bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal Genome-wide Association Study of Cognitive Impairment After Subarachnoid Hemorrhage: A Long-term Prospective Cohort Study
Authors: Hong Eun Pyo , Youn Dong Hyuk , Rhim Jong Kook , Park Jeong Jin , Jeon Jin Pyeong 
Published: May 2022

Abstract
Cognitive defection after subarachnoid hemorrhage (SAH) is highly possible to lead a vascular dementia. We performed a longitudinal genome-wide association study (GWAS) for the first time to identify genetic modifications associated with cognitive impairment following SAH in a long-term prospective cohort study. This GWAS involved 153 patients with SAH sharing 5,971,372 markers proceed after the genotype-imputation by the GenomeAsia 100K reference panel. Cox-proportional hazard regression and survival analyses were performed to estimate the hazard ratio (HR) and 95% confidence intervals (CI). Subsequently, a weighted polygenetic risk score (wPRS) was determined based on GWAS-driven loci and risk stratification. Cognitive impairment was observed in 65 patients (42.5%) during a mean follow-up of 37.7 ± 12.4 months. Five novel genome-wide signals including rs138753053 (PDCD6IP-LOC101928135, HR = 28.33, p = 3.4×10− 8), rs56823384 (LINC00499, HR = 12.47, p = 2.8×10− 9), rs145397166 (CASC15, HR = 11.16, p = 1.7×10− 8), rs10503670 (LPL-SLC18A1, HR = 2.88, p = 4.0×10− 8), and rs76507772 (IRS2, HR = 5.99, p = 3.5×10− 8) were significantly associated with cognitive impairment following SAH. After adjusting for clinical covariates, their association was still statistically significant. Among them, the IRS2 region formed the strongest linkage disequilibrium block, tagging five markers (Approximately r2 = 1). The wPRS based on the five markers showed nominal ability to predict cognitive impairment (AUROC = 0.745, 95% CI: 0.667–0.824). Tertile stratification was effective in predicting cognitive impairment especially in those with apolipoprotein ɛ3/ɛ3 (HR = 26.32, 95% CI: 9.95–69.67) and haptoglobin 2 − 1 (HR = 44.59, 95% CI: 8.61–231.08). Our study revealed novel susceptible loci for cognitive impairment that were longitudinally measured in patients with SAH. The clinical usefulness of the loci needs to be confirmed through follow-up studies.
An Unusual Presentation of Superior Mesenteric Venous Occlusion in Mild COVID-19
Authors: Batra Sakshi , Nair Asha G , Syal Kirtimaan 
Published: May 2022

Abstract
SARS-CoV-2, an etiological agent of COVID-19, has been reported to inflict remarkably diverse manifestations in different subjects across the globe. Though patients with COVID-19 predominantly have fever, respiratory and constitutional symptoms, atypical presentations are becoming increasingly evident. COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilization, and diffuse intravascular coagulation in moderate to severe symptomatic cases. In this case report, we are reporting thromboembolic complications of COVID-19 in a mild symptomatic subject incidentally diagnosed with mesenteric venous occlusion with no abdominal symptoms. Early recognition of the abdominal symptoms, diagnosis, initiation of anticoagulants, and timely surgical intervention may improvise the outcome in a patient with COVID-19 Infection-induced mesenteric thrombosis. Superior mesenteric artery and venous thrombosis may lead to subsequent ischemia necessitating emergency laparotomy. Thus, the usage of low-dose anticoagulants in all the patients of COVID-19 irrespective of the categorization into mild, moderate, and severe COVID-19 disease should be considered.
Noradrenaline induced PKC and PKA mediated translocation of Na-K ATPase α1-subunit to the plasma membrane in Neuro-2a cells
Authors: Kaur Manjeet , Mehta Rachna , Muthuswami Rohini , Mallick Birendra 
Published: May 2022

Abstract
Rapid Eye Movement Sleep (REM) maintains brain excitability by modulating the brain Na-K ATPase activity. Earlier, It was reported that REMS deprivation (REMSD) associated elevated NA increases the expression of Na-K ATPase subunit as well as its enzyme activity and that is likely to be the cause of REMSD associated increased brain excitability. The Na-K ATPase is a transmembrane protein present on the cell membrane surface as well as in many organelle membranes. To be responsible for increased excitability, the α1 subunit of the Na-K ATPase must be expressed on the outer surface of the neuronal membrane, which has been confirmed in this study. We used cell impermeable Enz-link-sulfo-NHS-SS biotin that exclusively labels external surface proteins. In this study, we have shown using the Neuro2a cell line that NA (50 µM) increased Na-K ATPase α1 protein abundance on the cell surface by acting on α1- as well as β-ARs (AR). It was also observed that Chelerythrine chloride (CC) or KT570, inhibitor of PKC and PKA, respectively blocked the effects. The results not only confirm our previous findings, but they offer molecular level explanations that REMSD-associated elevated NA acting on α- and β-AR increased Na-K ATPase α1 protein expression as well as its translocation on the neuronal membrane through PKC and PKA dependent process.
X, but not Y, chromosomal complement contributes to stroke sensitivity in aged animals
Authors: Qi Shaohua , Ngwa Conelius , Mamun Abdullah Al , Romana Sharmeen , Wu Ting , Marrelli Sean P. , Arnold Arthur P. , McCullough Louise D. , Liu Fudong 
Published: May 2022

Abstract
Post-menopausal women become vulnerable to stroke and have poorer outcomes and higher mortality than age-matched men and previous studies suggested that sex chromosomes play a vital role in mediating stroke sensitivity in the aged. It is unknown if this is due to effects of the X or Y chromosome. The present study used the XY* mice model (with four genotypes: XX and XO gonadal females, and XY and XXY gonadal males) to compare the effect of the X vs. Y chromosome compliment in stroke. Aged (18-20 months) and gonadectomized young (8-12 weeks) mice were subjected to a 60-min middle cerebral artery occlusion. Infarct volume and behavioral deficits were quantified 3 days after stroke. Microglia activation and infiltration of peripheral leukocytes in the aged ischemic brain were assessed by flow cytometry. Plasma inflammatory cytokine levels by ELISA and brain expression of two X chromosome linked genes, KDM6A and KDM5C by immunochemistry, were also examined. Both aged and young XX and XXY mice had worse stroke outcomes compared to XO and XY mice respectively; however, difference between XX vs. XXY or XO vs. XY aged mice was minimal. Mice with two copies of the X chromosome showed more robust microglial activation, higher brain infiltrating leukocytes, elevated plasma cytokine levels, and enhanced colocalization of KDM6A and KDM5C with Iba-1+ cells after stroke than mice with one X. The number of X chromosomes mediates stroke sensitivity in aged mice, which might be processed through the X chromosome linked genes and the inflammatory responses.
Segmentation of Acute Pulmonary Embolism in Computed Tomography Pulmonary Angiography Using the Deep Learning Method
Authors: Aydin Nevin , Cihan Çağatay , Celik Ozer , Aslan Ahmet Faruk , Odabas Alper , Alatas Füsun , Yıldırım Hüseyin 
Published: May 2022

Abstract
Background
Pulmonary embolism is a type of thromboembolism seen in the main pulmonary artery and its branches. This study aimed to diagnose acute pulmonary embolism using the deep learning method in computed tomographic pulmonary angiography (CTPA) and perform the segmentation of pulmonary embolism data.
Methods
The CTPA images of patients diagnosed with pulmonary embolism who underwent scheduled imaging were retrospectively evaluated. After data collection, the areas that were diagnosed as embolism in the axial section images were segmented. The dataset was divided into three parts as training, validation, and testing. The results were calculated by selecting 50% as the cut-off value for the intersection over union.
Results
Images were obtained from 1,550 patients. The mean age of the patients was 64.23 ± 15.45 years. A total of 2,339 axial computed tomography images obtained from the 1,550 patients were used. There were a total of 5,992 labels, with 1,879 images. PyTorch U-Net was used to train 400 epochs, and the best model, epoch 178, was recorded. In the testing group, the number of true positives was determined as 471 and false positives as 35, while 27 were not detected. The sensitivity of CTPA segmentation was 0.95, the precision value was 0.93, the F1 score value was 0.94, and the learning rate was 0.0001. The area under the curve value obtained in the receiver operating characteristic analysis was calculated as 0.88.
Conclusions
In this study, the segmentation of acute pulmonary embolism in CTPA performed using the deep learning method provided successful results.
Prior Employment Status and Obesity Do Not Predict Post-Stroke Fatigue
Authors: Cooper Zachary , Gilles Nadege , Levine Steven R. 
Published: May 2022

Abstract

Introduction: Post-stroke fatigue (PSF) is a common emotionally, cognitive, and physically debilitating condition following a stroke. The prevalence of PSF is between 38 – 74% of patients who have a stroke. There is a lack of understanding of the risk factors or predictors of PSF, including prior employment status and obesity. Methods: One hundred and twenty-one patients with a confirmed diagnosis of ischemic stroke in the past three years were enrolled into the study. Exclusion criteria included: severe aphasia and end stage concomitant diseases. PSF was assessed using the Fatigue Assessment Scale (FAS) (FAS: no fatigue ≤ 21, fatigue 22–50). Patients were then identified based on their employment status (previously worked) or obesity (BMI) and compared to the presence of PSF. Logistic regression analysis was used to predict dichotomized FAS score. Results: Of the 52 patients who were obese, 21 experienced PSF (40%), while 31 did not experience PSF (60%). Of the patients who were not obese (69), 27 experienced PSF (39%), while 42 did not experience PSF (61%). A Fisher’s exact test was applied to determine the association between PSF and obesity (p=1.000). A Fisher’s exact test was applied to show the association between PSF and employment status (p=0.384). 92 patients had previously worked (76%) and 29 had never worked (24%). Of the 92 patients who previously worked, 39 experienced PSF (42%), while 53 did not experience PSF (58%). Of the patients who never worked (29), 9 experienced PSF (31%), while 20 did not experience PSF (69%). In logistic regression, employment status did not independently predict dichotomized FAS (adjusted odds ratio 1.34, 95% confidence interval [ 0.51, 3.50 ], p=0.557). Conclusions: Previous employment status and obesity did not independently predict PSF in an urban, minority cohort.
Mid- to long-term cardiac magnetic resonance findings in elite athletes recovered from COVID-19 - results from one German Olympic medical center
Authors: Schneeweis Christopher , Diebold Katharina , Schramm Thomas , Syrek Christine , Predel Hans-Georg , Manka Robert , Zacher Jonas 
Published: May 2022

Abstract
Background There is a lack of cardiac magnetic resonance (CMR) data regarding mid- to long-term myocardial damage due to Covid-19 in elite athletes. Objective This study investigated mid-to long-term consequences of myocardial involvement after a Covid-19 infection in elite athletes. Methods Between January 2020 and October 2021, 27 athletes of the German Olympic centre Rhineland with confirmed Covid-19 infection were analyzed. 9 healthy non-athlete volunteers served as control. CMR was performed in mean 182 days (SD 99) after initial positive test result. Results CMR did not reveal any signs of acute myocarditis in regard to the current Lake Louise criteria or myocardial damage in any of the 26 elite athletes with previous Covid-19 infection. Nevertheless, 92 % of the athletes experienced a symptomatic course and 54 % reported lasting symptoms for more than 4 weeks. In one male athlete CMR revealed an arrhythmogenic right ventricular cardiomyopathy (ARVC) and this athlete was excluded from the study. Athletes had significantly enlarged left and right ventricle volumes and increased left ventricular myocardial mass in comparison to the healthy control group (LVEDVi 103.4 vs. 91.1 ml/m 2 p=0.031; RVEDVi 104.1 vs. 86.6 ml/m 2 p=0.007; and LVMi 59.0 vs. 46.2 g/m 2 p=0.002). Conclusion Our findings suggest that the risk for mid-to long-term myocardial damage seems to be very low to negligible in elite athletes. No conclusions can be drawn regarding myocardial injury in the acute phase of infection nor about possible long-term myocardial effects in the general population.
Retrospective cohort study of the effectiveness of the Sputnik V and EpiVacCorona vaccines against the SARS-CoV-2 Delta variant in Moscow (June-July 2021)
Authors: Matveeva Olga , Ershov Alexander 
Published: May 2022

Abstract
Objective.
The goal of the study was to evaluate the epidemiological effectiveness of the Sputnik V and EpiVacCorona vaccines against COVID-19.
Method.
This work is a retrospective cohort study of COVID-19 patients. The cohort created by the Moscow Health Department included more than 300,000 infected people who sought medical care in June and July 2021.
Results.
Analysis of data revealed a tendency for the increase in the Sputnik V vaccine effectiveness (VE) as the severity of the disease increased. Protection was the lowest for mild disease, and it was more pronounced for severe disease. We also observed a decrease in VE with increasing age. For the youngest group (18–50 years old), the estimated VE in preventing death in June 2021 was 95% (95% CI 64–100), and for the older group (50 + years old), it was 74% (95% CI 67–87). The estimated protection against a severe form of the disease in the 18-50-year-old group was above 81% (CI 95% 72–93), and in the 50 + years-old group, it was above 68% (CI 95% 65–82). According to our analysis, EpiVacCorona proved to be an ineffective vaccine and therefore cannot protect against COVID-19.
Non-linear Model-based Control of Neural Cell Dynamics
Authors: Yue Rongting , Tomastik Ryan , Dutta Abhishek 
Published: May 2022

Abstract
The human brain consists of 100 billion neurons connected to each other with synapses, with more than 10 thousand of them per neuron. When a neuron reaches a threshold voltage, due to the summation of currents flowing in from synapses or by external stimulation, the neuron fires with an action potential, observed as a voltage spike. It is this nonlinear firing behavior together with firing rate that gives rise to synaptic plasticity and forms the basis of memory, perception, action, and behavior. A perturbed firing of the underlying neuron can therefore evolve into undesirable mental states linked to various neurological disorders. Closed-loop control of the firing rate of the neuron is thus desirable, but very challenging due to the underlying highly nonlinear dynamics. A Hodgkin-Huxley model of the nonlinear neural dynamics in terms of its membrane potential with respect to current stimulation is developed together with its underlying ion channel dynamics in terms of gating variables. The model is linearized at operating point and lead, lag and lead-lag compensators are synthesized. Next, a dynamic inversion nonlinear controller, a robust incremental dynamic inversion controller, and a model predictive controller are derived to directly regulate the nonlinear neuron dynamics in terms of controlled firing. The synthesis of lead, lag, lead-lag, dynamic inversion, model predictive control-based feedback controllers over the nonlinear dynamics of the neuron led to controlled firing and a fast response that was robust to stochastic synaptic noise.
Reflexões sobre as legislações e práticas de proteção social no Brasil e em Portugal para o enfrentamento à violência contra meninas (crianças e adolescentes) de 2000 a 2015
Authors: Barros Nivia Valença , Freitas Rita de Cássia Santos , Barros Maria Izabel Valença 
Published: May 2022

Reflete-se sobre as práticas de proteção social e a legislação brasileira e portuguesa, no que tange ao enfrentamento a violência contra meninas (crianças e adolescentes), nos primeiros anos do século XXI (2000– 2015). Ao analisar tais ações destacamos o caráter sexista e excludente, ainda presentes, sem, contudo, menosprezar,os avanços obtidos para este segmento social pós-redemocratização do Brasil nos anos de 1990, e em Portugal, pós 25 de abril de 1974. Para apresentar tal temática efetuamos uma análise das legislaçõesque foram desenvolvidas neste período e as focalizamos como resultante de pressões de movimentos sociais e como uma importante forma de enfrentamento a violência contra meninas. E, neste mesmo sentido destacamos algumas das ações de proteção social realizadas no período como um elemento fundamental para o combate a tais violências e, em especial, destacamos as ações e articulações do movimento feminista em ambos os países.
Role of Biological Mediators of Tumor-Associated Macrophages in
Breast Cancer Progression
Authors: Li Yan , Ganesan Kumar , Chen Jianping 
Published: May 2022

Background:
Breast cancer (BRCA) has become the most common cancer
worldwide. The tumor microenvironment (TME) in the breast exerts a crucial role in promoting
BRCA initiation, progression, and metastasis. Tumor-associated macrophages
(TAMs) are the primary component of tumor-infiltrating immune cells through biological
mediators that convert TME into malignant tumors. Combinations of these biological
mediators can promote tumor growth, metastasis, angiogenesis, and immune suppression
and limit the anti-tumor activity of conventional chemotherapy and radiotherapy.

Objectives:
The present study aimed to highlight the functions of several biological mediators
in the breast thatgenerate TME into malignant tumors. Furthermore, this review offers
a rationale for TAM-targeted therapy as a novel treatment strategy for BRCA

Results:
This review emphasizes TAM-associated biological mediators of TME, viz., cancer-
associated fibroblasts, endothelial cells, adipocytes, tumor-derived exosomes, extracellular
matrix, and other immune cells, which facilitate TME in malignant tumors. Evidence
suggests that the increased infiltration of TAMs and elevated expression of TAMrelated
genes are associated with a poor prognosis of BRCA. Based on these findings,
TAM-targeted therapeutic strategies, including inhibitors of CSF-1/CSF-1R, CCL2/CCR2,
CCL5-CCR5, bisphosphonate, nanoparticle, and exosomal-targeted delivery have
been developed, and are currently being employed in intervention trials.

Conclusion:
This review concludes the roles of biological mediators of TME that interact
with TAMs in BRCA, providing a rationale for TAM-targeted therapy as a novel
treatment approach for BRCA.
A Review on an Artificial Intelligence Based Ophthalmic Application
Authors: Kothandan Sudhakar , Radhakrishnan Arun , Kuppusamy Gowthamarajan 
Published: May 2022

Abstract:
Artificial intelligence is the leading branch of technology and innovation. The utility of artificial intelligence
in the field of medicine is also remarkable. From drug discovery and development to introducing
products to the market, artificial intelligence can play its role. As people age, they are more prone to be affected
by eye diseases around the globe. Early diagnosis and detection help minimize the risk of vision loss and
provide a quality life. With the help of artificial intelligence, the workload of humans and manmade errors can
be reduced to an extent. The need for artificial intelligence in the area of ophthalmic is also significant. In this
review, we elaborated on the use of artificial intelligence in the field of pharmaceutical product development,
mainly with its application in ophthalmic care. AI in the future has a high potential to increase the success rate
in the drug discovery phase has already been established. The application of artificial intelligence for drug
development, diagnosis, and treatment is also reported with the scientific evidence in this paper.
Effects of Musk Volatile Compounds on Attenuated Nerve Injury and Improving
Post-cerebral Ischemic Exercise Functions
Authors: Wang Dan , Zhang Meng-Meng , Wu Chun-Jie , Liang Qi , Wei Da-Neng , He Lin , Ye Xun 
Published: May 2022

Background:
Reperfusion Injury Acute ischemic stroke is increasing in people recently and Musk, as a commonly used Traditional Chinese Medicine (TCM), has been suggested as a potential agent against acute ischemic stroke, but the efficacies and underlying mechanisms of it remain unknown.

Objective:
This study was aimed to tested the hypotheses that volatile compounds of musk could attenuate nerve injury and identify the bioactive compounds and potential mechanisms of Musk.

Method:
Transient middle cerebral artery occlusion (MCAO) model in vivo in Sprague-Dawley rats (SD rats) was used to test this hypothesis. Collecting ingredients of Musk and their related targets were discerned from the Gas chromatography-olfactory mass spectrometry (GC-O-MS) experiment. Then the potential mechanisms and targets of the compounds were searched by network pharmacology techniques. Finally, the pathway was verified by Western Bolt (WB).

Results:
First, Musk treatment significantly up-regulated the relative levels of AKT1, PI3KA, and VEGFA in the hippocampus, and improved the sport functions in the post-MCAO ischemic rats in vivo. Next, twenty potential flavor active compounds were recognized by GC-O-MS. A total of 89 key targets including HIF-1, PIK3CA, TNF signaling pathway, and VEGF were identified. AKT1, HIF1A, PIK3CA, and VEGFA were viewed as the most important genes, which were validated by molecular docking simulation.

Conclusion:
The Volatile compounds of musk can attenuate nerve injury and improving post-cerebral ischemic exercise functions by HIF1A pathways, and the combined data provide novel insight for Musk volatile compounds developed as new drug for improving reperfusion injury in acute ischemic stroke.
N-acetyl Cysteine Inhibits Cell Proliferation and Differentiation of LPSInduced MC3T3-E1 Cells Via Regulating Inflammatory Cytokines
Authors: Guo Ling , Li Wangyang , Zhang Hui , Chen Junchi , Tan Yujie , Li Ailing 
Published: May 2022

Background:Peri-implantitis is one of the most common complications in oral implantation and could lead to the loss of the function of bone tissues around implants.Methods:This study used lipopolysaccharide (LPS) as a stimulant for MC3T3-E1 cells and N-acetyl cysteine (NAC) as an inhibitor to inhibit the effect of LPS to investigate the effect of NAC on the expression of bone formation related factors and inflammatory related factors of osteoblasts under the action of LPS.Results:In this study, we found that the cell proliferation and cell differentiation were significantly promoted when NAC concentrations were between 0 ~ 0.5 mM, but was inhibited when the concentration exceeded 0.5 mM. LPS had a slightly promoting effect on the cell proliferation before 20 μg /mL but inhibited the cell proliferation after 20 μg/mL. LPS reduced protein and gene expressions of Runx2, ALP and BGP and increased protein and gene expressions of NF-κB and TNF-α. NAC reversibly regulated the LPS’s regulation on the expression of MC3T3-E1 cell cytokine gene and protein.Conclusion:The optimal NAC concentration for treating MC3T3-E1 cells is 0.5 mM and the optimal LPS concentration for stimulating MC3T3-E1 cells is 20 μg/mL. NAC plays an active role in regulating the differentiation of MC3T3-E1 cells, and can inhibit LPS to regulate the differentiation of MC3T3-E1 cells. NAC promotes the expression of osteogenic factor of MC3T3-E1cells and inhibits the expression of inflammatory cytokines.