bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Correlates and Prognostic Impact of Cognitive Dysfunction in Patients With Heart Failure and Preserved Ejection Fraction: Insights From PARAGON-HF
Authors: Shen Li , Dewan Pooja , Ferreira João Pedro , Cunningham Jonathan W. , 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: October 2024

BACKGROUND:
Cognitive impairment is common in patients with heart failure and preserved ejection fraction but its clinical correlates and prognostic associations are poorly understood.

METHODS:
We analyzed cognitive function, using the Mini-Mental State Examination (MMSE), in patients with heart failure and preserved ejection fraction enrolled in a prespecified substudy of the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction). Logistic regression analyses were performed to determine the variables associated with lower MMSE scores at baseline and postbaseline decline in MMSE scores at 48 weeks. Cox proportional hazards regression and semiparametric proportional rates models were used to examine the risk of clinical outcomes related to baseline MMSE scores, and decline in MMSE scores during follow-up, adjusted for prognostic variables including NT-proBNP (N-terminal pro-B-type natriuretic peptide).

RESULTS:
At baseline, cognitive function was normal (MMSE score 28–30) in 1809 of 2895 patients (62.5%), borderline (score 24–27) in 794 (27.4%), and impaired (score <24) in 292 (10.1%). Variables associated with both a lower MMSE score at baseline and a decline in score from baseline included older age, a history of stroke or transient ischemic attack, and lower serum albumin. Compared with those with baseline MMSE scores of 28 to 30, patients in the lower MMSE score categories had a stepwise increase in the risk of the composite of time to first heart failure hospitalization or cardiovascular death, with an adjusted hazard ratio of 1.27 (95% CI, 1.06–1.53) for those with scores of 24 to 27 and 1.58 (95% CI, 1.21–2.06) for those with scores <24, respectively. These associations were also found for the individual components of the composite and all-cause death. Likewise, cognitive impairment was associated with a 50% higher risk of total (first and repeat) heart failure hospitalizations and cardiovascular deaths. Examining the change in MMSE score from baseline, a decrease in MMSE score during follow-up was associated with a higher risk of death.

CONCLUSIONS:
In patients with heart failure and preserved ejection fraction, even modest baseline impairment of cognitive function was associated with worse outcomes, including death. A decline in MMSE score during follow-up was a strong predictor of mortality, independent of other prognostic variables.
Somatic
GNAQ
,
CTNNB1
, and
CACNA1C
Mutations in Cat Aldosterone-Secreting Tumors
Authors: Watson Alice , Syme Harriet , Brown Morris 
Published: October 2024

BACKGROUND:

Primary aldosteronism (PA) is a common cause of human hypertension. Somatic mutations in
KCNJ5
,
CACNA1D
,
ATP1A1
, and
ATP2B3
are found in at least 80% of aldosterone-producing adenomas, which cause unilateral PA in humans. Somatic mutations have been identified infrequently in 7 other genes; few of these were known to play a role in aldosterone secretion before the discovery of their mutations. Interrogating somatic mutations in the domestic cat, in which spontaneous PA is also known to occur, might improve the understanding of normal adrenal gland physiology and the pathophysiology of PA.

METHODS:
DNA and RNA extracted from tissue from 13 cats with unilateral aldosterone-secreting tumors, including 8 carcinomas and 5 adenomas, underwent whole genome sequencing, targeted Sanger sequencing, and RNA sequencing. Single-nucleotide substitution variants were filtered to select those with a predicted deleterious effect on protein function and a suspected role in aldosterone secretion.

RESULTS:

Probable functional somatic single-nucleotide polymorphisms (n=8) were found in 3 adenomas and 2 carcinomas. Mutations with predicted significant effects were identified in 2 genes also mutated in human PA;
GNAQ
and
CTNNB1
, and in a residue of
CACNA1C
analogous to a common
CACNA1D
mutation. In contrast to humans,
CACNA1C
expression was much greater than
CACNA1D
in both feline tumor and nontumor adrenal tissue. No mutations were identified in
KCNJ5
,
CACNA1D
,
ATP1A1
, or
ATP2B3.

CONCLUSIONS:
Similar mutations were identified in cats to those found in humans. It is, therefore, likely that both species have shared underlying selection pressures for mutations that increase aldosterone secretion.
Perinatal Caffeine Administration Improves Outcomes in an Ovine Model of Neonatal Hypoxia-Ischemia
Authors: Mike Jana K. , White Yasmine , Ha Janica , Iranmahboub Ariana , Hawkins Cheryl , Hutchings Rachel S. , Vento Christian , Manzoor Hadiya , Wang Aijun , Goudy Brian D. , Vali Payam , Lakshminrusimha Satyan , Gobburu Jogarao V.S. , Long-Boyle Janel , Fineman Jeffrey R. , Ferriero Donna M. , Maltepe Emin 
Published: October 2024

BACKGROUND:
Neonatal hypoxic-ischemic encephalopathy disproportionately affects low- and middle-income countries, where ≈96% of affected infants reside. The current standard of care, therapeutic hypothermia, is frequently ineffective in this setting, likely because injury may be occurring earlier during labor. Here, we studied the pharmacokinetics, safety, and efficacy of perinatal caffeine administration in near-term lambs following global ischemic injury to support the development of earlier treatment strategies targeting the fetus in utero as well as the infant postnatally.

METHODS:
Ewes were randomly assigned to receive either 1 g IV caffeine citrate or placebo before delivery and placental transport assessed. Near-term lambs (141–143 days) of both sexes were subjected to severe global hypoxia-ischemia utilizing an acute umbilical cord occlusion model. Lambs that received caffeine in utero also received 20 mg/kg IV caffeine citrate following resuscitation and 10 mg/(kg·d) IV for 2 days. An additional cohort received 60 mg/kg followed by 30 mg/(kg·d) (low dose versus high dose) postnatally. Biochemical, histological, and neurological outcome measures in lambs were assessed over a 6-day period.

RESULTS:
Perinatal caffeine administration demonstrated excellent placental transport kinetics and was well tolerated with lamb plasma levels comparable to those targeted in neonates with apnea of prematurity. Caffeine administration resulted in a systemic immunomodulatory effect, evidenced by significant reductions in proinflammatory IP-10 levels. Treated lambs demonstrated improved neurodevelopmental outcomes, while histological analysis revealed that caffeine reduced gray matter injury and attenuated inflammation in the cingulate and parasagittal cortex. This neuroprotective effect was greater and via a different mode of action than we previously reported for azithromycin. A higher caffeine dosing regimen demonstrated significant toxicity.

CONCLUSIONS:
Perinatal caffeine administration is well tolerated, attenuates systemic and brain inflammation, and contributes to improvements in histological and neurological outcomes in an ovine model of neonatal hypoxic-ischemic encephalopathy.
Differentiation of MS lesions through analysis of microvascular distribution
Authors: Sundvall Linda , Mikkelsen Irene Klærke , Eskildsen Simon F. , Hjørringgaard Mette Madsen , Nygaard Mikkel , Rasmussen Peter Vestergaard , Petersen Thor , Østergaard Leif 
Published: October 2024

Abstract
Conventional MRI is crucial for diagnosing multiple sclerosis (MS) but lacks precision, leading to the clinico-radiological paradox and misdiagnosis risk, especially when confronted with unspecific lesions not related to MS. Advancements in perfusion-weighted imaging (PWI) with an algorithm designed for diseases with anticipated contrast agent extravasation offer insight into microvascular impairment and flow heterogeneity. Our study aimed to assess these factors in MS patients and their association with clinically relevant white matter injury and disease course. We evaluated 60 adults with white matter lesions (WML), including 50 diagnosed with MS or MS syndromes and 10 non-diseased symptomatic controls (SC) with unspecific WML. MRI included conventional three-dimensional (3D) T2-weighted fluid-attenuated inversion recovery (T2-FLAIR), 3D magnetization-prepared two rapid acquisition gradient-echo (MP2RAGE), post-contrast 3D T1-weighted (T1) images, and Dynamic Susceptibility Contrast (DSC) PWI at 3T. WML masks of “unspecific T2-FLAIR lesions”, “MS T2-FLAIR lesions”, and “MS T1-lesions” were manually outlined and validated by a neuroradiologist. DSC-derived parameters were analyzed in WML masks and healthy-appearing tissue. MS T2-FLAIR lesions showed increased flow heterogeneity and vasodilation compared to unspecific T2-FLAIR lesions in SC, as well as compared to unspecific T2-FLAIR lesions within the MS group. MS T1-lesions exhibited more homogenized flow. Our findings suggest that DSC-PWI, combined with lesion delineation, can provide clinically relevant differentiation of MS lesions from unspecific WML, highlighting potential microvascular pathology previously overlooked in MS.
The Neural Specificity of Interference Resolution in Phonological, Semantic, and Visual Domains at Different Ages
Authors: Grégoire Coline , Attout Lucie , Phillips Christophe , Rifon Lucas , Hody Louis , Majerus Steve 
Published: October 2024

Abstract
The question of whether cognitive control is specific to certain domains or domain-general remains an extensively debated question at both cognitive and neural levels. This study examined the neural substrates associated with resistance to interference (RI) in phonological, semantic, and visual domains by using strictly matched tasks and determining the domain-general or domain-specific manner in which aging affects the neural substrates associated with RI. In an fMRI experiment, young and older participants performed a similarity judgment task with phonological, semantic, or visual interference buildup. For both age groups, domain-specific RI effects were observed at the univariate level, with increased involvement in the phonological domain of the right angular gyrus and the right lingual gyrus, in the semantic domain of the bilateral inferior frontal gyrus, the bilateral superior parietal and angular gyri and the left middle temporal gyrus, and in the visual domain of the middle/superior frontal gyri and occipital gyri. At the multivariate level, although RI effects could be decoded from neural patterns in the bilateral inferior frontal gyrus for all domains and age groups, between-domain prediction of RI conditions was associated with Bayesian evidence for the null hypothesis. This study supports the domain specificity of neural substrates associated with RI while stressing its age independency.
Sinonasal Phosphaturic Mesenchymal Tumors Without Any Nasal Symptoms: A Case Report and Literature Review
Authors: Zhu Jin-Yu , Li Yan-Qing , Yuan Hui 
Published: October 2024

Objective: We present a case of phosphaturic mesenchymal tumor (PMT) in the left ethmoid without any nasal symptoms in a 63-year-old woman. Initially diagnosed with postmenopausal osteoporosis, 2-year history of hypophosphatemia and a significantly higher uptake of Fluorine-18 (18F)-AlF-NOTA-octreotide (18F-OC) in the left ethmoid sinus, provided crucial information for accurate diagnosis. Methods: We presented a case with chart review and conducted review of the literature. Results: The patient endured 1-year history of weakness and bone pain but without any nasal symptoms before a tissue diagnosis was eventually reached. It is a challenging diagnosis to make-patients present with non-specific clinical symptoms and the culprit neoplasm is often tiny in size and difficult to detect. It emphasizes the importance of thorough patient history-taking and the whole-body functional imaging. Conclusions: Sinonasal PMTs are rare, and because of this most otolaryngologists are unfamiliar with its clinical presentation. This case highlights the importance of early diagnosis to enable prompt intervention and reduce the burden of associated symptoms.
Impact of preoperative computed tomography scan on neurological outcomes in coronary artery bypass grafting patients: A propensity-score analysis
Authors: Cefarelli Mariano , Malvindi Pietro Giorgio , Bifulco Olimpia , Buratto Beatrice , Berretta Paolo , Zingaro Carlo , Capestro Filippo , Pierri Michele Danilo , Alfonsi Jacopo , D’Alfonso Alessandro , Di Eusanio Marco 
Published: October 2024

Introduction Neurological complications pose significant risks in coronary artery bypass grafting (CABG). This study explores the potential benefits of preoperative chest computed tomography (CT) in optimizing outcomes and reducing neurological events in high-risk CABG patients. Methods From January 2017 to June 2023, a retrospective cohort study of CABG patients categorized groups based on preoperative chest CT use. Multivariate analysis evaluated the associations between CT imaging and patient characteristics, followed by propensity match analysis to balance preoperative features across groups. Results The study included 1786 patients, with 435 having undergone preoperative CT and 1351 without. Propensity matching created two well-balanced groups of 413 patients each. At multivariate analysis, CT patients were elderly (71.1 ± 8.9 years; p = 0.03) with a higher incidence of pulmonary disease (19.5%; p < 0.01), peripheral arterial disease (29.2%; p < 0.01), and previous cerebrovascular disease (23.4%; p = 0.02). In the matched CT cohort, the perioperative cerebral stroke rate was 0.7% (vs. 1.9% in without preoperative CT [WCT] cohort; p = 0.223), and the 30-day mortality rate was 0.2% (vs. 1.7% in WCT cohort; p = 0.069). Patients who had a preoperative CT study presented a higher prevalence of porcelain aorta (6.3% vs. 1.5%; p = 0.0003) and required more often a no-touch aorta procedure (20.3% vs. 14.5%; p = 0.035). Conclusions Patients undergoing preoperative chest CT before CABG were typically older and had systemic atherosclerosis and pulmonary disease. Propensity-matched analysis indicated low mortality and perioperative cerebral stroke rates in these high-risk patients. These findings support the integration of chest CT into preoperative evaluations for high-risk patients to develop tailored strategies in coronary artery bypass surgery.
Exploring the Potential Antidiabetic Effects of Alkannin (A Naphthoquinone Compound): in vivo and in silico Studies
Authors: Saeed Mohd , Shoaib Ambreen , Azmi Lubna , Al-Shammary Asma , Alam Md Jahoor , Albulaihed Yazeed , Balaramnavar Vishal M , Bonde Chandrakant , Kausar Mohd Adnan , Abdelgadir Abdelmuhsin , Alqathani Saad Saeed , Ansari Irfan Ahmad 
Published: October 2024

Background It is estimated that the plant has been utilized in India’s traditional medical system for close to 2,500 years. Alkanin is a key active component in Boraginaceae medicinal plant roots. Many scientists are interested in this tiny molecule due to its biological potential. Objectives To examine the hypoglycemic effects of alkannin (a naphthoquinone pigment). Materials and Methods Initially, we determined the dosage of alkannin by conducting an acute oral toxicity study per Organisation for Economic Co-operation and Development guidelines. Subsequently, streptozocin was used to induce diabetes in mice, and we chose several parameters such as body weight, food and water intake, blood glucose level, and biochemical estimation for the in vivo evaluation. The enhanced pharmacokinetic features of alkannin, such as its better cytochromes P450 metabolism profiles and higher intestinal absorption as compared to glimepiride, were validated by in silico investigations utilizing Swiss ADME (Absorption, Distribution, Metabolism, and Excretion) and AutoDock Vina. Results In particular, blood glucose levels and body weight in the alkannin-treated group drastically decreased to 138 ± 1.45 mg/dL and 27.9±0.54 g, respectively, as compared with the diabetic-treated group. Moreover, alkaline phosphatase levels dropped to 57.26 ± 3.05 U/L in the alkannin group, suggesting enhanced liver and kidney functions. Creatinine levels also decreased from 1.44 ± 0.10 mg/dL to 0.92 ± 0.09 mg/dL, and serum glutamic oxaloacetic transaminase/aspartate aminotransferase levels decreased from 64.16 ± 3.14 U/L to 47.85 ± 2.01 U/L. Additionally, diabetic controls maintained cholesterol levels between 102.1 ± 11.46 mg/dL and 93.53 ± 2.61 mg/dL. With a considerable binding score of –9.2 kcal/mol for alkannin, molecular docking demonstrated a high degree of binding efficiency and robust interaction with biological targets. The docking results revealed that alkannin exhibits drug-like properties. In addition, it satisfies the lead likeness requirement and has a lower synthetic accessibility score compared to glimepiride. Conclusion The results revealed the promising characteristics and positive outcomes of alkannin, underscoring its potential as a viable candidate for further investigation and prospective advancement as a treatment drug for diabetes.
Economic Uncertainty and Impact of Governments’ Spending on Economic Growth: An Empirical Study of Emerging Market Economies*
Authors: Prathap Manu , Suresh Anoop K. , Seth Bichitrananda , Behera Samir Ranjan 
Published: October 2024

The COVID-19-led economic crisis has rekindled scholarly interest in the relationship between government spending and economic growth. Further, there is an emerging realm of empirical literature that focuses on the dynamics of this relationship during times of uncertainty. Against this backdrop, this study investigates the effect of government expenditure on economic growth during economic uncertainty and the role of economic confidence in the transmission mechanism of policy shocks utilizing a panel generalized method of moments (GMM) framework for 13 select emerging market economies (EMEs). The findings suggest that the beneficial impact of government spending during economic uncertainty is not significantly different from regular times; however, its effectiveness is enhanced during contractionary periods. Government spending, on the other hand, does not have a statistically significant effect during expansionary phases. Furthermore, unanticipated government spending boosts economic confidence, especially during contractionary phases. Governments in EMEs should implement countercyclical fiscal policies selectively to stimulate aggregate demand and facilitate economic recovery, prioritizing targeted spending in confidence-building initiatives and key sectors. Spending in high multiplier sectors during contractionary periods can boost economic activity and speed recovery, fostering stability and growth amidst uncertain economic conditions. JEL Classification E32, H30, H32
Content Analysis of Brief Telephonic Conversation with Parents of Children with Cleft Lip and Palate During Sustained Anticipatory Guidance Sessions
Authors: Esther K. , Muthu M.S. , Sagarkar Anitha R. , Saikia Ankita 
Published: October 2024

Objectives Cleft lip and palate (CLP) represents complex congenital anomalies that necessitate a comprehensive approach to care, involving multiple healthcare disciplines. The primary aim of the study is to explore the content of periodic telephone support calls between parents/caregivers of children with CLP and pediatric dentist during sustained anticipatory guidance. Design The qualitative analysis was conducted with the available telephonic recordings that was obtained from the STOP database. 40 recordings of 8 children were used for this study. The recorded interviews were translated and transcribed verbatim and analysed using the thematic content analysis method. Results The four major themes that were addressed by the dentist were the general health of the baby, oral health and development, surgery-related concerns and emotional support. It was also observed that the parents demonstrated a positive shift in oral health related behaviour significantly improving their child's oral hygiene practices. Conclusions The telephonic support calls offer valuable insights into the concerns and topics the parents of children with CLP are eager to discuss. These calls not only address general concerns, receiving emotional support from the professionals, demonstrate the health related behavior shift that takes place during SAG and reassures parents of their support.
Exploring the Impact of the β-Catenin Mutations in Hepatocellular Carcinoma: An In-Depth Review
Authors: Idrissi Yassine Alami , Rajabi Mohammad Reza , Beumer Jan H. , Monga Satdarshan P. , Saeed Anwaar 
Published: October 2024

Liver cancer, primarily hepatocellular carcinoma, represents a major global health issue with significant clinical, economic, and psychological impacts. Its incidence continues to rise, driven by risk factors such as hepatitis B and C infections, nonalcoholic steatohepatitis, and various environmental influences. The Wnt/β-Catenin signaling pathway, frequently dysregulated in HCC, emerges as a promising therapeutic target. Critical genetic alterations, particularly in the CTNNB1 gene, involve mutations at key phosphorylation sites on β-catenin’s N-terminal domain (S33, S37, T41, and S45) and in armadillo repeat domains (K335I and N387 K). These mutations impede β-catenin degradation, enhancing its oncogenic potential. In addition to genetic alterations, molecular and epigenetic mechanisms, including DNA methylation, histone modifications, and noncoding RNAs, further influence β-catenin signaling and tumor progression. However, β-catenin activation alone is insufficient for hepatocarcinogenesis; additional genetic “hits” are required for tumor initiation. Mutations or alterations in genes such as Ras, c-Met, NRF2, and LKB1, when combined with β-catenin activation, significantly contribute to HCC development and progression. Understanding these cooperative mutations provides crucial insights into the disease and reveals potential therapeutic strategies. The complex interplay between genetic variations and the tumor microenvironment, coupled with novel therapeutic approaches targeting the Wnt/β-Catenin pathway, offers promise for improved treatment of HCC. Despite advances, translating preclinical findings into clinical practice remains a challenge. Future research should focus on elucidating how specific β-catenin mutations and additional genetic alterations contribute to HCC pathogenesis, leveraging genetically clengineered mouse models to explore distinct signaling impacts, and identifying downstream targets. Relevant clinical trials will be essential for advancing personalized therapies and enhancing patient outcomes. This review provides a comprehensive analysis of β-Catenin signaling in HCC, highlighting its role in pathogenesis, diagnosis, and therapeutic targeting, and identifies key research directions to improve understanding and clinical outcomes.