bluuebunny/crossref_metadata_2025 huggingface dataset:
“It Just Kind of Feels Like a Different World Now:” Stress and Resilience for Adolescents With Type 1 Diabetes in the Era of COVID-19
Authors: O’Donnell Maeve B. , Hilliard Marisa E. , Cao Viena T. , Bradford Miranda C. , Barton Krysta S. , Hurtado Samantha , Duran Brenda , Perez Samantha Garcia , Rahman Kiswa S. , Scott Samantha , Malik Faisal S. , DeSalvo Daniel J. , Pihoker Catherine , Zhou Chuan , Rosenberg Abby R. , Yi-Frazier Joyce P.
Published: February 2022

Purpose

The COVID-19 pandemic has been a major stressor for adolescents. Given the unique implications of the pandemic for youth with type 1 diabetes (T1D), who already navigate multiple stressors as a function of their chronic condition, we aimed to describe the impact of the pandemic on adolescents with T1D and describe their coping strategies and resilience resources.

Research Method

In a 2-site (Seattle WA, Houston TX) clinical trial of a psychosocial intervention targeting stress/resilience, adolescents 13-18 years old with T1D ≥ 1 year and elevated diabetes distress were enrolled August 2020 – June 2021. Participants completed a baseline survey about the pandemic, including open-ended questions about the effects of the pandemic, what was helping them navigate, and how it impacted T1D management. Hemoglobin A1c (A1c) was extracted from clinical records. Free text responses were analyzed using an inductive content approach. Survey responses and A1c were summarized using descriptive statistics and associations were assessed by Chi-squared tests.

Results

Adolescents (n=122) were 56% female. 11% of adolescents reported diagnosis of COVID-19 and 12% had a family member/other important person die from COVID-19 complications. Adolescents described Social Relationships, Personal Health/Safety Practices, Mental Health, Family Relationships, and School to be primary areas affected by COVID-19. Helpful resources included: Learned Skills/Behaviors, Social Support/Community, and Meaning-Making/Faith. Among participants indicating that the pandemic had an impact on their T1D management (n=35), the most commonly described areas were: Food, Self-Care, Health/Safety, Diabetes Appointments, and Exercise. Compared to adolescents who reported minimal difficulty managing T1D during the pandemic (71%), those reporting moderate to extreme difficulty (29%) were more likely to have A1C ≥ 8% (80% vs. 43%, p<.01).

Conclusions

Results underscore the pervasive impact of COVID-19 on teens with T1D across multiple major life domains. Their coping strategies aligned with stress, coping, and resilience theories and suggest resilient responses in the face of stress. Despite experiencing pandemic-related stressors in many areas, diabetes-related functioning was relatively protected for most teens, highlighting their diabetes-specific resilience. Discussing the pandemic impact on T1D management may be an important focus for clinicians, especially for adolescents with diabetes distress and above-target A1C.
DNA Damage and Activation of cGAS/STING Pathway Induce Tumor Microenvironment Remodeling
Authors: Shen Rong , Liu Disheng , Wang Xiaoning , Guo Zhao , Sun Haonan , Song Yanfeng , Wang Degui
Published: February 2022

DNA damage occurs throughout tumorigenesis and development. The immunogenicity of DNA makes it an immune stimulatory molecule that initiates strong inflammatory responses. The cGAS/STING pathway has been investigated as a critical receptor in both exogenous and endogenous DNA sensing to activate the innate immune response. Growing lines of evidence have indicated that activation of the cGAS/STING pathway is critical in antitumor immunity. Recent studies have demonstrated the outstanding advancement of this pathway in tumor-combined immunotherapy; accordingly, increased studies focus on exploration of STING pathway agonists and analogues. However, current studies propose the potential use of the cGAS/STING pathway in tumor initiation and metastasis. Here, we review the molecular mechanisms and activation of the cGAS/STING pathway, and the relationship between DNA damage and this pathway, particularly highlighting the remodeling of immune contexture in tumor environment (TME) triggered by cascade inflammatory signals. A detailed understanding of TME reprogramming initiated by this pathway may pave the way for the development of new therapeutic strategies and rational clinical application.
Snail Augments Nuclear Deformability to Promote Lymph Node Metastasis of Head and Neck Squamous Cell Carcinoma
Authors: Chen Yin-Quan , Hung Chen-Yu , Wei Ming-Tzo , Kuo Jean-Cheng , Yang Muh-Hwa , Cheng Han-Ying , Chiou Arthur
Published: February 2022

Up to 50% of head and neck squamous cell carcinoma (HNSCC) patients have lymph node (LN) metastasis, resulting in poor survival rate. Numerous studies have supported the notion that the alterations of gene expression and mechanical properties of cancer cells play an important role in cancer metastasis. However, which genes and how they regulate the biomechanical properties of HNSCC cells to promote LN metastasis remains elusive. In this study, we used an LN-metastatic mouse model in vivo to generate an LN-metastatic head and neck squamous cell carcinoma cell line and compared the differences in the biomolecular and biomechanical properties of LN-metastatic and non-metastatic cells. Our results showed that LN-metastatic cells had a higher level of Snail expression compared to non-LN-metastatic cells. The higher Snail expression promoted the cellular invasion capability in confined environments, mainly by increasing the longitudinal strain of the cell nuclei, which could be attributed to the stronger cell traction force and softer nuclear stiffness. These two biomechanical changes were correlated, respectively, to a larger amount of focal adhesion and less amount of nuclear lamins. Taken together, our works revealed not only the biomechanical profiles of LN-metastatic cells but also the corresponding biomolecular expressions to pinpoint the key process in LN metastasis.
Identification and Quantification of Iron Metabolism Landscape on Therapy and Prognosis in Bladder Cancer
Authors: Song Xiaodong , Xin Sheng , Zhang Yucong , Mao Jiaquan , Duan Chen , Cui Kai , Chen Liang , Li Fan , Liu Zheng , Wang Tao , Liu Jihong , Liu Xiaming , Song Wen
Published: February 2022

The morbidity of bladder cancer (BLCA) is high and has gradually elevated in recent years. BLCA is also characterized by high recurrence and high invasiveness. Due to the drug resistance and lack of effective prognostic indicators, the prognosis of patients with BLCA is greatly affected. Iron metabolism is considered to be a pivot of tumor occurrence, progression, and tumor microenvironment (TME) in tumors, but there is little research in BLCA. Herein, we used univariate COX regression analysis to screen 95 prognosis-related iron metabolism-related genes (IMRGs) according to transcription RNA sequencing and prognosis information of the Cancer Genome Atlas (TCGA) database. TCGA-BLCA cohort was clustered into four distinct iron metabolism patterns (C1, C2, C3, and C4) by the non-negative matrix factorization (NMF) algorithm. Survival analysis showed that C1 and C3 patterns had a better prognosis. Gene set variant analysis (GSVA) revealed that C2 and C4 patterns were mostly enriched in carcinogenic and immune activation pathways. ESTIMATE and single sample gene set enrichment analysis (ssGSEA) also confirmed the level of immune cell infiltration in C2 and C4 patterns was significantly elevated. Moreover, the immune checkpoint genes in C2 and C4 patterns were observably overexpressed. Studies on somatic mutations showed that the tumor mutation burden (TMB) of C1 and C4 patterns was the lowest. Chemotherapy response assessment revealed that C2 pattern was the most sensitive to chemotherapy, while C3 pattern was the most insensitive. Then we established the IMRG prognosis signature (IMRGscore) by the least absolute shrinkage and selection operator (LASSO), including 13 IMRGs (TCIRG1, CTSE, ATP6V0A1, CYP2C8, RNF19A, CYP4Z1, YPEL5, PLOD1, BMP6, CAST, SCD, IFNG, and ASIC3). We confirmed IMRGscore could be utilized as an independent prognostic indicator. Therefore, validation and quantification of iron metabolism landscapes will help us comprehend the formation of the BLCA immunosuppressive microenvironment, guide the selection of chemotherapeutic drugs and immunotherapy, and predict the prognosis of patients.
Single-Cell RNA Sequencing of the Nucleus Pulposus Reveals Chondrocyte Differentiation and Regulation in Intervertebral Disc Degeneration
Authors: Han Shuo , Zhang Yiran , Zhang Xianjuan , Zhang Hao , Meng Shengwei , Kong Meng , Liu Xiaojie , Ma Xuexiao
Published: February 2022

The nucleus pulposus (NP), a heterogeneous tissue, is an essential functional component of the intervertebral disc. However, NP cell development route and regulation mechanism in intervertebral disc degeneration (IVDD) remain unknown. Here, we performed single-cell RNA sequencing of six NP samples with normal control, mild degeneration, and severe degeneration. Based on unbiased clustering of gene expression patterns from 30,300 single-cell RNA sequencing, we identified three cell lineage families of macrophages, endothelial, and chondrocyte cells and characterized seven chondrocyte subtypes, and defined two developmental pathways of the chondrocyte cell lineage families in the process of IVDD. Additionally, CellPhoneDB analysis revealed potential interactions between chondrocyte cells and other cells in IVDD. Chondrocytes in one of the differentiated orientations interact with macrophages and endothelial cells and have an inflammatory amplification effect, which were key factors causing IVDD. Collectively, these results revealed the dynamic cell landscape of IVDD development and offered new insights into the influence of NP cells differentiation on extracellular matrix homeostasis during degeneration, providing potential treatment targets for IVDD.
Embryonic Hypotaurine Levels Contribute to Strain-Dependent Susceptibility in Mouse Models of Valproate-Induced Neural Tube Defects
Authors: Steele John W. , Lin Ying Linda , Chen Nellie , Wlodarczyk Bogdan J. , Chen Qiuying , Attarwala Nabeel , Venkatesalu Madhu , Cabrera Robert M. , Gross Steven S. , Finnell Richard H.
Published: February 2022

Valproic acid (VPA, valproate, Depakote) is a commonly used anti-seizure medication (ASM) in the treatment of epilepsy and a variety of other neurological disorders. While VPA and other ASMs are efficacious for management of seizures, they also increase the risk for adverse pregnancy outcomes, including neural tube defects (NTDs). Thus, the utility of these drugs during pregnancy and in women of childbearing potential presents a continuing public health challenge. Elucidating the underlying genetic or metabolic risk factors for VPA-affected pregnancies may lead to development of non-teratogenic ASMs, novel prevention strategies, or more targeted methods for managing epileptic pregnancies. To address this challenge, we performed unbiased, whole embryo metabolomic screening of E8.5 mouse embryos from two inbred strains with differential susceptibility to VPA-induced NTDs. We identified metabolites of differential abundance between the two strains, both in response to VPA exposure and in the vehicle controls. Notable enriched pathways included lipid metabolism, carnitine metabolism, and several amino acid pathways, especially cysteine and methionine metabolism. There also was increased abundance of ω-oxidation products of VPA in the more NTD-sensitive strain, suggesting differential metabolism of the drug. Finally, we found significantly reduced levels of hypotaurine in the susceptible strain regardless of VPA status. Based on this information, we hypothesized that maternal supplementation with L-carnitine (400 mg/kg), coenzyme A (200 mg/kg), or hypotaurine (350 mg/kg) would reduce VPA-induced NTDs in the sensitive strain and found that administration of hypotaurine prior to VPA exposure significantly reduced the occurrence of NTDs by close to one-third compared to controls. L-carnitine and coenzyme A reduced resorption rates but did not significantly reduce NTD risk in the sensitive strain. These results suggest that genetic variants or environmental exposures influencing embryonic hypotaurine status may be factors in determining risk for adverse pregnancy outcomes when managing the health care needs of pregnant women exposed to VPA or other ASMs.
Tgfbr2 in Dental Pulp Cells Guides Neurite Outgrowth in Developing Teeth
Authors: Stanwick Monica , Barkley Courtney , Serra Rosa , Kruggel Andrew , Webb Amy , Zhao Yue , Pietrzak Maciej , Ashman Chandler , Staats Allie , Shahid Shifa , Peters Sarah B.
Published: February 2022

Transforming growth factor β (TGFβ) plays an important role in tooth morphogenesis and mineralization. During postnatal development, the dental pulp (DP) mesenchyme secretes neurotrophic factors that guide trigeminal nerve fibers into and throughout the DP. This process is tightly linked with dentin formation and mineralization. Our laboratory established a mouse model in which Tgfbr2 was conditionally deleted in DP mesenchyme using an Osterix promoter-driven Cre recombinase (Tgfbr2cko). These mice survived postnatally with significant defects in bones and teeth, including reduced mineralization and short roots. Hematoxylin and eosin staining revealed reduced axon-like structures in the mutant mice. Reporter imaging demonstrated that Osterix-Cre activity within the tooth was active in the DP and derivatives, but not in neuronal afferents. Immunofluorescence staining for β3 tubulin (neuronal marker) was performed on serial cryosections from control and mutant molars on postnatal days 7 and 24 (P7, P24). Confocal imaging and pixel quantification demonstrated reduced innervation in Tgfbr2cko first molars at both stages compared to controls, indicating that signals necessary to promote neurite outgrowth were disrupted by Tgfbr2 deletion. We performed mRNA-Sequence (RNA-Seq) and gene onotology analyses using RNA from the DP of P7 control and mutant mice to investigate the pathways involved in Tgfbr2-mediated tooth development. These analyses identified downregulation of several mineralization-related and neuronal genes in the Tgfbr2cko DP compared to controls. Select gene expression patterns were confirmed by quantitative real-time PCR and immunofluorescence imaging. Lastly, trigeminal neurons were co-cultured atop Transwell filters overlying primary Tgfbr2f/f DP cells. Tgfbr2 in the DP was deleted via Adenovirus-expressed Cre recombinase. Confocal imaging of axons through the filter pores showed increased axonal sprouting from neurons cultured with Tgfbr2-positive DP cells compared to neurons cultured alone. Axon sprouting was reduced when Tgfbr2 was knocked down in the DP cells. Immunofluorescence of dentin sialophosphoprotein in co-cultured DP cells confirmed reduced mineralization potential in cells with Tgfbr2 deletion. Both our proteomics and RNA-Seq analyses indicate that axonal guidance cues, particularly semaphorin signaling, were disrupted by Tgfbr2 deletion. Thus, Tgfbr2 in the DP mesenchyme appears to regulate differentiation and the cells’ ability to guide neurite outgrowth during tooth mineralization and innervation.
Using Drosophila Nephrocytes to Understand the Formation and Maintenance of the Podocyte Slit Diaphragm
Authors: van de Leemput Joyce , Wen Pei , Han Zhe
Published: February 2022

The podocyte slit diaphragm (SD) is an essential component of the glomerular filtration barrier and its disruption is a common cause of proteinuria and many types of kidney disease. Therefore, better understanding of the pathways and proteins that play key roles in SD formation and maintenance has been of great interest. Podocyte and SD biology have been mainly studied using mouse and other vertebrate models. However, vertebrates are limited by inherent properties and technically challengingin vivoaccess to the podocytes.Drosophilais a relatively new alternative model system but it has already made great strides. Past the initial obvious differences, mammalian podocytes and fly nephrocytes are remarkably similar at the genetic, molecular and functional levels. This review discusses SD formation and maintenance, and their dependence on cell polarity, the cytoskeleton, and endo- and exocytosis, as learned from studies in fly nephrocytes and mammalian podocytes. In addition, it reflects on the remaining gaps in our knowledge, the physiological implications for glomerular diseases and how we can leverage the advantagesDrosophilahas to offer to further our understanding.
The Dynamic Instability of the Aneuploid Genome
Authors: Garribba Lorenza , Santaguida Stefano
Published: February 2022

Proper partitioning of replicated sister chromatids at each mitosis is crucial for maintaining cell homeostasis. Errors in this process lead to aneuploidy, a condition in which daughter cells harbor genome imbalances. Importantly, aneuploid cells often experience DNA damage, which in turn could drive genome instability. This might be the product of DNA damage accumulation in micronuclei and/or a consequence of aneuploidy-induced replication stress in S-phase. Although high levels of genome instability are associated with cell cycle arrest, they can also confer a proliferative advantage in some circumstances and fuel tumor growth. Here, we review the main consequences of chromosome segregation errors on genome stability, with a special focus on the bidirectional relationship between aneuploidy and DNA damage. Also, we discuss recent findings showing how increased genome instability can provide a proliferation improvement under specific conditions, including chemotherapeutic treatments.
Triterpenoid Saponins From the Fruit of Acanthopanax senticosus (Rupr. & Maxim.) Harms
Authors: Liu Yan , Jiang Peng , Zhang Mei-Ling , Pan Juan , Guan Wei , Li Xiao-Mao , Yang Bing-You , Kuang Hai-Xue
Published: February 2022

Five new oleanane-type triterpenoid saponins (1–5), together with 24 known saponins (6–29) were isolated from the fruit of Acanthopanax senticosus. Their structures were determined by extensive spectroscopic analysis, including 1D, 2D nuclear magnetic resonance (NMR), and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), in combination with chemical methods (acid hydrolysis). The neuroinflammation model was established by lipopolysaccharide (LPS)-induced BV2 microglia, and the neuroprotective effects of all compounds (1–29) were evaluated.
AuPt Bimetallic Nanozymes for Enhanced Glucose Catalytic Oxidase
Authors: Chen Feixiang , Song Tianlin
Published: February 2022

Au metal nanoparticles as artificial nanozymes have attracted wide interest in biotechnology due to high stability and easy synthesis. Unfortunately, its catalytic activity is limited by the uniform surface electron distribution, fundamentally affecting the oxidation efficiency of glucose. Here, we synthesized AuPt bimetallic nanoparticles with unique surface electron structure due to the coupling effect of the two metal components, achieving improved glucose catalytic oxidase. Because of the effective work function difference between the two metals in AuPt, the electrons will transfer from Au to accumulate on Pt, simultaneously contributing to the substantial enhancement of Au-induced glucose oxidase and Pt-induced catalase performance. We systematically studied the enzyme-catalytic efficiency of AuPt with varied two metal proportions, in which Au:Pt at 3:1 showed the highest catalytic efficiency of glucose oxidase in solution. The AuPt nanoparticles were further co-cultured with cells and also showed excellent biological activity for glucose oxidase. This work demonstrates that the physicochemical properties between different metals can be exploited for engineering high-performance metal nanoparticle-based nanozymes, which opens up a new way to rationally design and optimize artificial nanozymes to mimic natural enzymes.
Prevalence of Clostridium difficile Infection in the Hematopoietic Transplantation Setting: Update of Systematic Review and Meta-Analysis
Authors: Luo Ying , Zhang Sumei , Shang Hua , Cui Weitong , Wang Qinglu , Zhu Bin
Published: February 2022

Hematopoietic stem cell transplant (HSCT) recipients are vulnerable to Clostridium difficile infection (CDI) due to risk factors such as immunosuppression, antimicrobial use, and frequent hospitalization. We systematically searched PubMed and Embase to screen relevant studies from April 2014 to November 2021. A meta-analysis was performed to identify the association between CDI and hematopoietic transplantation based on the standard mean difference and 95% confidence intervals (CIs). Among the 431 retrieved citations, we obtained 43 eligible articles, which included 15,911 HSCT patients at risk. The overall estimated prevalence of CDI was 13.2%. The prevalence of CDI among the 10,685 allogeneic transplantation patients (15.3%) was significantly higher than that among the 3,840 autologous HSCT recipients (9.2%). Different incidence rates of CDI diagnosis over the last 7 years were found worldwide, of which North America (14.1%) was significantly higher than Europe (10.7%) but not significantly different from the prevalence among Asia (11.6%). Notably, we found that the estimated prevalence of CDI diagnosed by polymerase chain reaction (PCR) (17.7%) was significantly higher than that diagnosed by enzyme immunoassay (11.5%), indicating a significant discrepancy in the incidence rate of CDI owing to differences in the sensibility and specificity of the detection methods. Recurrence of CDI was found in approximately 15% of the initial patients with CDI. Furthermore, 20.3% of CDI cases were severe. CDI was found to be a common complication among HSCT recipients, displaying an evident increase in the morbidity of infection.
Value of Fast MVO Identification From Contrast-Enhanced Cine (CE-SSFP) Combined With Myocardial Strain in Predicting Adverse Events in Patients After ST-Elevation Myocardial Infarction
Authors: Zhang Min , Lu Yuan , Li Zhi , Shao Yameng , Chen Lei , Yang Yu , Xi Jianning , Chen Minglong , Jiang Tingbo
Published: February 2022

Objectives

Cardiac magnetic resonance imaging (CMR) can be used for a one-step evaluation of myocardial function and pathological features after acute ST-elevation myocardial infarction (STEMI). We aimed to evaluate the value of fast microvascular occlusion (MVO) identification from contrast-enhanced steady-state free precession (CE-SSFP) combined with myocardial strain in predicting major cardiovascular adverse events (MACEs) in primary percutaneous coronary intervention (pPCI) patients with STEMI.

Methods

In total, 237 patients with STEMI who received pPCI and completed CMR scans within the following week were enrolled, MVO identification and the myocardial strain analysis were performed in CE-SSFP images without an additional method. The primary endpoint was the presence of MACE, which is defined as a composite of death, reinfarction, and congestive heart failure (HF).

Results

After 13 months of follow-up [interquartile range (IQR): 11–24], 30 patients (14%) developed MACE; the MVO (hazard ratio (HR) was 3.10; 95% CI: 1.14–8.99, p = 0.028), and the infarct size (IS) (HR: 1.03; 95% CI: 1.0–1.06, p = 0.042) and global longitudinal strain (GLS) (HR: 1.08; 95% CI: 1.01–1.17, p = 0.029) were finally associated with MACE. Receiver operating characteristic (ROC) analyses show that the area under the curve (AUC) of GLS was large (0.73 [95% CI, 0.63–0.82], p = 0.001), and the best cut-off was −11.8%, with 76.7% sensitivity and 58.9% specificity, which are greater than those of IS (0.70, 95% CI, 0.60–0.81, p < 0.001) and MVO (0.68, 95% CI, 0.58–0.78, p < 0.001). However, combining MVO and GLS resulted in a much greater finding (AUC = 0.775, 95% CI: 0.727–0.824, p < 0.001) and better sensitivity and specificity (83.3%, 66.5%).

Conclusion

Microvascular occlusion identification from contrast-enhanced cine combined with myocardial strain could be a quick and reliable option for patients with STEMI who underwent pPCI; it correlates well with the prognosis of patients with STEMI in terms of MACE.
A Contemporary Review of the Effects of Exercise Training on Cardiac Structure and Function and Cardiovascular Risk Profile: Insights From Imaging
Authors: Alhumaid Waleed , Small Stephanie D. , Kirkham Amy A. , Becher Harald , Pituskin Edith , Prado Carla M. , Thompson Richard B. , Haykowsky Mark J. , Paterson D. Ian
Published: February 2022

Exercise is a commonly prescribed therapy for patients with established cardiovascular disease or those at high risk for de novo disease. Exercise-based, multidisciplinary programs have been associated with improved clinical outcomes post myocardial infarction and is now recommended for patients with cancer at elevated risk for cardiovascular complications. Imaging studies have documented numerous beneficial effects of exercise on cardiac structure and function, vascular function and more recently on the cardiovascular risk profile. In this contemporary review, we will discuss the effects of exercise training on imaging-derived cardiovascular outcomes. For cardiac imaging via echocardiography or magnetic resonance, we will review the effects of exercise on left ventricular function and remodeling in patients with established or at risk for cardiac disease (myocardial infarction, heart failure, cancer survivors), and the potential utility of exercise stress to assess cardiac reserve. Exercise training also has salient effects on vascular function and health including the attenuation of age-associated arterial stiffness and thickening as assessed by Doppler ultrasound. Finally, we will review recent data on the relationship between exercise training and regional adipose tissue deposition, an emerging marker of cardiovascular risk. Imaging provides comprehensive and accurate quantification of cardiac, vascular and cardiometabolic health, and may allow refinement of risk stratification in select patient populations. Future studies are needed to evaluate the clinical utility of novel imaging metrics following exercise training.
Intravascular Lithotripsy in Calcified Coronary Lesions: A Single-Center Experience in “Real-World” Patients
Authors: Mastrangelo Angelo , Monizzi Giovanni , Galli Stefano , Grancini Luca , Ferrari Cristina , Olivares Paolo , Chiesa Mattia , Calligaris Giuseppe , Fabbiocchi Franco , Montorsi Piero , Bartorelli Antonio L.
Published: February 2022

Objectives

This study aims to describe the outcome of intravascular lithotripsy (IVL) when used with different indications and to assess the short- and long-term outcomes of IVL-facilitated percutaneous coronary intervention (PCI).

Background

Intravascular lithotripsy can improve the results of PCI of calcified coronary lesions with a low rate of periprocedural complications.

Methods

A total of 105 consecutive patients with 110 calcified lesions underwent IVL. A total of 87de novolesions were treated by IVL with the following indications: 25 before attempting other balloon-based devices (primary IVL), 51 after the failure of non-compliant balloon dilatation (secondary IVL), and 11 after stent implantation because of stent under expansion (bailout IVL). In 23 lesions, IVL was used for the treatment of in-stent restenosis (ISR). Effectiveness (angiographic success) and safety [major adverse cardiovascular events (MACEs) and IVL-related procedural complications] endpoints were assessed.

Results

Angiographic success was achieved in 84.6% of lesions. Early MACEs were periprocedural MI only, ranging from 6.7 to 20% depending on MI definition. The flow-limiting dissections rate was 2.7%. A total of five (4.5%) IVL balloons ruptured during treatment with subsequent vessel perforation in 1 case. MACEs at 12 months were 13.3%, with TLR occurring in 8 lesions (12% primary IVL, 0% secondary IVL, 0% bailout IVL, and 21.7% IVL for ISR,p= 0.002).

Conclusion

Treatment of calcified coronary lesions with IVL in a “real-world” setting can be performed with high success, low rate of procedural complications, and an acceptable MACEs rate. Target lesion failure may be more frequent when IVL is performed for the treatment of ISR due to calcium-mediated stent under expansion.
Functional Tricuspid Regurgitation: Behind the Scenes of a Long-Time Neglected Disease
Authors: Vinciguerra Mattia , Sitges Marta , Luis Pomar Jose , Romiti Silvia , Domenech-Ximenos Blanca , D'Abramo Mizar , Wretschko Eleonora , Miraldi Fabio , Greco Ernesto
Published: February 2022

Severe tricuspid valve regurgitation has been for a long time a neglected valve disease, which has only recently attracted an increasing interest due to the notable negative impact on the prognosis of patients with cardiovascular disease. It is estimated that around 90% of tricuspid regurgitation is diagnosed as “functional” and mostly secondary to a primary left-sided heart disease and, therefore, has been usually interpreted as a benign condition that did not require a surgical management. Nevertheless, the persistence of severe tricuspid regurgitation after left-sided surgical correction of a valve disease, particularly mitral valve surgery, has been associated to adverse outcomes, worsening of the quality of life, and a significant increase in mortality rate. Similar results have been found when the impact of isolated severe tricuspid regurgitation has been studied. Current knowledge is shifting the “functional” categorization toward a more complex and detailed pathophysiological classification, identifying various phenotypes with completely different etiology, natural history and, potentially, an invasive management. The aim of this review is to offer a comprehensive guide for clinicians and surgeons with a systematic description of “functional” tricuspid regurgitation subtypes, an analysis centered on the effectiveness of existing surgical techniques and a focus on the emergent percutaneous procedures. This latter may be an attractive alternative to a standard surgical approach in patients with high-operative risk or isolated tricuspid regurgitation.
Physical Inactivity Is Associated With Post-discharge Mortality and Re-hospitalization Risk Among Swedish Heart Failure Patients—The HARVEST-Malmö Study
Authors: Zaghi Amir , Holm Hannes , Korduner Johan , Dieden Anna , Molvin John , Bachus Erasmus , Jujic Amra , Magnusson Martin
Published: February 2022

Background

Several studies have examined the role of physical activity as a predictor of heart failure (HF) mortality and morbidity. Here, we aimed to evaluate the role of self-reported physical activity as an independent risk factor of post-discharge mortality and re-hospitalization in patients hospitalized for HF, as well as study the association between physical activity and 92 plasma proteins associated with cardiovascular disease (CVD).

Methods

Four-hundred-and-thirty-four patients hospitalized for HF (mean age 75 years; 32% women) were screened for physical activity derived from questionnaires in the Swedish national public health survey. The median follow-up time to death and re-hospitalization was 835 (interquartile range, 390–1,432) and 157 (43–583) days, respectively. Associations between baseline reported physical activity, mortality and re-hospitalization risk were analyzed using multivariable Cox regression analysis. Plasma samples from 295 study participants were analyzed with a proximity extension assay consisting of 92 proteins. Associations between proteins and physical activity were explored using a false discovery rate of <5%, and significant associations were taken forward to multivariate analyses.

Results

In the multivariate Cox regression model, physical inactivity, defined as physical activity time <1 h throughout the week was associated with increased risk of all-cause mortality (HR 1.71; CI95% 1.26–2.31; p = 5.9 × 10−4) as well as all-cause re-hospitalization (HR 1.27; CI95% 1.01–1.60; p = 0.038). Further, physical inactivity was associated with elevated plasma levels of Metalloproteinase inhibitor 4, Soluble interleukin 1 receptor-like 1, Elafin and Transferrin receptor protein 1, which are implicated in myocardial fibrosis, migration and apoptosis.

Conclusions

Self-reported low weekly physical activity is associated with increased risk of mortality and re-hospitalization in patients hospitalized for HF independent of traditional risk factors. Furthermore, physical inactivity was associated with elevated levels of 4 proteins linked to cardiovascular disease.
Predicting Clinical Events Based on Raw Text: From Bag-of-Words to Attention-Based Transformers
Authors: Roussinov Dmitri , Conkie Andrew , Patterson Andrew , Sainsbury Christopher
Published: February 2022

Identifying which patients are at higher risks of dying or being re-admitted often happens to be resource- and life- saving, thus is a very important and challenging task for healthcare text analytics. While many successful approaches exist to predict such clinical events based on categorical and numerical variables, a large amount of health records exists in the format of raw text such as clinical notes or discharge summaries. However, the text-analytics models applied to free-form natural language found in those notes are lagging behind the break-throughs happening in the other domains and remain to be primarily based on older bag-of-words technologies. As a result, they rarely reach the accuracy level acceptable for the clinicians. In spite of their success in other domains, the superiority of deep neural approaches over classical bags of words for this task has not yet been convincingly demonstrated. Also, while some successful experiments have been reported, the most recent break-throughs due to the pre-trained language models have not yet made their ways into the medical domain. Using a publicly available healthcare dataset, we have explored several classification models to predict patients' re-admission or a fatality based on their discharge summaries and established that 1) The performance of the neural models used in our experiments convincingly exceeds those based on bag-of-words by several percentage points as measured by the standard metrics. 2) This allows us to achieve the accuracy typically acceptable by the clinicians as of practical use (area under the ROC curve above 0.70) for the majority of our prediction targets. 3) While the pre-trained attention-based transformer performed only on par with the model that averages word embeddings when applied to full length discharge summaries, the transformer still handles shorter text segments substantially better, at times with the margin of 0.04 in the area under the ROC curve. Thus, our findings extend the success of pre-trained language models reported in other domains to the task of clinical event prediction, and likely to other text-classification tasks in the healthcare analytics domain. 4) We suggest several models to overcome the transformers' major drawback (their input size limitation), and confirm that this is crucial to achieve their top performance. Our modifications are domain agnostic, and thus can be applied in other applications where the text inputs exceed 200 words. 5) We have successfully demonstrated how non-text attributes (such as patient age, demographics, type of admission etc.) can be combined with text to gain additional improvements for several prediction targets. We include extensive ablation studies showing the impact of the training size, and highlighting the tradeoffs between the performance and the resources needed.
Bottom Current Modification of Turbidite Lobe Complexes
Authors: Fuhrmann A. , Kane I. A. , Schomacker E. , Clare M. A. , Pontén Anna
Published: February 2022

Submarine lobes form at the distal end of sediment gravity flow systems and are globally important sinks for sediment, anthropogenic pollutants and organic carbon, as well as forming hydrocarbon and CO2reservoirs. Deep-marine, near bed or bottom currents can modify gravity flow pathways and sediment distribution by directly interacting with the flow or by modifying seafloor morphology. Deciphering the nature of gravity- and bottom currents interaction, particularly in ancient systems, remains a challenge due to the lack of integrated datasets and the necessary oceanographic framework. Here we analyse high-resolution 3D seismic reflection and core data from the Upper Cretaceous interval offshore Tanzania to reveal the interaction of turbidite lobes with fine-grained sediment waves and contourite drift deposits. Contourite drift morphology governs the large-scale confinement style and shape of lobes that range from frontally confined and crescent shaped, to laterally confined and elongated, to semi-confined lobes. Core data reveals massive to cross-laminated high density turbidites in the lobe axis position that show no direct interaction between gravity flows and contour currents. Lobe off-axis and fringe deposits consist of parallel- and ripple-laminated, low density turbidites, which are inter-bedded with bioturbated, muddy siltstones that represent the toes of contourite drifts. Starved ripples, and streaks of up to fine-grained sandstone above individual turbidite beds indicate reworking by bottom currents. This facies distribution reflects the temporal interaction of quasi-steady bottom currents and turbidity currents that interact with the topography and build lobes over short periods of time. Frontally confined turbidity currents form lobes in a fill-and-spill fashion, in which the confinement of turbidity currents causes rapid deposition and obscures any bottom current signal. Lateral confinement causes increased turbidity current runout length, and promotes the development of lobe fringes with a high proportion of bottom current reworked sands. During times when sediment gravity flows are subordinate, contourites accumulate on top of the lobe, confining the next flow and thus modifying the overall stacking pattern of the lobe complex. Although sediment volumes of these bottom current modified lobe complexes are comparable to other deep-marine systems, bottom currents considerably influence facies distribution and deposit architecture.
Merging Satellite and in situ Data to Assess the Flux of Terrestrial Dissolved Organic Carbon From the Mackenzie River to the Coastal Beaufort Sea
Authors: Bertin Clément , Matsuoka Atsushi , Mangin Antoine , Babin Marcel , Le Fouest Vincent
Published: February 2022

In response to global warming, the Arctic is undergoing rapid and unprecedented changes that alter the land-to-sea forcing in large Arctic rivers. Improving our knowledge of terrestrial dissolved organic carbon (tDOC) flux to the coastal Arctic Ocean (AO) is thus critical and timely as these changes strongly alter the biogeochemical cycles on AO shelves. In this study, we merged riverinein situtDOC concentrations with satellite ocean-color estimates retrieved at the land-marine interface of the Mackenzie Delta to make a first assessment of the tDOC export from its main outlets to the shelf. We combined tDOC and river discharge data to develop a regression model that simulated tDOC concentrations and fluxes from daily to interannual (2003–2017) time scales. We then compared the simulated satellite-derived estimates to those simulated by the model constrained byin situtDOC data only. As the satellite tDOC estimates reflect the delta effect in terms of tDOC enrichment and removal, our results inform us of how much tDOC can potentially leave the delta to reach the ocean (1.44 ± 0.14 TgC.yr−1). The chemodynamic relationships and the model suggest contrasting patterns between Shallow Bay and the two easternmost delta outlets, which can be explained by the variability in their geomorphological settings. At the seasonal scale and for all outlets, the satellite-derived tDOC export departs from the estimate based onin situtDOC data only. During the river freshet in May, the satellite-derived tDOC export is, on average, ∼15% (Shallow Bay) to ∼20% (Beluga Bay) lower than the in situ-derived estimate. This difference was the highest (−60%) in 2005 and exceeds 30% over most of the last decade, and can be explained by qualitative and quantitative differences between the tDOCin situand tDOCsatdatasets in a period when the freshet is highly variable. In contrast, in summer and fall, the satellite-derived tDOC export is higher than the in situ-derived estimate. The temporal difference between the satellite and in situ-derived export estimates suggests that predicting seasonal tDOC concentrations and fluxes from remote Arctic deltas to the coastal AO remains a challenge for assessing their impact on already changing carbon fluxes.
Experimental Simulation of Burial Diagenesis and Subsequent 2D-3D Characterization of Sandstone Reservoir Quality
Authors: Charlaftis Dimitrios , Dobson Katherine J. , Jones Stuart J. , Lakshtanov Dmitry , Crouch Jonathan , Cook Jennie
Published: February 2022

Characterization of deeply buried sandstones and their reservoir quality is of paramount importance for exploring, developing, and subsurface storage of energy resources. High reservoir quality in deeply buried sandstones is commonly correlated with the occurrence of grain coatings that inhibit quartz cementation. The development of reliable models that can predict reservoir quality relies on incorporating quantitative understanding of these diagenetic processes. Hydrothermal experiments simulating burial diagenesis were integrated with multi-scale X-ray tomography to quantify the 3-dimensional evolution of grain coating volume and porosity with increasing temperature; while microscopic and automated quantitative mineralogy analysis were used to track the associated mineralogical alterations. To simulate reservoir evolution, sandstone samples from the Lower Jurassic Cook Formation (Oseberg Field, 30/6-17R, Norway) were exposed to a silica supersaturated Na2CO3 (0.1 M) solution for up to 360 h at temperatures of 100–250°C. The experimental results show the main porosity and permeability reduction window is associated with pore-filling kaolinite, and lies between 150 and 200°C, above which little change occurs. Volumetric increases in grain coating start to occur at ∼150°C through precipitation of authigenic chlorite, and continue to 250°C, irrespective of the experimental duration. Together with preexisting siderite coatings, the newly precipitated chlorite prevents the loss of reservoir quality by inhibiting quartz overgrowth development. Pore flow simulations based on the observed temperature-dependent 3-dimensional pore networks allow us to characterize pore-throat and permeability evolution and gain quantitative understanding of the impact of diagenetic overprinting on deeply buried sandstone reservoirs.
Correlation of Seismicity With Faults in the South Korea Plateau in the East Sea (Japan Sea) and Seismic Hazard Assessment
Authors: Kim Han-Joon , Moon Seonghoon , Jou Hyeong-Tae , Kim Kwang-Hee , Yi Bo Yeon
Published: February 2022

The South Korea Plateau (SKP) is a structural high at the eastern continental margin of the Korean Peninsula. Earthquakes occur frequently in the SKP although they are not larger than ML5.0 in magnitude. The SKP is a region of highly rifted continental crust engraved with rifts created during back-arc rifting in the NW Pacific subduction zone that led to the separation of the SW Japan Arc in the Cenozoic. The Bandal, Onnuri, and Okgye Rifts are well-defined rifts in the SKP. Multichannel seismic profiles show that the rifts in the SKP are bounded by large-offset normal faults and their subsided basement is deformed by domino-style faulting. A close spatial correlation is recognized between the epicentral locations of earthquakes with relatively large magnitude and the rift-bounding fault of the Onnuri Rift. The faults in the SKP is interpreted to be reactivated with strike-slip since the middle Miocene. The maximum expected magnitude of earthquakes (Mmax) computed statistically using the catalog including instrumentally recorded seismicity is ML5.42. However, Mmax estimated from the catalog including instrumentally recorded seismicity and historical records increases to ML6.67.
The Effect of Antioxidants on Sperm Quality Parameters and Pregnancy Rates for Idiopathic Male Infertility: A Network Meta-Analysis of Randomized Controlled Trials
Authors: Li Kun-peng , Yang Xue-song , Wu Tao
Published: February 2022

Purpose

Male infertility is a global public health issue recognized by the WHO. Recently, antioxidants are increasingly used to treat idiopathic male infertility. However, the lack of available evidence has led to the inability to rank the effects of antioxidants on the sperm quality parameters and pregnancy rate of infertile men. This network meta-analysis studied the effects of different antioxidants on the sperm quality and pregnancy rate of idiopathic male infertility.

Methods

We searched PubMed, Embase, Web of Science, and Cochrane Library databases for randomized controlled trials (RCTs). The weighted mean difference (WMD) and odds ratio (OR) were applied for the comparison of continuous and dichotomous variables, respectively, with 95% CIs. The outcomes were sperm motility, sperm concentration, sperm morphology, and pregnancy rate.

Results

A total of 23 RCTs with 1,917 patients and 10 kids of antioxidants were included. l-Carnitine, l-carnitine+l-acetylcarnitine, coenzyme-Q10, ω-3 fatty acid, and selenium were more efficacious than placebo in sperm quality parameters. l-Carnitine was ranked first in sperm motility and sperm morphology (WMD 6.52% [95% CI: 2.55% to 10.05%], WMD 4.96% [0.20% to 9.73%]). ω-3 fatty acid was ranked first in sperm concentration (WMD 9.89 × 106/ml, [95% CI: 7.01 to 12.77 × 106/ml]). In terms of pregnancy rate, there was no significant effect as compared with placebo.

Conclusions

l-Carnitine was ranked first in sperm motility and sperm morphology. ω-3 fatty acid was ranked first in sperm concentration. Coenzyme-Q10 had better effective treatment on sperm motility and concentration. Furthermore, high-quality RCTs with adequate sample sizes should be conducted to compare the outcomes of different antioxidants.
A Meta-Analysis of the Effect of Sodium Glucose Cotransporter-2 Inhibitors on Metabolic Parameters in Patients With Polycystic Ovary Syndrome
Authors: Sinha Binayak , Ghosal Samit
Published: February 2022

Objective

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among women of childbearing age and is associated with multiple morbidities. However, treatment for this condition is mainly applied for symptomatic relief and does not address the complex pathophysiology of this condition. This meta-analysis was conducted on the usage of sodium-glucose cotransporter 2 inhibitors (SGLT-2is) in PCOS because this group of drugs presents an attractive strategy to address the metabolic and hormonal defects by managing the pathophysiological defects observed in this syndrome.

Methods

We included prospective trials that enrolled patients with established PCOS and compared an SGLT-2i group versus a control group with at least 2 weeks of follow-up. The standardized mean difference (SMD) was used for effect size estimation from individual studies and was pooled using the fixed effect model.

Results

We included four trials with a pooled population of 158 patients with documented PCOS who received either an SGLT-2i or standard management. From a metabolic perspective, significant improvements were observed in the reduction in body weight (SMD: -0.68, 95% CI -1.16 to -0.19, <0.01), fasting plasma glucose (FPG) (SMD: -0.59, 95% CI -0.99 to -0.19, P<0.01), and insulin resistance as assessed with the HOMA-IR (SMD: -0.39, 95% CI -0.76 to -0.03, P=0.03). In addition, a significant improvement was noted in dehydroepiandrosterone sulphate (DHEAS) levels (SMD: -0.55, 95% CI -0.94 to -0.16, P<0.01).

Conclusion

SGLT-2i use is associated with salutary outcomes of metabolic and anthropometric markers of PCOS and likely favourable hormonal effects.

Clinical Trial Registration

[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021268564], PROSPERO 2021 CRD42021268564.