bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impaired sensitivity to thyroid hormones and carotid plaque in patients with coronary heart disease: A RCSCD-TCM study in China
Authors: Liu Yijia , Li Zhu , Yang Tong , Li Lin , Yu Lu , Liu Fanfan , Ni Tongyao , Gao Shan , Li Chunjie , Yang Rongrong , Yu Chunquan 
Published: September 2022

ContextPrevious studies on the association between thyroid function and carotid plaque have shown contradictory results, which may be attributable to the sensitivity to thyroid hormone indices. This study aimed to analyze the association between thyroid hormone sensitivity and risk of carotid plaque in patients with coronary heart disease (CHD) and further explore this association according to sex, age, smoking, and drinking status.MethodsThis large-scale, multi-center, retrospective, cross-sectional study included 6679 patients with CHD (age 35–75). Central sensitivity to thyroid hormone was evaluated by the thyroid feedback quantile-based index (TFQI), parametric thyroid feedback quantile-based index (PTFQI), thyroid-stimulating hormone index (TSHI), and thyrotroph thyroxine resistance index (TT4RI). Peripheral sensitivity to thyroid hormone was assessed by free triiodothyronine/free thyroxine (FT3/FT4) ratio. Taking no carotid plaque as a reference, this study used logistic regression to analyze the association between central and peripheral thyroid hormone sensitivity and carotid plaque in patients with CHD.ResultsOf the 6679 patients with CHD, 4843 (72.50%) had carotid plaque. In the multi-adjusted models, the TFQI (odds ratio [OR]: 1.50; 95% confidence interval [CI]: 1.26–1.78; P &lt; 0.001), PTFQI (OR: 1.76; 95% CI: 1.46–2.12; P &lt; 0.001), TSHI (OR: 1.21; 95% CI: 1.10–1.33; P &lt; 0.001), and TT4RI (OR: 1.00; 95% CI: 1.00–1.01; P = 0.003) were positively associated with the risk of carotid plaque. Compared with that in females and people &gt; 60 years, the OR value for carotid plaque was higher in males and people ≤ 60 years. Similarly, smokers and drinkers had higher OR values for carotid plaque than non-smokers and non-drinkers. Conversely, FT3/FT4 ratio (OR: 0.75; 95% CI: 0.70–0.81; P &lt; 0.001) was negatively associated with carotid plaque, and the OR value for carotid plaque was lower in males, patients ≤ 60 years, smokers, and drinkers.ConclusionThis study showed that thyroid hormone sensitivity is significantly associated with carotid plaque in patients with CHD. This association is more significant in males, patients ≤ 60 years, smokers, and drinkers.
Time evolution of cytokine profiles associated with mortality in COVID-19 hospitalized patients
Authors: Sánchez-de Prada Laura , Gorgojo-Galindo Óscar , Fierro Inmaculada , Martínez-García Ana María , de Quintana Guillermo Sarmentero-López , Gutiérrez-Bustillo Rocío , Pelaez-Jareño María Teresa , Álvarez-Fuente Elisa , Gómez-Sánchez Esther , Tamayo Eduardo , Tamayo-Velasco Álvaro , Martín-Fernández Marta 
Published: September 2022

BackgroundHigh cytokine levels have been associated with severe COVID-19 disease. Although many cytokine studies have been performed, not many of them include combinatorial analysis of cytokine profiles through time. In this study we investigate the association of certain cytokine profiles and its evolution, and mortality in SARS-CoV2 infection in hospitalized patients.MethodsSerum concentration of 45 cytokines was determined in 28 controls at day of admission and in 108 patients with COVID-19 disease at first, third and sixth day of admission. A principal component analysis (PCA) was performed to characterize cytokine profiles through time associated with mortality and survival in hospitalized patients.ResultsAt day of admission non-survivors present significantly higher levels of IL-1α and VEGFA (PC3) but not through follow up. However, the combination of HGF, MCP-1, IL-18, eotaxine, and SCF (PC2) are significantly higher in non-survivors at all three time-points presenting an increased trend in this group through time. On the other hand, BDNF, IL-12 and IL-15 (PC1) are significantly reduced in non-survivors at all time points with a decreasing trend through time, though a protective factor. The combined mortality prediction accuracy of PC3 at day 1 and PC1 and PC2 at day 6 is 89.00% (p&lt;0.001).ConclusionsHypercytokinemia is a hallmark of COVID-19 but relevant differences between survivors and non-survivors can be early observed. Combinatorial analysis of serum cytokines and chemokines can contribute to mortality risk assessment and optimize therapeutic strategies. Three clusters of cytokines have been identified as independent markers or risk factors of COVID mortality.
Animal-borne video cameras reveal differences in northern fur seal foraging behavior related to prey size selection
Authors: Kuhn Carey E. , Sterling Jeremy T. , McCormley Molly , Birkemeier Burlyn , Sar Angel , Flock Audrey , Mordy Calvin W. 
Published: September 2022

A key aspect of foraging ecology research is understanding how predator foraging behavior and success are influenced by variation in prey resources. For northern fur seals (Callorhinus ursinus), an understanding of predator-prey relationships is critical to help identify potential causes for the unexplained population decline in Alaska. To examine how foraging behavior differs based on prey size selection, we equipped northern fur seals on St. Paul and St. George islands (Alaska, USA) in September (2017, n=6) and August (2018, n=4, and 2019, n=3) with satellite-linked dive recorders and animal-borne video cameras. We categorized prey capture attempts based on relative prey size (small vs. large) and examined differences in capture depth, time of day, water temperature, and depth relative to the mixed-layer. Successful prey captures (n= 2224) primarily occurred at night (89.7 ± 3.1%) and small prey accounted for the majority of captures (70.5 ± 13.2%), but there was significant variation among individuals. Large prey were captured at nearly twice the depth of small prey (42.9 ± 3.7 m and 23.1 ± 1.8 m, respectively) and the proportion of large prey caught during the day was 3 times higher than at night (0.77 ± 0.1 vs. 0.25 ± 0.1). There was no relationship between prey size and water temperature after we accounted for temperature changes with depth. The highest proportion of prey captures occurred below the mixed-layer depth regardless of prey size, but the proportion of small prey captures above mixed-layer depth was double that of large prey. This enhanced understanding of northern fur seal prey capture behavior will be pivotal for better interpretation of decades of historical dive and diet data and can provide insight into how northern fur seals may respond to future variation in prey resources, which is essential to develop ecosystem-based approaches for northern fur seal conservation.
Engineered electrospun poly(lactic-co-glycolic acid)/Si3N4 nanofiber scaffold promotes osteogenesis of mesenchymal stem cell
Authors: Zhou Changsong , Su Shenghui , Fan Jiwen , Lin Jiuzao , Wang Xiaoyong 
Published: September 2022

Nanofibers show promise as bone tissue engineering scaffolds (BTESs). In this study, electrospun poly (lactic-co-glycolic acid) (PLGA)/silicon nitride (Si3N4) composite nanofiber membranes were formed and the osteogenesis capability of mesenchymal stem cells (MSC) from the scaffold marrow was investigated. By modifying the different properties of Si3N4 in the PLGA, two hybrid scaffolds were successfully prepared, including the PLGA/Si3N4 (1 wt.%) nanofiber scaffold and PLGA/Si3N4 (2 wt.%) nanofiber scaffold. The diameter of the fiber nanofiber scaffold PLGA/Si3N4 was decreased and the mechanical strength was increased compared to PLGA. In vitro studies showed better cell adhesion and proliferation on the PLGA/Si3N4 nanofiber scaffold compared to the PLGA nanofiber scaffold. The integration of Si3N4 promoted osteogenesis capacity by increasing the gene expression of bone-related proteins (BMP2, ALP, OPN, COL1a1, Runx2, and OCN), calcium deposits, and support of ALP activity compared to those for the PLGA nanofiber scaffold. Similarly, the PLGA/Si3N4 (2 wt.%) nanofiber scaffold showed better mechanics and biological activity compared to the PLGA/Si3N4 (1 wt.%) nanofiber scaffold. Overall, the PLGA/Si3N4 nanofiber scaffold showed potential as a promising hybrid scaffold for bone regeneration.
Short-term blood pressure variability and outcomes in non-dialysis chronic kidney disease
Authors: Wang Ge , Ma Kai , Ma Zhilan , Guo Xiaoyan , Wang Yan , Ma Lan , Qi Chenchen , Li Yan , Zhou Xiaoling 
Published: September 2022

BackgroundBlood pressure variability (BPV) is associated with cardiovascular and all-cause mortality, and has been demonstrated in dialysis patients, but has been poorly studied and remains controversial in non-dialysis chronic kidney disease (CKD) patients. We investigated the effect of short-term BPV on prognosis in this population.MethodsA total of 245 stage 1–4 CKD patients with 24-h ambulatory blood pressure recordings were recruited. BPV was evaluated by standard deviation, coefficient of variation, and variation independent of the mean, respectively. All subjects were followed up to the composite end-point event or until January 15, 2020. Patients were divided into two groups based on 24-h median variation independent of the mean, and demographics, laboratory indicators and echocardiogram results were compared. Logistic regression was used to analyze the risk factors for increased BPV. Multivariate Cox regression and Kaplan-Meier survival analysis were used to explore the relationship between BPV and renal prognosis and major cardiovascular events.ResultsThe mean age was 42.07 ± 12.66 years, with 141 males (57.55%). Multivariate Logistic regression analysis showed that high BMI (OR 1.110, P = 0.017), hyperkalemia (OR 2.227, P = 0.040), increased left ventricular end-diastolic diameter (OR 1.103, P = 0.010) and hypertension (OR 2.525, P = 0.002) were independent risk factors for high BPV. Kaplan-Meier survival analysis showed that renal and cardiovascular outcomes were better in the low BPV group than in the high BPV group (P = 0.006; P = 0.002). After adjusting for age, sex and traditional kidney related risk factors, BPV were not independently associated with renal outcomes. High BPV (HR 4.662, P = 0.017) was the main independent risk factor for major cardiovascular events in CKD.ConclusionsIn non-dialysis CKD, short-term BPV was associated with major cardiovascular disease but not renal progression. BMI, hypertension, potassium balance, and left ventricular end-diastolic diameter influenced short-term BPV.
Self-supervised learning mechanism for identification of eyelid malignant melanoma in pathologic slides with limited annotation
Authors: Wang Linyan , Jiang Zijing , Shao An , Liu Zhengyun , Gu Renshu , Ge Ruiquan , Jia Gangyong , Wang Yaqi , Ye Juan 
Published: September 2022

PurposeThe lack of finely annotated pathologic data has limited the application of deep learning systems (DLS) to the automated interpretation of pathologic slides. Therefore, this study develops a robust self-supervised learning (SSL) pathology diagnostic system to automatically detect malignant melanoma (MM) in the eyelid with limited annotation.DesignDevelopment of a self-supervised diagnosis pipeline based on a public dataset, then refined and tested on a private, real-world clinical dataset.SubjectsA. Patchcamelyon (PCam)-a publicly accessible dataset for the classification task of patch-level histopathologic images. B. The Second Affiliated Hospital, Zhejiang University School of Medicine (ZJU-2) dataset – 524,307 patches (small sections cut from pathologic slide images) from 192 H&amp;E-stained whole-slide-images (WSIs); only 72 WSIs were labeled by pathologists.MethodsPatchcamelyon was used to select a convolutional neural network (CNN) as the backbone for our SSL-based model. This model was further developed in the ZJU-2 dataset for patch-level classification with both labeled and unlabeled images to test its diagnosis ability. Then the algorithm retrieved information based on patch-level prediction to generate WSI-level classification results using random forest. A heatmap was computed for visualizing the decision-making process.Main outcome measure(s)The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity were used to evaluate the performance of the algorithm in identifying MM.ResultsResNet50 was selected as the backbone of the SSL-based model using the PCam dataset. This algorithm then achieved an AUC of 0.981 with an accuracy, sensitivity, and specificity of 90.9, 85.2, and 96.3% for the patch-level classification of the ZJU-2 dataset. For WSI-level diagnosis, the AUC, accuracy, sensitivity, and specificity were 0.974, 93.8%, 75.0%, and 100%, separately. For every WSI, a heatmap was generated based on the malignancy probability.ConclusionOur diagnostic system, which is based on SSL and trained with a dataset of limited annotation, can automatically identify MM in pathologic slides and highlight MM areas in WSIs by a probabilistic heatmap. In addition, this labor-saving and cost-efficient model has the potential to be refined to help diagnose other ophthalmic and non-ophthalmic malignancies.
Small extracellular vesicles as a multicomponent biomarker platform in urinary tract carcinomas
Authors: K Szeliski , T Drewa , M Pokrywczyńska 
Published: September 2022

Extracellular vesicles are a large group of nano-sized vesicles released by all cells. The variety of possible cargo (mRNAs, miRNAs, lncRNAs, proteins, and lipids) and the presence of surface proteins, signaling molecules, and receptor ligands make them a rich source of biomarkers for malignancy diagnosis. One of the groups gathering the most interest in cancer diagnostic applications is small extracellular vesicles (sEVs), with ≤200 nm diameter, mainly composed of exosomes. Many studies were conducted recently, evaluating the diagnostic potential of sEVs in urinary tract carcinomas (UTCs), discovering and clinically evaluating various classes of biomarkers. The amount of research concerning different types of UTCs understandably reflects their incidence. sEV cargos getting the most interest are non-coding RNAs (miRNA and lncRNA). However, implementation of other approaches such as metabolomic and proteomic analysis is also evaluated. The results of many studies indicate that sEVs have an essential role in the cancer process and possess many possible diagnostic and prognostic applications for UTC. The relative ease of obtaining biofluids rich in sEVs (urine and blood) confirms that sEVs are essential for UTC detection in the liquid biopsy approach. A noticeable rise in research quality is observed as more researchers are aware of the research standardization necessity, which is essential for considering the clinical application of their findings.
Immunotherapy with corticosteroids in anti-neural autoantibody-associated cognitive impairment: Retrospective case series
Authors: Hansen Niels , Hirschel Sina , Rentzsch Kristin , Wiltfang Jens , Malchow Berend , Fitzner Dirk 
Published: September 2022

BackgroundAnti-neural autoantibody-associated cognitive impairment is an increasing phenomenon in memory clinics deserving more attention to applying immunotherapy such as methylprednisolone to improve cognition. Our study aims to investigate the usefulness of intravenous high-dosage corticosteroids in a small cohort of patients suffering from anti-neural autoantibody-associated cognitive impairment.Materials and methodsWe included in our retrospective case series seven patients presenting diverse neural autoantibodies and cognitive impairments varying from a mild impairment to dementia. We conducted neuropsychological and psychopathological investigations before and after the application of high intravenous methylprednisolone therapy over a 6-month period. Neuropsychological function was assessed by the CERAD (Consortium to Establish a Registry for Alzheimer’s Disease) test battery. Patients were also characterized by assessing their patient files for demographic and clinical data.ResultsThe patients’ cognitive subdomains did not improve according to CERAD in their z-scores before and after immunotherapy. We noted a non-significant trend toward an improvement in semantic fluency and verbal memory consolidation. Patients did not do worse in 4 of 12 (33%) cognitive subdomains in the CERAD test battery. Furthermore, mood dysfunction lessened as a non-significant trend in specific psychopathological features such as reduced affective symptoms, loss of drive, and ruminations. Affective symptoms, loss of drive and ruminations were reduced by 43% after immunotherapy.DiscussionOur small pilot study revealed no relevant alleviation of cognitive dysfunction in patients with neural autoantibodies. However, mood dysfunction became less obvious in specific functions concerning affect, drive, and rumination. However, we do not know whether methylprednisolone affects mood dysfunction, as some patients were taking antidepressant drugs at the same time. Our results might indicate that methylprednisolone immunotherapy is associated with impeding the progression of cognitive dysfunction and reducing mood dysfunction. Further large-scale, placebo-controlled studies in a more homogeneous patient population presenting a uniform pattern of neural autoantibodies should be undertaken.
Weakly activated core neuroinflammation pathways were identified as a central signaling mechanism contributing to the chronic neurodegeneration in Alzheimer’s disease
Authors: Li Fuhai , Eteleeb Abdallah M. , Buchser William , Sohn Christopher , Wang Guoqiao , Xiong Chengjie , Payne Philip R. , McDade Eric , Karch Celeste M. , Harari Oscar , Cruchaga Carlos 
Published: September 2022

ObjectivesNeuroinflammation signaling has been identified as an important hallmark of Alzheimer’s disease (AD) in addition to amyloid β plaques (Aβ) and neurofibrillary tangles (NFTs). However, the molecular mechanisms and biological processes of neuroinflammation remain unclear and have not well delineated using transcriptomics data available. Our objectives are to uncover the core neuroinflammation signaling pathways in AD using integrative network analysis on the transcriptomics data.Materials and methodsFrom a novel perspective, i.e., investigating weakly activated molecular signals (rather than the strongly activated molecular signals), we developed integrative and systems biology network analysis to uncover potential core neuroinflammation signaling targets and pathways in AD using the two large-scale transcriptomics datasets, i.e., Mayo Clinic (77 controls and 81 AD samples) and ROSMAP (97 controls and 260 AD samples).ResultsOur analysis identified interesting core neuroinflammation signaling pathways, which are not systematically reported in the previous studies of AD. Specifically, we identified 7 categories of signaling pathways implicated on AD and related to virus infection: immune response, x-core signaling, apoptosis, lipid dysfunctional, biosynthesis and metabolism, and mineral absorption signaling pathways. More interestingly, most of the genes in the virus infection, immune response, and x-core signaling pathways are associated with inflammation molecular functions. The x-core signaling pathways were defined as a group of 9 signaling proteins: MAPK, Rap1, NF-kappa B, HIF-1, PI3K-Akt, Wnt, TGF-beta, Hippo, and TNF, which indicated the core neuroinflammation signaling pathways responding to the low-level and weakly activated inflammation and hypoxia and leading to the chronic neurodegeneration. It is interesting to investigate the detailed signaling cascades of these weakly activated neuroinflammation signaling pathways causing neurodegeneration in a chronic process, and consequently uncover novel therapeutic targets for effective AD treatment and prevention.ConclusionsThe potential core neuroinflammation and associated signaling targets and pathways were identified using integrative network analysis on two large-scale transcriptomics datasets of AD.
Systemic immune inflammatory index is an independent predictor for the requirement of decompressive craniectomy in large artery occlusion acute ischemic stroke patients after mechanical thrombectomy
Authors: Li Wen-Cai , Zhou Yun-Xiang , Zhu Gang , Zeng Kai-Liang , Zeng Hai-Yong , Chen Jian-Sheng , Deng Yi-Fan , Qin Zhong-Zong , Luo Hong-Hai 
Published: September 2022

Background and purposeFollowing mechanical thrombectomy (MT), patients with large artery occlusive acute ischemic stroke (LAO-AIS) often have cerebral herniation due to its complications, resulting in poor prognosis. Decompressive craniectomy (DC) can markedly improve patient prognosis. This study aimed to verify the predictive value of clinical parameters such as the systemic immune-inflammatory index (SII) for DC in patients with LAO-AIS after MT.MethodsClinical data of a total of 173 patients with LAO-AIS treated with MT between January 2020 and January 2022 were retrospectively analyzed. Patients receiving DC were grouped into an experimental group or a control group (no DC). The patients were randomly divided into the training set (n = 126, 75%) and validation set (n = 43, 25%). Multivariate logistic regression was used to construct a nomogram predictive model.ResultsThe SII value in the experimental group (median: 2851.1×109/L) was significantly higher than that in the control group (median: 1898.6 × 109/L) (P = 0.019). Receiver operating characteristic (ROC) analyses showed that the best cutoff value of the SII was 2505.7 × 109/L with a sensitivity of 55%, a specificity of 75.8%, and an area under the curve (AUC) of 0.649. Multivariate logistic regression indicated that the SII was an independent predictor for performing DC in patients with LAO-AIS after MT (OR = 3.579, 95% CI = 1.360–9.422, P = 0.01). The AUC was 0.728 in the training set and 0.583 in the validation set. The average error of the calibration curve was 0.032 in the training set and 0.023 in the validation set. The average error was relatively small and consistent in the training set and validation set. The C-index of the nomogram was 0.804 suggesting good accuracy.ConclusionsThe SII at admission is an independent predictor for the requirement of DC in patients with LAO-AIS after MT. The SII-based nomogram helps doctors make decisions on whether DC is needed timely and rationally, and thereby may improve the prognosis of these patients.