bluuebunny/crossref_metadata_2025 huggingface dataset:
Does the El Niño-Southern Oscillation Affect the Combined Impact of the Atlantic Multidecadal Oscillation and Pacific Decadal Oscillation on the Precipitation and Surface Air Temperature Variability over South America?
Authors: Kayano Mary T. , Cerón Wilmar L. , Andreoli Rita V. , Souza Rodrigo A. F. , Avila-Diaz Alvaro , Zuluaga Cristian Felipe , Carvalho Leila M. V.
Published: January 2022

Previous studies have shown that the Atlantic Multidecadal Oscillation (AMO) and Pacific Decadal Oscillation (PDO) have combined effects on the precipitation (PRP) variability over South America. The combined impacts have been assessed considering four mean states as the averages of the variable anomalies during sub-periods overlapping time intervals of the PDO and AMO phases. Since these sub-periods include years under El Niño-Southern Oscillation (ENSO) extremes, the extent to which these years’ occurrence affects the averaged anomaly patterns during different mean states is investigated. The analyses are done for the PRP and surface air temperature (SAT) during the austral winter (June to August) and summer (December to February) of the 1901–2014 period using a composite technique. The nonlinear ENSO response in each mean state for a variable corresponds to the sum of the anomaly composites of the El Niño and La Niña events. In each mean state, the nonlinear PRP and SAT anomalies are not negligible and show similar patterns of the corresponding mean state, with larger magnitudes. For both seasons and all mean states, these similarities are more pronounced for SAT than for PRP. Thus, the ENSO variability affects the mean state’s PRP and SAT anomaly patterns in different ways. As far as we know, analyses of the nonlinear ENSO response of the South American climate during distinct mean states were not performed before. Our results also indicate that the ENSO variability should be considered in the studies of the low-frequency modes and their effects on the mean state over South America. The results presented could be relevant for climate monitoring and modeling studies.
Projections of Future Drought by CMIP5 Multimodel Ensembles in Central Asia
Authors: Ta Zhijie , Li Kaiyu , Yu Yang , Yang Meilin
Published: January 2022

Future changes in drought characteristics in Central Asia are projected at the regional scale using 21 climate models from phase 5 of the Coupled Model Intercomparison Project (CMIP5). Based on the standardized precipitation index (SPI) and standardized precipitation evapotranspiration index (SPEI), drought characteristics were characterized by drought frequency at 1-, 3-, and 12-month timescales. The drought duration was analyzed based on SPI1 and SPEI1. Drought indices were calculated by the multimodel ensemble (MME) from 21 CMIP5 models. The varimax rotation method was used to identify drought conditions for the entire area and seven drought subregions. In general, the projection results of future drought in Central Asia are related to the choice of drought index, and SPI and SPEI show different results. The drought frequency based on SPEI1, SPEI3, and SPEI12 showed an increasing trend in the future periods, that is, the drought frequency based on monthly, seasonal, and annual timescales will show an increase trend in the future periods. However, for SPI1, SPI3, and SPI12, the drought frequency will decrease in the future. SPI projected that the duration of drought will decrease in the future, while SPEI mainly showed an increasing trend. The results of the study should be of sufficient concern to policymakers to avoid land degradation, crop loss, water resource deficit, and economic loss.
A Straightforward Sufficiency Proof for a Nonparametric Problem of Bolza in the Calculus of Variations
Authors: Licea Gerardo Sánchez
Published: January 2022

We study a variable end-points calculus of variations problem of Bolza containing inequality and equality constraints. The proof of the principal theorem of the paper has a direct nature since it is independent of some classical sufficiency approaches invoking the Hamiltonian-Jacobi theory, Riccati equations, fields of extremals or the theory of conjugate points. In contrast, the algorithm employed to prove the principal theorem of the article is based on elementary tools of the real analysis.
A New Hybrid Triple Bottom Line Metrics and Fuzzy MCDM Model: Sustainable Supplier Selection in the Food-Processing Industry
Authors: Thanh Nguyen Van , Lan Nguyen Thi Kim
Published: January 2022

Vietnam’s food processing and production industries in the past have managed to receive many achievements, contributing heavily to the growth of the country’s economic growth, especially the production index. Even with an increase of 7% per year over the past five years, the industry currently also faces problems and struggles that require business managers to rewrite legal documents and redevelop the business environment as well as the production conditions in order to compete better and use the available resources. Xanthan gum (a food additive and a thickener) is one of the most used ingredients in the food-processing industry. Xanthan gum is utilized in a number of variety of products such as canned products, ice cream, meats, breads, candies, drinks, milk products, and many others. Therefore, in order to improve competitiveness, the stage of selecting raw-material suppliers is a complicated task. The purpose of this study was to develop a new composite model using Triple Bottom Line Metrics, the Fuzzy Analytical Hierarchy Process (FAHP) method, and the Combined Compromise Solution (CoCoSo) algorithm for the selection of suppliers. The application process was accomplished for the Xanthan-gum (β-glucopyranose (C35H49O29)n) supplier selection in a food processing industry. In this study, the model building, solution, and application processes of the proposed integrated model for the supplier selection in the food-processing industry are presented.
Raman Diagnostics of Cathode Materials for Li-Ion Batteries Using Multi-Wavelength Excitation
Authors: Heber Marcel , Hofmann Kathrin , Hess Christian
Published: January 2022

Lithium-ion batteries have been commonly employed as power sources in portable devices and are of great interest for large-scale energy storage. To further enhance the fundamental understanding of the electrode structure, we report on the use of multi-wavelength Raman spectroscopy for the detailed characterization of layered cathode materials for Li-ion batteries (LiCoO2, LiNixCo1−xO2, LiNi1/3Mn1/3Co1/3O2). Varying the laser excitation from the UV to the visible (257, 385, 515, 633 nm) reveals wavelength-dependent changes in the vibrational profile and overtone/combination bands, originating from resonance effects in LiCoO2. In mixed oxides, the influence of resonance effects on the vibrational profile is preserved but mitigated by the presence of Ni and/or Mn, highlighting the influence of resonance Raman spectroscopy on electronic structure changes. The use of UV laser excitation (257, 385 nm) is shown to lead to a higher scattering efficiency towards Ni in LiNi1/3Mn1/3Co1/3O2 compared to visible wavelengths, while deep UV excitation at 257 nm allows for the sensitive detection of surface species and/or precursor species reminiscent of the synthesis. Our results demonstrate the potential of multi-wavelength Raman spectroscopy for the detailed characterization of cathode materials for lithium-ion batteries, including phase/impurity identification and quantification, as well as electronic structure analysis.
Design and Evaluation of Engineered Extracellular Vesicle (EV)-Based Targeting for EGFR-Overexpressing Tumor Cells Using Monobody Display
Authors: Komuro Hiroaki , Aminova Shakhlo , Lauro Katherine , Woldring Daniel , Harada Masako
Published: January 2022

Background: Extracellular vesicles (EVs) are attracting interest as a new class of drug delivery vehicles due to their intrinsic nature of biomolecular transport in the body. We previously demonstrated that EV surface modification with tissue-specific molecules accomplished targeted EV-mediated DNA delivery. Methods: Here, we describe reliable methods for (i) generating EGFR tumor-targeting EVs via the display of high-affinity monobodies and (ii) in vitro measurement of EV binding using fluorescence and bioluminescence labeling. Monobodies are a well-suited class of small (10 kDa) non-antibody scaffolds derived from the human fibronectin type III (FN3) domain. Results: The recombinant protein consists of the EGFR-targeting monobody fused to the EV-binding domain of lactadherin (C1C2), enabling the monobody displayed on the surface of the EVs. In addition, the use of bioluminescence or fluorescence molecules on the EV surface allows for the assessment of EV binding to the target cells. Conclusions: In this paper, we describe methods of EV engineering to generate targeted delivery vehicles using monobodies that will have diverse applications to furnish future EV therapeutic development, including qualitative and quantitative in vitro evaluation for their binding capacity.
Impact of the Process Variables on the Yield of Mesenchymal Stromal Cells from Bone Marrow Aspirate Concentrate
Authors: Jeyaraman Madhan , Bingi Shiva Kumar , Muthu Sathish , Jeyaraman Naveen , Packkyarathinam Rathinavelpandian Perunchezhian , Ranjan Rajni , Sharma Shilpa , Jha Saurabh Kumar , Khanna Manish , Rajendran Sree Naga Sowndary , Rajendran Ramya Lakshmi , Gangadaran Prakash
Published: January 2022

Human bone marrow (BM) has been highlighted as a promising source of mesenchymal stromal cells (MSCs) containing various growth factors and cytokines that can be potentially utilized in regenerative procedures involving cartilage and bone. However, the proportion of MSCs in the nucleated cell population of BM is only around 0.001% to 0.01% thereby making the harvesting and processing technique crucial for obtaining optimal results upon its use in various regenerative processes. Although several studies in the literature have given encouraging results on the utility of BM aspiration concentrate (BMAC) in various regenerative procedures, there is a lack of consensus concerning the harvesting variables such as choice of anesthetic agent to be used, site of harvest, size of the syringe to be used, anticoagulant of choice, and processing variables such as centrifugation time, and speed. In this review article, we aim to discuss the variables in the harvesting and processing technique of BMAC and their impact on the yield of MSCs in the final concentrate obtained from them.
Geometric Parameter Identification of Medical Robot Based on Improved Beetle Antennae Search Algorithm
Authors: Kou Bin , Ren Dongcheng , Guo Shijie
Published: January 2022

To improve the accuracy of common intelligent algorithms when identifying the parameters of geometric error in medical robots, this paper proposes an improved beetle antennae search algorithm (RWSAVSBAS). We first establish a model for the kinematic error in medical robots, and then add the random wandering behavior of the wolf colony algorithm to the search process of the beetle antennae search algorithm to strengthen its capability for local search. Following this, we improve the global convergence ability of the beetle antennae search algorithm by using the simulated annealing algorithm. We compare the accuracy of end positioning of the proposed algorithm with the frog-jumping algorithm and the beetle antennae search algorithm with variable step length through simulations. The results show that the proposed algorithm has a higher accuracy of convergence, and can significantly improve the accuracy of end positioning of the medical robot.
The Promising Role of Mushrooms as a Therapeutic Adjuvant of Conventional Cancer Therapies
Authors: Plácido Ana Isabel , Roque Fátima , Morgado Manuel
Published: January 2022

Complementary and alternative medicine (CAM) has been fronted as an alternative due to its potential for holistic treatment. Many CAMs are plant-derived, including algae and mushrooms that have been used widely in many parts of the world, where they are regarded as biological response modifiers. The purpose of this article was to review the role of mushrooms as an adjuvant in conventional therapies, to reveal the therapeutic substances of mushrooms as an adjuvant in conventional therapies, to bring together the available scientific data on the medical effects of mushrooms in oncology, and verify its efficacy and safety. A literature search was conducted in September 2021 on the MEDLINE-PubMed and Cochrane databases to identify relevant randomized controlled trials or clinical trials studies addressing the use of whole mushroom formulations as complementary therapy during conventional cancer treatment.: The findings from the present study suggest that mushrooms may act as a potentiator of host defense mechanisms and decrease adverse events for patients with cancer undergoing conventional therapies. New protocols to conduct clinical trials are needed to elucidate the possible active mechanisms and clinical benefits of these fungi in various types of cancer.
Comparative Investigation of Gene Regulatory Processes Underlying Avian Influenza Viruses in Chicken and Duck
Authors: Klees Selina , Schlüter Johanna-Sophie , Schellhorn Jendrik , Bertram Hendrik , Kurzweg Antje Christine , Ramzan Faisal , Schmitt Armin Otto , Gültas Mehmet
Published: January 2022

The avian influenza virus (AIV) mainly affects birds and not only causes animals’ deaths, but also poses a great risk of zoonotically infecting humans. While ducks and wild waterfowl are seen as a natural reservoir for AIVs and can withstand most virus strains, chicken mostly succumb to infection with high pathogenic avian influenza (HPAI). To date, the mechanisms underlying the susceptibility of chicken and the effective immune response of duck have not been completely unraveled. In this study, we investigate the transcriptional gene regulation underlying disease progression in chicken and duck after AIV infection. For this purpose, we use a publicly available RNA-sequencing dataset from chicken and ducks infected with low-pathogenic avian influenza (LPAI) H5N2 and HPAI H5N1 (lung and ileum tissues, 1 and 3 days post-infection). Unlike previous studies, we performed a promoter analysis based on orthologous genes to detect important transcription factors (TFs) and their cooperation, based on which we apply a systems biology approach to identify common and species-specific master regulators. We found master regulators such as EGR1, FOS, and SP1, specifically for chicken and ETS1 and SMAD3/4, specifically for duck, which could be responsible for the duck’s effective and the chicken’s ineffective immune response.
Effect of Coronary Artery Disease on COVID-19—Prognosis and Risk Assessment: A Systematic Review and Meta-Analysis
Authors: Szarpak Lukasz , Mierzejewska Malgorzata , Jurek Jonasz , Kochanowska Anna , Gasecka Aleksandra , Truszewski Zenon , Pruc Michal , Blek Natasza , Rafique Zubaid , Filipiak Krzysztof J. , Denegri Andrea , Jaguszewski Milosz J.
Published: January 2022

Coronary artery disease (CAD) is the leading cause of death worldwide. Patients with pre-existing CAD were shown to have a more severe course of COVID-19, but this association has not been clarified. We performed a meta-analysis to determine the association between CAD and COVID-19 outcomes. We searched Scopus, Medline (PubMed), Web of Science, Embase, and Cochrane databases up to 2 November 2021. There were 62 studies with a total population of 49,286 patients included in the meta-analysis. CAD occurrence in survivor vs. non-survivor groups varied and amounted to 9.2% vs. 22.9%, respectively (OR = 0.33; 95%CI: 0.29 to 0.39; I2 = 70%; p < 0.001). CAD was also associated with increased severity of COVID-19 disease and was (10.8% vs. 5.6%, respectively, for severe vs. non-severe groups (OR = 2.28; 95%CI: 1.59 to 3.27; I2 = 72%; p < 0.001). The role of history of CAD in mortality and severe condition in COVID-19 presents itself as prominent—although a risk of bias in retrospective trials needs to be assessed, in case of our meta-analysis the statistically significant results when it comes to higher mortality among patients with CAD compared to non-CAD patients, a more severe condition observed in patients with CAD, and a visibly more frequent admission to intensive care unit in patients with CAD, it seems that an incidence of cardiovascular events plays a role in COVID-19 prognosis.
Single-Cell Sequencing Reveals an Intrinsic Heterogeneity of the Preovulatory Follicular Microenvironment
Authors: Wu Huihua , Zhu Rui , Zheng Bo , Liao Guizhi , Wang Fuxin , Ding Jie , Li Hong , Li Mingqing
Published: January 2022

The follicular microenvironment, including intra-follicular granulosa cells (GCs), is responsible for oocyte maturation and subsequent ovulation. However, the functions of GCs and cellular components of the follicular microenvironment in preovulatory follicles have not been extensively explored. Here, we surveyed the single-cell transcriptome of the follicular microenvironment around MII oocytes in six human preovulatory follicles in in vitro fertilization. There were six different cell types in the preovulatory follicles, including GCs and various immune cells. In GCs, we identified nine different functional clusters with different functional transcriptomic profiles, including specific clusters involved in inflammatory responses and adhesive function. Follicular macrophages are involved in immune responses, extracellular matrix remoulding and assist GCs in promoting the oocyte meiotic resumption. Interestingly, we observed that the specific terminal state subcluster of GCs with high levels of adhesive-related molecules should result in macrophage recruitment and residence, further contributing to an obvious heterogeneity of the immune cell proportion in preovulatory follicles from different patients. Our results provide a comprehensive understanding of the transcriptomic landscape of the preovulatory follicular microenvironment at the single-cell level. It provides valuable insights into understanding the regulation of the oocyte maturation and ovulation process, offering potential clues for the diagnosis and treatment of oocyte-maturation-related and ovulation-related diseases.
Cellulose Nanofiber-Based Aerogels from Wheat Straw: Influence of Surface Load and Lignin Content on Their Properties and Dye Removal Capacity
Authors: Morcillo-Martín Ramón , Espinosa Eduardo , Rabasco-Vílchez Laura , Sanchez Laura M. , de Haro Jorge , Rodríguez Alejandro
Published: January 2022

Water pollution is one of the most serious problems worldwide. Nanocellulose-based aerogels usually show excellent adsorption capacities due to their high aspect ratio, specific surface area and surface charge, making them ideal for water purification. In this work, (ligno)cellulose nanofibers (LCNFs/CNFs) from wheat straw residues were obtained using two types of pre-treatments: mechanical (Mec) and TEMPO-mediated oxidization (TO), to obtain different consistency (0.2, 0.4, 0.6 and 0.8) bioaerogels, and their adsorption capacities as dye removers were further studied. The materials were characterized in terms of density, porosity and mechanical properties. An inversely proportional relationship was observed between the consistencies of the aerogels and their achieved densities. Despite the increase in density, all samples showed porosities above 99%. In terms of mechanical properties, the best results were obtained for the 0.8% consistency LCNF and CNF-Mec aerogels, reaching 67.87 kPa and 64.6 kPa for tensile strength and Young’s modulus, respectively. In contrast, the adsorption capacity of the aerogels was better for TEMPO-oxidized aerogels, reaching removal rates of almost 100% for the CNF-TO5 samples. Furthermore, the residual lignin content in LCNF-Mec aerogels showed a great improvement in the removal capacity, reaching rates higher than 80%, further improving the cost efficiency of the samples due to the reduction in chemical treatments.
A Novel 16-Genes Signature Scoring System as Prognostic Model to Evaluate Survival Risk in Patients with Glioblastoma
Authors: Yu Zunpeng , Du Manqing , Lu Long
Published: January 2022

Previous studies have found that gene expression levels are associated with prognosis and some genes can be used to predict the survival risk of glioblastoma (GBM) patients. However, most of them just built the survival-related gene signature, and personal survival risk can be evaluated only in group. This study aimed to find the prognostic survival related genes of GBM, and construct survival risk prediction model, which can be used to evaluate survival risk by individual. We collected gene expression data and clinical information from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Cox regression analysis and LASSO-cox regression analysis were performed to get survival-related genes and establish the overall survival prediction model. The ROC curve and Kaplan Meier analysis were used to evaluate the prediction ability of the model in training set and two independent cohorts. We also analyzed the biological functions of survival-related genes by GO and KEGG enrichment analysis. We identified 99 genes associated with overall survival and selected 16 genes (IGFBP2, GPRASP1, C1R, CHRM3, CLSTN2, NELL1, SEZ6L2, NMB, ICAM5, HPCAL4, SNAP91, PCSK1N, PGBD5, INA, UCHL1 and LHX6) to establish the survival risk prediction model. Multivariate Cox regression analysis indicted that the risk score could predict overall survival independent of age and gender. ROC analyses showed that our model was more robust than four existing signatures. The sixteen genes can also be potential transcriptional biomarkers and the model can assist doctors on clinical decision-making and personalized treatment of GBM patients.
Targeting Systemic Sclerosis from Pathogenic Mechanisms to Clinical Manifestations: Why IL-6?
Authors: Cardoneanu Anca , Burlui Alexandra Maria , Macovei Luana Andreea , Bratoiu Ioana , Richter Patricia , Rezus Elena
Published: January 2022

Systemic sclerosis (SS) is a chronic autoimmune disorder, which has both cutaneous and systemic clinical manifestations. The disease pathogenesis includes a triad of manifestations, such as vasculopathy, autoimmunity, and fibrosis. Interleukin-6 (IL-6) has a special role in SS development, both in vascular damage and in the development of fibrosis. In the early stages, IL-6 participates in vascular endothelial activation and apoptosis, leading to the release of damage-associated molecular patterns (DAMPs), which maintain inflammation and autoimmunity. Moreover, IL-6 plays an important role in the development of fibrotic changes by mediating the transformation of fibroblasts into myofibroblasts. All of these are associated with disabling clinical manifestations, such as skin thickening, pulmonary fibrosis, pulmonary arterial hypertension (PAH), heart failure, and dysphagia. Tocilizumab is a humanized monoclonal antibody that inhibits IL-6 by binding to the specific receptor, thus preventing its proinflammatory and fibrotic actions. Anti-IL-6 therapy with Tocilizumab is a new hope for SS patients, with data from clinical trials supporting the favorable effect, especially on skin and lung damage.
Metformin Inhibits ROS Production by Human M2 Macrophages via the Activation of AMPK
Authors: Nassif Rana M. , Chalhoub Elias , Chedid Pia , Hurtado-Nedelec Margarita , Raya Elia , Dang Pham My-Chan , Marie Jean-Claude , El-Benna Jamel
Published: January 2022

Metformin (1,1-dimethylbiguanide hydrochloride) is the most commonly used drug to treat type II diabetic patients. It is believed that this drug has several other beneficial effects, such as anti-inflammatory and anticancer effects. Here, we wanted to evaluate the effect of metformin on the production of reactive oxygen species (ROS) by human macrophages. Macrophages are generated in vivo from circulating monocytes depending on the local tissue environment. In vitro proinflammatory macrophages (M1) and anti-inflammatory macrophages (M2) can be generated by culturing monocytes in the presence of different cytokines, such as GM-CSF or M-CSF, respectively. We show that metformin selectively inhibited human monocyte differentiation into proinflammatory macrophages (M1) without inhibiting their differentiation into anti-inflammatory macrophages (M2). Moreover, we demonstrate that, in response to LPS, M2 macrophages produced ROS, which could be very harmful for nearby tissues, and metformin inhibited this process. Interestingly, metformin with LPS induced activation of the adenosine-monophosphate-activated protein kinase (AMPK) and pharmacological activation of AMPK by AICAR, a known AMPK activator, decreased ROS production, whereas the deletion of AMPK in mice dramatically enhanced ROS production in different types of immune cells. These results suggest that metformin exhibits anti-inflammatory effects by inhibiting the differentiation of human monocytes into M1 macrophages and by limiting ROS production by macrophages via the activation of AMPK.
Gene Expression Analysis of Aggressive Adult Xp11.2 Translocation Renal Cell Carcinoma at Clinical Stage T1N0M0 to Identify Potential Prognostic and Therapeutic Biomarkers
Authors: Park Jee Soo , Lee Myung Eun , Jang Won Sik , Kim Jongchan , Park Se Mi , Ham Won Sik
Published: January 2022

Xp11.2 translocation renal cell carcinoma (tRCC), involving transcription factor E3 (TFE3) gene fusions, is a rare and aggressive RCC variant when present in adults and has been recently recognized as a unique entity in RCC. Biomarkers and treatment guidelines do not exist for patients with aggressive Xp11.2 tRCC. The aim was to identify and evaluate therapeutic biomarkers for aggressive Xp11.2 tRCC. RNA sequencing was performed using formalin-fixed, paraffin-embedded tissues from 11 adult patients with clinical T1N0M0 Xp11.2 tRCC, including three patients with aggressive characteristics (recurrence or cancer-specific death after nephrectomy). Thirty genes were differentially expressed between the aggressive and non-aggressive groups, even after adjustment, and were associated with KEGG pathways related to the aggressiveness of Xp11.2 tRCC. PIK3R2, involved in various KEGG pathways, including the PI3K/AKT/mTOR pathway, was overexpressed in the Xp11.2 tRCC cell lines UOK120 and UOK146. The PI3K pathway inhibitor LY294002 showed a significant therapeutic benefit. This study provides the first candidate biomarker, PIK3R2, for aggressive clinical T1N0M0 Xp11.2 tRCC. Furthermore, this study is the first to recommend a targeted drug, LY294002, for aggressive Xp11.2 tRCC based on the molecular pathophysiology.
TSC/mTOR Pathway Mutation Associated Eosinophilic/Oncocytic Renal Neoplasms: A Heterogeneous Group of Tumors with Distinct Morphology, Immunohistochemical Profile, and Similar Genetic Background
Authors: Pivovarcikova Kristyna , Alaghehbandan Reza , Vanecek Tomas , Ohashi Riuko , Pitra Tomas , Hes Ondrej
Published: January 2022

A number of recently described renal tumor entities share an eosinophilic/oncocytic morphology, somewhat solid architectural growth pattern, and tendency to present as low-stage tumors. The vast majority of such tumors follow a non-aggressive clinical behavior. In this review, we discuss the morphological, immunohistochemical, and molecular genetic profiles of the three most recent novel/emerging renal entities associated with TSC/mTOR pathway mutations. These are eosinophilic solid and cystic renal cell carcinoma, eosinophilic vacuolated tumors, and low-grade oncocytic tumors, which belong to a heterogeneous group of renal tumors, demonstrating mostly solid architecture, eosinophilic/oncocytic cytoplasm, and overlapping morphological and immunohistochemical features between renal oncocytoma and chromophobe renal cell carcinoma. All three tumors also share a molecular genetic background with mutations in the mTORC1 pathway (TSC1/TSC2/mTOR/RHEB). Despite the common genetic background, it appears that the tumors with TSC/mTOR mutations represent a diverse group of distinct renal neoplasms.
Histologic-Based Tumor-Associated Immune Cells Status in Clear Cell Renal Cell Carcinoma Correlates with Gene Signatures Related to Cancer Immunity and Clinical Outcomes
Authors: Ohe Chisato , Yoshida Takashi , Ikeda Junichi , Tsuzuki Toyonori , Ohashi Riuko , Ohsugi Haruyuki , Atsumi Naho , Yamaka Ryosuke , Saito Ryoichi , Yasukochi Yoshiki , Higasa Koichiro , Kinoshita Hidefumi , Tsuta Koji
Published: January 2022

The three-tier immunophenotype (desert, excluded, and inflamed) and the four-tier immunophenotype (cold, immunosuppressed, excluded, and hot) have been linked to prognosis and immunotherapy response. This study aims to evaluate whether immunophenotypes of clear cell renal cell carcinoma, identified on hematoxylin and eosin-stained slides, correlate with gene expression signatures related to cancer immunity, and clinical outcomes. We evaluated tumor-associated immune cells (TAICs) status using three methodologies: three-tier immunophenotype based on the location of TAICs, four-tier immunophenotype considering both the location and degree of TAICs and inflammation score focusing only on the degree of TAICs, using a localized clear cell renal cell carcinoma cohort (n = 436) and The Cancer Genome Atlas (TCGA)-KIRC cohort (n = 162). We evaluated the association of the TAICs status assessed by three methodologies with CD8 and PD-L1 immunohistochemistry and immune gene expression signatures by TCGA RNA-sequencing data. All three methodologies correlated with immunohistochemical and immune gene expression signatures. The inflammation score and the four-tier immunophenotype showed similarly higher accuracy in predicting recurrence-free survival and overall survival compared to the three-tier immunophenotype. In conclusion, a simple histologic assessment of TIACs may predict clinical outcomes and immunotherapy responses.
Sex, Allergic Diseases and Omalizumab
Authors: Sirufo Maria Maddalena , De Pietro Francesca , Ginaldi Lia , De Martinis Massimo
Published: January 2022

Gender differences are increasingly emerging in every area of medicine including drug therapy; however, specific gender-targeted studies are infrequent. Sex is a fundamental variable, which cannot be neglected. When optimizing therapies, gender pharmacology must always be considered in order to improve the effectiveness and safety of the use of drugs. Knowledge of gender differences promotes appropriate use of therapies and greater health protection for both genders. Further development of gender research would make it possible to report on differences in the assimilation and response of the female organism as compared to the male, in order to identify potential risks and benefits that can be found between genders. Furthermore, a better understanding of sex/gender-related influences, with regard to pharmacological activity, would allow the development of personalized “tailor-made” medicines. Here, we summarize the state of knowledge on the role of sex in several allergic diseases and their treatment with omalizumab, the first biologic drug authorized for use in the field of allergology.
Ultrasensitive Aptasensors for the Detection of Viruses Based on Opto-Electrochemical Readout Systems
Authors: Divya  , Dkhar Daphika S , Kumari Rohini , Mahapatra Supratim , Kumar Rahul , Chandra Pranjal
Published: January 2022

Viral infections are becoming the foremost driver of morbidity, mortality and economic loss all around the world. Treatment for diseases associated to some deadly viruses are challenging tasks, due to lack of infrastructure, finance and availability of rapid, accurate and easy-to-use detection methods or devices. The emergence of biosensors has proven to be a success in the field of diagnosis to overcome the challenges associated with traditional methods. Furthermore, the incorporation of aptamers as bio-recognition elements in the design of biosensors has paved a way towards rapid, cost-effective, and specific detection devices which are insensitive to changes in the environment. In the last decade, aptamers have emerged to be suitable and efficient biorecognition elements for the detection of different kinds of analytes, such as metal ions, small and macro molecules, and even cells. The signal generation in the detection process depends on different parameters; one such parameter is whether the labelled molecule is incorporated or not for monitoring the sensing process. Based on the labelling, biosensors are classified as label or label-free; both have their significant advantages and disadvantages. Here, we have primarily reviewed the advantages for using aptamers in the transduction system of sensing devices. Furthermore, the labelled and label-free opto-electrochemical aptasensors for the detection of various kinds of viruses have been discussed. Moreover, numerous globally developed aptasensors for the sensing of different types of viruses have been illustrated and explained in tabulated form.
A Real-Time PPG Peak Detection Method for Accurate Determination of Heart Rate during Sinus Rhythm and Cardiac Arrhythmia
Authors: Han Dong , Bashar Syed Khairul , Lázaro Jesús , Mohagheghian Fahimeh , Peitzsch Andrew , Nishita Nishat , Ding Eric , Dickson Emily L. , DiMezza Danielle , Scott Jessica , Whitcomb Cody , Fitzgibbons Timothy P. , McManus David D. , Chon Ki H.
Published: January 2022

Objective: We have developed a peak detection algorithm for accurate determination of heart rate, using photoplethysmographic (PPG) signals from a smartwatch, even in the presence of various cardiac rhythms, including normal sinus rhythm (NSR), premature atrial contraction (PAC), premature ventricle contraction (PVC), and atrial fibrillation (AF). Given the clinical need for accurate heart rate estimation in patients with AF, we developed a novel approach that reduces heart rate estimation errors when compared to peak detection algorithms designed for NSR. Methods: Our peak detection method is composed of a sequential series of algorithms that are combined to discriminate the various arrhythmias described above. Moreover, a novel Poincaré plot scheme is used to discriminate between basal heart rate AF and rapid ventricular response (RVR) AF, and to differentiate PAC/PVC from NSR and AF. Training of the algorithm was performed only with Samsung Simband smartwatch data, whereas independent testing data which had more samples than did the training data were obtained from Samsung’s Gear S3 and Galaxy Watch 3. Results: The new PPG peak detection algorithm provides significantly lower average heart rate and interbeat interval beat-to-beat estimation errors—30% and 66% lower—and mean heart rate and mean interbeat interval estimation errors—60% and 77% lower—when compared to the best of the seven other traditional peak detection algorithms that are known to be accurate for NSR. Our new PPG peak detection algorithm was the overall best performers for other arrhythmias. Conclusion: The proposed method for PPG peak detection automatically detects and discriminates between various arrhythmias among different waveforms of PPG data, delivers significantly lower heart rate estimation errors for participants with AF, and reduces the number of false negative peaks. Significance: By enabling accurate determination of heart rate despite the presence of AF with rapid ventricular response or PAC/PVCs, we enable clinicians to make more accurate recommendations for heart rate control from PPG data.
Dynamic Patterns of Sex Chromosome Evolution in Neognath Birds: Many Independent Barriers to Recombination at the ATP5F1A Locus
Authors: Kimball Rebecca T. , Braun Edward L.
Published: January 2022

Avian sex chromosomes evolved after the divergence of birds and crocodilians from their common ancestor, so they are younger than the better-studied chromosomes of mammals. It has long been recognized that there may have been several stages to the evolution of avian sex chromosomes. For example, the CHD1 undergoes recombination in paleognaths but not neognaths. Genome assemblies have suggested that there may be variation in the timing of barriers to recombination among Neognathae, but there remains little understanding of the extent of this variability. Here, we look at partial sequences of ATP5F1A, which is on the avian Z and W chromosomes. It is known that recombination of this gene has independently ceased in Galliformes, Anseriformes, and at least five neoavian orders, but whether there are other independent cessations of recombination among Neoaves is not understood. We analyzed a combination of data extracted from published chromosomal-level genomes with data collected using PCR and cloning to identify Z and W copies in 22 orders. Our results suggest that there may be at least 19 independent cessations of recombination within Neognathae, and 3 clades that may still be undergoing recombination (or have only recently ceased recombination). Analyses of ATP5F1A protein sequences revealed an increased amino acid substitution rate for W chromosome gametologs, suggesting relaxed purifying selection on the W chromosome. Supporting this hypothesis, we found that the increased substitution rate was particularly pronounced for buried residues, which are expected to be more strongly constrained by purifying selection. This highlights the dynamic nature of avian sex chromosomes, and that this level of variation among clades means they should be a good system to understand sex chromosome evolution.
Deprivation of Auditory Experience Influences Numerosity Discrimination, but Not Numerosity Estimation
Authors: Tonelli Alessia , Togoli Irene , Arrighi Roberto , Gori Monica
Published: January 2022

Number sense is the ability to estimate the number of items, and it is common to many species. Despite the numerous studies dedicated to unveiling how numerosity is processed in the human brain, to date, it is not clear whether the representation of numerosity is supported by a single general mechanism or by multiple mechanisms. Since it is known that deafness entails a selective impairment in the processing of temporal information, we assessed the approximate numerical abilities of deaf individuals to disentangle these two hypotheses. We used a numerosity discrimination task (2AFC) and an estimation task, in both cases using sequential (temporal) or simultaneous (spatial) stimuli. The results showed a selective impairment of the deaf participants compared with the controls (hearing) in the temporal numerosity discrimination task, while no difference was found to discriminate spatial numerosity. Interestingly, the deaf and hearing participants did not differ in spatial or temporal numerosity estimation. Overall, our results suggest that the deficit in temporal processing induced by deafness also impacts perception in other domains such as numerosity, where sensory information is conveyed in a temporal format, which further suggests the existence of separate mechanisms subserving the processing of temporal and spatial numerosity.
Modulating Cognitive–Motor Multitasking with Commercial-off-the-Shelf Non-Invasive Brain Stimulation
Authors: Ward Nathan , Hussey Erika , Wooten Thomas , Marfeo Elizabeth , Brunyé Tad T.
Published: January 2022

One growing area of multitasking research involves a focus on performing cognitive and motor tasks in tandem. In these situations, increasing either cognitive or motor demands has implications for performance in both tasks, an effect which is thought to be due to competing neural resources. Separate research suggests that non-invasive brain stimulation may offer a means to mitigate performance decrements experienced during multitasking. In the present study, we investigated the degree to which a commercially available non-invasive brain stimulation device (Halo Sport) alters balance performance in the presence of different types of cognitive demands. Specifically, we tested if performing a secondary cognitive task impacts postural sway in healthy young adults and if we could mitigate this impact using transcranial direct current stimulation (tDCS) applied over the primary motor cortex. Furthermore, we included conditions of unstable and stable surfaces and found that lower surface stability increased postural sway. In addition, we found that cognitive load impacted postural sway but in the opposite pattern we had anticipated, with higher sway found in the single-task control condition compared to executive function conditions. Finally, we found a small but significant effect of tDCS on balance with decreased sway for active (compared to sham) tDCS.
Identification of an IL-4-Related Gene Risk Signature for Malignancy, Prognosis and Immune Phenotype Prediction in Glioma
Authors: Qi Ying , Yang Xinyu , Ji Chunxia , Tang Chao , Xie Liqian
Published: January 2022

Background: Emerging molecular and genetic biomarkers have been introduced to classify gliomas in the past decades. Here, we introduced a risk signature based on the cellular response to the IL-4 gene set through Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. Methods: In this study, we provide a bioinformatic profiling of our risk signature for the malignancy, prognosis and immune phenotype of glioma. A cohort of 325 patients with whole genome RNA-seq expression data from the Chinese Glioma Genome Atlas (CGGA) dataset was used as the training set, while another cohort of 667 patients from The Cancer Genome Atlas (TCGA) dataset was used as the validating set. The LASSO model identified a 10-gene signature which was considered as the optimal model. Results: The signature was confirmed to be a good predictor of clinical and molecular features involved in the malignancy of gliomas. We also identified that our risk signature could serve as an independently prognostic biomarker in patients with gliomas (p < 0.0001). Correlation analysis showed that our risk signature was strongly correlated with the Tregs, M0 macrophages and NK cells infiltrated in the microenvironment of glioma, which might be a supplement to the existing incomplete innate immune mechanism of glioma phenotypes. Conclusions: Our IL-4-related gene signature was associated with more aggressive and immunosuppressive phenotypes of gliomas. The risk score could predict prognosis independently in glioma, which might provide a new insight for understanding the IL-4 involved mechanism of gliomas.
Neurological and Neuroimaging Features of CYB5R3-Related Recessive Hereditary Methemoglobinemia Type II
Authors: Nicita Francesco , Sabatini Letizia , Alesi Viola , Lucignani Giulia , Sallicandro Ester , Sferra Antonella , Bertini Enrico , Zanni Ginevra , Palumbo Giuseppe
Published: January 2022

Recessive hereditary methemoglobinemia (RHM) due to NADH-cytochrome b5 reductase deficiency is a rare disease caused by pathogenic variants in CYB5R3. Unlike type I, in RHM type II (RHM2), the enzymatic defect affects erythrocytes and all body tissues, thus resulting in cyanosis and neurological impairment. Although the first description of RHM2 dates back to the mid-1950s, detailed clinical and neuroimaging information are available for only a few patients. Here, we describe a new patient with RHM2 that harbors an unreported homozygous 31 Kb deletion involving part of CYB5R3, and showing a peculiar neuroimaging pattern resembling a ponto-cerebellar hypoplasia-like condition. A careful review of the available literature was performed with the aim of better delineating neurological and neuroimaging as well as the genotypic spectra of this extremely rare disease.
Cognitive Impairment in Secondary Progressive Multiple Sclerosis: Effect of Disease Duration, Age, and Progressive Phenotype
Authors: Brochet Bruno , Clavelou Pierre , Defer Gilles , De Seze Jérôme , Louapre Céline , Magnin Eloi , Ruet Aurélie , Thomas-Anterion Catherine , Vermersch Patrick
Published: January 2022

Background: Cognitive deficits are common in multiple sclerosis (MS) and affect patients at all stages of the disease, regardless of phenotype. Aims: This literature review focuses the cognitive deficits observed in secondary progressive MS (SPMS). It is mainly based on studies that compared the frequency and main characteristics of cognitive deficits in SPMS with other phenotypes. Methods: A bibliographic search was carried out using the PubMed database with the following keywords: multiple sclerosis, secondary-progressive, cognition. Results: Thirteen studies were initially selected that were published in English, reporting the neuropsychological data of a sample of at least 30 patients with SPMS, comparing them with patients with other phenotypes. Studies suggest that there is an association between the duration of the disease and the frequency and extent of the cognitive disorders. Studies also showed that the SP form is associated with an increased frequency of cognitive impairment and with an increased severity as compared to relapsing-remitting MS (RRMS). Compared to RRMS, progressive forms of MS are associated with more severe impairment in certain cognitive areas, such as episodic verbal memory, information processing speed, working memory, or verbal fluency. Two studies showed that cognitive performances decline overtime in SPMS. Conclusion: Cognitive disorders are more frequent and more severe in the SP form than in relapsing course of MS. The profile of cognitive impairment encountered in the SP form also appears to be different from those found in the other phenotypes.
Clinical Implications of Prominent Cortical Vessels on Susceptibility-Weighted Imaging in Acute Ischemic Stroke Patients Treated with Recanalization Therapy
Authors: Oh Misun , Lee Minwoo
Published: January 2022

Prominent cortical vessels on susceptibility-weighted imaging (PCV–SWI) correlate with poor leptomeningeal collaterals. However, little is known about PCV–SWI in recanalization therapy-treated patients with anterior circulation large vessel occlusions (LVO). We investigated PCV–SWI-based assessment of leptomeningeal collaterals and outcome predictions in 100 such patients in an observational study. We assessed PCV–SWI using the Alberta Stroke Program Early CT Score and evaluated leptomeningeal collaterals on multiphase CT angiography (mCTA). Predictive abilities were analyzed using multivariable logistic regression and area of receiver operating curves (AUCs). The extent of PCV–SWI correlated with leptomeningeal collaterals on mCTA (Spearman test, r = 0.77; p < 0.001); their presence was associated with worse functional outcomes and a lower successful recanalization rate (adjusted odds ratios = 0.24 and 0.23, 95% CIs = 0.08–0.65 and 0.08–0.65, respectively). The presence of PCV–SWI predicted outcomes better than good collaterals on mCTA did (C-statistic = 0.84 vs. 0.80; 3-month modified Rankin Scale (mRS) 0–2 = 0.75 vs. 0.67 for successful recanalization). Comparison of AUCs showed that they had similar abilities for predicting outcomes (p = 0.68 for 3-month mRS 0–2; p = 0.23 for successful recanalization). These results suggest that PCV–SWI is a useful feature for assessing leptomeningeal collaterals in acute ischemic stroke patients with anterior circulation LVO and predicting outcomes after recanalization therapy.