], and [Formula: see text] ions cm[Formula: see text], respectively. In order to observe structural and optical properties of un-irradiated and irradiated nanocomposites, Raman Spectroscopy, Energy Dispersive X-ray (EDX), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Photoluminescence (PL) and Diffuse Reflectance Spectroscopy (DRS) analysis were performed. From Raman analysis, vibration modes confirmed the presence of different phases of TiO2 and CuO. EDX analysis clearly demonstrates the presence of Cu, Ti, and O peaks. SEM images depict agglomerated spherical nanoparticles having diameters in the range of 40–94[Formula: see text]nm. From TEM analysis, mean diameter of 56.1[Formula: see text]nm is observed for unirradiated and 33.7[Formula: see text]nm for Ar[Formula: see text] irradiated CuO/TiO2 nanoparticles in nanocomposite for fluence rates of [Formula: see text] ions cm[Formula: see text], [Formula: see text] ions cm[Formula: see text], and [Formula: see text] ions cm[Formula: see text]. HR-TEM and SAED images represent the polycrystalline nature of these nanocomposites. Among the three peaks of PL spectra in UV–Visible region, first two peaks were observed at 356[Formula: see text]nm, and 419[Formula: see text]nm but the third peak is little shifted from 488[Formula: see text]nm with the increase in fluence rate. Values of band gap are reduced from 3.29[Formula: see text]eV to 3.17[Formula: see text]eV as the fluence rate is increased, as calculated from results of diffuse reflectance spectroscopy.
IDH1 Inhibition Potentiates Chemotherapy Efficacy in Pancreatic Cancer
Authors: Zarei Mehrdad , Hajihassani Omid , Hue Jonathan J. , Loftus Alexander W. , Graor Hallie J. , Nakazzi Faith , Naji Parnian , Boutros Christina S. , Uppin Vinayak , Vaziri-Gohar Ali , Shalaby Akram S. , Asara John M. , Rothermel Luke D. , Brody Jonathan R. , Winter Jordan M. 
Published: June 2024

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is associated with a 5-year overall survival rate of just 13%, and development of chemotherapy resistance is nearly universal. PDAC cells overexpress wild-type isocitrate dehydrogenase 1 (IDH1) that can enable them to overcome metabolic stress, suggesting it could represent a therapeutic target in PDAC. Here, we found that anti-IDH1 therapy enhanced the efficacy of conventional chemotherapeutics. Chemotherapy treatment induced reactive oxygen species (ROS) and increased tricarboxylic acid cycle activity in PDAC cells, along with the induction of wild-type IDH1 expression as a key resistance factor. IDH1 facilitated PDAC survival following chemotherapy treatment by supporting mitochondrial function and antioxidant defense to neutralize ROS through the generation of α-ketoglutarate and NADPH, respectively. Pharmacologic inhibition of wild-type IDH1 with ivosidenib synergized with conventional chemotherapeutics in vitro and potentiated the efficacy of subtherapeutic doses of these drugs in vivo in murine PDAC models. This promising treatment approach is translatable through available and safe oral inhibitors and provides the basis of an open and accruing clinical trial testing this combination (NCT05209074).
Significance: Targeting IDH1 improves sensitivity to chemotherapy by suppressing mitochondrial function and inducing oxidative stress, supporting the potential of the combination as an effective strategy for treating pancreatic cancer.
Genome-Wide Methylation Analysis Reveals a
KCNK3
-Prominent Causal Cascade on Hypertension
Authors: Huang Dandan , Shang Wenlong , Xu Mengtong , Wan Qiangyou , Zhang Jin , Tang Xiaofeng , Shen Yujun , Wang Yan , Yu Ying 
Published: June 2024

BACKGROUND:
Despite advances in understanding hypertension’s genetic structure, how noncoding genetic variants influence it remains unclear. Studying their interaction with DNA methylation is crucial to deciphering this complex disease’s genetic mechanisms.

METHODS:

We investigated the genetic and epigenetic interplay in hypertension using whole-genome bisulfite sequencing. Methylation profiling in 918 males revealed allele-specific methylation and methylation quantitative trait loci. We engineered rs1275988
T/C
mutant mice using CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9), bred them for homozygosity, and subjected them to a high-salt diet. Telemetry captured their cardiovascular metrics. Protein-DNA interactions were elucidated using DNA pull-downs, mass spectrometry, and Western blots. A wire myograph assessed vascular function, and analysis of the
Kcnk3
gene methylation highlighted the mutation’s role in hypertension.

RESULTS:

We discovered that DNA methylation–associated genetic effects, especially in non-cytosine-phosphate-guanine (non-CpG) island and noncoding distal regulatory regions, significantly contribute to hypertension predisposition. We identified distinct methylation quantitative trait locus patterns in the hypertensive population and observed that the onset of hypertension is influenced by the transmission of genetic effects through the demethylation process. By evidence-driven prioritization and in vivo experiments, we unearthed rs1275988 in a cell type–specific enhancer as a notable hypertension causal variant, intensifying hypertension through the modulation of local DNA methylation and consequential alterations in
Kcnk3
gene expression and vascular remodeling. When exposed to a high-salt diet, mice with the rs1275988
C/C
genotype exhibited exacerbated hypertension and significant vascular remodeling, underscored by increased aortic wall thickness. The C allele of rs1275988 was associated with elevated DNA methylation levels, driving down the expression of the
Kcnk3
gene by attenuating Nr2f2 (nuclear receptor subfamily 2 group F member 2) binding at the enhancer locus.

CONCLUSIONS:
Our research reveals new insights into the complex interplay between genetic variations and DNA methylation in hypertension. We underscore hypomethylation’s potential in hypertension onset and identify rs1275988 as a causal variant in vascular remodeling. This work advances our understanding of hypertension’s molecular mechanisms and encourages personalized health care strategies.
Effect of Sacubitril/Valsartan on Cognitive Function in Patients With Heart Failure With Preserved Ejection Fraction: A Prespecified Analysis of PARAGON-HF
Authors: Dewan Pooja , Shen Li , Pedro Ferreira João , Jhund Pardeep S. , Anand Inder S. , Chandra Alvin , Chiang Lu-May , Claggett Brian , Desai Akshay S. , Gong Jianjian , Lam Carolyn S.P. , Lefkowitz Martin P. , Maggioni Aldo P. , Martinez Felipe , Packer Milton , Redfield Margaret M. , Rouleau Jean L. , van Veldhuisen Dirk J. , Zannad Faiez , Zile Michael R. , Solomon Scott D. , McMurray John J.V. 
Published: June 2024

BACKGROUND:
A hypothetical concern has been raised that sacubitril/valsartan might cause cognitive impairment because neprilysin is one of several enzymes degrading amyloid-β peptides in the brain, some of which are neurotoxic and linked to Alzheimer-type dementia. To address this, we examined the effect of sacubitril/valsartan compared with valsartan on cognitive function in patients with heart failure with preserved ejection fraction in a prespecified substudy of PARAGON-HF (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction).

METHODS:
In PARAGON-HF, serial assessment of cognitive function was conducted in a subset of patients with the Mini-Mental State Examination (MMSE; score range, 0–30, with lower scores reflecting worse cognitive function). The prespecified primary analysis of this substudy was the change from baseline in MMSE score at 96 weeks. Other post hoc analyses included cognitive decline (fall in MMSE score of ≥3 points), cognitive impairment (MMSE score <24), or the occurrence of dementia-related adverse events.

RESULTS:

Among 2895 patients included in the MMSE substudy with baseline MMSE score measured, 1453 patients were assigned to sacubitril/valsartan and 1442 to valsartan. Their mean age was 73 years, and the median follow-up was 32 months. The mean±SD MMSE score at randomization was 27.4±3.0 in the sacubitril/valsartan group, with 10% having an MMSE score <24; the corresponding numbers were nearly identical in the valsartan group. The mean change from baseline to 96 weeks in the sacubitril/valsartan group was −0.05 (SE, 0.07); the corresponding change in the valsartan group was −0.04 (0.07). The mean between-treatment difference at week 96 was −0.01 (95% CI, −0.20 to 0.19;
P
=0.95). Analyses of a ≥3-point decline in MMSE, decrease to a score <24, dementia-related adverse events, and combinations of these showed no difference between sacubitril/valsartan and valsartan. No difference was found in the subgroup of patients tested for apolipoprotein E ε4 allele genotype.

CONCLUSIONS:
Patients with heart failure with preserved ejection fraction in PARAGON-HF had relatively low baseline MMSE scores. Cognitive change, measured by MMSE, did not differ between treatment with sacubitril/valsartan and treatment with valsartan in patients with heart failure with preserved ejection fraction.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01920711.
Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone Improves Diastolic Dysfunction in Preclinical Nondiabetic Chronic Kidney Disease
Authors: Lima Posada Ixchel , Soulié Matthieu , Stephan Yohan , Palacios Ramirez Roberto , Bonnard Benjamin , Nicol Lionel , Pitt Bertram , Kolkhof Peter , Mulder Paul , Jaisser Frederic 
Published: June 2024

Background
The mineralocorticoid receptor plays a significant role in the development of chronic kidney disease (CKD) and associated cardiovascular complications. Classic steroidal mineralocorticoid receptor antagonists are a therapeutic option, but their use in the clinic is limited due to the associated risk of hyperkalemia in patients with CKD. Finerenone is a nonsteroidal mineralocorticoid receptor antagonist that has been recently investigated in 2 large phase III clinical trials (FIDELIO‐DKD [Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease] and FIGARO‐DKD [Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease]), showing reductions in kidney and cardiovascular outcomes.

Methods and Results
We tested whether finerenone improves renal and cardiac function in a preclinical nondiabetic CKD model. Twelve weeks after 5/6 nephrectomy, the rats showed classic signs of CKD characterized by a reduced glomerular filtration rate and increased kidney weight, associated with left ventricular (LV) diastolic dysfunction and decreased LV perfusion. These changes were associated with increased cardiac fibrosis and reduced endothelial nitric oxide synthase activating phosphorylation (ser 1177). Treatment with finerenone prevented LV diastolic dysfunction and increased LV tissue perfusion associated with a reduction in cardiac fibrosis and increased endothelial nitric oxide synthase phosphorylation. Curative treatment with finerenone improves nondiabetic CKD‐related LV diastolic function associated with a reduction in cardiac fibrosis and increased cardiac phosphorylated endothelial nitric oxide synthase independently from changes in kidney function. Short‐term finerenone treatment decreased LV end‐diastolic pressure volume relationship and increased phosphorylated endothelial nitric oxide synthase and nitric oxide synthase activity.

Conclusions
We showed that the nonsteroidal mineralocorticoid receptor antagonist finerenone reduces renal hypertrophy and albuminuria, attenuates cardiac diastolic dysfunction and cardiac fibrosis, and improves cardiac perfusion in a preclinical nondiabetic CKD model.
Multiplex Imaging for Cell Phenotyping of Early Human Atherosclerosis
Authors: Elishaev Maria , Li Boaz , Zhou Annie , Salim Kevin , Leeper Nicholas J. , Francis Gordon A. , Lai Chi , Wang Ying 
Published: June 2024

Background
Previous studies using animal models and cultured cells suggest that vascular smooth muscle cells (SMCs) and inflammatory cytokines are important players in atherogenesis. Validating these findings in human disease is critical to designing therapeutics that target these components. Multiplex imaging is a powerful tool for characterizing cell phenotypes and microenvironments using biobanked human tissue sections. However, this technology has not been applied to human atherosclerotic lesions and needs to first be customized and validated.

Methods and Results

For validation, we created an 8‐plex imaging panel to distinguish foam cells from SMC and leukocyte origins on tissue sections of early human atherosclerotic lesions (n=9). The spatial distribution and characteristics of these foam cells were further analyzed to test the association between SMC phenotypes and inflammation. Consistent with previous reports using human lesions, multiplex imaging showed that foam cells of SMC origin outnumbered those of leukocyte origin and were enriched in the deep intima, where the lipids accumulate in early atherogenesis. This new technology also found that apoptosis or the expression of pro‐inflammatory cytokines were not more associated with foam cells than with nonfoam cells in early human lesions. More CD68
+
SMCs were present among SMCs that highly expressed interleukin‐1β. Highly inflamed SMCs showed a trend of increased apoptosis, whereas leukocytes expressing similar levels of cytokines were enriched in regions of extracellular matrix remodeling.

Conclusions
The multiplex imaging method can be applied to biobanked human tissue sections to enable proof‐of‐concept studies and validate theories based on animal models and cultured cells.
Understanding Observed Precipitation Change and the New Climate Normal from the Perspective of Daily Weather Types in the Southeast United States
Authors: Qian Jian-Hua , Viner Brian , Noble Stephen , Werth David , Wermter Joseph , Chiswell Steven , Li Cuihua 
Published: June 2024

Abstract
Observed precipitation changes in the Southeast United States (SEUS) are spatially heterogeneous. Most of the inland SEUS and eastern Gulf Coast become drier, and the East Coast north of Charleston, South Carolina, and southern Florida become wetter from the old 30-yr period of 1961–90 to the recent period of 1991–2020. The observed climate change is examined from the perspective of daily weather types (WTs). A k-means clustering analysis has been conducted using daily 850-hPa circulation for 1948–2021. The obtained 10 WTs peak in different seasons, respectively. The frequencies and precipitation intensity of the WTs have been analyzed. A winter WT characterized by a western Appalachian trough (WAT) and a summer WT featuring North Atlantic subtropical high (NASH) have a rising trend of annual frequency from 1948 to 2021. An Appalachian high in the autumn has a decreasing frequency but becomes drier and stronger. Some precipitation intensity change and small location shift have also been observed. The drying up on the eastern Gulf Coast and the inland area of the SEUS is mainly caused by the weakened southwesterly low-level jet (LLJ) on the western flank of the NASH that reduces rain in the spring, the less frequent but stronger and drier Appalachian high in the summer and autumn, and the weaker and more western located Plains trough (PT) in the winter, spring, and autumn. The precipitation increase in the East Coast and southern Florida is majorly due to more frequent, stronger, and rainier troughs along the western Appalachian as well as the East Coast.
Mucocutaneous Leishmaniasis Rhinology Complications: A Rare Presentation
Authors: Ratna Sujay , Edalati Shaun , Darwish Mohamed , Gray Mingyang , Iloreta Alfred Marc 
Published: June 2024

Objective: This case report presents a unique manifestation of Mucocutaneous Leishmaniasis (MCL) in a 56-year-old woman with chronic nasal symptoms. Initially diagnosed with chronic sinusitis and septal perforation, the patient’s history of a childhood sandfly bite and subsequent episodes of Leishmaniasis, revealed after nasal surgery, provided crucial information for accurate diagnosis. Methods: A retrospective review was conducted on this patient’s electronic medical record. Results: The patient’s life-long struggle with nasal obstruction, congestion, and a septal perforation initially masked the underlying MCL. Sinus surgery and persistent symptoms further complicated the diagnostic process. Only after postoperative complications, including grainy skin texture extending into the nasal passages, did the patient recall the sandfly bite, prompting reevaluation and diagnosis of MCL. The case highlights the challenges of diagnosing MCL due to its varied presentation and potential mimicry of other chronic nasal conditions. It emphasizes the importance of thorough patient history-taking, especially when symptoms are atypical or persistent. Additionally, the report underscores the potential for unexpected postoperative complications in MCL patients and the need for vigilance in recognizing and assessing them. Conclusion: This case contributes to the understanding of MCL’s diverse clinical presentation and the importance of early diagnosis and multidisciplinary management for prompt intervention and improved outcomes.
Post-COVID Neurocognitive Disorder and Its Relation with Interleukin: A Hospital-based Cross-sectional Study
Authors: Anjum Ajmal , Hussain Arshad 
Published: June 2024

Background: The aim of this study was to determine the relationship between post-COVID neurocognitive symptoms and interleukin-6 levels. Methods: This was a hospital-based cross-sectional study wherein patients complaining of forgetfulness post-infection with coronavirus disease-2019 (COVID-19) were taken up for study ( n = 53) from February 2023 to June 2023. The forgetfulness was characterized using the memory subscale of Postgraduate Institute-Battery of Brain Dysfunction (PGI-BBD). In addition, sociodemographic data were collected from patients. After obtaining written informed consent, 3 mL of peripheral venous blood was collected from patients, and interleukin-6 levels were measured. Other inflammatory markers, like C-reactive protein (CRP), were also measured. Results: The mean age of participants was 46.11 ± 8.58 years. Twenty-nine (54.72%) respondents were female, and 24 (45.28%) were male. Most (62.2%) of the patients in the study suffered from mild-to-moderate severity of COVID-19 infection. Among these patients, 43.3% had impairment in recent memory, 32 patients (60.3%) had impairment in attention and concentration, 54.7% had impairment in delayed recall, and 33.9% had impairment in immediate recall. Impairment in delayed recall was associated with a raised level of interleukin-6 ( P = .0048 [ P < .05]). Conclusion: Patients with impaired recall on PGI-BBD post-infection with COVID-19 have raised levels of interleukin-6, suggesting the role of neuroinflammation in post-COVID neurocognitive symptoms. Interleukin-6 is a marker of neuroinflammation that has been linked to cognitive decline in various studies. It can be used to predict cognitive decline and also aid in diagnosis.
Phonological Awareness and Word Decoding Skills in the Early Readers of Kannada
Authors: Prabhu Shwetha , Venkatasubban Vangmayee , Bhat Jayashree Sunil , Somashekara Haralakatta Shivananjappa 
Published: June 2024

Background: Phonological awareness has been recognized as a significant predictor of word-decoding skills in alphabetical languages. These languages differ in phonology, orthography, and how they are mapped for word decoding. However, the literature has debated its role in orthographically consistent languages. The present research aims to explore phonological awareness and its contribution to word decoding for early readers of Kannada. Methods: The study included 50 typically developing Grade I children learning to read Kannada from schools with Kannada as a medium of instruction. Phonological awareness skills were assessed using developmentally appropriate tasks at different linguistic grain sizes and varied linguistic operations. Word-level reading abilities were evaluated using a pseudoword decoding task. Results: The results indicated that the children were sensitive to syllables but not to rhymes and phonemes. A one-way repeated measure of analysis of variance demonstrated a significant main effect of task complexity on the performance across phonological awareness tasks. Pearson’s correlation coefficient revealed a significant positive correlation between the performance on phonological awareness and pseudoword reading. The regression analysis indicated that phonological awareness tasks contributed significantly to word decoding. However, initial and medial syllable stripping evolved as independent and significant contributors to pseudoword decoding in Kannada. Conclusion: The present study concludes that phonological awareness at the syllable level emerges early and significantly contributes to word decoding in early readers of Kannada.