bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative Temporal Viromics
Authors: Fletcher-Etherington Alice , Weekes Michael P.
Published: June 2021

The abundance, localization, modifications, and protein-protein interactions of many host cell and virus proteins can change dynamically throughout the course of any viral infection. Studying these changes is critical for a comprehensive understanding of how viruses replicate and cause disease, as well as for the development of antiviral therapeutics and vaccines. Previously, we developed a mass spectrometry–based technique called quantitative temporal viromics (QTV), which employs isobaric tandem mass tags (TMTs) to allow precise comparative quantification of host and virus proteomes through a whole time course of infection. In this review, we discuss the utility and applications of QTV, exemplified by numerous studies that have since used proteomics with a variety of quantitative techniques to study virus infection through time.
Modeling and Control of Malware Propagation in Wireless IoT Networks
Authors: Yan Qing , Song Lipeng , Zhang Chenlu , Li Jing , Feng Shanshan
Published: June 2021

Wireless Internet of Things (IoT) devices densely populate our daily life, but also attract many attackers to attack them. In this paper, we propose a new Heterogeneous Susceptible-Exposed-Infected-Recovered (HSEIR) epidemic model to characterize the effect of heterogeneity of infected wireless IoT devices on malware spreading. Based on the proposed model, we obtain the basic reproduction number, which represents the threshold value of diffusion and governs that the malware is diffusion or not. Also, we derive the malware propagation scale under different cases. These analyses provide theoretical guidance for the application of defense techniques. Numerical simulations validated the correctness and effectiveness of theoretical results. Then, by using Pontryagin’s Minimum Principle, optimal control strategy is proposed to seek time-varying cost-effective solutions against malware outbreaks. More numerical results also showed that some control strategies, such as quarantine and vaccination, should be taken at the beginning of the malware outbreak immediately and become less necessary after a certain period. However, the repairing and fixing strategy, for example applying antivirus patches, would be keep on going constantly.
Effects of the Na+/H+ Ion Exchanger on Susceptibility to COVID-19 and the Course of the Disease
Authors: Cumhur Cure Medine , Cure Erkan
Published: June 2021

The Na+/H+ ion exchanger (NHE) pumps Na+ inward the cell and H+ ion outside the cell. NHE activity increases in response to a decrease in intracellular pH, and it maintains intracellular pH in a narrow range. Patients with obesity, diabetes, and hypertension and the elderly are prone to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The angiotensin II (Ang II) level is high in chronic diseases such as diabetes, hypertension, and obesity. Ang II is the main stimulator of NHE, and an increased Ang II level causes prolonged NHE activation in these patients. The long-term increase in NHE activity causes H+ ions to leave the cell in patients with diabetes, hypertension, and obesity. Increasing H+ ions outside the cell lead to an increase in oxidative stress and reactive oxygen species. H+ ion flows into the cell due to the increased oxidative stress. This vicious circle causes intracellular pH to drop. Although NHE is activated when intracellular pH decreases, there is prolonged NHE activation in chronic diseases such as aforementioned. Novel coronavirus disease 2019 (COVID-19) progression may be more severe and mortal in these patients. SARS-CoV-2 readily invades the cell at low intracellular pH and causes infection. The renin-angiotensin system and NHE play a vital role in regulating intracellular pH. The reduction of NHE activity or its prolonged activation may cause susceptibility to SARS-CoV-2 infection by lowering intracellular pH in patients with diabetes, hypertension, and obesity. Prolonged NHE activation in these patients with COVID-19 may worsen the course of the disease. Scientists continue to investigate the mechanism of the disease and the factors that affect its clinical progression.
Investigation of Plantago ovata Husk as Pharmaceutical Excipient for Solid Dosage Form (Orodispersible Tablets)
Authors: Abbas Sarmad , Sherazi Mehrin , Khan Amjad , Alyami Hamad S. , Latif Muhammad , Qureshi Zia-Ur-Rahman , Majeedullah  , Asad Muhammad Hassham Hassan Bin
Published: June 2021

The objective of the study was to investigate the suitability of the Plantago ovata (PO) husk as a pharmaceutical excipient. Various phytoconstituents of the husk were determined according to the standard test procedures. The Plantago ovata husk was evaluated for various pharmaceutical parameters related to flow, swelling index, and compressibility index. Orodispersible tablets (ODTs) were prepared, containing different concentrations (2.5, 3, 5, 7.5, 10, and 15% w/w) of the Plantago ovata husk. Before compression, all the formulations were evaluated for their flow. Compressed ODTs were evaluated for physical characteristics (physical appearance, weight and weight variation, thickness, and moisture content), mechanical strength (crushing strength, specific crushing strength, tensile strength, and friability), disintegration behavior (disintegration time and oral disintegration time), drug content, and in vitro drug release. Phytochemical evaluation of the Plantago ovata husk confirmed the presence of various phytoconstituents like alkaloids, tannins, glycosides, saponins, flavonoids, and phenols. SEM photograph of the Plantago ovata husk showed that it has a fibrous structure, with a porous and rough surface. The Plantago ovata husk had a high swelling index (380%) which decreased by pulverization (310%). Precompression evaluation of the powder blend for all the formulations of ODTs showed good flow properties, indicating that the Plantago ovata husk improved the rheological characteristics of the powder blend. Compressed ODTs had good mechanical strength, and their friability was within the official limits (<1%). Best disintegration was observed with formulation F‐6 containing 10% w/w of the Plantago ovata husk. It is concluded that the Plantago ovata husk can be used as a disintegrant in the formulation of ODTs.
Fixed Point Approximation for a Class of Generalized Nonexpansive Mappings in Hadamard Spaces
Authors: Ullah Kifayat , Ahmad Junaid , Khan Akbar Ali , de la Sen Manuel
Published: June 2021

In this paper, we establish strong and

Δ

convergence results for mappings satisfying condition

B

γ
,
μ

through a newly introduced iterative process called JA iteration process. A nonlinear Hadamard space is used the ground space for establishing our main results. A novel example is provided for the support of our main results and claims. The presented results are the good extension of the corresponding results present in the literature.
A New Family of Degenerate Poly-Genocchi Polynomials with Its Certain Properties
Authors: Khan Waseem A. , Ali Rifaqat , Alzobydi Khaled Ahmad Hassan , Ahmed Naeem
Published: June 2021

In this paper, we introduce a new type of degenerate Genocchi polynomials and numbers, which are called degenerate poly-Genocchi polynomials and numbers, by using the degenerate polylogarithm function, and we derive several properties of these polynomials systematically. Then, we also consider the degenerate unipoly-Genocchi polynomials attached to an arithmetic function, by using the degenerate polylogarithm function, and investigate some identities of those polynomials. In particular, we give some new explicit expressions and identities of degenerate unipoly polynomials related to special numbers and polynomials.
A Machine Learning-Based Prediction Model for Preterm Birth in Rural India
Authors: Raja Rakesh , Mukherjee Indrajit , Sarkar Bikash Kanti
Published: June 2021

Preterm birth (PTB) in a pregnant woman is the most serious issue in the field of Gynaecology and Obstetrics, especially in rural India. In recent years, various clinical prediction models for PTB have been developed to improve the accuracy of learning models. However, to the best of the authors’ knowledge, most of them suffer from selecting the most accurate features from the medical dataset in linear time. The present paper attempts to design a machine learning model named as risk prediction conceptual model (RPCM) for the prediction of PTB. In this paper, a feature selection approach is proposed based on the notion of entropy. The novel approach is used to find the best maternal features (responsible for PTB) from the obstetrical dataset and aims to predict the classifier’s accuracy at the highest level. The paper first deals with the review of PTB cases (which is neglected in many developing countries including India). Next, we collect obstetrical data from the Community Health Centre of rural areas (Kamdara, Jharkhand). The suggested approach is then applied on collected data to identify the excellent maternal features (text-based symptoms) present in pregnant women in order to classify all birth cases into term birth and PTB. The machine learning part of the model is implemented using three different classifiers, namely, decision tree (DT), logistic regression (LR), and support vector machine (SVM) for PTB prediction. The performance of the classifiers is measured in terms of accuracy, specificity, and sensitivity. Finally, the SVM classifier generates an accuracy of 90.9%, which is higher than other learning classifiers used in this study.
Sonoelectrochemical Synthesis of Antibacterial Active Silver Nanoparticles in Rhamnolipid Solution
Authors: Shepida Mariana , Kuntyi Orest , Sozanskyi Martyn , Sukhatskiy Yuriy
Published: June 2021

The results of studies of the synthesis of AgNPs colloidal solutions by cyclic voltammetry (E from +1.0 to −1.0 V) in rhamnolipid (RL) solutions and the use of soluble anodes in the ultrasound field (22 kHz) are presented. It is shown that the algorithm of anodic dissolution—reduction of Ag(I)—nucleation, and formation of AgNPs makes it possible to obtain nanoparticles with the size from 1 nm to 3 nm. It was found that with an increase in the RL concentration from 1 g/L to 4 g/L, the anodic and cathodic currents increase as well as the rate of AgNPs formation, respectively. The rate of nanoparticles formation also increases with an increase in temperature from 20°C to 60°C, and it corresponds to the diffusion‐kinetic range of action of this factor. Moreover, the size of AgNPs depends little on the temperature. The character of the UV‐Vis pattern of AgNPs colloidal solutions in RL (with an absorption maximum of 415 nm) is the same over a wide range of nanoparticle concentrations. The curves practically do not change in time, which indicate the stability of anodic and cathodic processes during prolonged sonoelectrochemical synthesis. The cyclic voltammetry curves practically do not change in time, which indicate the stability of anodic and cathodic processes during prolonged sonoelectrochemical synthesis. The antimicrobial activity of synthesized AgNPs solutions to strains of Escherichia coli, Candida albicans, and Staphylococcus aureus was established.
Study on the Mechanical Properties of Red Clay under Drying‐Wetting Cycles
Authors: Qi Yanli , Bai MingZhou , Zhou Hao , Shi Hai , Li Pengxiang , He Bohu
Published: June 2021

To study the mechanical properties of red clay under repeated dry and wet cycle test conditions, in this paper, the disturbed red clay in an engineering area in Liuzhou, Guangxi Province, was taken as the research object. By artificially controlling different dry and wet cycles in the laboratory, a direct shear test and triaxial consolidation drainage test were carried out on the red clay samples after different dry and wet cycles. The stress‐strain curve and change rule of corresponding c and φ values were obtained. The results showed that, in both the direct shear test and the triaxial test, the shear strength parameters of red clay decreased with an increase in the number of dry and wet cycles and the attenuation was most obvious during the first cycle. With an increase in the number of dry and wet cycles, the attenuation gradually decreased. The constitutive model of the deviatoric stress and strain curve of red clay under dry and wet cycles was a plastic‐hardening type. By analyzing the variation in parameters in the P‐H model, the relationship between c, φ, and the number of dry and wet cycles n was obtained. The results showed that the parameters had different degrees of attenuation with the action of dry and wet cycles. To explain the above rules, some samples under different drying‐wetting cycles were selected for environmental electron microscope scanning, and appropriate assumptions were made based on the microstructure.
Tumor Purity Coexpressed Genes Related to Immune Microenvironment and Clinical Outcomes of Lung Adenocarcinoma
Authors: Bai Ming , Pan Qi , Sun Chen
Published: June 2021

Purpose. Lung cancer tissue includes tumor tissue, stromal cells, immune cells, and epithelial cells. These nontumor cells dilute the tumor purity in lung cancer tissues. Tumor purity plays an essential role in the immune response to lung cancer. At present, the biological processes related to the purity of lung cancer tumors remains unclear. Methods. We measured tumor purity in 486 lung carcinoma tissues from TCGA-LUAD FPKM by using the “estimate” R package. Lung carcinoma tumor mutation burden was calculated by analyzing TCGA single nucleotide polymorphism data. The immune cell proportion was also evacuated via the CIBERSORT method. Lung carcinoma samples with

P
<
0.05

were considered significant. Based on the tumor purity and lung carcinoma gene matrix, we performed weighted gene coexpression network analysis (WGCNA), and the tumor purity-related module was identified. Then, we analyzed the functions of the factors involved in the module. We screened the coexpressed factors related to clinical outcome and immunophenotype. Finally, expression levels of these factors were measured at tissue and single-cell levels. Results. A lung cancer tumor purity correlated coexpression network was determined. Five coexpressed genes (CD4, CD53, EVI2B, PLEK, and SASH3) were identified as tumor purity coexpressed genes that negatively correlated with tumor purity. Because the factors in the coexpression network often participate in similar biological processes, we found that CD4, CD53, EVI2B, PLEK, and SASH3 were most related to positive regulation of cytokine production and interleukin−2 production through functional enrichment. In a clinical phenotype analysis, we found that these five factors can be used as independent prognostic risk factors. We found that these factors were significantly negatively correlated with tumor purity and positively correlated with the immune score in the immunophenotyping analysis. Using GSEA analysis, we found that the antigen processing and presentation pathway were related to the five tumor coexpressed genes mentioned above. SASH3 and CD53 were used to conduct a prognostic model based on the interaction analysis of the Support Vector Machine and the Least Absolute Shrinkage and Selection Operator. SASH3 was verified to be related to CD8A using a single-cell analysis. Conclusion. Tumor purity-related coexpression factors in the tumor microenvironment have essential clinical, genomic, and biological significance in lung cancer. These coexpression factors (SASH3 and CD53) can be used to classify tumor purity phenotypes and to predict clinical outcomes.
Multiobjective Contactless Delivery on Medical Supplies under Open-Loop Distribution
Authors: Li Huilin , Xiong Ke , Xie Xiuming
Published: June 2021

With the development and popularity of intelligent store terminals, contactless distribution has been a hot talk on medical supplies using intelligent express boxes. Based on the traditional vehicle routing problem, this paper considers the sharing economy and open-loop distribution reality hotspots and considers the optimization of carbon emissions in contactless distribution. The travel distance and load capacity are the key factors affecting carbon emissions. The carbon emission model proposes dual goals of minimizing distribution costs and carbon emissions. It constructs a distribution path planning model with multiple distribution stations. To solve this problem with multidepot optimization, we design a hybrid genetic algorithm, and according to the strategy of customer distance clustering analysis, the dispatching of vehicles is divided into three steps. The principle of elite crossing is applied to avoid the solution to fall into local optimum. The experimental results show that the proposed model and optimization algorithm can get a tradeoff between the logistics cost and carbon emissions.
Changes in Vegetative and Reproductive Growth and Quality Parameters of Strawberry (Fragaria × ananassa Duch.) cv. Chandler Grown at Different Substrates
Authors: Zahid Noosheen , Maqbool Mehdi , Hamid Abdul , Shehzad Muhammad , Tahir Majid Mahmood , Mubeen Khuram , Muhammad Rashad Javeed Hafiz , Rehman Haseeb Ur , Ali Mazhar , Ali Asgar , O’Reilly Patrick , Shah Syed Zulfiqar Ali
Published: June 2021

Growth substrates (polyester wool, rice husk, and wheat straw), along with soil as control treatment, were compared for vegetative growth, yield, and quality of strawberry cv. Chandler. All growth substrates tested showed good results in terms of growth rate as compared with control. Strawberry plants grown in polyester wool showed the highest (89.50%) survival rate as compared to rice husk (70.50%), wheat straw (64.63%), and control (67.56%). Moreover, a significant increase was observed among number of flowers, fruits, and yield in plants grown in polyester wool. Besides, a significant high amount of total soluble solids (TSS) (12.38 ºBrix), titratable acidity (TA) (1.21%), ash (0.72%), vitamin C (37.39 mg/100 g), total carotenoids (3.90 µg/100 g), and total anthocyanins (3.47 cyanidine-3-glucoside/100 g) was recorded in fruits grown in polyester wool as compared to control. From these results, it can be concluded that the use of polyester wool as a growth substrate for strawberries can give higher yield and better fruit quality.
Toward Greater Precision in Cancer Radiotherapy
Authors: Nickoloff Jac A.
Published: June 2021

The cellular DNA damage response (DDR) is a key factor in tumor suppression and tumor responses to genotoxic chemo- and radiotherapy. Master DDR regulators include three phosphatidyl inositol 3′ kinase–related kinases (PIKK) called ATM, ATR, and the catalytic subunit of DNA-dependent protein kinase, DNA-PKcs. Among their many functions, PIKKs regulate repair of DNA double-strand breaks (DSB) by homologous recombination (HR) and nonhomologous end-joining (NHEJ). Ionizing radiation induces DSBs that are either widely dispersed and efficiently repaired, or clustered and poorly repaired by the dominant NHEJ pathway. The inefficient repair of clustered DSBs by NHEJ shifts repair toward the competing HR pathway. In this issue of Cancer Research, Zhou and colleagues revealed a novel synthetic lethal approach in which the greater dependency on HR to repair clustered DSBs induced by protons is exploited to enhance killing of tumor cells and tumor xenografts by suppressing HR with an ATM inhibitor or mutant BRCA1. This is an important step toward precision cancer radiotherapy.

See related article by Zhou et al., p. 3333
What It Takes to Transform a T Cell
Authors: Spasevska Ivana , Myklebust June H.
Published: June 2021

The role of fusion genes and cancer driver genes in malignant transformation has traditionally been explored using transgenic or chimeric mouse models. It has been challenging to develop models that fully resemble the characteristics and morphology of human cancers. This applies to anaplastic large-cell lymphoma (ALCL), a malignancy classified as a peripheral T-cell lymphoma. It is still unclear at which stage of T-cell development ALCL can occur, as well as the early molecular events required for malignant transformation. In this issue of Cancer Research, Pawlicki and colleagues introduced the NPM–ALK fusion gene and mutant variants into primary T cells from healthy donors. By monitoring transduced T-cell clones over time, they demonstrated that transformed T cells undergo a progressive loss of T-cell identity accompanied with upregulation of epithelial-to-mesenchymal transition program and reemergence of an immature, thymic profile. Introduction of NPM–ALK was, however, not sufficient to convert healthy T cells to malignant clones, as this process required activation of T-cell receptor signaling. The study sets the stage for modeling early genetic changes in human tumors.

See related article by Pawlicki et al., p. 3241
Complementary Role of Circulating Tumor DNA Assessment and Tissue Genomic Profiling in Metastatic Renal Cell Carcinoma
Authors: Zengin Zeynep B. , Weipert Caroline , Salgia Nicholas J. , Dizman Nazli , Hsu Joann , Meza Luis , Chehrazi-Raffle Alexander , Muddasani Ramya , Salgia Sabrina , Malhotra Jasnoor , Chawla Neal , Philip Errol J. , Kiedrowski Lesli , Maughan Benjamin L. , Rathi Nityam , Goel Divyam , Choueiri Toni K. , Agarwal Neeraj , Pal Sumanta K.
Published: June 2021

Purpose:

The role of circulating cell-free tumor DNA (ctDNA) as an adjunct to tissue genomic profiling is poorly defined in metastatic renal cell carcinoma (mRCC). In this study, we aim to validate previous findings related to genomic alteration (GA) frequency in ctDNA and determine the concordance between ctDNA and tissue-based profiling in patients with mRCC.

Experimental Design:

Results of 839 patients with mRCC who had ctDNA assessment with a Clinical Laboratory Improvement Amendments (CLIA)-certified ctDNA assay between November 2016 and December 2019 were collected. Tissue-based genomic profiling was collected when available and concordance analysis between blood- and tissue-based testing was performed.

Results:

ctDNA was assessed in 839 patients (comprising 920 samples) with mRCC. GAs were detected in 661 samples (71.8%). Tissue-based GAs were assessed in 112 patients. Limiting our analyses to a common 73-/74-gene set and excluding samples with no ctDNA detected, a total of 228 mutations were found in tissue and blood. Mutations identified in tissue (34.7%; 42/121) were also identified via ctDNA, whereas 28.2% (42/149) of the mutations identified in liquid were also identified via tissue. Concordance between ctDNA and tissue-based profiling was inversely related to the time elapsed between these assays.

Conclusions:

This study confirms the feasibility of ctDNA profiling in the largest mRCC cohort to date, with ctDNA identifying multiple actionable alterations. It also demonstrates that ctDNA and tissue-based genomic profiling are complementary, with both platforms identifying unique alterations, and confirms that the frequency of unique alterations increases with greater temporal separation between tests.
In Situ Analysis of N-Linked Glycans as Potential Biomarkers of Clinical Course in Human Prostate Cancer
Authors: Conroy Lindsey R. , Stanback Alexandra E. , Young Lyndsay E.A. , Clarke Harrison A. , Austin Grant L. , Liu Jinze , Allison Derek B. , Sun Ramon C.
Published: June 2021

Prostate cancer is the most common cancer in men worldwide. Despite its prevalence, there is a critical knowledge gap in understanding factors driving disparities in survival among different cohorts of patients with prostate cancer. Identifying molecular features separating disparate populations is an important first step in prostate cancer research that could lead to fundamental hypotheses in prostate biology, predictive biomarker discovery, and personalized therapy. N-linked glycosylation is a cotranslational event during protein folding that modulates a myriad of cellular processes. Recently, aberrant N-linked glycosylation has been reported in prostate cancers. However, the full clinical implications of dysregulated glycosylation in prostate cancer has yet to be explored. Herein, we performed direct on-tissue analysis of N-linked glycans using matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) from tissue microarrays of over 100 patient tumors with over 10 years of follow-up metadata. We successfully identified a panel of N-glycans that are unique between benign and prostate tumor tissue. Specifically, high-mannose as well as tri-and tetra-antennary N-glycans were more abundant in tumor tissue and increase proportionally with tumor grade. Further, we expanded our analyses to examine the N-glycan profiles of Black and Appalachian patients and have identified unique glycan signatures that correlate with recurrence in each population. Our study highlights the potential applications of MALDI-MSI for digital pathology and biomarker discovery for prostate cancer.

Implications:

MALDI-MSI identifies N-glycan perturbations in prostate tumors compared with benign tissue. This method can be utilized to predict prostate cancer recurrence and study prostate cancer disparities.
Indoleamine-2,3-Dioxygenase Activates Wnt/β-Catenin Inducing Kidney Fibrosis after Acute Kidney Injury
Authors: Pan Binbin , Zhang Hao , Hong Yali , Ma Mengqing , Wan Xin , Cao Changchun
Published: June 2021

Introduction: As disorder of tryptophan metabolism is common in CKD, the rate-limiting enzyme of tryptophan, indoleamine-2,3-dioxygenase (IDO), has been reported to be involved in CKD, while the accurate mechanism remains unknown. This study was designed to explore correlations between IDO and kidney fibrosis after ischemia-reperfusion injury (IRI). Methods: Wild-type (WT) mice and IDO knockout (IDO−/−) mice were divided into the sham group and acute kidney injury (AKI) group. Mice in the sham group underwent dorsal incision and exposure of renal pedicle without clamping renal artery, while mice in the AKI group received unique renal artery IRI, and the contralateral kidney was removed at day 13 after IRI. Blood and IRI kidneys were collected at day 14. Kidney function was analyzed by measuring serum Cr and BUN. Morphology was analyzed by tissue periodic acid-Schiff (PAS) staining and Masson staining. Further, fibrosis markers and Wnt/β-catenin pathway proteins were determined by Western blot. Prostaglandin E2 (PGE2) was administrated for 2 weeks after the IRI mice model was established to observe whether it ameliorates kidney fibrosis after IRI. Results: WT AKI mice revealed elevated expression of IDO compared with WT sham mice. Kidney function of IDO−/− AKI mice showed better than that of WT AKI mice. PAS staining exhibited less loss of tubular epithelial cells and atrophy tubules in IDO−/− AKI mice. Furthermore, kidney fibrosis areas and the expressions of fibrosis markers, including α-SMA, fibronectin, and vimentin, were increased in WT AKI mice. In addition, GSK-3β and β-catenin were significantly declined in IDO−/− AKI mice. On top of that, PGE2 administration revealed inhibited IDO expression and that reducing GSK-3β and β-catenin resulting in lower expressions of α-SMA, fibronectin, and vimentin in WT AKI mice. Conclusions: IRI could increase IDO expression to activate Wnt/β-catenin pathway resulting kidney fibrosis. PGE2 could ameliorate kidney fibrosis via inhibiting IDO expression.
Calcineurin Inhibitor Toxicity in Solid Organ Transplantation
Authors: Karolin Andrea , Genitsch Vera , Sidler Daniel
Published: June 2021

Calcineurin inhibitors (CNIs) have a substantial role in maintaining immunosuppression after solid organ transplantation (SOT). These drugs have a narrow therapeutic window, and individual doses and drug treatment monitoring are necessary. Still, a substantial proportion of patients suffer from short- or long-term calcineurin inhibitor toxicity (CNT), including kidney function impairment, hypertension, neurotoxicity, and metabolic disturbances. The authors discuss pathophysiology, clinical presentation, and histological features of CNT, with focus on renal manifestations. Furthermore, we elucidate recent and ongoing attempts to reduce the burden of CNT in SOT including CNI-sparing and CNI-free regimens.
Mechanism and Priority of Botulinum Neurotoxin A versus Sacral Neuromodulation for Refractory Overactive Bladder: A Review
Authors: Zhang Yanping , Ji Fengping , Liu Erpeng , Wen Jian Guo
Published: June 2021

Background: The treatment of common overactive bladder (OAB) has reached a consensus, but there is not a clear answer to the treatment of refractory OAB (ROAB). ROAB is defined as nonresponsive to treatment with behavioural and oral therapies. The disease can influence the physical and mental health of patients, cause poor quality of life, and create an urgent socio-economic burden. With the advancement of medical treatment, the treatment of OAB has improved significantly in the last 2 decades, especially ROAB, by the usage of botulinum neurotoxin A (BoNT-A) and sacral neuromodulation (SNM). Many studies have demonstrated their effectiveness and safety. However, which therapy is the optimal method remains unclear for patients with ROAB, and the exact mechanism involved in the procedures is still unknown. Summary: This review is to clarify the mechanisms, advantages, and disadvantages of SNM and BoNT-A in treatment of ROAB, and determine whether there is an order effect of SNM and BoNT-A in managing ROAB. Key Messages: BoNT-A and SNM mainly act on the peripheral nervous system and central nervous system, respectively. But BoNT-A and SNM may partly act on the central and peripheral nervous systems, separately. SNM may be a better choice than BoNT-A in the long time. At the same time, BoNT-A and SNM can treat the ROAB as the first and next steps, and the sequence of both would not affect the effectiveness of each other.
Influence of Intracochlear Air on Experimental Pressure Measurements
Authors: Riemann Conrad , Sudhoff Holger , Todt Ingo
Published: June 2021

Introduction: Intracochlear pressure changes have been assumed to play a central role in hearing preservation during cochlear implantation. The pressure in different settings has been evaluated (temporal bones vs. cochlea models) and was found to have advantages and disadvantages. Experimentally, problems have been discussed to influence the results substantially. Objective: The aim of the present study was to evaluate the effect of intracochlear air on the measurements in a cochlea model by using a fiber optic pressure sensor. Materials and Methods: The experiments were performed in an uncurled 3D printed full cochlea model. A microfiber-optic pressure sensor was inserted, and intracochlear pressures were evaluated under 3 conditions: (1) cochlea model filled to 100% with fluid, (2) cochlea model filled with air, and (3) cochlea model filled to approximately 50% with fluid. Since the cochlea model is transparent, a direct visualization of air under the microscope was possible when performing the insertions. Results: In the first condition, the mean intracochlear pressure at the end of the insertion was 0.044 psi (SD 0.012, 95% CI). In the second setting, the results were similar. In the last scenario, with 50% filling, the mean intracochlear pressure was statistically significantly different with a mean value of 0.074 psi (SD 0.013, 95% CI) (p < 0.0044, ANOVA). Besides this, in the last condition with 50% fluid, a plateau was formed when the fiber optic reached the air portion. Conclusion: The results obtained in a 3D printed full cochlea model show the importance of a direct evaluation of air inside the experimental setting. The exclusion of intracochlear air should be an important factor for the choice of the model for intracochlear pressure measurement (temporal bone vs. cochlea model).
Comparison between Cerebroplacental Ratio and Umbilicocerebral Ratio in Predicting Adverse Perinatal Outcome in Pregnancies Complicated by Late Fetal Growth Restriction: A Multicenter, Retrospective Study
Authors: Di Mascio Daniele , Herraiz Ignacio , Villalain Cecilia , Buca Danilo , Morales-Rossello Jose , Loscalzo Gabriela , Sileo Filomena Giulia , Finarelli Alessandra , Bertucci Emma , Facchinetti Fabio , Rizzo Giuseppe , Brunelli Roberto , Giancotti Antonella , Muzii Ludovico , Maruotti Giuseppe Maria , Carbone Luigi , D’Amico Alice , Tinari Sara , Morelli Roberta , Cerra Chiara , Nappi Luigi , Greco Pantaleo , Liberati Marco , Galindo Alberto , D’Antonio Francesco
Published: June 2021

Introduction: The role of cerebroplacental ratio (CPR) or umbilicocerebral ratio (UCR) to predict adverse intrapartum and perinatal outcomes in pregnancies complicated by late fetal growth restriction (FGR) remains controversial. Methods: This was a multicenter, retrospective cohort study involving 5 referral centers in Italy and Spain, including singleton pregnancies complicated by late FGR, as defined by Delphi consensus criteria, with a scan 1 week prior to delivery. The primary objective was to compare the diagnostic accuracy of the CPR and UCR for the prediction of a composite adverse outcome, defined as the presence of either an adverse intrapartum outcome (need for operative delivery/cesarean section for suspected fetal distress) or an adverse perinatal outcome (intrauterine death, Apgar score <7 at 5 min, arterial pH <7.1, base excess of >−11 mEq/mL, or neonatal intensive care unit admission). Results: Median CPR absolute values (1.11 vs. 1.22, p = 0.018) and centiles (3 vs. 4, p = 0.028) were lower in pregnancies with a composite adverse outcome than in those without it. Median UCR absolute values (0.89 vs. 0.82, p = 0.018) and centiles (97 vs. 96, p = 0.028) were higher. However, the area under the curve, 95% confidence interval for predicting the composite adverse outcome showed a poor predictive value: 0.580 (0.512–0.646) for the raw absolute values of CPR and UCR, and 0.575 (0.507–0.642) for CPR and UCR centiles adjusted for gestational age. The use of dichotomized values (CPR <1, UCR >1 or CPR <5th centile, UCR >95th centile) did not improve the diagnostic accuracy. Conclusion: The CPR and UCR measured in the week prior delivery are of low predictive value to assess adverse intrapartum and perinatal outcomes in pregnancies with late FGR.
Eficácia da manobra de Valsalva modificada como tratamento para reversão de taquicardia supraventricular: revisão sistemática
Authors: Ferreira Mario Henrique Quim , Fumagalli Beatriz Cheregati , Teixeira Ana Beatriz
Published: June 2021

Introdução: a taquicardia supraventricular é uma arritmia frequente com prevalência de 2,29 a cada 1000 pessoas. Tratamentos medicamentosos e elétrico já são bem delineados em diretrizes como da American Heart Association, porém, acompanhados de risco de efeitos incomodativos ao paciente como falta de ar e sensação de compressão torácica. A estimulação não medicamentosa do nervo vago, como a manobra Valsalva convencional, apresenta pouco efeito colateral, porém, baixa eficácia com cerca de 17% de conversões. Neste cenário, um novo método de estimulação parassimpática tem sido promissor na terapia inicial não medicamentosa: a manobra de Valsalva modificada. Esta consiste na elevação dos membros inferiores após uma expiração contra resistência, visando atingir um maior grau de estimulação vagal. Objetivo: avaliar a taxa de sucesso na reversão de taquicardias supraventriculares pela manobra modificada, por análise dos resultados da execução desta manobra, bem como comparando-a com a manobra de Valsalva convencional. Metodologia: foram feitas pesquisas no banco de dados da Scielo e PubMed pelos termos “tachycardia AND modified Valsalva maneuver”. Artigos publicados 2005 a 2020 foram selecionados e passaram por uma filtragem individual de seus conteúdos (título, abstract e metodologias) buscando homogeneizar assim os resultados. Resultados e Discussão: o artigo apresentado pela Scielo não condizia com este tipo de estudo, e dentre os 29 relacionados pelo PubMed, após filtragem de tempo e critérios de análise individual, 9 trabalhos foram compilados nesta revisão, sendo que 3 fazem uma avaliação isolada da manobra modificada enquanto 6 demonstram uma comparação direta entre as manobras. Todos apontam uma maior eficácia na cardioversão da arritmia pela manobra modificada em comparação com a convencional, sendo uma média das porcentagens de resolução de 48,3% contra 19,6%, respectivamente, sem diferenças significativas nos eventos adversos. Conclusão: A manobra Valsalva modificada gerou uma maior reversão da arritmia do que aqueles que utilizaram a convencional, sem acréscimos de efeitos colaterais e expondo menor número de pacientes a terapias medicamentosas ou cardioversões elétricas.
Mechanical Complications of Acute Myocardial Infarction: A Scientific Statement From the American Heart Association
Authors: Damluji Abdulla A. , van Diepen Sean , Katz Jason N. , Menon Venu , Tamis-Holland Jacqueline E. , Bakitas Marie , Cohen Mauricio G. , Balsam Leora B. , Chikwe Joanna ,   on behalf of the American Heart Association Council on Clinical Cardiology; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Surgery and Anesthesia; and Council on Cardiovascular and Stroke Nursing
Published: June 2021

Over the past few decades, advances in pharmacological, catheter-based, and surgical reperfusion have improved outcomes for patients with acute myocardial infarctions. However, patients with large infarcts or those who do not receive timely revascularization remain at risk for mechanical complications of acute myocardial infarction. The most commonly encountered mechanical complications are acute mitral regurgitation secondary to papillary muscle rupture, ventricular septal defect, pseudoaneurysm, and free wall rupture; each complication is associated with a significant risk of morbidity, mortality, and hospital resource utilization. The care for patients with mechanical complications is complex and requires a multidisciplinary collaboration for prompt recognition, diagnosis, hemodynamic stabilization, and decision support to assist patients and families in the selection of definitive therapies or palliation. However, because of the relatively small number of high-quality studies that exist to guide clinical practice, there is significant variability in care that mainly depends on local expertise and available resources.
Cardiolipin Remodeling Defects Impair Mitochondrial Architecture and Function in a Murine Model of Barth Syndrome Cardiomyopathy
Authors: Zhu Siting , Chen Ze’e , Zhu Mason , Shen Ying , Leon Leonardo J. , Chi Liguo , Spinozzi Simone , Tan Changming , Gu Yusu , Nguyen Anh , Zhou Yi , Feng Wei , Vaz Frédéric M. , Wang Xiaohong , Gustafsson Asa B. , Evans Sylvia M. , Kunfu Ouyang , Fang Xi
Published: June 2021

Background:

Cardiomyopathy is a major clinical feature in Barth syndrome (BTHS), an X-linked mitochondrial lipid disorder caused by mutations in
Tafazzin
(
TAZ
), encoding a mitochondrial acyltransferase required for cardiolipin remodeling. Despite recent description of a mouse model of BTHS cardiomyopathy, an in-depth analysis of specific lipid abnormalities and mitochondrial form and function in an in vivo BTHS cardiomyopathy model is lacking.

Methods:

We performed in-depth assessment of cardiac function, cardiolipin species profiles, and mitochondrial structure and function in our newly generated
Taz
cardiomyocyte-specific knockout mice and Cre-negative control mice (n≥3 per group).

Results:

Taz
cardiomyocyte-specific knockout mice recapitulate typical features of BTHS and mitochondrial cardiomyopathy. Fewer than 5% of cardiomyocyte-specific knockout mice exhibited lethality before 2 months of age, with significantly enlarged hearts. More than 80% of cardiomyocyte-specific knockout displayed ventricular dilation at 16 weeks of age and survived until 50 weeks of age. Full parameter analysis of cardiac cardiolipin profiles demonstrated lower total cardiolipin concentration, abnormal cardiolipin fatty acyl composition, and elevated monolysocardiolipin to cardiolipin ratios in Taz cardiomyocyte-specific knockout, relative to controls. Mitochondrial contact site and cristae organizing system and F1F0-ATP synthase complexes, required for cristae morphogenesis, were abnormal, resulting in onion-shaped mitochondria. Organization of high molecular weight respiratory chain supercomplexes was also impaired. In keeping with observed mitochondrial abnormalities, seahorse experiments demonstrated impaired mitochondrial respiration capacity.

Conclusions:

Our mouse model mirrors multiple physiological and biochemical aspects of BTHS cardiomyopathy. Our results give important insights into the underlying cause of BTHS cardiomyopathy and provide a framework for testing therapeutic approaches to BTHS cardiomyopathy, or other mitochondrial-related cardiomyopathies.
Managing Atrial Fibrillation in Patients With Heart Failure and Reduced Ejection Fraction: A Scientific Statement From the American Heart Association
Authors: Gopinathannair Rakesh , Chen Lin Y. , Chung Mina K. , Cornwell William K. , Furie Karen L. , Lakkireddy Dhanunjaya R. , Marrouche Nassir F. , Natale Andrea , Olshansky Brian , Joglar Jose A. ,   on behalf of the American Heart Association Electrocardiography and Arrhythmias Committee and Heart Failure and Transplantation Committee of the Council on Clinical Cardiology; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Hypertension; Council on Lifestyle and Cardiometabolic Health; and the Stroke Council
Published: June 2021

Atrial fibrillation and heart failure with reduced ejection fraction are increasing in prevalence worldwide. Atrial fibrillation can precipitate and can be a consequence of heart failure with reduced ejection fraction and cardiomyopathy. Atrial fibrillation and heart failure, when present together, are associated with worse outcomes. Together, these 2 conditions increase the risk of stroke, requiring oral anticoagulation in many or left atrial appendage closure in some. Medical management for rate and rhythm control of atrial fibrillation in heart failure remain hampered by variable success, intolerance, and adverse effects. In multiple randomized clinical trials in recent years, catheter ablation for atrial fibrillation in patients with heart failure and reduced ejection fraction has shown superiority in improving survival, quality of life, and ventricular function and reducing heart failure hospitalizations compared with antiarrhythmic drugs and rate control therapies. This has resulted in a paradigm shift in management toward nonpharmacological rhythm control of atrial fibrillation in heart failure with reduced ejection fraction. The primary objective of this American Heart Association scientific statement is to review the available evidence on the epidemiology and pathophysiology of atrial fibrillation in relation to heart failure and to provide guidance on the latest advances in pharmacological and nonpharmacological management of atrial fibrillation in patients with heart failure and reduced ejection fraction. The writing committee’s consensus on the implications for clinical practice, gaps in knowledge, and directions for future research are highlighted.
A new genus Viperinus Park with descriptions of two new species, and two new species of the genus Protolychnis Meyrick, 1925 (Lepidoptera, Gelechioidea, Lecithoceridae) in Kenya and Tanzania, with a checklist of the world species
Authors: PARK KYU-TEK , KOO JUN-MO
Published: June 2021

A new genus Viperinus Park, gen. nov., belonging to Torodorinae (Lecithoceridae), is proposed, with descriptions of two new species, V. orbiosus Park & Koo sp. nov. from Kenya and V. pyknoistus Park & Koo, sp. nov. from Uganda. Furthermore, two new species of Protolychnis Meyrick, 1925, P. oculiella Park & Koo, sp. nov. and P. morogorensis Park & Koo, sp. nov., are described from Kenya and Tanzania, respectively. In addition, P. petiliella Park, 2020 is reported for the first time from Tanzania. The new genus, Viperinus is very similar to Protolychnis in the superficial characters, but it is separated from the latter by having unique characters in genitalia: a pair of processes arising from base of each valva in the male genitalia and a polygonal signal plate in the female genitalia. Images of adults and genitalia of the four new species are provided, and a checklist of Protolychnis Meyrick is also given.
First record of the myrmicine ant genus Syllophopsis Santschi, 1915 (Hymenoptera: Formicidae) from India with description of a new species
Authors: AKBAR SHAHID ALI , BHARTI HIMENDER , KANTURSKI MARIUSZ , WACHKOO AIJAZ AHMAD
Published: June 2021

Here we describe and illustrate Syllophopsis peetersi sp. nov. from Silent Valley National Park, a biodiversity hotspot region of the Western Ghats of India. The discovery also marks a first native report of the genus from the Indian subcontinent. Scanning Electron Microscopy (SEM) analysis was carried out to elucidate the general morphology and sensilla of the new species. The new species is similar to congeners from Madagascar, but with larger differences from species that occur elsewhere.
Clustering Analysis of Autumn Weather Regimes in the Northeast United States
Authors: Coe David , Barlow Mathew , Agel Laurie , Colby Frank , Skinner Christopher , Qian Jian-Hua
Published: June 2021

A k-means clustering method is applied to daily ERA5 500-hPa heights, sea level pressure, and 850-hPa winds, 1979–2008, to identify characteristic weather types (WTs) for September–November for the northeast United States. The resulting WTs are analyzed in terms of structure, frequency of occurrence, typical progressions, precipitation and temperature characteristics, and relation to teleconnections. The WTs are used to make a daily circulation-based distinction between early and late autumn and consider shifts in seasonality. Seven WTs are identified for the autumn season, representing a range of trough and ridge patterns. The largest average values of precipitation and greatest likelihood of extremes occur in the Midwestern Trough and Atlantic Ridge patterns. The greatest likelihood of extreme temperatures occurs in the Northeast Ridge. Some WTs are strongly associated with the phase of the North Atlantic Oscillation and Pacific–North America pattern, with frequency of occurrence for several WTs changing by more than a factor of 2. The two most common progressions between the WTs are one most frequent in September, Mid-Atlantic Trough to Northeast Ridge to Mid-Atlantic Trough, and one most frequent in mid-October–November, Midwestern Trough to Northeast Trough to Midwestern Trough. This seasonality allows for a daily WT-based distinction between early and late season. A preliminary trend analysis indicates an increase in early season WTs later in the season and a decrease in late season WTs earlier in the season; that is, a shift toward a longer period of warm season patterns and a shorter, delayed period of cold season patterns.
A Recent Increase in Long-Lived Heatwaves in China Under the Joint Influence of South Asia and Western North Pacific Subtropical Highs
Authors: LI Na , XIAO Ziniu , ZHAO Liang
Published: June 2021

Long-lived (≥6 days) heatwaves (HWs) have strong social impacts with serious health implications. Using homogenized historical daily temperatures from China and ECMWF reanalysis data, this study investigates its frequency between 1979 and 2018 and driving mechanisms. It is found that the occurrence of HWs is strongly associated with the joint actions of the South Asian high and the western North Pacific subtropical high, which can be described by a synergy index measured by the boundary distance between the two subtropical high-pressure systems. When the synergy index is positive, there are more long-lived HWs occurrence in the east of the Tibetan Plateau, the lower reaches of the Yangtze River and the southern region in China, and vice versa. A Mann-Kendall test shows a significant interdecadal shift around 2004/2005 towards increased occurrence that is consistent with enhanced subtropical high systems. This study shows the important roles of large-scale dynamic systems in regional climate extremes and their future changes.