bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case Report: Leaflet Thrombosis After Transcatheter Aortic Valve Replacement With Worsening Heart Failure—A Successful Resolution Using Non-vitamin K Antagonist Oral Anti-coagulant
Authors: Liang Kae-Woei , Yu Chu-Leng , Lin Wei-Wen , Lee Wen-Lieng 
Published: December 2021

Background: Transcatheter aortic valve replacement (TAVR) is indicated for treating symptomatic severe aortic valve stenosis (AS) with intermediate-to-high surgical risks. Few reports are available on managing leaflet thrombosis after TAVR with worsening heart failure.Case Summary: A 77-year-old man with severe AS and coronary artery disease (CAD) received a successful TAVR with Edwards Sapien 3 valve. A year later, the patient developed a worsening heart failure with pulmonary edema, new-onset atrial fibrillation (Af), an increase in mean trans-aortic valve pressure gradient to 48 mmHg, worsening mitral regurgitation (MR), and pulmonary hypertension (PH). The response of the patient to intravenous diuretics and inotropic treatments was poor. Multi-slice CT (MDCT) revealed hypo-attenuated thrombus and thickened transcatheter heart valve leaflets. A non-vitamin K antagonist oral anti-coagulant (NOAC) was added to treat the new-onset Af and leaflet thrombosis on top of the con-current single antiplatelet for CAD. A series of follow-up echocardiograms showed a progressive decrease in trans-aortic valve pressure gradient to 17 mmHg and reductions in MR and PH. Three months after the NOAC treatment, MDCT revealed the resolution of hypo-attenuated thrombus and thickened leaflets. Symptoms of heart failure were also improved gradually.Discussion: Worsening heart failure or an increase in trans-aortic valve pressure gradient after TAVR warranted further MDCT studies. Leaflet thrombosis can be resolved after using NOAC as in our present case.
Normal Ranges of Right Atrial Strain and Strain Rate by Two-Dimensional Speckle-Tracking Echocardiography: A Systematic Review and Meta-Analysis
Authors: Hosseinsabet Ali , Mahmoudian Roshanak , Jalali Arash , Mohseni-Badalabadi Reza , Davarpasand Tahereh 
Published: December 2021

Background: Normal range values of right atrial (RA) phasic function markers are essential for the identification of normal and abnormal values, comparison with reference values, and the clinical meaning of obtained values. Accordingly, we aimed to define the normal range values of RA phasic function markers obtained by 2D speckle-tracking echocardiography through a meta-analysis and determine the main sources of heterogeneity among reported values.Methods: PUBMED, SCOPUS, and EMBASE databases were searched for the following keywords: “right atrial/right atrium” and “strain/speckle/deformation” and “echocardiography.” Studies were selected that included a human healthy adult group without any cardiovascular diseases or risk factors and that were written in the English language. For the calculation of each marker of RA phasic functions, a random-effect model was used. Meta-regression was employed to define the major sources of variabilities among reported values.Results: Fifteen studies that included 2,469 healthy subjects were selected for analysis. The normal range values for RA strain and strain rate were 42.7% (95% CI, 39.4 to 45.9%) and 2.1 s−1 (95% CI, 2.0 to 2.1 s−1) during the reservoir phase, respectively, 23.6% (95% CI, 20.7 to 26.6%) and −1.9 s−1 (95% CI, −2.2 to −1.7 s−1) during the conduit phase, correspondingly, and 16.1% (95% CI, 13.6 to 18.6%) and −1.8 s−1 (95% CI, −2.0 to −1.5 s−1) during the contraction phase, respectively. The sources of heterogeneity for the normal range of these markers were the number of participants, the type of software, the method of global value calculation, the right ventricular fractional area change, the left ventricular (LV) ejection fraction, the RA volume index, sex, the heart rate, the diastolic blood pressure, the body mass index, and the body surface area.Conclusions: Using 2D speckle-tracking echocardiography, we defined normal values for RA phasic function markers and identified the sources of heterogeneity as demographic, anthropometric, hemodynamic, and echocardiography factors.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021236578, identifier: CRD42021236578.
Permafrost Dynamics and Degradation in Polar Arctic From Satellite Radar Observations, Yamal Peninsula
Authors: Teshebaeva Kanayim , van Huissteden Ko J. , Echtler Helmut , Puzanov Alexander V. , Balykin Dmitry N. , Sinitsky Anton I. , Kovalevskaya Nelley M. , Dolman Han A. J. 
Published: December 2021

We investigate permafrost surface features revealed from satellite radar data in the Siberian arctic at the Yamal peninsula. Surface dynamics analysis based on SRTM and TanDEM-X DEMs shows up to 2 m net loss of surface relief between 2000 and 2014 indicating a highly dynamic landscape. Surface features for the past 14 years reflect an increase in small stream channels and a number of new lakes that developed, likely caused by permafrost thaw. We used Sentinel-1 SAR imagery to measure permafrost surface changes. Owing to limited observation data we analyzed only 2 years. The InSAR time-series has detected surface displacements in three distinct spatial locations during 2017 and 2018. At these three locations, 60–120 mm/yr rates of seasonal surface permafrost changes are observed. Spatial location of seasonal ground displacements aligns well with lithology. One of them is located on marine sediments and is linked to anthropogenic impact on permafrost stability. Two other areas are located within alluvial sediments and are at the top of topographic elevated zones. We discuss the influence of the geologic environment and the potential effect of local upwelling of gas. These combined analyses of InSAR time-series with analysis of geomorphic features from DEMs present an important tool for continuous process monitoring of surface dynamics as part of a global warming risk assessment.
Early Initiation of Temozolomide Therapy May Improve Response in Aggressive Pituitary Adenomas
Authors: Das Liza , Gupta Nidhi , Dutta Pinaki , Walia Rama , Vaiphei Kim , Rai Ashutosh , Radotra Bishan Dass , Gupta Kirti , Sreedharanunni Sreejesh , Ahuja Chirag Kamal , Bhansali Anil , Tripathi Manjul , Sood Ridhi , Dhandapani Sivashanmugam 
Published: December 2021

IntroductionAggressive pituitary adenomas (APAs) are, by definition, resistant to optimal multimodality therapy. The challenge lies in their early recognition and timely management. Temozolomide is increasingly being used in patients with APAs, but evidence supporting a favorable response with early initiation is lacking.MethodsThis was a single-center study of all patients with APAs who received at least 3 cycles of temozolomide (150–200 mg/m2). Their baseline clinico-biochemical and radiological profiles were recorded. Immunohistochemical evaluation for cell-cycle markers O6-methylguanine-DNA methyltransferase (MGMT), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6), MutL homolog 1 (MLH1), and postmeiotic segregation increased 2 (PMS2) was performed, and h-scores (product of the number of positive cells and staining intensity) were calculated. Response was assessed in terms of radiological response using the RECIST criteria. Patients with controlled disease (≥30% reduction in tumor volume) were classified as responders.ResultsThe study comprised 35 patients (48.6% acromegaly, 37.1% prolactinomas, and 14.3% non-functioning pituitary adenomas). The median number of temozolomide (TMZ) cycles was 9 (IQR 6–14). Responders constituted 68.6% of the cohort and were more likely to have functional tumors, a lower percentage of MGMT-positive staining cells, and lower MGMT h-scores. There was a significantly longer lag period in the initiation of TMZ therapy in non-responders as compared with responders (median 36 vs. 15 months, p = 0.01). ROC-derived cutoffs of 31 months for the duration between diagnosis and TMZ initiation, low-to-intermediate MGMT positivity (40% tumor cells), and MGMT h-score of 80 all had a sensitivity exceeding 80% and a specificity exceeding 70% to predict response.ConclusionEarly initiation of TMZ therapy, functional tumors, and low MGMT h-score predict a favorable response to TMZ in APAs.
Live Birth Rate in Patients With Premature Ovarian Insufficiency During Long-Term Follow-Up Under Hormone Replacement With or Without Ovarian Stimulation
Authors: Ishizuka Bunpei , Furuya Masataka , Kimura Machiko , Kamioka Eri , Kawamura Kazuhiro 
Published: December 2021

We analyzed data from 466 patients with premature ovarian insufficiency (POI) who wished to have a biological child and were followed up while undergoing hormone replacement (HR) therapy with or without ovarian stimulation (OS) between April 2014 and December 2020. OS was conducted in 6891 cycles in 429 patients (Group OS), whereas only HR (Group HR) was conducted in 1117 cycles in 37 patients. The follicle growth rate was 48.3% (207/429) per patient in Group OS and 5.4% (2/37) in Group HR (p&lt;0.01). There were 51 live births (LBs) in 50 patients during follow-up. In Group OS, the LB rate was 5.8% (47/807) in cycles where in vitro fertilization (IVF) and embryo transfer were attempted (Group IVF), and 1.3% (3/236) in cycles where intrauterine insemination/timed intercourse was attempted (p&lt;0.01). No pregnancies occurred in Group HR. Among the patients in Group IVF, the LB rate was significantly higher in patients aged &lt;35 years at the initiation of follow-up than in patients who started at later ages (p&lt;0.01). Among the cases who achieved an LB, 39 were patients with idiopathic POI (Group IVF-1, n=297) and seven were patients who had undergone surgical treatment for benign ovarian tumors (Group IVF-2, n=50); however, no LBs occurred in patients who had undergone treatment for malignancy (n=17), and only one in patients with chromosomal abnormalities (n=22). The LB rate per case in the patients in Group IVF-1 and those aged &lt;35 years at the start of follow-up (Group IVF-1-a) was 24.1% (26/108), which was higher than those of the other age groups. The LB rate per case in the patients in Group IVF-1-a with &lt;4 years of amenorrhea was 37.3% (19/51), and that in the patients in Group IVF-2 with &lt;4 years of amenorrhea was 21.2% (7/33). These results suggest that infertility treatment is possible in some patients with POI, especially those that can be classified in Group IVF-1-a and Group IVF-2 with &lt;4 years of amenorrhea. Therefore, OS combined with HR therapy should be considered for such patients before attempts at oocyte donation.
The Innovative Method of Purifying Polluted Air in the Region of an Inversion Layer
Authors: Jędrzejek F. , Gryboś D. , Zyśk J. , Leszczyński J. , Szarłowicz K. , Stobiński M. , Kubica B. , Suwała W. 
Published: December 2021

Formation of the inversion layer causes a lack of vertical movement of the atmosphere and the occurrence of long-lasting high concentrations of pollution. The new invention makes use of shock waves, created by explosions of a mixture of flammable gases and air. These shock waves destroy the structure of the temperature inversion layer in the atmosphere and restore natural convection. Restoring vertical movements within the atmosphere causes a reduction in air pollution at the ground level. The system was tested at full technical scale in the environment. Preliminary effects indicate an average 24% reduction in PM10 concentration in the smog layer at ground level up to 20 m, with the device operating in 11-min series consisting of 66 explosions. It was also shown that the device is able to affect a larger area, at least 4 km2.
Downregulation of hsa_circRNA_0001400 Helps to Promote Cell Apoptosis Through Disruption of the circRNA_0001400–miR-326 Sponge in Cervical Cancer Cells
Authors: Cai Yantao , Li Chuyu , Peng Fang , Yin Shuanghong , Liang Huiyi , Su Jiyan , Li Lin , Yang Anping , Liu Hui , Yang Chuansheng , Luo Dixian , Xia Chenglai 
Published: December 2021

Background: In recent years, circular RNAs (circRNAs) have been reported to serve as essential regulators in several human cancers. Nevertheless, the function and mechanism of circRNAs in cervical cancer remain elusive.Methods: Flow cytometry assays were performed to measure cell apoptosis and cell cycle. Colony Formation and transwell chamber were performed to measure cell migration and invasion. Double luciferase reporter for gene analysis was used to detect the interaction between hsa-circRNA_0001400, miR-326, and Akt. Relative protein levels were determined by immunoblotting and relative gene levels were determined by quantitative real-time PCR. Tumor Xenograft Modeling was used to evaluate the effect of hsa_circRNA_0001400_siRNA in vivo.Results: In the present study, we showed that hsa_circRNA_0001400 was highly expressed in cervical cancer tissues relative to in matched normal tissue. We found that hsa_circRNA_0001400_siRNA significantly promoted the apoptosis of cervical cancer cells and arrested the cell cycle and migration of cervical cancer cells. We showed that hsa_circRNA_0001400_siRNA can inhibit the protein expression of Akt and that the inhibition of miR-326 could rescue the inhibition of Akt in cervical cancer cells. We found that has-miR-326 was downregulated in cervical cancer tissues and hsa_circRNA_0001400_siRNA could increase the gene expression of has-miR-326. We also observed that hsa_circRNA_0001400_siRNA inhibited the growth and angiogenesis of SiHa xenografts in nude mice.Conclusion: In conclusion, this study provides evidence that the hsa_circRNA_0001400–miR-326–Akt network promotes cervical cancer progression. Notably, our findings demonstrate the novel antitumor effects of hsa_circRNA_0001400_siRNA in cervical cancer.
X Chromosome Inactivation Pattern and Pregnancy Outcome of Female Carriers of Pathogenic Heterozygous X-Linked Deletions
Authors: Zhao Yuanyin , Li Jia , Dai Limeng , Ma Yongyi , Bai Yun , Guo Hong 
Published: December 2021

Prenatal risk assessment of carriers of heterozygous X-linked deletion is a big challenge due to the phenotypic modification induced by X chromosome inactivation (XCI). Herein, we described four Chinese pedigrees with maternal-inherited X-deletions above 1 Mb. The pathogenic evaluation revealed that all X-deletions are harmful to heterozygous carriers; however, the asymptomatic pregnant female carriers in these families tremendously complicate the prognostic assessment of the unborn heterozygous embryos. In this study, we detected the XCI pattern of 11 female carriers of heterozygous X-linked deletions and 4 non-carrier females in these families and performed the first prenatal XCI pattern analysis in a fetal female carrier of heterozygous PCDH19-deletion to make risk prediction. In an adult female who lost one copy of the terminal of X chromosome short arm (Xp), a region enriching a large number of XCI escapees, the expression level of representative XCI escape genes was also detected. Pregnancy outcomes of all families were followed up or retrospected. Our research provides clinical evidence that X-deletions above 1 Mb are indeed associated with extremely skewed XCI. The favorable skewed XCI in combination with potential compensatory upregulation of XCI escapees would protect some but not all female carriers with pathogenic X-deletion from severe clinical consequences, mainly depending on the specific genetic contents involved in the deletion region. For PCDH19-disorder, the XCI pattern is considered as the decisive factor of phenotype expression, of which prenatal XCI assay using uncultured amniocytes could be a practicable way for risk prediction of this disease. These results provide valuable information about the usage of XCI assay in the prenatal risk assessment of heterozygous X-linked deletions.
Neutrophil Expression of T and B Immunomodulatory Molecules in HIV Infection
Authors: Márquez-Coello Mercedes , Ruiz-Sánchez Cristina , Martín-Aspas Andrés , Fernández Gutiérrez Del Álamo Clotilde , Illanes-Álvarez Francisco , Cuesta-Sancho Sara , Girón-González José-Antonio 
Published: December 2021

ObjectiveEvaluate the expression of B and T cell immunomodulatory molecules in polymorphonuclear neutrophils (PMN) in HIV-infected patients.MethodsHIV load, bacterial translocation and neutrophils’ expression of T [programmed death ligand, interleukin-10+, arginase 1+] and B [BAFF, APRIL] molecules were analyzed in different cohorts and time points: a control group of 25 healthy individuals and two groups of HIV-infected patients. Group 1 of patients included 35 untreated patients, studied at baseline and after antiretroviral therapy (ART). Group 2 was composed of 25 patients with undetectable viral load after a median of 101 months of ART prior to inclusion in the study.ResultsCompared with the control group, group 1 patients showed increased bacterial translocation and their PMN had a significantly higher expression of T and B-cell immunomodulatory molecules, both at baseline and after 12 months of ART. Group 2 patients showed reduced bacterial translocation levels when compared with group 1 patients after 12 months of treatment. PMN expression of B-cell modulators was similar between group 2 patients and healthy controls, although the expression of T-cell modulators remained increased.ConclusionIn HIV-infected patients, the expression of B-cell stimulatory and T-cell suppressive molecules by neutrophils was increased at baseline and after a limited time of therapy. After a prolonged period of ART, only PMNs expression of T-cell immunosuppressive molecules remained elevated.
An Intranasal OMV-Based Vaccine Induces High Mucosal and Systemic Protecting Immunity Against a SARS-CoV-2 Infection
Authors: van der Ley Peter A. , Zariri Afshin , van Riet Elly , Oosterhoff Dinja , Kruiswijk Corine P. 
Published: December 2021

The development of more effective, accessible, and easy to administer COVID-19 vaccines next to the currently marketed mRNA, viral vector, and whole inactivated virus vaccines is essential to curtailing the SARS-CoV-2 pandemic. A major concern is reduced vaccine-induced immune protection to emerging variants, and therefore booster vaccinations to broaden and strengthen the immune response might be required. Currently, all registered COVID-19 vaccines and the majority of COVID-19 vaccines in development are intramuscularly administered, targeting the induction of systemic immunity. Intranasal vaccines have the capacity to induce local mucosal immunity as well, thereby targeting the primary route of viral entry of SARS-CoV-2 with the potential of blocking transmission. Furthermore, intranasal vaccines offer greater practicality in terms of cost and ease of administration. Currently, only eight out of 112 vaccines in clinical development are administered intranasally. We developed an intranasal COVID-19 subunit vaccine, based on a recombinant, six-proline-stabilized, D614G spike protein (mC-Spike) of SARS-CoV-2 linked via the LPS-binding peptide sequence mCramp (mC) to outer membrane vesicles (OMVs) from Neisseria meningitidis. The spike protein was produced in CHO cells, and after linking to the OMVs, the OMV-mC-Spike vaccine was administered to mice and Syrian hamsters via intranasal or intramuscular prime-boost vaccinations. In all animals that received OMV-mC-Spike, serum-neutralizing antibodies were induced upon vaccination. Importantly, high levels of spike-binding immunoglobulin G (IgG) and A (IgA) antibodies in the nose and lungs were only detected in intranasally vaccinated animals, whereas intramuscular vaccination only induced an IgG response in the serum. Two weeks after their second vaccination, hamsters challenged with SARS-CoV-2 were protected from weight loss and viral replication in the lungs compared to the control groups vaccinated with OMV or spike alone. Histopathology showed no lesions in lungs 7 days after challenge in OMV-mC-Spike-vaccinated hamsters, whereas the control groups did show pathological lesions in the lung. The OMV-mC-Spike candidate vaccine data are very promising and support further development of this novel non-replicating, needle-free, subunit vaccine concept for clinical testing.
A Novel TGF-β Risk Score Predicts the Clinical Outcomes and Tumour Microenvironment Phenotypes in Bladder Cancer
Authors: Liu Zhi , Qi Tiezheng , Li Xiaowen , Yao Yiyan , Othmane Belaydi , Chen Jinbo , Zu Xiongbing , Ou Zhenyu , Hu Jiao 
Published: December 2021

BackgroundThe TGF-β pathway plays critical roles in numerous malignancies. Nevertheless, its potential role in prognosis prediction and regulating tumour microenvironment (TME) characteristics require further elucidation in bladder cancer (BLCA).MethodsTGF-β-related genes were comprehensively summarized from several databases. The TCGA-BLCA cohort (training cohort) was downloaded from the Cancer Genome Atlas, and the independent validation cohorts were gathered from Xiangya Hospital (Xinagya cohort) and Gene Expression Omnibus. Initially, we identified differentially expressed TGF-β genes (DEGs) between cancer and normal tissues. Subsequently, univariate Cox analysis was applied to identify prognostic DEGs, which were further used to develop the TGF-β risk score by performing LASSO and multivariate Cox analyses. Then, we studied the role of the TGF-β risk score in predicting prognosis and the TME phenotypes. In addition, the role of the TGF-β risk score in guiding precision treatments for BLCA has also been assessed.ResultsWe successfully constructed a TGF-β risk score with an independent prognostic prediction value. A high TGF-β risk score indicated an inflamed TME, which was supported by the positive relationships between the risk score, enrichment scores of anticancer immunity steps, and the infiltration levels of tumour-infiltrating immune cells. In addition, the risk score positively correlated with the expression of several immune checkpoints and the T cell inflamed score. Consistently, the risk score was positively related to the enrichment scores of most immunotherapy-positive pathways. In addition, the sensitivities of six common chemotherapeutic drugs were positively associated with the risk score. Furthermore, higher risk score indicated higher sensitivity to radiotherapy and EGFR-targeted therapy. On the contrary, patients with low-risk scores were more sensitive to targeted therapies, including the blockade of FGFR3 and WNT-β-catenin networks.ConclusionsWe first constructed and validated a TGF-β signature that could predict the prognosis and TME phenotypes for BLCA. More importantly, the TGF-β risk score could aid in individual precision treatment for BLCA.