bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experimental Myocardial Infarction Elicits Time-Dependent Patterns of Vascular Hypoxia in Peripheral Organs and in the Brain
Authors: David Hélène , Ughetto Aurore , Gaudard Philippe , Plawecki Maëlle , Paiyabhroma Nitchawat , Zub Emma , Colson Pascal , Richard Sylvain , Marchi Nicola , Sicard Pierre 
Published: January 2021

Aims: Microvascular alterations occurring after myocardial infarction (MI) may represent a risk factor for multi-organ failure. Here we used in vivo photoacoustic (PA) imaging to track and define the changes in vascular oxygen saturation (sO2) occurring over time after experimental MI in multiple peripheral organs and in the brain.Methods and Results: Experimental MI was obtained in BALB/c mice by permanent ligation of the left anterior descending artery. PA imaging (Vevo LAZR-X) allowed tracking mouse-specific sO2 kinetics in the cardiac left ventricular (LV) anterior wall, brain, kidney, and liver at 4 h, 1 day, and 7 days post-MI. Here we reported a correlation between LV sO2 and longitudinal anterior myocardial strain after MI (r = −0.44, p &lt; 0.0001, n = 96). Acute LV dysfunction was associated with global hypoxia, specifically a decrease in sO2 level in the brain (−5.9%), kidney (−6.4%), and liver (−7.3%) at 4 and 24 h post-MI. Concomitantly, a preliminary examination of capillary NG2DsRed pericytes indicated cell rarefication in the heart and kidney. While the cardiac tissue was persistently impacted, sO2 levels returned to pre-MI levels in the brain and in peripheral organs 7 days after MI.Conclusions: Collectively, our data indicate that experimental MI elicits precise trajectories of vascular hypoxia in peripheral organs and in the brain. PA imaging enabled the synchronous tracking of oxygenation in multiple organs and occurring post-MI, potentially enabling a translational diagnostic modality for the identification of vascular modifications in this disease setting.
Maternal Smoking Leads to Larger Cleft Palate Defects
Authors: Lacerda Rosa Helena Wanderley , Furtado Paulo Germano Cavalcanti , Vieira Alexandre Rezende 
Published: January 2021

Background: Oral clefts are birth defects that affect 500–1,000 livebirths depending on the geographic area. Maternal smoking increases the risk of stillbirths, prematurity, low birth weight, and oral clefts.Methods: In this case series, we measured the cleft palate defect of 10 children born from mothers who smoked during pregnancy and compared with measurements of 36 children born from mothers who did not smoke.Results: Palate defects tended to be larger in the group that the mother smoked during pregnancy.Conclusion: Smoking during pregnancy aggravates the size of the cleft defect in the palate.
Identification of Key Modules and Hub Genes of Annulus Fibrosus in Intervertebral Disc Degeneration
Authors: Wang Hantao , Liu Wenhui , Yu Bo , Yu Xiaosheng , Chen Bin 
Published: January 2021

Background: Intervertebral disc degeneration impairs the quality of patients lives. Even though there has been development of many therapeutic strategies, most of them remain unsatisfactory due to the limited understanding of the mechanisms that underlie the intervertebral disc degeneration.Questions/purposes: This study is meant to identify the key modules and hub genes related to the annulus fibrosus in intervertebral disc degeneration (IDD) through: (1) constructing a weighted gene co-expression network; (2) identifying key modules and hub genes; (3) verifying the relationships of key modules and hub genes with IDD; and (4) confirming the expression pattern of hub genes in clinical samples.Methods: The Gene Expression Omnibus provided 24 sets of annulus fibrosus microarray data. Differentially expressed genes between the annulus fibrosus of degenerative and non-degenerative intervertebral disc samples have gone through the Gene Ontology (GO) and pathway analysis. The construction of a gene network and classification of genes into different modules were conducted through performing Weighted Gene Co-expression Network Analysis. The identification of modules and hub genes that were most related to intervertebral disc degeneration was proceeded. In order to verify the relationships of the module and hub genes with intervertebral disc degeneration, Ingenuity Pathway Analysis was operated. Clinical samples were adopted to help verify the hub gene expression profile.Results: One thousand one hundred ninety differentially expressed genes were identified. Terms and pathways associated with intervertebral disc degeneration were presented by GO and pathway analysis. The construction of a Weighted Gene Coexpression Network was completed and clustering differentially expressed genes into four modules was also achieved. The module with the lowest P-value and the highest absolute correlation coefficient was selected and its relationship with intervertebral disc degeneration was confirmed by Ingenuity Pathway Analysis. The identification of hub genes and the confirmation of their expression profile were also realized.Conclusions: This study generated a comprehensive overview of the gene networks underlying annulus fibrosus in intervertebral disc degeneration.Clinical Relevance: Modules and hub genes identified in this study are highly associated with intervertebral disc degeneration, and may serve as potential therapeutic targets for intervertebral disc degeneration.
Identification of Functional lncRNAs Associated With Ovarian Endometriosis Based on a ceRNA Network
Authors: Bai Jian , Wang Bo , Wang Tian , Ren Wu 
Published: January 2021

BackgroundEndometriosis is a common gynecological disease affecting women of reproductive age; however, the mechanisms underlying this condition are not fully clear. The aim of this study was to identify functional long non-coding RNAs (lncRNAs) associated with ovarian endometriosis for potential use as biomarkers and therapeutic targets.MethodsRNA-seq profiles of paired ectopic (EC) and eutopic (EU) endometrial samples from patients with ovarian endometriosis were downloaded from the publicly available Gene Expression Omnibus (GEO) database. Bioinformatics algorithms were used to construct a network of ovarian endometriosis-related competing endogenous RNAs (ceRNAs) and to detect functional lncRNAs.ResultsA total of 4,213 mRNAs, 1,474 lncRNAs, and 221 miRNAs were identified as being differentially expressed between EC and EU samples, and an ovarian endometriosis-related ceRNA network was constructed through analysis of these differentially expressed RNAs. H19 and GS1-358P8.4 were identified as key ovarian endometriosis-related lncRNAs through topological feature analysis, and RP11-96D1.10 was identified using a random walk with restart algorithm.ConclusionBased on bioinformatics analysis of a ceRNA network, we identified the lncRNAs H19, GS1-358P8.4, and RP11-96D1.10 as being strongly associated with ovarian endometriosis. These three lncRNAs hold potential as targets for medical therapy and as diagnostic biomarkers. Further studies are needed to elucidate the detailed biological function of these lncRNAs in the pathogenesis of endometriosis.
High-Sensitivity Refractive Index Sensor Based on a Cascaded Core-Offset and Macrobending Single-Mode Fiber Interferometer
Authors: Teng Chuanxin , Zhu Yongjie , Yu Fangda , Deng Shijie , Yuan Libo , Zheng Jie , Cheng Yu 
Published: January 2021

A high-sensitivity Mach–Zehnder interferometer (MZI) based on the cascaded core-offset and macrobending fiber structure is proposed for refractive index (RI) measurement. The core-offset structure makes the fiber core mode couple to the cladding modes, and some of them recouple back to the fiber core at the macrobending structure forming a model interference effect. The liquid RI can be measured by monitoring the spectral shift of the modal interference. The RI sensing performances for the interferometers with different macrobending radii and core offsets are investigated experimentally. Experimental results show that when the core offset is 2 μm and the macrobending radius is 5.5 mm, the sensitivity can reach 699.95 nm/RIU for the RI of 1.43. The temperature dependence for the proposed sensor is also tested, and a temperature sensitivity of 0.112 nm/°C is obtained.
“Push and Pull”: Biomechanics of the Pollination Apparatus of Oncidium spp.
Authors: Thielen Marc , Voigt Dagmar , Gallenmüller Friederike , Speck Thomas , Gorb Stanislav 
Published: January 2021

Comprising ca. 28,000, species the Orchidaceae constitute one of the most species-rich plant families. Orchids differ from other monocotyledons i.a., in the formation of so-called pollinaria, which are entities consisting of pollen grains aggregated into compact pollinia and accessory structures, a viscidium and mostly also a pollinium stalk. The viscidium releases an adhesive material that attaches the pollinarium to a pollinator. Pollinaria are part of a complex pollination apparatus that enables the orchids to colonize niches in which only a few individuals of the respective pollinator occur infrequently. Because the aggregated pollen grains are removed from the flower at once, the development of a mechanical barrier ensuring that only suitable pollinators are able to access the flowers and more importantly to remove the pollen are important selective traits. In this paper we describe the functional morphology of the pollination apparatus in two orchid species,Oncidium wentworthianumandO. otogaya, by experimentally mimicking the pollination process. Furthermore, we analyzed the mechanical resistance of this apparatus by means of force measurements and showed that it most probably constitutes a hierarchical two-stage barrier. The first stage consists of the presence of the anther cap that not only protects the pollinia, but also serves to prevent premature removal of young and unripe pollinaria from the flower. As soon as the pollinaria are ripe, the anther cap sheds and the second stage of the mechanical barrier takes effect, a severable bond between pollinarium and rostellum. This bond can be overcome by a potential pollinator, applying a load of at least 10.8 mN (O. otogaya) or 12.6 mN (O. wentworthianum), respectively, on the viscidium which at the same time disengages the pollinarium from its anchorage. The adhesive material produced by the viscidium creates sufficient adhesive contact between pollinarium and pollinator. Potential pollinators, such asCentrisspp. orTrigonaspp. bees, should be well able to exert such forces by pushing their head/forebody into the orchid flowers. Thus, whether a pollinator is able to detach the pollinarium depends on both how forcefully it can push and how strongly it can pull the orchid pollination apparatus.
Numeric Rating Scales Show Prolonged Post-exertional Symptoms After Orthostatic Testing of Adults With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Authors: van Campen C (Linda) M. C. , Rowe Peter C. , Verheugt Freek W. A. , Visser Frans C. 
Published: January 2021

Introduction: Muscle pain, fatigue, and concentration problems are common among individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). These symptoms are commonly increased as part of the phenomenon of postexertional malaise (PEM). An increase in the severity of these symptoms is described following physical or mental exercise in ME/CFS patients. Another important symptom of ME/CFS is orthostatic intolerance, which can be detected by head-up tilt testing (HUT). The effect of HUT on PEM has not been studied extensively. For this purpose, we assessed numeric rating scales (NRS) for pain, fatigue, and concentration pre- and post-HUT. As pain is a core symptom in fibromyalgia (FM), we subgrouped ME/CFS patients by the presence or absence of FM.Methods and Results: In eligible ME/CFS patients who underwent HUT, NRS of pain, fatigue, and concentration were obtained pre-HUT, immediately after HUT, at 24 and 48 h, and at 7 days posttest. We studied 174 ME/CFS patients with FM, 104 without FM, and 30 healthy controls (HC). Values for all symptoms were unchanged for HC pre- and post-HUT. Compared with pre-HUT, the three NRS post-HUT were significantly elevated in both ME/CFS patient groups even after 7 days. NRS pain was significantly higher at all time points measured in the ME/CFS patients with FM compared with those without FM. In ME/CFS patients, the maximum fatigue and concentration scores occurred directly post-HUT, whereas pain perception reached the maximum 24 h post-HUT.Conclusion: NRS scores of pain, fatigue, and concentration were significantly increased even at 7 days post-HUT compared with pre-HUT in ME/CFS patients with and without FM, suggesting that orthostatic stress is an important determinant of PEM.
Association of Viral Load in SARS-CoV-2 Patients With Age and Gender
Authors: Mahallawi Waleed H. , Alsamiri Ali Dakhilallah , Dabbour Alaa Faisal , Alsaeedi Hamdah , Al-Zalabani Abdulmohsen H. 
Published: January 2021

Background: The coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a global public health emergency. Age and sex are two important factors associated with risks and outcomes of various diseases. COVID-19 morbidity also seems to be affected by patient age and sex. It has been found that older age groups have more severe COVID-19 symptoms and higher fatality rates while children tend to have lower prevalence and milder symptoms than adults.Methods: The study reviewed electronic medical records of COVID-19 patients from Madinah city, Saudi Arabia. The study included all cases who tested positive (n = 3,006) between March 20 and May 22, 2020. Data were obtained from the Health Electronic Surveillance Network (HESN) database.Results: Approximately 80% of the study sample were males and half were in the 30–40-year-old age group. The Ct value of the whole sample ranged from 15.08 to 35, with a mean of 27.44 (SD: 5.23; 95% C.I. = 27.25–27.66). The means of Ct values varied between age groups from 27.05 to 27.82. Analysis of the mean differences between age groups using one-way ANOVA indicated no statistically significant difference among the groups (F6,2999 = 1.63; p-value = 0.135). A comparison of mean Ct values of males (n = 2,422) and females (n = 584) revealed that males had a statistically significant higher mean Ct value (27.61 ± 5.20) than females (26.72 ± 5.31). The difference between the means of the two groups was −0.89 (95% C.I. = −1.36 to −0.42; t-test −3.71; df = 3,004; p-value &lt; 0.001).Conclusion: The study found no statistically significant difference in viral loads between age groups. It showed that females had a higher SARS-CoV-2 viral load compared to males. The findings have implications for preventive strategies. Further studies are needed to correlate viral load with clinical symptoms and outcomes.
Immunologic “Cold” Squamous Cell Carcinomas of the Head and Neck Are Associated With an Unfavorable Prognosis
Authors: Ribbat-Idel Julika , Perner Sven , Kuppler Patrick , Klapper Luise , Krupar Rosemarie , Watermann Christian , Paulsen Finn-Ole , Offermann Anne , Bruchhage Karl-Ludwig , Wollenberg Barbara , Idel Christian 
Published: January 2021

Background: Head and neck squamous cell carcinoma (HNSCC) represents a common cancer worldwide. Past therapeutic advances have not significantly improved HNSCC prognosis. Therefore, it is necessary to further stratify HNSCC, especially with recent advances in tumor immunology.Methods: Tissue microarrays were assembled from tumor tissue samples and were complemented with comprehensive clinicopathological data of n = 419 patients. H&amp;E whole slides from resection specimen (n = 289) were categorized according to their immune cell infiltrate as “hot,” “cold,” or “excluded.”Results: Investigating tumor immune cell patterns, we found significant differences in survival rates. Immunologic “hot” and “excluded” HNSCCs are associated with better overall survival than “cold” HNSCC patients (p &lt; 0.05). Interestingly, the percentage of all three patterns is nearly identical in p16 positive and negative HNSCCs.Conclusions: Using a plain histological H&amp;E approach to categorize HNSCC as being immunologic “hot,” “cold,” or “excluded” can offer a forecast of patients' prognosis and may thus aid as a potential prognostic tool in routine pathology reports. This “hot-cold-excluded” scheme needs to be applied to more HNSCC cohorts and possibly to other cancer types to determine prognostic meaning, e.g., regarding OS or DFS. Furthermore, our cohort reflects epidemiological data in the national, European, and international context. It may, therefore, be of use for future HNSCC characterization.
Immune Cell Infiltration of the Primary Tumor Microenvironment Predicted the Treatment Outcome of Chemotherapy With or Without Bevacizumab in Metastatic Colorectal Cancer Patients
Authors: Wang Yixing , Dong Jun , Quan Qi , Liu Shousheng , Chen Xiuxing , Cai Xiuyu , Qiu Huijuan , Zhang Bei , Guo Guifang 
Published: January 2021

BackgroundWith the interest in cancer immunotherapy, it may be possible to combine immunotherapy with bevacizumab and chemotherapy. We evaluated whether tumor-infiltrating immune cells are associated with the efficacy of chemotherapy with or without bevacizumab for the treatment of metastatic colorectal cancer (mCRC).MethodsThis study enrolled mCRC patients on standard treatment with available detailed data and tumor tissue at Sun Yat-sen University Cancer Center between July 1, 2005, and October 1, 2017. CD3+ and CD8+ T cell densities examined by immunohistochemistry in both the tumor core (CT) and invasive margin (IM) were summed as the Immunoscore, and the CD8+/CD3+ T cell ratio was calculated. The predictive and prognostic efficacies of tumor-infiltrating immune cells for progression-free survival (PFS) and overall survival (OS) were analyzed with Kaplan-Meier and Cox analyses.ResultsThe CD8+/CD3+ T cell ratio in the microenvironment was an independent prognostic factor for OS (28.12 mo vs. 16.56 mo, P = 0.017) among the 108 studied patients. In the chemotherapy only group, patients with a high Immunoscore had a high overall response rate (ORR, 40.0% vs. 60.0%, P = 0.022), those with a low CD8+/CD3+ T cell ratio in the microenvironment had a significantly longer PFS (8.64 mo vs. 6.01 mo, P = 0.017), and those with a high CD3+ T cell density in the CT had a longer OS (16.56 mo vs. 25.66 mo, P = 0.029). In the chemotherapy combined with bevacizumab group, patients with a higher CD8+ T cell density in the IM had a longer PFS (7.62 mo vs. 11.66 mo, P = 0.034) and OS (14.55 mo vs. 23.72 mo, P = 0.033).ConclusionImmune cells in primary tumors play an important role in predicting mCRC treatment efficacy. CD8 predicts the effect of bevacizumab plus chemotherapy, while CD3 and CD8/CD3 predict chemotherapy efficacy.
Consecutive Hypoalbuminemia Predicts Inferior Outcome in Patients With Diffuse Large B-Cell Lymphoma
Authors: Wei Xiaolei , Zheng Jingxia , Zhang Zewen , Liu Qiongzhi , Zhan Minglang , Huang Weimin , Chen Junjie , Wei Qi , Wei Yongqiang , Feng Ru 
Published: January 2021

The prognostic value of albumin changes between diagnosis and end-of-treatment (EoT) in diffuse large B-cell lymphoma (DLBCL) remains unknown. We retrospectively analyzed 574 de novo DLBCL patients treated with R-CHOP from our and two other centers. All patients were divided into a training cohort (n = 278) and validation cohort (n = 296) depending on the source of the patients. Overall survival (OS) and progression-free survival (PFS) were analyzed by the method of Kaplan–Meier and Cox proportional hazard regression model. In the training cohort, 163 (58.6%) patients had low serum albumin at diagnosis, and 80 of them were present with consecutive hypoalbuminemia at EoT. Patients with consecutive hypoalbuminemia showed inferior OS and PFS (p = 0.010 and p = 0.079, respectively). Similar survival differences were also observed in the independent validation cohort (p = 0.006 and p = 0.030, respectively). Multivariable analysis revealed that consecutive hypoalbuminemia was an independent prognostic factor OS [relative risk (RR), 2.249; 95% confidence interval (CI), 1.441–3.509, p &lt; 0.001] and PFS (RR, 2.001; 95% CI, 1.443–2.773, p &lt; 0.001) in all DLBCL patients independent of IPI. In conclusion, consecutive hypoalbuminemia is a simple and effective adverse prognostic factor in patients with DLBCL, which reminds us to pay more attention to patients with low serum albumin at EoT during follow-up.
Analgesic Effects of Lipid Raft Disruption by Sphingomyelinase and Myriocin via Transient Receptor Potential Vanilloid 1 and Transient Receptor Potential Ankyrin 1 Ion Channel Modulation
Authors: Horváth Ádám , Payrits Maja , Steib Anita , Kántás Boglárka , Biró-Süt Tünde , Erostyák János , Makkai Géza , Sághy Éva , Helyes Zsuzsanna , Szőke Éva 
Published: January 2021

Transient Receptor Potential (TRP) Vanilloid 1 and Ankyrin 1 (TRPV1, TRPA1) cation channels are expressed in nociceptive primary sensory neurons, and integratively regulate nociceptor and inflammatory functions. Lipid rafts are liquid-ordered plasma membrane microdomains rich in cholesterol, sphingomyelin and gangliosides. We earlier showed that lipid raft disruption inhibits TRPV1 and TRPA1 functions in primary sensory neuronal cultures. Here we investigated the effects of sphingomyelinase (SMase) cleaving membrane sphingomyelin and myriocin (Myr) prohibiting sphingolipid synthesis in mouse pain models of different mechanisms. SMase (50 mU) or Myr (1 mM) pretreatment significantly decreased TRPV1 activation (capsaicin)-induced nocifensive eye-wiping movements by 37 and 41%, respectively. Intraplantar pretreatment by both compounds significantly diminished TRPV1 stimulation (resiniferatoxin)-evoked thermal allodynia developing mainly by peripheral sensitization. SMase (50 mU) also decreased mechanical hyperalgesia related to both peripheral and central sensitizations. SMase (50 mU) significantly reduced TRPA1 activation (formalin)-induced acute nocifensive behaviors by 64% in the second, neurogenic inflammatory phase. Myr, but not SMase altered the plasma membrane polarity related to the cholesterol composition as shown by fluorescence spectroscopy. These are the first in vivo results showing that sphingolipids play a key role in lipid raft integrity around nociceptive TRP channels, their activation and pain sensation. It is concluded that local SMase administration might open novel perspective for analgesic therapy.