bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fatty Acids Differentially Modulate Insulin-Stimulated Endothelial Nitric Oxide Production by an Akt-lndependent Pathway
Authors: Lynn Matthew A. , Rupnow Heidi L. , Kleinhenz Dean J. , Kanner William A. , Dudley Samuel C. , Hart C. Michael 
Published: March 2023

Background Insulin increases endothelial nitric oxide (NO) production by activating endothelial nitric oxide synthase (eNOS) through protein kinase B (Akt)-mediated phosphorylation of serine residue 1179 (p-eNOS serine 1179). Because fatty acids modulate insulin-stimulated Akt signaling cascades in smooth muscle cells, we hypothesized that fatty acids would differentially regulate endothelial Akt signaling, eNOS phosphorylation, and NO production. Methods Porcine pulmonary artery endothelial cells (PAECs) were treated for 3 hours with 100 μM oleic (18:1) or eicosapentaenoic (20:5) acids or with an equivalent volume of ethanol vehicle (0.1%). PAECs were then treated with graded concentrations (109–10-5 M) of insulin or incubated overnight (24 hours) in culture medium without fatty acids before insulin treatment. Activation and phosphorylation of Akt and eNOS were determined by immunoblotting. NO production was measured with a chemiluminescence NO analyzer or with a NO-selective carbon fiber microelectrode. Results Insulin-stimulated Akt phosphorylation, eNOS phosphorylation, and NO production. The phosphatidylinositol-3 kinase inhibitor wortmannin attenuated insulin-stimulated Akt activation and NO production. Treatment with the co-3 fatty acid 20:5, but not 18:1, enhanced insulin-stimulated NO production but failed to alter insulin-stimulated Akt activation or eNOS serine 1179 phosphorylation. Conclusion Individual fatty acyl species have distinct effects on insulin-stimulated endothelial NO production. Although fatty acids alter Akt signaling in muscle cells, the current results indicate that fatty acids do not modulate endothelial NO production through alterations in insulin-stimulated, Akt-mediated eNOS phosphorylation.
Parasympathetic Effects on Heart Rate Recovery after Exercise
Authors: Kannankeril Prince J. , Le Francis K. , Kadish Alan H. , Goldberger Jeffrey J. 
Published: March 2023

Background Exercise and its recovery period are associated with increased risk of death relative to sedentary periods. They are also accompanied by dynamic changes in autonomic tone. Little information is available regarding parasympathetic effects during high-intensity exercise and recovery. Methods Ten normal subjects (five women; age 33 ± 2 years) underwent exercise testing on a bicycle ergometer. On day 1, subjects exercised to maximum tolerated workload using a graded protocol with 5 minutes at maximal workload (peak heart rate achieved 174.7 ± 5.4 bpm). On day 2, subjects performed the identical exercise protocol as on day 1; 1 minute into the maximum exercise stage, atropine (0.04 mg/kg) was administered. Heart rate was recorded every minute during exercise, and an electrocardiogram was recorded every minute in recovery for 10 minutes. The parasympathetic effect on heart rate was defined by the difference in heart rate with and without atropine. Results The parasympathetic effect during maximal exercise was 3.4 to 6 bpm ( p < .05). During recovery, a large parasympathetic effect on heart rate was noted by 1 minute (22.8 bpm; p < .0002), increased until 4 minutes, and then remained stable until 10 minutes. Despite faster heart rates with parasympathetic blockade, the P–R interval was shorter ( p < .002), consistent with a significant parasympathetic effect on the atrioventricular node in recovery. Evaluation of the Q–T–R–R relationship on the 2 days demonstrated significant changes in both the slope ( p < .0001) and the intercept ( p < .0001), consistent with a modification of ventricular repolarization by parasympathetic tone in recovery. Conclusion These data indicate that in normal subjects, parasympathetic effects persist during high-intensity exercise and are prominent in the early phases of recovery. These parasympathetic effects may play an important role in prevention of sudden cardiac death during these periods of increased risk.
Mental Health in Adults With ADHD: Examining the Relationship With Cardiorespiratory Fitness
Authors: Ogrodnik Michelle , Karsan Sameena , Heisz Jennifer J. 
Published: March 2023

Objective: The mental health of adults with ADHD was compared to neurotypical controls, and associations between cardiorespiratory fitness (CRF) and mental health were examined. Method: Seventy-two participants ( n = 36 with ADHD) completed demographic questions assessing ADHD and mental health symptoms. CRF was estimated using the 6-Minute Walk Test and a self-perception question. Results: Those with ADHD had significantly poorer mental health outcomes than controls ( p < .001), with 50% of adults with ADHD reporting severe to extremely severe symptoms of depression, anxiety, or stress. Critically, lower CRF was associated with worse depression, anxiety, and stress (all p ≤ .03) across both groups. Within the ADHD group, those with higher estimated CRF had significantly lower stress. Among participants with less severe ADHD symptoms, those with higher perceived CRF had significantly lower depressive symptoms. Conclusion: In our cross-sectional study, participants with ADHD had poorer mental health than neurotypical controls, and higher fitness was associated with better mental health.
Relationship Between Inhibitory Control and Arithmetic in Elementary School Children With ADHD: The Mediating Role of Working Memory
Authors: Lee Clara. S. C. 
Published: March 2023

Objectives: To test if inhibitory control was a significant predictor for arithmetic in children with ADHD and if the relationship between inhibitory control and arithmetic was mediated by working memory. Methods: Eighty-four children (ADHD, n = 54; Non-ADHD, n = 30) were tested on their interference control, behavioral inhibition, working memory, and arithmetic. Regression analysis was used to test the predictive role of inhibitory control in arithmetic. Moreover, mediation analysis was done to test whether working memory mediated the relationship between inhibitory control and arithmetic memory. Results: Interference control but not behavioral inhibition was a significant predictor for arithmetic. In addition, interference control had direct and indirect effects via working memory on arithmetic. Conclusions: Results demonstrated that inhibitory control contributed to arithmetic in children with ADHD. Furthermore, interference control had direct and indirect effects via working memory on arithmetic, suggesting interventions for arithmetic difficulties should involve training on both inhibition and working memory.
Microphthalmia and anterior segment dysgenesis due to a double gene variant in GJA8 and CRYGC
Authors: Zhou Lin , Wang Ganghua , Hu Bin , Jiang Hui , Jiang Fanwen , Xu Zhuping 
Published: March 2023

Introduction To report a family with severe ocular disorder caused by double gene variants in causative genes of autosomal dominant cataracts, GJA8 and CRYGC. Case presentation A 5-month-old boy with poor vision and enophthalmos was referred to our hospital. Further ocular examination showed horizontal nystagmus, iris abnormalities with pinpoint pupils, and extreme microphthalmia with axial right and left eye lengths of 13.48 mm and 13.75 mm, respectively. Digenic heterozygous variants (c.269T > G, p.Leu90Arg in CRYGC and c.151G > A, p.Asp51Asn in GJA8) have been detected based on the whole exome sequencing. His mother, who carried variant in CRYGC (c.269T > G, p.Leu90Arg), had nuclear cataract, microcornea and nystagmus, while his father, who carried variant in GJA8 (c.151G > A, p.Asp51Asn), showed bilateral membranous cataract, microphthalmia, sclerocornea, glaucoma, and nystagmus. Conclusions To our knowledge, this is the first report of a patient with variants in two cataract-related genes. Importantly, patient with double heterozygous variants in two dominantly inherited genes may suffer more serious phenotypes than those with heterozygous variant in a single dominantly inherited gene. Whole exome or genome sequencing is necessary for a genetic diagnosis in case of multiple gene variants.
Evaluation of pure subarachnoid hemorrhage after mechanical thrombectomy in a series of 781 consecutive patients
Authors: Benalia Victor HC , Aghaebrahim Amin , Cortez Gustavo M , Sauvageau Eric , Hanel Ricardo A 
Published: March 2023

Introduction Subarachnoid hyperdensity is commonly seen on postoperative computed tomography scans within 24 h after mechanical thrombectomy. The impact on patients’ outcomes remains uncertain. We present a real-world experience evaluating periprocedural factors associated with the development of subarachnoid hemorrhage (SAH) and its impact on outcomes of patients with acute stroke undergoing mechanical thrombectomy. Methods A single-center, retrospective analysis was performed between January 2016 and August 2021, including all consecutive patients who underwent thrombectomy. Our study aimed to evaluate periprocedural factors associated with subarachnoid hemorrhage within 24 h of the intervention, and the potential impact on patients' outcome. Results Of 781 patients, 44 patients (5.63%) demonstrated pure SAH within 24 h of the intervention. Patients from the SAH group were more likely to have tandem occlusion (15.9% vs. 5.2%, p = .003), aspiration using reperfusion pump system (81.4% vs. 66.8%, p = .047), intraoperative complications (9.1% vs. 0.9%; p < .001), longer puncture-to-recanalization times (45 min vs 29 min, p = .042) and a higher median number of passes to achieve recanalization (1 vs. 3, p = .002). There was no statistically significant difference in the long-term functional outcome between the groups. Conclusion We suggest that dual-energy computed tomography could better distinguish between blood and pure contrast stagnation. Still, SAH was not associated with an unfavorable outcome in stroke patients undergoing thrombectomy.
Subclavian to carotid artery bypass for a case of ocular ischemic syndrome
Authors: Sadri Babak S , Low David W , Jackson Oksana A , Jackson Benjamin M , Belkin Nathan 
Published: March 2023

Background Ocular Ischemic Syndrome (OIS) is a rare, vision threatening condition associated with severe carotid artery disease. There are few cases of OIS reported in the literature. Methods We present the case of a 54-year-old male with history of multiple previous carotid interventions including a right carotid stent, who presented with right-sided OIS. Results CTA and angiogram showed a severe calcific plaque causing restenosis of the right carotid stent, with a patent right internal carotid artery (ICA) in the very distal neck. The right common carotid artery (CCA) was patent but diseased with ulcerated plaque extending proximally to below the level of the clavicle. The left CCA was chronically occluded from its origin all the way to the bifurcation. Given our patient’s surgical history, the imperative to revascularize the ipsilateral carotid, and a diffusely diseased ipsilateral CCA, he was successfully treated with an ipsilateral subclavian to internal carotid bypass. Conclusion There is paucity of data regarding the best approach for carotid revascularization in OIS. This case report discusses our unique perioperative decision making as well as relevant literature.
English Language Medical Schools in China: An Analysis of International Medical Graduates Practicing in the UK
Authors: Rashid Mohammed Ahmed , Smith Victoria , Mayberry John Francis 
Published: March 2023

OBJECTIVES From 2006, the Ministry of Education in China has approved universities to provide undergraduate medical training in English, targeting fee-paying international students. Students on these courses can face challenges in their clinical training, particularly in the domains of communication and professionalism. This study examines the proportion of doctors qualified from such medical schools who are currently listed on the UK medical register. METHODS The UK General Medical Council register of medical practitioners was searched to identify doctors qualified from 33 Chinese medical schools who provide education in the English language. RESULTS As of February 2022, 502 doctors whose primary medical qualification is from a university offering English language education in China were registered on the UK medical register. Four hundred twenty-five (84.7%) of these doctors were aged 39 and under, approximately double the proportion of doctors in this age bracket overall. Three hundred forty nine (69.5%) were staff grade and associate specialist doctors, 109 (21.7%) were doctors in training, 36 (7.2%) were on the General Practitioner (GP) register, and 20 (4.0%) were on the specialist register. Among doctors in training, the most common specialty areas were in general practice and psychiatry that are both facing recruitment shortages in the UK at present. CONCLUSION A small but significant number of graduates whose medical training was in the English language in China are practicing medicine in the UK. These doctors are in younger age groups than the overall medical workforce, and are less likely to be in training, and specialist or GP posts. Among those in training, a high proportion are in GP and psychiatry training and could contribute to alleviating UK medical workforce shortages. Policymakers and educators should be mindful of the growing numbers of doctors qualified from these schools, and the additional support they may require considering the unique training environments they have encountered.
LncRNA GAS5 suppresses TGF-β1-induced transformation of pulmonary pericytes into myofibroblasts by recruiting KDM5B and promoting H3K4me2/3 demethylation of the PDGFRα/β promoter
Authors: Wang Yichun , Chen Diyu , Xie Han , Zhou Shuhua , Jia Mingwang , He Xiaobo , Guo Feifei , Lai Yihuan , Tang Xiao Xiao 
Published: March 2023

Abstract
Background
Idiopathic pulmonary fibrosis (IPF) is a condition that may cause persistent pulmonary damage. The transformation of pericytes into myofibroblasts has been recognized as a key player during IPF progression. This study aimed to investigate the functions of lncRNA growth arrest-specific transcript 5 (GAS5) in myofibroblast transformation during IPF progression.

Methods
We created a mouse model of pulmonary fibrosis (PF) via intratracheal administration of bleomycin. Pericytes were challenged with exogenous transforming growth factor-β1 (TGF-β1). To determine the expression of target molecules, we employed quantitative reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemical and immunofluorescence staining. The pathological changes in the lungs were evaluated via H&E and Masson staining. Furthermore, the subcellular distribution of GAS5 was examined using FISH. Dual-luciferase reporter assay, ChIP, RNA pull-down, and RIP experiments were conducted to determine the molecular interaction.

Results
GAS5 expression decreased whereas PDGFRα/β expression increased in the lungs of IPF patients and mice with bleomycin-induced PF. The in vitro overexpression of GAS5 or silencing of PDGFRα/β inhibited the TGF-β1-induced differentiation of pericytes to myofibroblasts, as evidenced by the upregulation of pericyte markers NG2 and desmin as well as downregulation of myofibroblast markers α-SMA and collagen I. Further mechanistic analysis revealed that GAS5 recruited KDM5B to promote H3K4me2/3 demethylation, thereby suppressing PDGFRα/β expression. In addition, KDM5B overexpression inhibited pericyte–myofibroblast transformation and counteracted the promotional effect of GAS5 knockdown on pericyte–myofibroblast transformation. Lung fibrosis in mice was attenuated by GAS5 overexpression but promoted by GAS5 deficiency.

Conclusion
GAS5 represses pericyte–myofibroblast transformation by inhibiting PDGFRα/β expression via KDM5B-mediated H3K4me2/3 demethylation in IPF, identifying GAS5 as an intervention target for IPF.
Resistive random access memory: introduction to device mechanism, materials and application to neuromorphic computing
Authors: Zahoor Furqan , Hussin Fawnizu Azmadi , Isyaku Usman Bature , Gupta Shagun , Khanday Farooq Ahmad , Chattopadhyay Anupam , Abbas Haider 
Published: March 2023

AbstractThe modern-day computing technologies are continuously undergoing a rapid changing landscape; thus, the demands of new memory types are growing that will be fast, energy efficient and durable. The limited scaling capabilities of the conventional memory technologies are pushing the limits of data-intense applications beyond the scope of silicon-based complementary metal oxide semiconductors (CMOS). Resistive random access memory (RRAM) is one of the most suitable emerging memory technologies candidates that have demonstrated potential to replace state-of-the-art integrated electronic devices for advanced computing and digital and analog circuit applications including neuromorphic networks. RRAM has grown in prominence in the recent years due to its simple structure, long retention, high operating speed, ultra-low-power operation capabilities, ability to scale to lower dimensions without affecting the device performance and the possibility of three-dimensional integration for high-density applications. Over the past few years, research has shown RRAM as one of the most suitable candidates for designing efficient, intelligent and secure computing system in the post-CMOS era. In this manuscript, the journey and the device engineering of RRAM with a special focus on the resistive switching mechanism are detailed. This review also focuses on the RRAM based on two-dimensional (2D) materials, as 2D materials offer unique electrical, chemical, mechanical and physical properties owing to their ultrathin, flexible and multilayer structure. Finally, the applications of RRAM in the field of neuromorphic computing are presented.
Macrophage-Derived MMP-9 and MMP-2 are Closely Related to the Rupture of the Fibrous Capsule of Hepatocellular Carcinoma Leading to Tumor Invasion
Authors: Cui Quanwei , Wang Xuben , Zhang Yongwei , Shen Yiqing , Qian Yeben 
Published: March 2023

Abstract
Background
Hepatocellular carcinoma (HCC) is an aggressive tumor with a poor clinical prognosis. Rupture of the fibrous capsule (FC) is a very important clinical phenomenon in the invasion and metastasis of HCC. FC is mainly composed of type I collagen (COL1A1). However, it is not clear what caused the FC rupture. In this study, we aimed to determine whether the rupture of FC in HCC patients was related to macrophage-derived MMP-9 and MMP-2, and their clinical diagnostic value for FC rupture.

Results
By performing immunohistochemical and immunofluorescence staining of ruptured FC and intact FC, the results showed that the ruptured area of FC aggregated a large number of macrophages with MMP-9 and MMP-2. Western blot analysis and Quantitative real-time PCR were used to assess the expression of MMP-9 and MMP-2 in the ruptured and relatively intact area of FC in ruptured FC patients, and the results revealed a significantly different expression of MMP-9 and MMP-2. ELISA experiments show that we could discriminate effectively between ruptured FC and intact FC by MMP-9 and MMP-2.

Conclusions
Taken together, macrophage-derived MMP-9 and MMP-2 were closely related to the rupture of the FC of HCC and subsequently led to the migration and invasion of the tumor cells through the ruptured area of FC to the para cancer. It is suggested that when performing surgical resection, it is necessary to expand the range of tumor resection for patients with ruptured FC and hence reduce the possibility of recurrence and metastasis in HCC patients.
Testicular impairment in Primary Adrenal Insufficiency caused by Nicotinamide Nucleotide Transhydrogenase (NNT) deficiency - a case report: implication of oxidative stress and importance of fertility preservation
Authors: Ferreux Lucile , Boumerdassi Yasmine , Dulioust Emmanuel , Bertagna Xavier , Roucher-Boulez Florence , Bourdon Mathilde , Thiounn Nicolas , Patrat Catherine 
Published: March 2023

Abstract
Introduction
Nicotinamide nucleotide transhydrogenase (NNT) gene deficiency has recently been shown to be involved in Primary Adrenal Insufficiency (PAI). NNT encodes an inner mitochondrial membrane protein that produces large amounts of NADPH. NADPH is used in several biosynthesis pathways and the oxidoreduction of free radicals by the glutathione and thioredoxin systems in mitochondria. Patients with PAI due to NNT deficiency may also exhibit extra-adrenal manifestations, usually including gonadal impairment.

Case report
We present the case of a 35-year-old patient referred to our center for primary infertility with non-obstructive azoospermia, in a context of PAI and obesity. PAI genetic exploration carried out at the age of thirty revealed NNT deficiency due to the presence of two deleterious mutations (one on each allele) in the NNT gene. Scrotal ultrasound revealed a right Testicular Adrenal Rest Tumor (TART). Intensification of glucocorticoid therapy over the course of 8 months failed to reduce the TART volume or improve sperm production and endocrine function. No spermatozoa were found after surgical exploration of both testes, and subsequent histopathological analysis revealed bilateral Sertoli cell-only syndrome. A retrospective review of the hypothalamic-pituitary-gonadic axis hormonal assessment over 20 years showed progressive impairment of testicular function, accelerated during adulthood, leading to hypergonadotropic hypogonadism and non-obstructive azoospermia when the patient reached his thirties, while the PAI remained controlled over the same period.

Conclusion
This case report provides, for the first time, direct evidence of complete germ line loss in an azoospermic man with NNT deficiency. Additional data further support the hypothesis of a determinant role of oxidative cellular damage due to reactive oxygen species (ROS) imbalance in the severe gonadal impairment observed in this NNT-deficient patient. Early and regular evaluation of gonadal function should be performed in patients with PAI, especially with NNT deficiency, as soon as the patients reach puberty. Fertility preservation options should then be provided in early adulthood for these patients.
Avoiding background knowledge: literature based discovery from important information
Authors: Preiss Judita 
Published: March 2023

AbstractBackgroundAutomatic literature based discovery attempts to uncover new knowledge by connecting existing facts: information extracted from existing publications in the form of$$A \rightarrow B$$A→Band$$B \rightarrow C$$B→Crelations can be simply connected to deduce$$A \rightarrow C$$A→C. However, using this approach, the quantity of proposed connections is often too vast to be useful. It can be reduced by using subject$$\rightarrow$$→(predicate)$$\rightarrow$$→object triples as the$$A \rightarrow B$$A→Brelations, but too many proposed connections remain for manual verification.ResultsBased on the hypothesis that only a small number of subject–predicate–object triples extracted from a publication represent the paper’s novel contribution(s), we explore using BERT embeddings to identify these before literature based discovery is performed utilizing only these, important, triples. While the method exploits the availability of full texts of publications in the CORD-19 dataset—making use of the fact that a novel contribution is likely to be mentioned in both an abstract and the body of a paper—to build a training set, the resulting tool can be applied to papers with only abstracts available. Candidate hidden knowledge pairs generated from unfiltered triples and those built from important triples only are compared using a variety of timeslicing gold standards.ConclusionsThe quantity of proposed knowledge pairs is reduced by a factor of$$10^3$$103, and we show that when the gold standard is designed to avoid rewarding background knowledge, the precision obtained increases up to a factor of 10. We argue that the gold standard needs to be carefully considered, and release as yet undiscovered candidate knowledge pairs based on important triples alongside this work.