bluuebunny/crossref_metadata_2025 huggingface dataset:
AMPD1 Is Associated With the Immune Response and Serves as a Prognostic Marker in HER2-Positive Breast Cancer
Authors: Wang Long , Zhang Xue , Wang Mengxue , Li Yunhai , Xu Jiali , Wei Jiaying , Li Hongzhong , Ren Guosheng , Yin Xuedong
Published: November 2021

Background

Although immunotherapy has been used in the treatment of metastatic triple negative breast cancer (TNBC), its therapeutic influence on human epidermal growth factor receptor 2 (HER2)-positive subtype remains controversial. It is therefore imperative to find biomarkers that can predict the immune response in HER2+ BC.

Methods

ESTIMATE was utilized to compute the ImmuneScore and StromalScore from data obtained from TCGA database, and differentially expressed genes (DEGs) were identified. In addition, univariate Cox regression was used to assess candidate genes such as AMPD1, CD33, and CCR5. Gene set enrichment analysis (GSEA) was used to further understand AMPD1-associated pathways. Moreover, immunohistochemical analyses were performed to further reveal the relationship among AMPD1, CD4 and CD8 genes.

Results

The expression of AMPD1 was markedly associated with disease outcome and tumor-infiltrating immune cells (TICs). In addition, AMPD1 was associated with lymph node status, age and the expression of PD-L1 and PD-L2. High AMPD1 expression was linked to longer overall survival (OS). Upregulated expression of AMPD1 correlated with the enrichment of immune-related signaling pathways. In addition, immunohistochemical analyses demonstrated a co-expression profile among AMPD1, CD4 and CD8 genes.

Conclusions

Taken together, our data demonstrated that AMPD1 might serve as a novel biomarker for predicting the immune response and disease outcome in HER2+ BC.
Calcium-Dependent Ion Channels and the Regulation of Arteriolar Myogenic Tone
Authors: Jackson William F.
Published: November 2021

Arterioles in the peripheral microcirculation regulate blood flow to and within tissues and organs, control capillary blood pressure and microvascular fluid exchange, govern peripheral vascular resistance, and contribute to the regulation of blood pressure. These important microvessels display pressure-dependent myogenic tone, the steady state level of contractile activity of vascular smooth muscle cells (VSMCs) that sets resting arteriolar internal diameter such that arterioles can both dilate and constrict to meet the blood flow and pressure needs of the tissues and organs that they perfuse. This perspective will focus on the Ca2+-dependent ion channels in the plasma and endoplasmic reticulum membranes of arteriolar VSMCs and endothelial cells (ECs) that regulate arteriolar tone. In VSMCs, Ca2+-dependent negative feedback regulation of myogenic tone is mediated by Ca2+-activated K+(BKCa) channels and also Ca2+-dependent inactivation of voltage-gated Ca2+channels (VGCC). Transient receptor potential subfamily M, member 4 channels (TRPM4); Ca2+-activated Cl−channels (CaCCs; TMEM16A/ANO1), Ca2+-dependent inhibition of voltage-gated K+(KV) and ATP-sensitive K+(KATP) channels; and Ca2+-induced-Ca2+release through inositol 1,4,5-trisphosphate receptors (IP3Rs) participate in Ca2+-dependent positive-feedback regulation of myogenic tone. Calcium release from VSMC ryanodine receptors (RyRs) provide negative-feedback through Ca2+-spark-mediated control of BKCachannel activity, or positive-feedback regulation in cooperation with IP3Rs or CaCCs. In some arterioles, VSMC RyRs are silent. In ECs, transient receptor potential vanilloid subfamily, member 4 (TRPV4) channels produce Ca2+sparklets that activate IP3Rs and intermediate and small conductance Ca2+activated K+(IKCaand sKCa) channels causing membrane hyperpolarization that is conducted to overlying VSMCs producing endothelium-dependent hyperpolarization and vasodilation. Endothelial IP3Rs produce Ca2+pulsars, Ca2+wavelets, Ca2+waves and increased global Ca2+levels activating EC sKCaand IKCachannels and causing Ca2+-dependent production of endothelial vasodilator autacoids such as NO, prostaglandin I2and epoxides of arachidonic acid that mediate negative-feedback regulation of myogenic tone. Thus, Ca2+-dependent ion channels importantly contribute to many aspects of the regulation of myogenic tone in arterioles in the microcirculation.
Integration of Microfluidics, Photonic Integrated Circuits and Data Acquisition and Analysis Methods in a Single Platform for the Detection of Swine Viral Diseases
Authors: Manessis Georgios , Mourouzis Christos , Griol Amadeu , Zurita-Herranz David , Peransi Sergio , Sanchez Carlos , Giusti Alessandro , Gelasakis Athanasios I. , Bossis Ioannis
Published: November 2021

Viral diseases challenge the health and welfare of pigs and undermine the sustainability of swine farms. Their efficient control requires early and reliable diagnosis, highlighting the importance of Point of Care (POC) diagnostics in veterinary practice. The objective of this study was to validate a novel POC system that utilizes Photonic Integrated Circuits (PICs) and microfluidics to detect swine viral pathogens using oral fluids and Porcine Parvovirus (PPV) and Porcine Circovirus 2 (PCV-2) as proofs of concept. The sensitivity and specificity of the device were calculated for both viruses, and Receiver Operating Characteristic (ROC) curves were drawn. PPV had an Area Under Curve (AUC) value of 0.820 (95% CI: 0.760 to 0.880, p < 0.0001), and its optimal efficiency threshold of detection shifts was equal to 4.5 pm (68.6% sensitivity, 77.1% specificity and Limit of Detection (LOD) value 106 viral copies/mL). PCV-2 had an AUC value of 0.742 (95% CI: 0.670 to 0.815, p < 0.0001) and an optimal efficiency threshold of shifts equal to 6.5 pm (69.5% sensitivity, 70.3% specificity and LOD 3.3 × 105 copies/mL). In this work, it was proven that PICs can be exploited for the detection of swine viral diseases. The novel device can be directly deployed on farms as a POC diagnostics tool.
Neutrophil NET Formation with Microbial Stimuli Requires Late Stage NADPH Oxidase Activity
Authors: Parker Heather , Jones Harry , Kaldor Christopher , Hampton Mark , Winterbourn Christine
Published: November 2021

Neutrophils respond to a range of stimuli by releasing extracellular traps (NETs), a mesh consisting of chromatin plus granule and cytoplasmic proteins. We have investigated NET release in response to phorbol myristate acetate (PMA), Pseudomonas aeruginosa (PAO1), Staphylococcus aureus and Candida albicans, and the involvement of NADPH oxidase (NOX2) and myeloperoxidase (MPO) activities. An oxidative mechanism was involved with each stimulus, and the NOX2 inhibitor diphenylene iodonium (DPI) gave almost total inhibition. Notably, DPI added up to 60–90 min after stimulation still gave significant inhibition of subsequent NET formation. As most of the NOX2 activity had already occurred by that time, this indicates a requirement for late-stage low-level oxidant production. Inhibition of histone citrullination did not suppress NET formation, indicating that this was not the essential oxidant-dependent step. With PMA and P. aeruginosa PAO1, MPO activity played an important role in the induction of NETs and MPO inhibitors added up to 30–90 min after stimulation suppressed NET formation. NET formation with S. aureus and C. albicans was insensitive to MPO inhibition. Thus, MPO products are important with some stimuli but not others. Our results extend earlier observations with PMA and show that induction of NETs by microbial stimuli requires late stage oxidant production. Others have shown that NET formation involves NOX2-dependent elastase release from granules. As this is an early event, we conclude from our results that there is more than one oxidant-dependent step.
A Novel Approach to Enhance Crude Oil Recovery Ratio Using Selected Bacterial Species
Authors: Althalb Hakima , Elmusrati Izzeddin , Banat Ibrahim
Published: November 2021

The high viscosity and low flow properties of some crude oil make them difficult to extract from oil reservoirs. This study investigated the mechanisms responsible for the enhancement of oil recovery using fractured dolomite core models. Bacterial strains, Nocardia cyriacigeorgica, Bacillus species, and Pseudomonasputida, isolated from Libyan oil fields, had the ability to biotransform heavy crude oil by reducing its viscosity and converting heavier components into lighter ones. The efficiencies of the three bacterial strains were assessed using sand-packed column experiments through the injection of bacteria to mimic in-situ oil recovery. The optimum biotransformation values of Libyan Bouri crude oil were determined as 77.1, 61.2, and 61.1% using the Bacillus sp., P. putida, and Nocardia cyriacigeorgica, respectively, at 55 °C. Viscosity analyses showed that these strains resulted in the reduction of the viscosity of the crude oil at two different temperatures of 37 and 55 °C. The highest recovery of residual oil was about 11.3% using Bacillus sp. The study confirmed that the selected bacterial species were capable of displacing additional oil under simulated oil field conditions.
Improving Water Efficiency in a Municipal Indoor Swimming-Pool Complex: A Case Study
Authors: Silva Flora , Antão-Geraldes Ana M. , Zavattieri Carmem , Afonso Maria João , Freire Flávio , Albuquerque António
Published: November 2021

This study aimed to determine the water demand of a municipal swimming pool complex to propose water use efficiency measures. Concomitantly, the possibility of recycling and reusing the water from filter backwashing was evaluated. The pools consumed 25.6% of water, the filter backwashing 24.5%, and the showers 34.7%. Despite the current impossibility of reducing water consumption in pools and filter backwashing, it is feasible to promote more efficient use of water through reducing water consumption by adopting simple water-saving initiatives for showers, taps, and flushing cisterns. These were organized into three distinct scenarios: (a) flushing cistern volume adjustment and the replacement of washbasin and kitchen taps; (b) flushing cistern volume adjustment and shower replacement and (c) flushing cistern volume adjustment, shower, washbasin, and kitchen taps replacement. Under scenarios 1, 2, and 3, the water consumption reduction was 8.0, 13.2, and 20.4%, respectively. The initial investment for scenario 1 was €2290.5, €859.0 for scenario 2 and €3149.5 for scenario 3; the annual water bill reduction was €7115.4, €11,518.1, and €17,655.9, respectively. Therefore, the turnover of the investment was four (scenario 1), one (scenario 2), and three months (scenario 3). The filter washings attained the required standard for irrigation after being subjected to 15 h of sedimentation.
RFID Technology Serving Honey Bee Research: A Comprehensive Description of a 32-Antenna System to Study Honey Bee and Queen Behavior
Authors: Alburaki Mohamed , Madella Shayne , Corona Miguel
Published: November 2021

The fields of electronics and information technology have witnessed rapid development during the last decades, providing significant technical support to the field of biological sciences. Radio-Frequency Identification (RFID) technology has been used to automate the monitoring of animal location and behaviors in a wide range of vertebrate and invertebrate species, including social insects such as ants and honey bees (Apis mellifera L.). This technology relies on electromagnetic fields to identify and track transponders attached to objects automatically. Implementing new technologies to serve research purposes could be time consuming and require technical expertise from entomologists and researchers. Herein, we present a detailed description on how to harness RFID technology to serve honey bee research effectively. We describe how to build and operate a 32-antenna RFID system used to monitor various honey bee behaviors such as foraging, robbing, and queen and drone mating, which can be used in other social insects as well. Preliminary data related to queen nuptial flights were obtained using this unit and presented in this study. Virgin queens labeled with ≈5 mg transponders performed multiple (one to four) nuptial/orientation flights a day (9 a.m. to 5 p.m.) ranging from 8 to 145 s each. Contrary to virgin queens, no hive exit was recorded for mated queens. At full capacity, this unit can monitor up to 32 honey bee colonies concurrently and is self-sustained by a solar panel to work in remote areas. All materials, hardware, and software needed to build and operate this unit are detailed in this study, offering researchers and beekeepers a practical solution and a comprehensive source of information enabling the implementation of RFID technology in their research perspective.
Temperature-Dependent Viscosity of Organic Materials Characterized by Atomic Force Microscope
Authors: Qin Yiming , Ye Jianhuai , Ohno Paul , Nah Theodora , T. Martin Scot
Published: November 2021

The viscosity of atmospheric aerosol particles determines the equilibrium timescale at which a molecule diffuses into and out of particles, influencing processes such as gas–particle partitioning, light scattering, and cloud formation that can affect air quality and climate. This particle viscosity is sensitive to environmental conditions such as relative humidity and temperature. Current experimental techniques mainly characterize aerosol viscosity at room temperature. The influence of temperature on the viscosity of organic aerosol remains underexplored. Herein, the viscosity of atmospherically relevant organic materials was examined at a range of temperatures from 15 °C to 95 °C using an atomic force microscope (AFM) equipped with a temperature-controlled sample module. Dioctyl phthalate and sucrose were selected for investigation. Dioctyl phthalate served as the proxy for atmospherically relevant primary organic materials while sucrose served as the proxy for secondary organic materials. The resonant frequency responses of the AFM cantilever within dioctyl phthalate and sucrose were recorded. The link between the resonant frequency and material viscosity was established via a hydrodynamic function. Results obtained from this study were consistent with previously reported viscosities, thus demonstrating the critical capability of AFM in temperature-dependent viscosity measurements.
A Method for Monitoring State-of-Charge of Lithium-Ion Cells Using Multi-Sine Signal Excitation
Authors: Kim Jonghyeon , Kowal Julia
Published: November 2021

In this paper, a method for monitoring SoC of a lithium-ion battery cell through continuous impedance measurement during cell operation is introduced. A multi-sine signal is applied to the cell operating current, and the cell SoH and SoC can be simultaneously monitored via impedance at each frequency. Unlike existing studies in which cell impedance measurement is performed ex situ through EIS equipment, cell state estimation is performed in situ. The measured impedance takes into account cell temperature and cell SoH, enabling accurate SoC estimation. The measurement system configured for the experiment and considerations for the selection of measurement parameters are described, and the accuracy of cell SoC estimation is presented.
Projecting the Potential Distribution of Glossina morsitans (Diptera: Glossinidae) under Climate Change Using the MaxEnt Model
Authors: Zhou Ruobing , Gao Yuan , Chang Nan , Gao Tai , Ma Delong , Li Chao , Liu Qiyong
Published: November 2021

Glossina morsitans is a vector for Human African Trypanosomiasis (HAT), which is mainly distributed in sub-Saharan Africa at present. Our objective was to project the historical and future potentially suitable areas globally and explore the influence of climatic factors. The maximum entropy model (MaxEnt) was utilized to evaluate the contribution rates of bio-climatic factors and to project suitable habitats for G. morsitans. We found that Isothermality and Precipitation of Wettest Quarter contributed most to the distribution of G. morsitans. The predicted potentially suitable areas for G. morsitans under historical climate conditions would be 14.5 million km2, including a large area of Africa which is near and below the equator, small equatorial regions of southern Asia, America, and Oceania. Under future climate conditions, the potentially suitable areas are expected to decline by about −5.38 ± 1.00% overall, under all shared socioeconomic pathways, compared with 1970–2000. The potentially suitable habitats of G. morsitans may not be limited to Africa. Necessary surveillance and preventive measures should be taken in high-risk regions.
Analysis of 14C, 13C and Aspartic Acid Racemization in Teeth and Bones to Facilitate Identification of Unknown Human Remains: Outcomes of Practical Casework
Authors: Teglind Rebecka , Dawidson Irena , Balkefors Jonas , Alkass Kanar
Published: November 2021

The identification of unknown human remains represents an important task in forensic casework. If there are no clues as to the identity of the remains, then the age, sex, and origin are the most important factors to limit the search for a matching person. Here, we present the outcome of application of so-called bomb pulse radiocarbon (14C derived from above-ground nuclear bomb tests during 1955–1963) analysis to birthdate human remains. In nine identified cases, 14C analysis of tooth crowns provided an estimate of the true date of birth with an average absolute error of 1.2 ± 0.8 years. Analysis of 14C in tooth roots also showed a good precision with an average absolute error of 2.3 ± 2.5 years. Levels of 14C in bones can determine whether a subject has lived after 1955 or not, but more precise carbon turnover data for bones would be needed to calculate date of birth and date of death. Aspartic acid racemization analysis was performed on samples from four cases; in one of these, the year of birth could be predicted with good precision, whereas the other three cases are still unidentified. The stable isotope 13C was analyzed in tooth crowns to estimate provenance. Levels of 13C indicative of Scandinavian provenance were found in known Scandinavian subjects. Teeth from four Polish subjects all showed higher 13C levels than the average for Scandinavian subjects.
Can Fish and Shellfish Species from the Black Sea Supply Health Beneficial Amounts of Bioactive Fatty Acids?
Authors: Merdzhanova Albena , Panayotova Veselina , Dobreva Diana A. , Peycheva Katya
Published: November 2021

Fatty acids (FA) are among the most important natural biologically active compounds. A healthy diet involves the intake of different fatty acids especially from omega-3 (n-3) series. Seafood provides a very good source of polyunsaturated fatty acids (PUFAs), but in Bulgaria there is limited information regarding the n-3 PUFA contents in traditionally consumed seafood by the population. The aims of this study were to determine lipid content, omega-3 polyunsaturated fatty acids (EPA and DHA), and the recommended daily intake of eleven fish species, three bivalves, rapana, and shrimp harvested in the Western part of Black Sea, Bulgaria. Total lipids were extracted according to the method of Blight and Dyer and fatty acid composition was analyzed by GC/MS. Fatty acid profile showed differences among species. PUFA were found in high content among total lipids, especially in shellfish (60.67–68.9% of total lipids) compared to fish species (19.27–34.86% of total lipids). EPA was found in higher amounts in rapana (0.16 g/100 g ww) and two of pelagic species (up to 0.29 g/100 g ww), whereas DHA prevailed in demersal and the most of pelagic fish (0.16–1.92 g/100 g ww) and bivalves (0.16–1.92 g/100 g ww). The health beneficial n3/n6 and PUFA/SFA ratios were found in all analyzed species. The lower values of the lipid nutritional quality indices (AI < 1, TI < 1) and higher for h/H index (0.8–1.78 for fish and 1.52 to 4.67 for bivalves and shrimp) confirm that the commonly consumed Black Sea fish and shellfish may provide health benefits for local populations. This study shows the seafood amounts that can provide the minimum recommended intake of omega-3 polyunsaturated fatty acids.
Plant Group II LEA Proteins: Intrinsically Disordered Structure for Multiple Functions in Response to Environmental Stresses
Authors: Abdul Aziz Mughair , Sabeem Miloofer , Mullath Sangeeta Kutty , Brini Faical , Masmoudi Khaled
Published: November 2021

In response to various environmental stresses, plants have evolved a wide range of defense mechanisms, resulting in the overexpression of a series of stress-responsive genes. Among them, there is certain set of genes that encode for intrinsically disordered proteins (IDPs) that repair and protect the plants from damage caused by environmental stresses. Group II LEA (late embryogenesis abundant) proteins compose the most abundant and characterized group of IDPs; they accumulate in the late stages of seed development and are expressed in response to dehydration, salinity, low temperature, or abscisic acid (ABA) treatment. The physiological and biochemical characterization of group II LEA proteins has been carried out in a number of investigations because of their vital roles in protecting the integrity of biomolecules by preventing the crystallization of cellular components prior to multiple stresses. This review describes the distribution, structural architecture, and genomic diversification of group II LEA proteins, with some recent investigations on their regulation and molecular expression under various abiotic stresses. Novel aspects of group II LEA proteins in Phoenix dactylifera and in orthodox seeds are also presented. Genome-wide association studies (GWAS) indicated a ubiquitous distribution and expression of group II LEA genes in different plant cells. In vitro experimental evidence from biochemical assays has suggested that group II LEA proteins perform heterogenous functions in response to extreme stresses. Various investigations have indicated the participation of group II LEA proteins in the plant stress tolerance mechanism, spotlighting the molecular aspects of group II LEA genes and their potential role in biotechnological strategies to increase plants’ survival in adverse environments.
Identification of Risk Loci for Radiotoxicity in Prostate Cancer by Comprehensive Genotyping of TGFB1 and TGFBR1
Authors: Guhlich Manuel , Hubert Laura , Mergler Caroline Patricia Nadine , Rave-Fraenk Margret , Dröge Leif Hendrik , Leu Martin , Schmidberger Heinz , Rieken Stefan , Hille Andrea , Schirmer Markus Anton
Published: November 2021

Genetic variability in transforming growth factor beta pathway (TGFB) was suggested to affect adverse events of radiotherapy. We investigated comprehensive variability in TGFB1 (gene coding for TGFβ1 ligand) and TGFBR1 (TGFβ receptor-1) in relation to radiotoxicity. Prostate cancer patients treated with primary radiotherapy (n = 240) were surveyed for acute and late toxicity. Germline polymorphisms (n = 40) selected to cover the common genetic variability in TGFB1 and TGFBR1 were analyzed in peripheral blood cells. Human lymphoblastoid cell lines (LCLs) were used to evaluate a possible impact of TGFB1 and TGFBR1 genetic polymorphisms to DNA repair capacity following single irradiation with 3 Gy. Upon adjustment for multiplicity testing, rs10512263 in TGFBR1 showed a statistically significant association with acute radiation toxicity. Carriers of the Cytosine (C)-variant allele (n = 35) featured a risk ratio of 2.17 (95%-CI 1.41–3.31) for acute toxicity ≥ °2 compared to Thymine/Thymine (TT)-wild type individuals (n = 205). Reduced DNA repair capacity in the presence of the C-allele of rs10512263 might be a mechanistic explanation as demonstrated in LCLs following irradiation. The risk for late radiotoxicity was increased by carrying at least two risk genotypes at three polymorphic sites, including Leu10Pro in TGFB1. Via comprehensive genotyping of TGFB1 and TGFBR1, promising biomarkers for radiotoxicity in prostate cancer were identified.
Correction: Kaushal et al. Repurposing Niclosamide for Targeting Pancreatic Cancer by Inhibiting Hh/Gli Non-Canonical Axis of Gsk3β. Cancers 2021, 13, 3105
Authors: Kaushal Jyoti B. , Bhatia Rakesh , Kanchan Ranjana K. , Raut Pratima , Mallapragada Surya , Ly Quan P. , Batra Surinder K. , Rachagani Satyanarayana
Published: November 2021

The authors would like to make a correction to their published paper [...]
Providing Psychological Support to Parents of Childhood Cancer Survivors: ‘Cascade’ Intervention Trial Results and Lessons for the Future
Authors: Wakefield Claire E. , Sansom-Daly Ursula M. , McGill Brittany C. , Hetherington Kate , Ellis Sarah J. , Robertson Eden G. , Donoghoe Mark W. , McCarthy Maria , Kelada Lauren , Girgis Afaf , King Madeleine , Grootenhuis Martha , Anazodo Antoinette , Patterson Pandora , Lowe Cherie , Dalla-Pozza Luciano , Miles Gordon , Cohn Richard J.
Published: November 2021

We conducted a three-armed trial to assess Cascade, a four-module group videoconferencing cognitive behavior therapy (CBT) intervention for parents of childhood cancer survivors currently aged <18 years. We allocated parents to Cascade, an attention control (peer-support group), or a waitlist. The primary outcome was parents’ health-related quality of life (PedsQL-Family Impact/EQ-5D-5L) six months post-intervention. Parents also reported their anxiety/depression, parenting self-agency, fear of recurrence, health service and psychotropic medication use, engagement in productive activities, confidence to use, and actual use of, CBT skills, and their child’s quality of life. Seventy-six parents opted in; 56 commenced the trial. Cascade achieved good parent engagement and most Cascade parents were satisfied and reported benefits. Some parents expressed concerns about the time burden and the group format. Most outcomes did not differ across trial arms. Cascade parents felt more confident to use more CBT skills than peer-support and waitlisted parents, but this did not lead to more use of CBT. Cascade parents reported lower psychosocial health scores for their child than waitlisted parents. Cascade parents’ health service use, psychotropic medication use, and days engaged in productive activities did not improve, despite some improvements in waitlisted parents. Our trial was difficult to implement, but participants were largely satisfied. Cascade did not improve most outcomes, possibly because many parents were functioning well pre-enrolment. We used these findings to improve Cascade and will trial the new version in future.
Genomic and Transcriptomic Profiling of Brain Metastases
Authors: Wardell Christopher P. , Darrigues Emilie , De Loose Annick , Lee Madison P. , Gokden Murat , Makhoul Issam , Tackett Alan J. , Rodriguez Analiz
Published: November 2021

Brain metastases (BM) are the most common brain tumors in adults occurring in up to 40% of all cancer patients. Multi-omics approaches allow for understanding molecular mechanisms and identification of markers with prognostic significance. In this study, we profile 130 BM using genomics and transcriptomics and correlate molecular characteristics to clinical parameters. The most common tumor origins for BM were lung (40%) followed by melanoma (21%) and breast (15%). Melanoma and lung BMs contained more deleterious mutations than other subtypes (p < 0.001). Mutational signatures suggested that the bulk of the mutations were gained before metastasis. A novel copy number event centered around the MCL1 gene was found in 75% of all samples, suggesting a broader role in promoting metastasis. Unsupervised hierarchical cluster analysis of transcriptional signatures available in 65 samples based on the hallmarks of cancer revealed four distinct clusters. Melanoma samples formed a distinctive cluster in comparison to other BM subtypes. Characteristics of molecular profiles did not correlate with survival. However, patients with self-identified black race or those who did not receive radiation correlated with poor survival. These data identify potential new drivers of brain metastatic progression. Our data also suggest further investigation of sociodemographic and clinical features is needed in BM cohorts.
The Impact of Hyaluronic Acid on Tendon Physiology and Its Clinical Application in Tendinopathies
Authors: Oliva Francesco , Marsilio Emanuela , Asparago Giovanni , Frizziero Antonio , Berardi Anna Concetta , Maffulli Nicola
Published: November 2021

The physical–chemical, structural, hydrodynamic, and biological properties of hyaluronic acid within tendons are still poorly investigated. Medical history and clinical applications of hyaluronic acid for tendinopathies are still debated. In general, the properties of hyaluronic acid depend on several factors including molecular weight. Several preclinical and clinical experiences show a good efficacy and safety profile of hyaluronic acid, despite the absence of consensus in the literature regarding the classification according to molecular weight. In in vitro and preclinical studies, hyaluronic acid has shown physical–chemical properties, such as biocompatibility, mucoadhesivity, hygroscopicity, and viscoelasticity, useful to contribute to tendon healing. Additionally, in clinical studies, hyaluronic acid has been used with promising results in different tendinopathies. In this narrative review, findings encourage the clinical application of HA in tendinopathies such as rotator cuff, epicondylitis, Achilles, and patellar tendinopathy.
Zinc Ameliorates the Osteogenic Effects of High Glucose in Vascular Smooth Muscle Cells
Authors: Henze Laura A. , Estepa Misael , Pieske Burkert , Lang Florian , Eckardt Kai-Uwe , Alesutan Ioana , Voelkl Jakob
Published: November 2021

In diabetic patients, medial vascular calcification is common and associated with increased cardiovascular mortality. Excessive glucose concentrations can activate the nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-kB) and trigger pro-calcific effects in vascular smooth muscle cells (VSMCs), which may actively augment vascular calcification. Zinc is able to mitigate phosphate-induced VSMC calcification. Reduced serum zinc levels have been reported in diabetes mellitus. Therefore, in this study the effects of zinc supplementation were investigated in primary human aortic VSMCs exposed to excessive glucose concentrations. Zinc treatment was found to abrogate the stimulating effects of high glucose on VSMC calcification. Furthermore, zinc was found to blunt the increased expression of osteogenic and chondrogenic markers in high glucose-treated VSMCs. High glucose exposure was shown to activate NF-kB in VSMCs, an effect that was blunted by additional zinc treatment. Zinc was further found to increase the expression of TNFα-induced protein 3 (TNFAIP3) in high glucose-treated VSMCs. The silencing of TNFAIP3 was shown to abolish the protective effects of zinc on high glucose-induced NF-kB-dependent transcriptional activation, osteogenic marker expression, and the calcification of VSMCs. Silencing of the zinc-sensing receptor G protein-coupled receptor 39 (GPR39) was shown to abolish zinc-induced TNFAIP3 expression and the effects of zinc on high glucose-induced osteogenic marker expression. These observations indicate that zinc may be a protective factor during vascular calcification in hyperglycemic conditions.
Intratumoral Heterogeneity Promotes Collective Cancer Invasion through NOTCH1 Variation
Authors: Torab Peter , Yan Yue , Ahmed Mona , Yamashita Hironobu , Warrick Joshua I. , Raman Jay D. , DeGraff David J. , Wong Pak Kin
Published: November 2021

Cellular and molecular heterogeneity within tumors has long been associated with the progression of cancer to an aggressive phenotype and a poor prognosis. However, how such intratumoral heterogeneity contributes to the invasiveness of cancer is largely unknown. Here, using a tumor bioengineering approach, we investigate the interaction between molecular subtypes within bladder microtumors and the corresponding effects on their invasiveness. Our results reveal heterogeneous microtumors formed by multiple molecular subtypes possess enhanced invasiveness compared to individual cells, even when both cells are not invasive individually. To examine the molecular mechanism of intratumoral heterogeneity mediated invasiveness, live single cell biosensing, RNA interference, and CRISPR-Cas9 gene editing approaches were applied to investigate and control the composition of the microtumors. An agent-based computational model was also developed to evaluate the influence of NOTCH1 variation on DLL4 expression within a microtumor. The data indicate that intratumoral variation in NOTCH1 expression can lead to upregulation of DLL4 expression within the microtumor and enhancement of microtumor invasiveness. Overall, our results reveal a novel mechanism of heterogeneity mediated invasiveness through intratumoral variation of gene expression.
Murine Trophoblast Stem Cells and Their Differentiated Cells Attenuate Zika Virus In Vitro by Reducing Glycosylation of the Viral Envelope Protein
Authors: Neupane Biswas , Fendereski Mona , Nazneen Farzana , Guo Yan-Lin , Bai Fengwei
Published: November 2021

Zika virus (ZIKV) infection during pregnancy can cause devastating fetal neuropathological abnormalities, including microcephaly. Most studies of ZIKV infection in pregnancy have focused on post-implantation stage embryos. Currently, we have limited knowledge about how a pre-implantation stage embryo deals with a viral infection. This study investigates ZIKV infection on mouse trophoblast stem cells (TSCs) and their in vitro differentiated TSCs (DTSCs), which resemble the cellular components of the trophectoderm layer of the blastocyst that later develops into the placenta. We demonstrate that TSCs and DTSCs are permissive to ZIKV infection; however, ZIKV propagated in TSCs and DTSCs exhibit substantially lower infectivity, as shown in vitro and in a mouse model compared to ZIKV that was generated in Vero cells or mouse embryonic fibroblasts (MEFs). We further show that the low infectivity of ZIKV propagated in TSCs and DTSCs is associated with a reduced level of glycosylation on the viral envelope (E) proteins, which are essential for ZIKV to establish initial attachment by binding to cell surface glycosaminoglycans (GAGs). The decreased level of glycosylation on ZIKV E is, at least, partially due to the low-level expression of a glycosylation-related gene, Hexa, in TSCs and DTSCs. Furthermore, this finding is not limited to ZIKV since similar observations have been made as to the chikungunya virus (CHIKV) and West Nile virus (WNV) propagated in TSCs and DTSCs. In conclusion, our results reveal a novel phenomenon suggesting that murine TSCs and their differentiated cells may have adapted a cellular glycosylation system that can limit viral infectivity by altering the glycosylation of viral envelope proteins, therefore serving as a unique, innate anti-viral mechanism in the pre-implantation stage embryo.
Impaired Skeletal Muscle Development and Regeneration in Transglutaminase 2 Knockout Mice
Authors: Budai Zsófia , Al-Zaeed Nour , Szentesi Péter , Halász Hajnalka , Csernoch László , Szondy Zsuzsa , Sarang Zsolt
Published: November 2021

Skeletal muscle regeneration is triggered by local inflammation and is accompanied by phagocytosis of dead cells at the injury site. Efferocytosis regulates the inflammatory program in macrophages by initiating the conversion of their inflammatory phenotype into the healing one. While pro-inflammatory cytokines induce satellite cell proliferation and differentiation into myoblasts, growth factors, such as GDF3, released by healing macrophages drive myoblast fusion and myotube growth. Therefore, improper efferocytosis may lead to impaired muscle regeneration. Transglutaminase 2 (TG2) is a versatile enzyme participating in efferocytosis. Here, we show that TG2 ablation did not alter the skeletal muscle weights or sizes but led to the generation of small size myofibers and to decreased grip force in TG2 null mice. Following cardiotoxin-induced injury, the size of regenerating fibers was smaller, and the myoblast fusion was delayed in the tibialis anterior muscle of TG2 null mice. Loss of TG2 did not affect the efferocytic capacity of muscle macrophages but delayed their conversion to Ly6C−CD206+, GDF3 expressing cells. Finally, TG2 promoted myoblast fusion in differentiating C2C12 myoblasts. These results indicate that TG2 expressed by both macrophages and myoblasts contributes to proper myoblast fusion, and its ablation leads to impaired muscle development and regeneration in mice.
Perinatal Outcomes in Premature Placental Calcification and the Association of a Color Doppler Study: Report from a Tertiary Care Hospital in Eastern India
Authors: Dash Sudarshan , Das Banya , Panda Soumya Ranjan , Rajguru Monalisa , Jena Pramila , Mishra Abheepsa , Rath Sudhanshu Kumar
Published: November 2021

Introduction: Placental calcification, identified before the 36th week of gestational age, is known as premature placental calcification (PPC). PPC could be a clue for the poor fetal outcome. However, its association with adverse perinatal outcomes is yet to be confirmed. Objective: The primary objective was to determine and compare the perinatal outcomes in pregnancies with and without documented premature placental calcification. Methodology: The present study was a prospective cohort study performed from October 2017 to September 2019. We consecutively enrolled 494 antenatal women who presented to our antenatal OPD after taking consent to participate in our study. Transabdominal sonographies were conducted between 28–36 weeks of gestation to document placental maturity. We compared maternal and fetal outcomes between those who were identified with grade III placental calcification (n = 140) and those without grade III placental calcification (n = 354). Results: The incidence of preeclampsia, at least one abnormal Doppler index, obstetrics cholestasis, placental abruption, and FGR (fetal growth restriction) pregnancies were significantly higher in the group premature placental calcification. We also found a significantly increased incidence of Low APGAR (Appearance, Pulse, Grimace, Activity, and Respiration) scores, NICU (Neonatal Intensive Care Unit) Admission, Abnormal CTG (cardiotocography), meconium-stained liquor, and low birth weight babies in those with grade III placental calcification. Conclusion: Clinicians should be aware of documenting placental grading while performing ultrasonography during 28 to 36 weeks. Ultrasonographically, the absence of PPC can define a subcategory of low-risk pregnant populations which probably need no referral to specialized centers and can be managed in these settings.
InGaN-Based microLED Devices Approaching 1% EQE with Red 609 nm Electroluminescence on Semi-Relaxed Substrates
Authors: White Ryan C. , Li Hongjian , Khoury Michel , Lynsky Cheyenne , Iza Michael , Keller Stacia , Sotta David , Nakamura Shuji , DenBaars Steven P.
Published: November 2021

In this paper, we report the successful demonstration of bright InGaN-based microLED devices emitting in the red spectral regime grown by metal organic chemical vapor deposition (MOCVD) on c-plane semi-relaxed InGaN substrates on sapphire. Through application of an InGaN/GaN base layer scheme to ameliorate high defect density and maintain appropriate lattice constant throughout the growth, high-In quantum wells (QWs) can be grown with improved crystal quality. Improvement to the design of the growth scheme also yields higher power output resulting in an increase to the external quantum efficiency (EQE). Combined, these two improvements allow for an 80 × 80 μm2 microLED device emitting at 609 nm to achieve 0.83% EQE. Furthermore, the true In content of the QW is measured using atomic probe tomography (APT) to confirm the improved In incorporation during high temperature active region growth. These developments represent advancement toward the realization of bright, highly efficient red III-nitride LEDs to be used in RGB applications under one material system.
Intraoperative Guidance Using Hyperspectral Imaging: A Review for Surgeons
Authors: Barberio Manuel , Benedicenti Sara , Pizzicannella Margherita , Felli Eric , Collins Toby , Jansen-Winkeln Boris , Marescaux Jacques , Viola Massimo Giuseppe , Diana Michele
Published: November 2021

Hyperspectral imaging (HSI) is a novel optical imaging modality, which has recently found diverse applications in the medical field. HSI is a hybrid imaging modality, combining a digital photographic camera with a spectrographic unit, and it allows for a contactless and non-destructive biochemical analysis of living tissue. HSI provides quantitative and qualitative information of the tissue composition at molecular level in a contrast-free manner, hence making it possible to objectively discriminate between different tissue types and between healthy and pathological tissue. Over the last two decades, HSI has been increasingly used in the medical field, and only recently it has found an application in the operating room. In the last few years, several research groups have used this imaging modality as an intraoperative guidance tool within different surgical disciplines. Despite its great potential, HSI still remains far from being routinely used in the daily surgical practice, since it is still largely unknown to most of the surgical community. The aim of this study is to provide clinical surgeons with an overview of the capabilities, current limitations, and future directions of HSI for intraoperative guidance.
Lack of Association between Chlamydophila psittaci and Ocular Adnexal MALT Lymphoma in Korean Patients—Is the Geographic or Genetic Difference Significant?
Authors: Cho Uiju , Cho Inju , Lee Sung Hak , Yang Suk Woo , Cho Seok Goo , Lee Youn Soo , Lee Hye Won , Park Gyeongsin
Published: November 2021

Clamydophila psittaci (C. psittaci) has been proposed to be an etiologic factor in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) in the ocular adnexa. However, the pathogenetical significance of the infection has not been fully elucidated. Many previous studies have shown controversial results regarding C. psittaci detection rates in said patients, ranging from 0 to 87%. We investigated the presence of C. psittaci in a single institutional cohort (n = 150) of ocular adnexal MALT lymphoma (OAML) patients in Korea. We tried to exclude the methodological biases derived from the different primer sets in polymerase chain reaction-based studies. For that reason, we applied five sets of primers, including four previously reported and one newly designed primer set. There was no case of C. psittaci-positive OAML in repeated trials validated with appropriate positive and negative controls. All 150 cases showed negative results with five primer sets. These results suggest that the pathogenetic role of C. psittaci in ocular adnexal MALT lymphoma might have been overestimated to date, at least in the Korean population. Therefore, the molecular diagnosis of C. psittaci is considered a very low priority.
Diagnostic Approaches for COVID-19 and Its Associated Complications
Authors: Wang Ivan E. , Cooper Grant , Mousa Shaker A.
Published: November 2021

With almost 4 million deaths worldwide from the COVID-19 pandemic, the efficient and accurate diagnosis and identification of COVID-19-related complications are more important than ever. Scales such as the pneumonia severity index, or CURB-65, help doctors determine who should be admitted to the hospital or the intensive care unit. To properly treat and manage admitted patients, standardized sampling protocols and methods are required for COVID-19 patients. Using PubMed, relevant articles since March 2020 on COVID-19 diagnosis and its complications were analyzed. Patients with COVID-19 had elevated D-dimer, thrombomodulin, and initial factor V elevation followed by decreased factor V and factor VII and elevated IL-6, lactate dehydrogenase, and c-reactive protein, which indicated coagulopathy and possible cytokine storm. Patients with hypertension, newly diagnosed diabetes, obesity, or advanced age were at increased risk for mortality. Elevated BUN, AST, and ALT in severe COVID-19 patients was associated with acute kidney injury or other organ damage. The gold standard for screening COVID-19 is reverse transcriptase polymerase chain reaction (RT-PCR) using sputum, oropharyngeal, or nasopharyngeal routes. However, due to the low turnover rate and limited testing capacity of RT-PCR, alternative diagnostic tools such as CT-scan and serological testing (IgM and IgG) can be considered in conjunction with symptom monitoring. Advancements in CRISPR technology have also allowed the use of alternative COVID-19 testing, but unfortunately, these technologies are still under FDA review and cannot be used in patients. Nonetheless, increased turnover rates and testing capacity allow for a bright future in COVID-19 diagnosis.
Program Quality and Developmental Outcomes Related to Youth Volleyball in Ethiopia: Assessing Relationships and Variations
Authors: Mussema Abdulaziz , Tadesse Tefera , Melkamu Zelalem
Published: November 2021

This study aims to assess program quality and developmental outcomes of a youth volleyball project in one of the regional states in Ethiopia, and further examine variations between groups across gender and project site zones. We applied a cross-sectional survey design, collecting quantitative data from youth volleyball players (n = 215) with a mean age of 16.18 years (SD = 0.69) through a self-reported questionnaire. The results indicated that young players’ perceptions did not vary significantly across gender, except for the mean score of the perceived experience variable for girls (M = 2.68, SD = 0.318) was significantly higher than the mean score of boys (M = 2.58, SD = 0.258). One-way (project site zone) analyses of variance (ANOVAs) identified that youth volleyball projects in the central zone were consistently rated higher than those in the western zone, except for the current practice rating. Moreover, correlation analysis results indicated the presence of a significant relationship, both within and between program quality and developmental outcome variables. Furthermore, the results of regression analysis indicated that the program quality variables together predicted each of the developmental outcomes, accounting for 18.9% to 31.7% of the variances. It is concluded that the quality of the youth volleyball program in Ethiopia varies considerably across the project site zones and the program quality variables significantly relate to the developmental outcomes measured with differential effects. The data from this study reveals several practical applications for Ethiopia and beyond in terms of guiding youth volleyball projects. Moreover, the findings of the study showed that youth sport and the manner in which it is structured and delivered to youth players influences the attainment of positive developmental outcomes. These results suggest that contextual differences really do have an effect on the quality of youth sport program processes and developmental outcomes.