bluuebunny/crossref_metadata_2025 huggingface dataset:
Exosomes: Biological Pharmaceutical Nanovectors for Theranostics
Authors: Thomas Shindu C. , Kim Jin-Woo , Pauletti Giovanni M. , Hassett Daniel J. , Kotagiri Nalinikanth
Published: January 2022

Exosomes are natural cell-derived nanovesicles of endocytic origin that enable cellular crosstalk by transferring encapsulated molecular cargos across biological barriers, thereby holding significantly complex implications in the etiology and progression of diverse disease states. Consequently, the development of exosomes-based nano-theranostic strategies has received immense consideration for advancing therapeutic interventions and disease prognosis. Their favorable biopharmaceutical properties make exosomes a unique nanoparticulate carrier for pharmaceutical drug delivery. This review provides an update on the contemporary strategies utilizing exosomes for theranostic applications in nanomedicine. In addition, we provide a synopsis of exosomal features and insights into strategic modifications that control in vivo biodistribution. We further discuss their opportunities, merits and pitfalls for cell/tissue targeted drug delivery in personalized nanotherapy.
Tokenizing Behavior Change: A Pathway for the Sustainable Development Goals
Authors: Barclay Iain , Cooper Michael , Hackel Jakob , Perrin Paul
Published: January 2022

To be successful and sustainable, social impact programs require individuals and groups to change aspects of their behavior. As blockchain-based tokens are increasingly adopted to target social outcomes, it is important to properly define these activities as “behavior change interventions” and assess their design and management as such—otherwise, there is significant risk of possible unintended consequences. Designing tokens as behavior change interventions requires new constructs beyond those currently in use to model the interdependence of digital and social ecosystems, and integration of token engineering, cryptoeconomics, and behavioral skill sets to test token designs within various ecosystems. New token design and testing protocols that integrate behavior measures around the targeted social outcomes are needed, to fill a critical gap in current practice. Hence, new standards, operational frameworks, and ethics are needed to guide the use of tokens at scale, as tools to achieve social impacts such as attaining the United Nations’ Sustainable Development Goals. Meeting these needs requires a collaborative approach between token design actors (computer scientists, cryptoeconomists, token engineers, etc.) and social impact practitioners who will be increasingly called upon to use tokens as behavior change tools. This paper begins to identify common ground and address areas to further develop research and practice of tokens being used for social impact.
LncPep: A Resource of Translational Evidences for lncRNAs
Authors: Liu Teng , Wu Jingni , Wu Yangjun , Hu Wei , Fang Zhixiao , Wang Zishan , Jiang Chunjie , Li Shengli
Published: January 2022

Long noncoding RNAs (lncRNAs) are a type of transcript that is >200 nucleotides long with no protein-coding capacity. Accumulating studies have suggested that lncRNAs contain open reading frames (ORFs) that encode peptides. Although several noncoding RNA-encoded peptide-related databases have been developed, most of them display only a small number of experimentally validated peptides, and resources focused on lncRNA-encoded peptides are still lacking. We used six types of evidence, coding potential assessment tool (CPAT), coding potential calculator v2.0 (CPC2), N6-methyladenosine modification of RNA sites (m6A), Pfam, ribosome profiling (Ribo-seq), and translation initiation sites (TISs), to evaluate the coding potential of 883,804 lncRNAs across 39 species. We constructed a comprehensive database of lncRNA-encoded peptides, LncPep (http://www.shenglilabs.com/LncPep/). LncPep provides three major functional modules: 1) user-friendly searching/browsing interface, 2) prediction and BLAST modules for exploring novel lncRNAs and peptides, and 3) annotations for lncRNAs, peptides and supporting evidence. Taken together, LncPep is a user-friendly and convenient platform for discovering and investigating peptides encoded by lncRNAs.
m6A: An Emerging Role in Programmed Cell Death
Authors: Tang Fajuan , Chen Lin , Gao Hu , Xiao Dongqiong , Li Xihong
Published: January 2022

Programmed cell death is an active extinction process, including autophagy, ferroptosis, pyroptosis, apoptosis, and necroptosis. m6A is a reversible RNA modification which undergoes methylation under the action of methylases (writers), and is demethylated under the action of demethylases (erasers). The RNA base site at which m6A is modified is recognized by specialized enzymes (readers) which regulate downstream RNA translation, decay, and stability. m6A affects many aspects of mRNA metabolism, and also plays an important role in promoting the maturation of miRNA, the translation and degradation of circRNA, and the stability of lncRNA. The regulatory factors including writers, erasers and readers promote or inhibit programmed cell death via up-regulating or down-regulating downstream targets in a m6A-dependent manner to participate in the process of disease. In this review, we summarize the functions of m6A with particular reference to its role in programmed cell death.
Comparison of Tendon Development Versus Tendon Healing and Regeneration
Authors: He Peiwen , Ruan Dengfeng , Huang Zizhan , Wang Canlong , Xu Yiwen , Cai Honglu , Liu Hengzhi , Fei Yang , Heng Boon Chin , Chen Weishan , Shen Weiliang
Published: January 2022

Tendon is a vital connective tissue in human skeletal muscle system, and tendon injury is very common and intractable in clinic. Tendon development and repair are two closely related but still not fully understood processes. Tendon development involves multiple germ layer, as well as the regulation of diversity transcription factors (Scx et al.), proteins (Tnmd et al.) and signaling pathways (TGFβ et al.). The nature process of tendon repair is roughly divided in three stages, which are dominated by various cells and cell factors. This review will describe the whole process of tendon development and compare it with the process of tendon repair, focusing on the understanding and recent advances in the regulation of tendon development and repair. The study and comparison of tendon development and repair process can thus provide references and guidelines for treatment of tendon injuries.
Putative Prevention of XML Injection Against Myocardial Ischemia Is Mediated by PKC and PLA2 Proteins
Authors: Jin Ling , Yin Qianqian , Mao Yiqing , Gao Yuanxu , Han Qing , Mei Ruisi , Xue Lixiang , Tan Huanran , Li Hui
Published: January 2022

Background: Xinmailong (XML) injection is a CFDA-approved traditional Chinese medicine with clinical value for heart failure treatment. The present investigation was aimed to evaluate the potential protective roles of this injection on myocardial ischemia and the underlying molecular mechanism.

Methods: In our study, we selected two models of myocardial ischemia rats. Rats were randomly divided into six groups, with saline or XML administrated 4 days before ischemia model establishment. ECG of different time intervals and biochemical parameters of end point were measured. The potential mechanisms of the protective role of XML were explored using system pharmacology and molecular biology approaches.

Results: Myocardial ischemia rats demonstrated abnormal ECG and serum levels of cTnT. Pretreatment with XML significantly attenuated these damages, especially the medium doses. GO and KEGG analysis revealed that the 90 putative target genes were associated with pathways of fatty acid absorption/metabolism, inflammation, RAAS, and vascular smooth muscle. Further network pharmacology method identified five main chemical ingredients and potential targets of XML injection for myocardial ischemia. Mechanically, the beneficial effect of XML injection was mediated by the reactive oxygen species (ROS) inhibition and inflammation attenuation via regulating the expression levels of targets of PKC and PLA2.

Conclusion: These findings indicate that XML exerts protective effects against myocardial injury, with attenuated ROS production, apoptosis, and inflammation. Therefore, we speculate that XML may be an alternative supplementary therapeutic agent for myocardial ischemia prevention.
Accelerate the Electrolyte Perturbed-Chain Statistical Associating Fluid Theory–Density Functional Theory Calculation With the Chebyshev Pseudo-Spectral Collocation Method. Part II. Spherical Geometry and Anderson Mixing
Authors: Sun Yunhao , Dai Zhengxing , Shen Gulou , Lu Xiaohua , Ling Xiang , Ji Xiaoyan
Published: January 2022

To improve the efficiency of electrolyte perturbed-chain statistical associating fluid theory–density functional theory (ePC-SAFT-DFT) calculation of the confined system, in this work, first, the Chebyshev pseudo-spectral collocation method was extended to the spherical pores. Second, it was combined with the Anderson mixing algorithm to accelerate the iterative process. The results show that the Anderson mixing algorithm can reduce the computation time significantly. Finally, based on the accelerated ePC-SAFT-DFT program, a systematic study of the effects of the temperature, pressure, pore size, and pore shape on the CO2 solubilities in the ionic liquids (ILs) confined inside the silica nanopores was conducted. Based on the simulation results, to obtain high CO2 solubilities in the ILs confined in silica, a better option is to use the silica material with a narrow spherical pore, and the IL-anion should be selected specifically considering that it has a more significant impact on the absorption enhancement effect.
Functionalized Multi-Walled Carbon Nanotube–Based Aptasensors for Diclofenac Detection
Authors: Zou Yi , Griveau Sophie , Ringuedé Armelle , Bedioui Fethi , Richard Cyrille , Slim Cyrine
Published: January 2022

Driven by the increasing concern about the risk of diclofenac (DCF) residues as water pollutants in the aqueous environment and the growing need for its trace determination, a simple but sensitive electrochemical aptasensor for the trace detection of DCF was developed. To construct the aptasensor, the amine-terminated DCF aptamer was covalently immobilized on the surface of the carboxylic acid–functionalized multi-walled carbon nanotube (f-MWCNT)–modified glassy carbon electrode (GCE) through EDC/NHS chemistry. The f-MWCNTs provide a reliable matrix for aptamer immobilization with high grafting density, while the aptamer serves as a biorecognition probe for DCF. The obtained aptasensor was incubated with DCF solutions at different concentrations and was then investigated by electrochemical impedance spectroscopy (EIS). It displays two linear ranges of concentration for DCF detection, from 250 fM to 1pM and from 1 pM to 500 nM with an extremely low detection limit of 162 fM. Also, the developed biosensor shows great reproducibility, acceptable stability, and reliable selectivity. Therefore, it offers a simple but effective aptasensor construction strategy for trace detection of DCF and is anticipated to show great potential for environmental applications.
Severe COVID-19 Is Associated With an Altered Upper Respiratory Tract Microbiome
Authors: Shilts Meghan H. , Rosas-Salazar Christian , Strickland Britton A. , Kimura Kyle S. , Asad Mohammad , Sehanobish Esha , Freeman Michael H. , Wessinger Bronson C. , Gupta Veerain , Brown Hunter M. , Boone Helen H. , Patel Viraj , Barbi Mali , Bottalico Danielle , O’Neill Meaghan , Akbar Nadeem , Rajagopala Seesandra V. , Mallal Simon , Phillips Elizabeth , Turner Justin H. , Jerschow Elina , Das Suman R.
Published: January 2022

Background

The upper respiratory tract (URT) is the portal of entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and SARS-CoV-2 likely interacts with the URT microbiome. However, understanding of the associations between the URT microbiome and the severity of coronavirus disease 2019 (COVID-19) is still limited.

Objective

Our primary objective was to identify URT microbiome signature/s that consistently changed over a spectrum of COVID-19 severity.

Methods

Using data from 103 adult participants from two cities in the United States, we compared the bacterial load and the URT microbiome between five groups: 20 asymptomatic SARS-CoV-2-negative participants, 27 participants with mild COVID-19, 28 participants with moderate COVID-19, 15 hospitalized patients with severe COVID-19, and 13 hospitalized patients in the ICU with very severe COVID-19.

Results

URT bacterial load, bacterial richness, and within-group microbiome composition dissimilarity consistently increased as COVID-19 severity increased, while the relative abundance of an amplicon sequence variant (ASV), Corynebacterium_unclassified.ASV0002, consistently decreased as COVID-19 severity increased.

Conclusions

We observed that the URT microbiome composition significantly changed as COVID-19 severity increased. The URT microbiome could potentially predict which patients may be more likely to progress to severe disease or be modified to decrease severity. However, further research in additional longitudinal cohorts is needed to better understand how the microbiome affects COVID-19 severity.
Antigen Discovery in Circulating Extracellular Vesicles From Plasmodium vivax Patients
Authors: Aparici-Herraiz Iris , Gualdrón-López Melisa , Castro-Cavadía Carlos J. , Carmona-Fonseca Jaime , Yasnot María Fernanda , Fernandez-Becerra Carmen , del Portillo Hernando A.
Published: January 2022

Plasmodium vivax is the most widely distributed human malaria parasite with 7 million annual clinical cases and 2.5 billion people living under risk of infection. There is an urgent need to discover new antigens for vaccination as only two vaccine candidates are currently in clinical trials. Extracellular vesicles (EVs) are small membrane-bound vesicles involved in intercellular communication and initially described in reticulocytes, the host cell of P. vivax, as a selective disposal mechanism of the transferrin receptor (CD71) in the maturation of reticulocytes to erythrocytes. We have recently reported the proteomics identification of P. vivax proteins associated to circulating EVs in P. vivax patients using size exclusion chromatography followed by mass spectrometry (MS). Parasite proteins were detected in only two out of ten patients. To increase the MS signal, we have implemented the direct immuno-affinity capture (DIC) technique to enrich in EVs derived from CD71-expressing cells. Remarkably, we identified parasite proteins in all patients totaling 48 proteins and including several previously identified P. vivax vaccine candidate antigens (MSP1, MSP3, MSP7, MSP9, Serine-repeat antigen 1, and HSP70) as well as membrane, cytosolic and exported proteins. Notably, a member of the Plasmodium helical interspersed sub-telomeric (PHIST-c) family and a member of the Plasmodium exported proteins, were detected in five out of six analyzed patients. Humoral immune response analysis using sera from vivax patients confirmed the antigenicity of the PHIST-c protein. Collectively, we showed that enrichment of EVs by CD71-DIC from plasma of patients, allows a robust identification of P. vivax immunogenic proteins. This study represents a significant advance in identifying new antigens for vaccination against this human malaria parasite.
Exercise-Induced Cardiac Fatigue in Recreational Ultramarathon Runners at Moderate Altitude: Insights From Myocardial Deformation Analysis
Authors: Wolff Sebastián , Picco José M. , Díaz-González Leonel , Valenzuela Pedro L. , Gonzalez-Dávila Emanuel , Santos-Lozano Alejandro , Matile Pablo , Wolff David , Boraita Araceli , Lucia Alejandro
Published: January 2022

Background

Controversy exists on the actual occurrence of exercise-induced cardiac fatigue (EICF) with ultraendurance exercise, as well as on whether factors such as age or training status might predispose to this condition. The present study aimed to assess the occurrence of EICF among recreational ultramarathon runners, as well as to determine potential predictive factors.

Methods

Nineteen male recreational runners (42 ± 12yrs) participated in a 55-km trial race at moderate altitude (1,800–2,500 m). Participants were evaluated before and after the race using Doppler echocardiography and myocardial deformation analysis. EICF was determined as a reduction >5% of either left ventricular global longitudinal strain (LVGLS) or right ventricular free wall strain (RVFWS). Demographical (age, body mass index), training (training experience, volume and intensity), competition (finishing time, relative intensity) and biochemical variables (blood lactate, creatine kinase [CK] and CK-MB) were assessed as predictors of EICF.

Results

A significant reduction in LVGLS (20.1 ± 2.1% at baseline vs. 18.8 ± 2.4% at post-race, p = 0.026), but not in RVFWS (27.4 ± 7.0 vs. 24.6 ± 5.3%, p = 0.187), was observed after the race. EICF was present in 47 and 71% of the participants attending to the decrease in LVGLS and RVFWS, respectively. No associations were found between any of the analyzed variables and EICF except for age, which was associated with the magnitude of decrement of RVFWS (r = 0.58, p = 0.030).

Conclusions

Ultramarathon running at moderate altitude seems to induce EICF in a considerable proportion of recreational athletes.
Importance of Acute Anterior Angulation in Double Aortic Arch Needing Attention at Primary Surgery
Authors: Beeman Arun , Ramaswamy Madhavan , Srinivasan Yadav , Rudrappa Siddartha , Christov Georgi , Marek Jan , Derrick Graham , Muthialu Nagarajan
Published: January 2022

Background

Vascular rings are rare congenital abnormalities of the aortic arch. There are many embryological variants including a double aortic arch. In symptomatic children, division of ring and release of airway structures may be sufficient. Persistence of symptoms can be related to an anterior angle formed between the two arches. The aim of this study is to evaluate the clinical efficacy in improving symptoms and on changing this angle at the primary surgery.

Methods

All children who had surgery for double aortic arch between 2005 and 2020, were studied. Relevant factors were analyzed for persistent symptoms including anatomical substrates and surgical details.

Results

A total of 87 out of 224 children had surgery for a double aortic arch. At presentation, airway symptoms (n = 74/87) were more common than esophageal symptoms (n = 27/87). Early onset symptoms within 1 year were seen in 49 children. In addition to division of one arch, surgical steps also included realigning the anterior left arch, thereby eliminating the acute angle in 36 children (after 2014). After surgery, symptom relief within 12 months following surgery was seen in 64% of children (56 out of 87) but in 27 out of 36 children (75%) with additional surgical modification, as against 29 out of 51 (57%) in those with division of the arch. Symptoms persisted beyond 1 year needing reintervention in eight children.

Conclusion

Anterior arch angulation plays an important role in double aortic arch by causing a “nutcracker” phenomenon. Repair in double aortic arch should consider this aspect and include modification of surgical steps by realigning the corresponding aortic arch branches and an anterior pexy in selected cases.
WSSNet: Aortic Wall Shear Stress Estimation Using Deep Learning on 4D Flow MRI
Authors: Ferdian Edward , Dubowitz David J. , Mauger Charlene A. , Wang Alan , Young Alistair A.
Published: January 2022

Wall shear stress (WSS) is an important contributor to vessel wall remodeling and atherosclerosis. However, image-based WSS estimation from 4D Flow MRI underestimates true WSS values, and the accuracy is dependent on spatial resolution, which is limited in 4D Flow MRI. To address this, we present a deep learning algorithm (WSSNet) to estimate WSS trained on aortic computational fluid dynamics (CFD) simulations. The 3D CFD velocity and coordinate point clouds were resampled into a 2D template of 48 × 93 points at two inward distances (randomly varied from 0.3 to 2.0 mm) from the vessel surface (“velocity sheets”). The algorithm was trained on 37 patient-specific geometries and velocity sheets. Results from 6 validation and test cases showed high accuracy against CFD WSS (mean absolute error 0.55 ± 0.60 Pa, relative error 4.34 ± 4.14%, 0.92 ± 0.05 Pearson correlation) and noisy synthetic 4D Flow MRI at 2.4 mm resolution (mean absolute error 0.99 ± 0.91 Pa, relative error 7.13 ± 6.27%, and 0.79 ± 0.10 Pearson correlation). Furthermore, the method was applied on in vivo 4D Flow MRI cases, effectively estimating WSS from standard clinical images. Compared with the existing parabolic fitting method, WSSNet estimates showed 2–3 × higher values, closer to CFD, and a Pearson correlation of 0.68 ± 0.12. This approach, considering both geometric and velocity information from the image, is capable of estimating spatiotemporal WSS with varying image resolution, and is more accurate than existing methods while still preserving the correct WSS pattern distribution.
Platelets and Antiplatelet Medication in COVID-19-Related Thrombotic Complications
Authors: Schrottmaier Waltraud C. , Pirabe Anita , Pereyra David , Heber Stefan , Hackl Hubert , Schmuckenschlager Anna , Brunnthaler Laura , Santol Jonas , Kammerer Kerstin , Oosterlee Justin , Pawelka Erich , Treiber Sonja M. , Khan Abdullah O. , Pugh Matthew , Traugott Marianna T. , Schörgenhofer Christian , Seitz Tamara , Karolyi Mario , Jilma Bernd , Rayes Julie , Zoufaly Alexander , Assinger Alice
Published: January 2022

Coronavirus disease 2019 (COVID-19) induces a hypercoagulatory state that frequently leads to thromboembolic complications. Whereas anticoagulation is associated with reduced mortality, the role of antiplatelet therapy in COVID-19 is less clear. We retrospectively analyzed the effect of anticoagulation and antiplatelet therapy in 578 hospitalized patients with COVID-19 and prospectively monitored 110 patients for circulating microthrombi and plasma markers of coagulation in the first week of admission. Moreover, we determined platelet shape change and also thrombi in postmortem lung biopsies in a subset of patients with COVID-19. We observed no association of antiplatelet therapy with COVID-19 survival. Adverse outcome in COVID-19 was associated with increased activation of the coagulation cascade, whereas circulating microthrombi did not increase in aggravated disease. This was in line with analysis of postmortem lung biopsies of patients with COVID-19, which revealed generally fibrin(ogen)-rich and platelet-low thrombi. Platelet spreading was normal in severe COVID-19 cases; however, plasma from patients with COVID-19 mediated an outcome-dependent inhibitory effect on naïve platelets. Antiplatelet medication disproportionally exacerbated this platelet impairment in plasma of patients with fatal outcome. Taken together, this study shows that unfavorable outcome in COVID-19 is associated with a profound dysregulation of the coagulation system, whereas the contribution of platelets to thrombotic complications is less clear. Adverse outcome may be associated with impaired platelet function or platelet exhaustion. In line, antiplatelet therapy was not associated with beneficial outcome.
Postload Plasma Glucose but Not Fasting Plasma Glucose Had a Greater Predictive Value for Cardiovascular Disease in a Large Prospective Cohort Study in Southwest China
Authors: Wang Yingying , Yu Lisha , Wang Yiying , Zhou Jie , Wu Yanli , Liu Tao , Wang Na , Fu Chaowei
Published: January 2022

Background

Uncertainty remains regarding the relevance of glycemia, though below the threshold for diabetes, for the risk of cardiovascular disease (CVD) among the Southwest Chinese. We aimed to examine the associations of the first-onset CVD with fasting plasma glucose (FPG) and 2-h postload glucose (2h-PG) in Southwest China.

Methods

The current study examined data from the Guizhou Population Health Cohort Study (GPHCS) of 9,280 participants aged 18 to 95 years recruited from 12 areas since 2010 in Guizhou Province, Southwest China. Participants were followed-up until December, 2020. Primary outcomes were the first onset of a composite of or one of major CVD events, including ischaemic stroke, haemorrhagic stroke and myocardial infarction. FPG, 2h-PG, other metabolic factors and some demographic factors were collected at baseline. Cox proportional hazards models were used to estimate the risk of CVD associated with FPG and 2h-PG. Sensitive analysis and stratified analysis were conducted among participants across different modifiable risk factors and demographic features

Results

During a median of 6.58 years of follow-up, of 7,593 participants with available data for analysis, 174 experienced at least one CVD events, 158 developed stroke (including 126 ischemic stroke and 39 Ischemic stroke events), and 24 developed myocardial infarction. The risk of major CVD events was significantly increased with elevated 2h-PG but not FPG. Compared with participants in the lowest tertile of 2h-PG, those in the highest tertile had a 1.87-fold (95%CI: 1.26–2.77) increased risk for overall CVD, a 1.82-fold (95%CI: 1.20–2.75) increased risk for overall Stroke, and a 1.82-fold (95%CI: 1.20–2.75) increased risk for ischemic stroke, respectively, after adjustment for age, sex, smoking, ethnic group, education level, systolic blood pressure (SBP), triglycerides (TG), body mass index (BMI) and waist circumference (WC). However, there was no relation of glycemia of haemorrhagic stroke or myocardial infarction (P > 0.05). The effect sizes in the associations of CVD with 2h-PG become enhanced among those within normal range of glycemia, SBP, TG, BMI, as well as those without hypertension, dyslipidemia.and obesity.

Conclusions

2h-PG, in contrast to FPG, is a significant indicator in predication of CVD in Southwest Chinese. Elevated 2h-PG, though below the below the threshold for diabetes, remains independently increased the risk of CVD.
Prevalence and Risk Factors of QTc Prolongation During Pregnancy
Authors: Luo Chaodi , Duan Zhenzhen , Jiang Yi , Liu Peng , Yan Yang , Han Dan
Published: January 2022

Background

Prolonged QT intervals have been observed in pregnant women, which predispose them to a higher risk of potentially lethal ventricular arrhythmias. This study was designed to evaluate the prevalence of QTc prolongation in Chinese hospitalized parturient women with single and twin pregnancies, and to explore potential risk factors associated with QTc prolongation.

Methods

This retrospective study included 1,218 patients from a large Chinese population between January 2014 and October 2020. Data from parturient women with single and twin pregnancies without pre-pregnancy cardiac diseases were collected. QTc was corrected by the Fridericia formula [QTc = QT/RR(1/3)], and QTc ≥ 460 ms for females was defined as prolonged QTc, QTc ≥ 500 ms was defined as severely prolonged QTc. The prevalence and common risk factors of QTc prolongation during pregnancy were analyzed in this cohort. Uni- and multivariable logistic regression analysis were performed to identify clinical parameters associated with QTc prolongation in this population.

Results

The prevalence of QTc prolongation was 48.19% among this population, 10.56% in single pregnancy, 89.44% in twin pregnancies. The prevalence of severely prolonged QTc was 23.48% among the total cohort, 0.49% in single pregnancy, and 46.47% in twin pregnancies. The mean QTc interval was significantly longer in twin pregnancies than in single pregnancy (498.65 ± 38.24 vs. 424.96 ± 27.67 ms, P < 0.001). Systolic blood pressure, diastolic blood pressure, total cholesterol, serum uric acid, gestational hypertension and twin pregnancies were associated with QTc prolongation in parturient women.

Conclusion

This is the first study to assess the prevalence and risk factors of QTc prolongation between single and twin pregnancies. QTc prolongation is more prevalent, and QTc intervals are significantly longer in twin pregnancies as compared to single pregnancy.
Diagnostic Value of Serum Concentration of Galectin-3 in Patients With Heart Failure With Preserved Ejection Fraction
Authors: Jiang Jing , Yang Baojun , Sun Ying , Jin Jing , Zhao Zhiying , Chen Songming
Published: January 2022

Background

Although the predictive value of galectin-3 for heart failure with preserved ejection fraction has been demonstrated, the diagnostic value remains unclear. The present study was performed to address this issue.

Hypothesis

Galectin-3 has diagnostic value for heart failure with preserved ejection fraction.

Methods

This is a diagnostic experiment. We conducted an observational study of 223 patients with combined symptoms of heart failure and diseases that can lead to heart failure with preserved ejection fraction. Patients were grouped into the heart failure group and control group in accordance with the 2016 European Society of Cardiology heart failure guidelines for heart failure with preserved ejection fraction. Baseline information and serum galectin-3 concentration were assessed within 24 h after admission.

Results

Serum galectin-3 concentration was significantly higher in the heart failure group compared with the control group. Binary logistic regression analysis showed that higher galectin-3 concentration was associated with the occurrence of heart failure with preserved ejection fraction. The area under the curve of galectin-3 was 0.763, indicating that galectin-3 has moderate diagnostic value for heart failure with preserved ejection fraction. Galectin-3 >15.974 ng/mL identified heart failure with preserved ejection fraction with 76.0% sensitivity and 71.9% specificity.

Conclusions

There was a correlation between galectin-3 and heart failure with preserved ejection fraction, and galectin-3 was an independent predictor of heart failure with preserved ejection fraction. The diagnostic value of galectin-3 for heart failure with preserved ejection fraction was moderate (AUC: 0.763, 95% CI: 0.696–0.821, P < 0.01, and the sensitivity is 76.0% while the specificity is 71.9% at the threshold 15.974 ng/mL) and was higher than that of interventricular septal thickness or E/A ratio.
Artificial Intelligence Models Do Not Ground Negation, Humans Do. GuessWhat?! Dialogues as a Case Study
Authors: Testoni Alberto , Greco Claudio , Bernardi Raffaella
Published: January 2022

Negation is widely present in human communication, yet it is largely neglected in the research on conversational agents based on neural network architectures. Cognitive studies show that a supportive visual context makes the processing of negation easier. We take GuessWhat?!, a referential visually grounded guessing game, as test-bed and evaluate to which extent guessers based on pre-trained language models profit from negatively answered polar questions. Moreover, to get a better grasp of models' results, we select a controlled sample of games and run a crowdsourcing experiment with subjects. We evaluate models and humans against the same settings and use the comparison to better interpret the models' results. We show that while humans profit from negatively answered questions to solve the task, models struggle in grounding negation, and some of them barely use it; however, when the language signal is poorly informative, visual features help encoding the negative information. Finally, the experiments with human subjects put us in the position of comparing humans and models' predictions and get a grasp about which models make errors that are more human-like and as such more plausible.
Acoustic Predictors of Active Fluid Expulsion From a Hydrothermal Vent Field, Offshore Taupō Volcanic Zone, New Zealand
Authors: Spain Erica , Lamarche Geoffroy , Lucieer Vanessa , Watson Sally J. , Ladroit Yoann , Heffron Erin , Pallentin Arne , Whittaker Joanne M.
Published: January 2022

Understanding fluid expulsion is key to estimating gas exchange volumes between the seafloor, ocean, and atmosphere; for locating key ecosystems; and geohazard modelling. Locating active seafloor fluid expulsion typically requires acoustic backscatter data. Areas of very-high seafloor backscatter, or “hardgrounds,” are often used as first-pass indicators of potential fluid expulsion. However, varying and inconsistent spatial relationships between active fluid expulsion and hardgrounds means a direct link remains unclear. Here, we investigate the links between water-column acoustic flares to seafloor backscatter and bathymetric metrics generated from two calibrated multibeam echosounders. Our site, the Calypso hydrothermal vent field (HVF) in the Bay of Plenty, Aotearoa/New Zealand, has an extensive catalogue of vents and seeps in <250 m water depth. We demonstrate a method to quantitatively link active fluid expulsion (flares) with seafloor characteristics. This allows us to develop predictive spatial models of active fluid expulsion. We explore whether data from a low (30 kHz), high (200 kHz), or combined frequency model increases predictive accuracy of expulsion locations. This research investigates the role of hardgrounds or surrounding sediment cover on the accuracy of predictive models. Our models link active fluid expulsion to specific seafloor characteristics. A combined model using both the 30 and 200 kHz mosaics produced the best results (predictive accuracy: 0.75; Kappa: 0.65). This model performed better than the same model using individual frequency mosaics as input. Model results reveal active fluid expulsion is not typically associated with the extensive, embedded hardgrounds of the Calypso HVF, with minimal fluid expulsion. Unconsolidated sediment around the perimeter of and between hardgrounds were more active fluid expulsion sites. Fluids exploit permeable pathways up to the seafloor, modifying and refashioning the seafloor. Once a conduit self-seals, fluid will migrate to a more permeable pathway, thus reducing a one-to-one link between activity and hardgrounds. Being able to remotely predict active and inactive regions of fluid expulsion will prove a useful tool in rapidly identifying seeps in legacy datasets, as well as textural metrics that will aid in locating nascent, senescent, or extinct seeps when a survey is underway.
Estimating the Shear-Wave Velocities of Shallow Sediments in the Yellow Sea Using Ocean-Bottom-Seismometer Multicomponent Scholte-Wave Data
Authors: Wang Yuan , You Qingyu , Hao Tianyao
Published: January 2022

Scholte-wave dispersion analysis is effective at imaging the relatively low shear-wave velocity of shallow marine sediments in marginal seas. The combination of a four-component ocean-bottom-seismometer (OBS) and a towed air-gun source can economically and effectively acquire the marine dispersive seismic data. Extracting higher-order dispersive Scholte wave modes is the most critical problem in the dispersion analysis method. The extremely low shear-wave velocity and severe attenuation in the top hundreds of meters of marginal sea sediment provide an uneven dispersive energy distribution for the four components of the Scholte wave data. The fundamental mode dispersive energy dominates in the vertical component and higher-order modes dominate in the horizontal component. We developed the method of the four-component OBS Scholte velocity-spectra stacking, which can effectively, rapidly, and robustly extract higher-order modes. We imaged the shear-wave velocity structure of complicated shallow marine sediment in the North Yellow Sea using an active OBS seismic profile with a large-volume air-gun array. The fourth higher-order Scholte wave mode can be imaged with the four-component velocity-spectra stacking method with a lower frequency range of 1.0–7.0 Hz. Only the second-order mode can be recognized from the dispersion energy image of the single vertical component. The joint inversion of multimode dispersion curves can provide more accuracy and deeper constraints for the inverted model; thus, the constraint depth with five modes increases by a factor of 1.9 compared with single fundamental mode inversion. The inverted profile suggests a low shear-wave velocity of 123–670 m/s and strong lateral variations within 350 m. The main regional geological structures are shown by the inverted shear-wave velocity structure.
A Prediction Model of Hydrodynamic Landslide Evolution Process Based on Deep Learning Supported by Monitoring Big Data
Authors: Wang Rubin , Zhang Kun , Qi Jian , Xu Weiya , Long Yan , Huang Haifeng
Published: January 2022

Owing to the complex formation mechanism of hydrodynamic landslides and the involvement of multiple influencing factors, the accuracy of the current prediction model of hydrodynamic landslide evolution process is unsatisfactory. This limitation prevents adequate monitoring and early warning on possible landslides in an area. To improve the accuracy of prediction model of hydrodynamic landslide evolution process supported by monitoring big data, the variational mode decomposition (VMD) and support vector regression (SVR) based on deep learning were integrated in the present study. Typical hydrodynamic landslide in the Three Gorges Reservoir Area (TGRA) in China is used as a case study for landslide displacement prediction. First, the VMD was utilized to decompose the cumulative displacement into the trend, periodic, and random terms. Then, external factors were decomposed into subsequences, and those characterized by periodicity and randomness were selected as input datasets. The associated displacement terms were then predicted using the Random Search–Support Vector Regression model. Finally, the total displacement was obtained by superimposing the three predicted components, and this was used to evaluate the performance of the model. The results show that the model improves the performance and accuracy of predicting the displacement associated with a hydrodynamic landslide, and the relative error is ≤2%.
The Effects of Endometrial Thickness on Pregnancy Outcomes of Fresh IVF/ICSI Embryo Transfer Cycles: An Analysis of Over 40,000 Cycles Among Five Reproductive Centers in China
Authors: Xu Jianing , Zhang Shaodi , Jin Lei , Mao Yundong , Shi Juanzi , Huang Rui , Han Xiao , Liang Xiaoyan , Zhang Cuilian
Published: January 2022

Objective

To investigate the effects of endometrial thickness (EMT) on pregnancy outcomes on hCG trigger day in fresh in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles.

Methods

A total of 42,132 fresh cycles between 1 January 2013 and 31 December 2019 were included in this retrospective cohort study. Data were collected from five reproductive centers of large academic or university hospitals in China. All patients were divided into different groups according to their endometrial thickness on hCG trigger day. Multivariate regression analysis, curve fitting and threshold effect analysis were performed.

Results

After adjusting for age, body mass index, infertility type, number of embryos transferred, number of retrieved oocytes and COS (controlled ovarian stimulation) protocols, significant associations were found between endometrial thickness and clinical pregnancy rate (adjusted odds ratio [aOR]: 1.05; 95% confidence interval [CI]: 1.06–1.08, P < 0.0001), live birth rate (aOR: 1.04; 95% CI: 1.03–1.05, P < 0.0001) as well as miscarriage rate(aOR: 0.96; 95% CI: 0.94 – 0.98, P < 0.0001). When the endometrial thickness was less than 12mm, the clinical pregnancy rate and live birth rate were increased significantly by 10% and 9%(OR:1.10; 95%CI: 1.08-1.12, OR:1.09; 95%CI: 1.07-1.11), respectively, along with the increase of each millimeter increment of endometrial thickness. However, when the EMT ranged from 12-15 mm, were stable at the ideal level, that were not significantly associated with EMT growth. Additionally, clinical pregnancy rate and live birth rate were slightly reduced by 6% and 4% when EMT was ≥15mm. Meanwhile, the miscarriage rate was significantly declined by 8% (OR:0.92; 95%CI: 0.90-0.95)with each millimeter increment of EMT. And when EMT was thicker than 12mm, the miscarriage rate didn’t change any more significantly.

Conclusions

Endometrial thickness exhibits a curvilinear relationship with pregnancy outcomes in fresh embryo transfer cycles. Clinical pregnancy rate, live birth rate and miscarriage rate may achieve their optimal level when EMT ≥ 12 mm, but some adverse pregnancy outcomes would be observed when EMT ≥15 mm especially for clinical pregnancy.
Intracranial Germinoma Misdiagnosed as Hyperthyroidism: A Case Report and Review of the Literature
Authors: Tian Juan , Wu Jialu , Yan Zhe , Huang Hui
Published: January 2022

Intracranial germ cell tumors (GCTs) are relatively rare, which account for 0.5% of all primary intracranial neoplasms. Intracranial germinomas most commonly occur in the pineal and suprasellar region, making up the majority of all intracranial GCTs. For its diversified clinical manifestations, the diagnosis is easily confused with other diseases. Here, we present a case of a 19-year-old boy with intracranial germinoma who was preliminarily misdiagnosed as hyperthyroidism for the symptoms of weight loss and thyroid dysfunction.
ANGPTL4 Expression in Ovarian Granulosa Cells Is Associated With Polycystic Ovary Syndrome
Authors: Jiang Qi , Pan Ye , Li Ping , Zheng Yanjun , Bian Yuehong , Wang Wenqi , Wu Guihua , Song Tian , Shi Yuhua
Published: January 2022

Objectives

This study aims to characterize the expression of ANGPTL4 in ovarian granulosa cells (GCs) and its association with polycystic ovary syndrome (PCOS).

Methods

This study included 104 PCOS patients and 112 women in control group undergoing in vitro fertilization-embryo transfer (IVF-ET) from the reproductive hospital affiliated with Shandong University from 2019 to 2021. By reverse transcription and real-time quantitative (RT-q) PCR, the mRNA expression of ANGPTL4 in GCs was assessed, and clinical information for these patients were then reviewed and analyzed.

Results

The RT-qPCR results showed that ANGPTL4 expression in the control group was significantly lower than that in the PCOS group (p = 0.000) and had positive association with AMH (r = 0.211), HOMA-IR (r = 0.174), LDL/HDL (r = 0.176), ApoB/ApoAI (r = 0.155), and TC/HDL (r = 0.189). Additionally, the high expression of ANGPTL4 in the ovarian granulosa cells might be an independent predictor in PCOS (OR: 3.345; 95% CI: 1.951–5.734) with a close contact with incidence of PCOS (AUC: 0.704; 95% CI: 0.633–0.774, p < 0.001).

Conclusions

Our study revealed higher ANGPTL4 expression in ovarian GCs with PCOS. Its association with glucose and lipid metabolism showed that ANGPTL4 might play an important role in PCOS metabolism and pathogenesis.
Ultrasound and Contrast-Enhanced Ultrasound Characteristics Associated With cN1 and Microscopic pN1 in Papillary Thyroid Carcinoma
Authors: Li Wen , Qiu Shusheng , Ren Ling , Li Qiuyang , Xue Shaowei , Li Jie , Zhang Yan , Luo Yukun
Published: January 2022

Objectives

Lymph node metastases (LNMs) could be stratified into clinical N1 (cN1) and microscopic pN1 (pathological N1), which bear different biological behavior and prognosis. Our study aimed to investigate the associations between LNMs and primary tumor’s US (ultrasound) and CEUS (contrast-enhanced ultrasound) characteristics based on the stratification of LNMs into cN1 and microscopic pN1 in papillary thyroid carcinoma (PTC).

Methods

From August 2019 to May 2020, 444 consecutive PTC patients who underwent preoperative neck US and CEUS evaluation were included. According to regional lymph node status, the patients were classified into cN1 group versus cN0 (clinical N0) group and microscopic pN1 group versus pN0 (pathological N0) group. For multiple PTCs, the largest one was selected for the evaluation of US, CEUS and clinical features. Univariate and multivariate analyses were performed to determine independent predictors of cN1 and microscopic pN1.

Results

85 cN1 versus 359 cN0 patients and 117 microscopic pN1 versus 242 pN0 patients were analyzed. Multivariate logistic regression analysis showed that <55-years-old (OR: 2.56 (1.08–6.04), male [OR: 2.18 (1.22–3.91)], large size [OR: 2.59 (1.71–3.92)], calcification [OR: 3.88 (1.58–9.51)], and hyper-enhancement [OR: 2.78 (1.22–6.30)] were independent risk factors of cN1, while <55-years-old [OR: 1.91 (1.04–3.51)], large size [OR: 1.56 (1.003–2.42)], multifocality [OR: 1.67 (1.04–2.66)] were independent risk factors of microscopic pN1.

Conclusions

For patients with PTC, young age, male, large size, calcification, and hyper-enhancement were independent predictors of cN1, while young age, large size and multifocality were independent predictors of microscopic pN1.
Migraine Is More Prevalent in Advanced-Stage Endometriosis, Especially When Co-Occuring with Adenomoysis
Authors: Wu Yingchen , Wang Hao , Chen Shengfu , Lin Yueming , Xie Xiaoqian , Zhong Guangzheng , Zhang Qingxue
Published: January 2022

Background

Emerging data suggest a significant association between migraine and endometriosis, however the relationship between migraine and endometriosis severity or adenomyosis is unclear. Our objectives were to explore the relationship between migraine and endometriosis, according to the endometriosis severity and co-exist with adenomyosis or not.

Methods

This case-control study of 167 endometriosis patients verified by surgery and 190 patients for other benign gynecological conditions (control subjects) was performed from September 2017 and January 2021. There is 49 adenomyosis detected by transvaginal ultrasound or histologic diagnosis among the endometriosis patients. Besides, we also included 41 adenomyosis but without endometriosis patients as a subgroup. All women completed a self-administered headache questionnaire and diagnosed as migraine according to the International Headache Society classification. The severity and stage of endometriosis was evaluated with revised American Society of Reproductive Medicine (rASRM) score. We used logistic regression to estimate the association between the presence of migraine and endometriosis severity while accounting for important confounders, including age, body mass index (BMI) and family history of migraine. We also estimate the risk of adenomyosis alone and adenomyosis with co-occurring endometriosis in migrainous women.

Results

Migraine was significantly more prevalent in endometriosis patients compared with controls (29.9% vs. 12.1%, p<0.05), but the prevalence was similar between isolated adenomyosis patients and controls (9.8% vs.12.1%, p>0.05). For all endometriosis and control participants, migraineurs were 4.6-times (OR=4.6; 95% CI 2.7-8.1) more likely to have severe endometriosis. However, the strength of the association decreased when the analysis examined in moderate stage (OR=3.6, 95% CI 2.1-6.2). The risk of mild and minimal endometriosis was not significant (OR=1.9, 95%CI 0.9-4.0; OR=1.6, 95% CI 0.8-3.4; respectively). When we divided the endometriosis patients according to whether co-occurring with adenomyosis. We found in migrainous women, the risk of endometriosis co-exist with adenomyosis increased, with nearly fivefold greater odds compared with control (OR=5.4;95% CI 3.0-9.5), and nearly two times higher than the risk of endometriosis without co-exist adenomyosis patients (OR=2.2; 95% CI 1.2-3.8).

Conclusion

Our study supports the strong association between migraine and endometriosis. We found migrainous women suffer more frequently from sever endometriosis, especially endometriosis with co-occurring adenomyosis. It is advisable to heighten suspicion for patients who presenting with either these conditions in order to optimize therapy.