bluuebunny/crossref_metadata_2025 huggingface dataset:
Crime and Building Rehabilitation or Demolition: A Dose-Response Analysis
Authors: Smirniotis Colette , Henderson Michael , Bailey Barbara A. , Kagawa Rose M. C.
Published: October 2022

Thousands of buildings in Cleveland, Ohio were demolished or rehabilitated since the Great Recession in the 2000s. Recent evidence suggests removing vacant and decaying buildings reduces violent and firearm-involved crime. This study examines the dose-response relationship between demolitions, rehabilitations, and crime. We use Bayesian spatiotemporal models to estimate the association of interest for five types of crime outcomes: violent crimes, violent crimes involving a firearm, drug crimes, and crimes often associated with building vacancy. We estimate associations in quarterly time periods from 2012 through 2017 in 569 hexagons approximately the size of a neighborhood (2000 feet, approximately 610 m, in diameter), stratified by vacancy level. Across vacancy levels, the majority of our models do not identify statistically significant associations between demolition and rehabilitation dose and crime incidence. However, in some cases, we identify positive associations between demolition and crime. These associations generally appeared at higher levels of demolition (2 or 3 or more demolitions) in areas characterized by medium to high levels of vacancy. We also find that the presence of a property rehabilitation is associated with an increase in drug crimes in areas with medium levels of vacancy.
Tracking Waste Management Information Disclosure Behavior Connected to Financial Performance through Moderating Variables
Authors: Bogdan Victoria , Sabău-Popa Claudia Diana , Boloș Marcel-Ioan , Popa Dorina-Nicoleta , Beleneși Mărioara
Published: October 2022

The current challenges of a circular economy exert a high pressure on manufacturing companies that generate waste to track and implement policies to reduce them and eliminate the toxicity of residues. Hence, the purpose of this study is to analyze the waste management information disclosure linked to the financial performance of companies and test the moderating effect of internal and external variables. The average waste management information disclosure index shows a poor disclosure score for the analyzed period, however, the waste disclosure index after reaching a minimum threshold in 2019 recorded an encouraging increase at the end of 2021. Applying the fixed effects model, ordinary least squares, and two-stage least squares method, the results revealed a positive and statistically significant relationship between management information disclosure and the return on assets, while for the current ratio the connection has been invalidated. A statistically significant influence of the environmental-sensitive industry status, board size, and productivity on the moderating variables was found for the return on assets, while for current ratio, there was none. As for the alternative metrics of financial performance, the results showed that a higher degree of management information disclosure will increase the return on equity and earnings per share, while in the case of liquidity, the results are not conclusive.
Unveiling Urinary Mutagenicity by the Ames Test for Occupational Risk Assessment: A Systematic Review
Authors: Barros Bela , Oliveira Marta , Morais Simone
Published: October 2022

Occupational exposure may involve a variety of toxic compounds. A mutagenicity analysis using the Ames test can provide valuable information regarding the toxicity of absorbed xenobiotics. Through a search of relevant databases, this systematic review gathers and critically discusses the published papers (excluding other types of publications) from 2001–2021 that have assessed urinary mutagenicity (Ames test with Salmonella typhimurium) in an occupational exposure context. Due to the heterogeneity of the study methods, a meta-analysis could not be conducted. The characterized occupations were firefighters, traffic policemen, bus drivers, mail carriers, coke oven and charcoal workers, chemical laboratory staff, farmers, pharmacy workers, and professionals from several other industrial sectors. The genetically modified bacterial strains (histidine dependent) TA98, TA100, YG1041, YG1021, YG1024 and YG1042 have been used for the health risk assessment of individual (e.g., polycyclic aromatic hydrocarbons) and mixtures of compounds (e.g., diesel engine exhaust, fire smoke, industrial fumes/dyes) in different contexts. Although comparison of the data between studies is challenging, urinary mutagenicity can be very informative of possible associations between work-related exposure and the respective mutagenic potential. Careful interpretation of results and their direct use for occupational health risk assessment are crucial and yet complex; the use of several strains is highly recommended since individual and/or synergistic effects of complex exposure to xenobiotics can be overlooked. Future studies should improve the methods used to reach a standardized protocol for specific occupational environments to strengthen the applicability of the urinary mutagenicity assay and reduce inter- and intra-individual variability and exposure source confounders.
MicroRNAs of Milk in Cells, Plasma, and Lipid Fractions of Human Milk, and Abzymes Catalyzing Their Hydrolysis
Authors: Kompaneets Ivan Yu. , Ermakov Evgeny A. , Buneva Valentina N. , Nevinsky Georgy A.
Published: October 2022

Human milk provides neonates with various components that ensure newborns’ growth, including protection from bacterial and viral infections. In neonates, the biological functions of many breast milk components can be very different compared with their functions in the body fluids of healthy adults. Catalytic antibodies (abzymes) that hydrolyze peptides, proteins, DNAs, RNAs, and oligosaccharides were detected, not only in the blood sera of autoimmune patients, but also in human milk. Non-coding microRNAs (18–25 nucleotides) are intra- and extracellular molecules of different human fluids. MiRNAs possess many different biological functions, including the regulation of several hundred genes. Five of them, miR-148a-3p, miR-200c-3p, miR-378a-3p, miR-146b-5p, and let-7f-5p, were previously found in milk in high concentrations. Here, we determined relative numbers of miRNA copies in 1 mg of analyzed cells, lipid fractions, and plasmas of human milk samples. The relative amount of microRNA decreases in the following order: cells ≈ lipid fraction > plasma. IgGs and sIgAs were isolated from milk plasma, and their activities in the hydrolysis of five microRNAs was compared. In general, sIgAs demonstrated higher miRNA-hydrolyzing activities than IgGs antibodies. The hydrolysis of five microRNAs by sIgAs and IgGs was site-specific. The relative activity of each microRNA hydrolysis was very dependent on the milk preparation. The correlation coefficients between the contents of five RNAs in milk plasma, and the relative activities of sIgAs compared to IgGs in hydrolyses, strongly depended on individual microRNA, and changed from −0.01 to 0.80. Thus, it was shown that milk contains specific antibodies (abzymes) that hydrolyze microRNAs specific for human milk.
Multi-Omics Reveals Mechanisms of Partial Modulation of COVID-19 Dysregulation by Glucocorticoid Treatment
Authors: Spick Matt , Campbell Amy , Baricevic-Jones Ivona , von Gerichten Johanna , Lewis Holly-May , Frampas Cecile F. , Longman Katie , Stewart Alexander , Dunn-Walters Deborah , Skene Debra J. , Geifman Nophar , Whetton Anthony D. , Bailey Melanie J.
Published: October 2022

Treatments for COVID-19 infections have improved dramatically since the beginning of the pandemic, and glucocorticoids have been a key tool in improving mortality rates. The UK’s National Institute for Health and Care Excellence guidance is for treatment to be targeted only at those requiring oxygen supplementation, however, and the interactions between glucocorticoids and COVID-19 are not completely understood. In this work, a multi-omic analysis of 98 inpatient-recruited participants was performed by quantitative metabolomics (using targeted liquid chromatography-mass spectrometry) and data-independent acquisition proteomics. Both ‘omics datasets were analysed for statistically significant features and pathways differentiating participants whose treatment regimens did or did not include glucocorticoids. Metabolomic differences in glucocorticoid-treated patients included the modulation of cortisol and bile acid concentrations in serum, but no alleviation of serum dyslipidemia or increased amino acid concentrations (including tyrosine and arginine) in the glucocorticoid-treated cohort relative to the untreated cohort. Proteomic pathway analysis indicated neutrophil and platelet degranulation as influenced by glucocorticoid treatment. These results are in keeping with the key role of platelet-associated pathways and neutrophils in COVID-19 pathogenesis and provide opportunity for further understanding of glucocorticoid action. The findings also, however, highlight that glucocorticoids are not fully effective across the wide range of ‘omics dysregulation caused by COVID-19 infections.
Exploring the Mystery of the Tetrahydrobiopterin Synthetic Defect Lethal Mutant leml from Birth to Death in the Silkworm Bombyx mori
Authors: Liang Dan , Shu Rui , Jiang Song , Xu Mengjun , Cai Yangyang , Qin Hongwei , Zhang Daobo , Feng Mengwei , Gao Junshan , Meng Yan
Published: October 2022

Tetrahydrobiopterin (BH4) is a vital coenzyme for several enzymes involved in diverse enzymatic reactions in animals, and BH4 deficiency can lead to metabolic and neurological disorders due to dysfunction in its metabolism. In the silkworm natural homozygous mutant leml, the key enzyme sepiapterin reductase (BmSPR) in the de novo synthesis pathway of BH4 is inactivated, resulting in severe deficiency of BH4 synthesis. However, it is not known why the leml larvae can survive to the second-instar stage and which pathways lead to their death when BH4 is deficient. Here, we quantified BH4 and found that the fertilized eggs contained large amounts of BH4 transferred from the mother to the offspring, maintaining its normal development in the embryo and the first instar. Subsequently, we investigated the multiple pathways in which BH4 is involved as a cofactor. The results showed that BH4 deficiency in silkworms blocked the melanin synthesis pathway, caused an insufficient degree of epidermal sclerosis, disordered tyrosine metabolism, and damaged mitochondria. On the other hand, BH4 deficiency led to the uncoupling of nitric oxide synthase (BmNOS), a reduced NO production, and a significantly reduced fat in fat body catalyzation by phospholipase A2, resulting in an impaired immune system. Meanwhile, the uncoupling of BmNOS increased the O2− content, damaged the DNA, and caused the apoptosis of the body cells. Taken together, BH4 is critical for the life and death of leml mutants. This study lays a foundation for the further exploration of lepidopteran insects and provides an important basis for the treatment of human BH4 deficiency-related diseases.
Changes in α-Farnesene and Phenolic Metabolism and the Expression of Associated Genes during the Development of Superficial Scald in Two Distinct Pear Cultivars
Authors: He Jingang , Feng Yunxiao , Cheng Yudou , Karuppanapandian Thirupathi , Wang Jinxiao , Guan Junfeng
Published: October 2022

Superficial scald is a postharvest physiological disorder that occurs in pear during and after cold storage. In this study, the superficial scald index; α-farnesene and its oxidation products, conjugated trienols (CTols); phenolic content; and the expression of its related genes were investigated in two different pear cultivars, ‘Wujiuxiang’ (Pyrus communis L.) and ‘Yali’ (Pyrus bretschneideri R.), following 115 days of cold storage at 0 °C followed by 7 days of shelf life at 20 °C. The results indicated that the superficial scald occurred after 115 days of cold storage and became more severe during the shelf life of the ‘Wujiuxiang’ pear, whereas no scald was observed in ‘Yali’. The α-farnesene levels increased rapidly at first and then decreased, while the CTols contents increased significantly in ‘Wujiuxiang’ as compared to ‘Yali’, and the expression levels of the genes involved in α-farnesene and CTols metabolism (HMGR1, HMGR2, GSTU7, GPX5, and GPX6), as well as the phenolic synthesis (PAL1, PAL2, C4H1, 4CL2, C3H, and ANR) of the peel, were significantly up-regulated at the onset of the superficial scald. In addition, the relative conductivity and contents of catechin and epicatechin were higher, and the expression level of the laccase gene (LAC7) significantly increased with the development of superficial scald, while lower contents of chlorogenic acid, arbutin, and isorhamnetin-3-3-glucoside, as well as the lower expression levels of a phenolic-synthesis-related gene (C4H3) and polyphenol oxidase genes (PPO1 and PPO5), were noticed in ‘Wujiuxiang’ as compared to ‘Yali’. The results indicated that the onset and progression of superficial scald were associated with the accumulation of CTols, cell membrane breakdown, and higher catechin, epicatechin, and rutin contents, as well as the expression of associated genes of the peels of pear fruit.
Next Steps in Prader-Willi Syndrome Research: On the Relationship between Genotype and Phenotype
Authors: Whittington Joyce , Holland Anthony
Published: October 2022

This article reviews what we know of the phenotype and genotype of Prader-Willi syndrome and hypothesizes two possible paths from phenotype to genotype. It then suggests research that may strengthen the case for one or other of these hypotheses.
Evolution of Gene Arrangements in the Mitogenomes of Ensifera and Characterization of the Complete Mitogenome of Schizodactylus jimo
Authors: Dan Zhi-Cuo , Guan De-Long , Jiang Tao , Wang Hang , Zhao Lu , Xu Sheng-Quan
Published: October 2022

Gene arrangement (relative location of genes) is another evolutionary marker of the mitogenome that can provide extensive information on the evolutionary mechanism. To explore the evolution of gene arrangements in the mitogenome of diversified Ensifera, we sequenced the mitogenome of the unique dune cricket species found in China and used it for phylogenetic analysis, in combination with 84 known Ensiferan mitogenomes. The mitogenome of Schizodactylus jimo is a 16,428-bp circular molecule that contains 37 genes. We identified eight types of gene arrangement in the 85 ensiferan mitogenomes. The gene location changes (i.e., gene translocation and duplication) were in three gene blocks: I-Q-M-ND2, rrnl-rns-V, and ND3-A-R-N-S-E-F. From the phylogenetic tree, we found that Schizodactylus jimo and most other species share a typical and ancient gene arrangement type (Type I), while Grylloidea has two types (Types II and III), and the other five types are rare and scattered in the phylogenetic tree. We deduced that the tandem replication–random loss model is the evolutionary mechanism of gene arrangements in Ensifera. Selection pressure analysis revealed that purifying selection dominated the evolution of the ensiferan mitochondrial genome. This study suggests that most gene rearrangements in the ensiferan mitogenome are rare accidental events.
Research into the Bioengineering of a Novel α-Conotoxin from the Milked Venom of Conus obscurus
Authors: Wiere Sean , Sugai Christopher , Espiritu Michael J. , Aurelio Vincent P. , Reyes Chloe D. , Yuzon Nicole , Whittal Randy M. , Tytgat Jan , Peigneur Steve , Bingham Jon-Paul
Published: October 2022

The marine cone snail produces one of the fastest prey strikes in the animal kingdom. It injects highly efficacious venom, often causing prey paralysis and death within seconds. Each snail has hundreds of conotoxins, which serve as a source for discovering and utilizing novel analgesic peptide therapeutics. In this study, we discovered, isolated, and synthesized a novel α3/5-conotoxins derived from the milked venom of Conus obscurus (α-conotoxin OI) and identified the presence of α-conotoxin SI-like sequence previously found in the venom of Conus striatus. Five synthetic analogs of the native α-conotoxin OI were generated. These analogs incorporated single residue or double residue mutations. Three synthetic post-translational modifications (PTMs) were synthetically incorporated into these analogs: N-terminal truncation, proline hydroxylation, and tryptophan bromination. The native α-conotoxin OI demonstrated nanomolar potency in Poecilia reticulata and Homosapiens muscle-type nicotinic acetylcholine receptor (nAChR) isoforms. Moreover, the synthetic α-[P9K] conotoxin OI displayed enhanced potency in both bioassays, ranging from a 2.85 (LD50) to 18.4 (IC50) fold increase in comparative bioactivity. The successful incorporation of PTMs, with retention of both potency and nAChR isoform selectivity, ultimately pushes new boundaries of peptide bioengineering and the generation of novel α-conotoxin-like sequences.
Ex Vivo Fluorescence Confocal Microscopy (FCM) Ensures Representative Tissue in Prostate Cancer Biobanking: A Feasibility Study
Authors: Titze Ulf , Sommerkamp Johannes , Stege Clara , Schneider Fried , Brochhausen Christoph , Schulz Birte , Titze Barbara , Abd Ali Furat , Pokupic Sasa , Sievert Karl-Dietrich , Hansen Torsten
Published: October 2022

Background: Biobanking of prostate carcinoma is particularly challenging due to the actual cancer within the organ often without clear margins. Frozen sections are to date the only way to examine the biobank material for its tumor content. We used ex vivo fluorescence confocal microscopy (FCM) to analyze biobank samples prior to cryoasservation. Methods: 127 punch biopsies were acquired from prostatectomy-specimens from 40 patients. These biopsies were analyzed with a Vivascope 2500-G4 prior to their transfer to the biobank. In difficult cases, larger samples of the prostatectomy specimens were FCM scanned in order to locate tumor foci. After patient acquisition, all samples were taken from the biobank and analyzed. We compared the results of the FCM examinations with the results of conventional histology and measured the DNA content. Results: With upstream FCM, the tumor content of biobank samples could be determined with high confidence. The detection rate of representative biobank samples was increased due to the rapid feedback. The biobank samples were suitable for further molecular analysis. Conclusion: FCM allows for the first time lossless microscopic analysis of biobank samples prior to their cryoasservation and guarantees representative tumor and normal tissue for further molecular analysis.
Targeting Deubiquitinating Enzymes (DUBs) That Regulate Mitophagy via Direct or Indirect Interaction with Parkin
Authors: Tsefou Eliona , Ketteler Robin
Published: October 2022

The quality control of mitochondria is critical for the survival of cells, and defects in the pathways required for this quality control can lead to severe disease. A key quality control mechanism in cells is mitophagy, which functions to remove damaged mitochondria under conditions of various stresses. Defective mitophagy can lead to a number of diseases including neurodegeneration. It has been proposed that an enhancement of mitophagy can improve cell survival, enhance neuronal function in neurodegeneration and extend health and lifespans. In this review, we highlight the role of deubiquitinating enzymes (DUBs) in the regulation of mitophagy. We summarise the current knowledge on DUBs that regulate mitophagy as drug targets and provide a list of small molecule inhibitors that are valuable tools for the further development of therapeutic strategies targeting the mitophagy pathway in neurodegeneration.
TMAO Upregulates Members of the miR-17/92 Cluster and Impacts Targets Associated with Atherosclerosis
Authors: Díez-Ricote Laura , Ruiz-Valderrey Paloma , Micó Víctor , Blanco Ruth , Tomé-Carneiro Joao , Dávalos Alberto , Ordovás José M. , Daimiel Lidia
Published: October 2022

Atherosclerosis is a hallmark of cardiovascular disease, and lifestyle strongly impacts its onset and progression. Nutrients have been shown to regulate the miR-17/92 cluster, with a role in endothelial function and atherosclerosis. Choline, betaine, and L-carnitine, found in animal foods, are metabolized into trimethylamine (TMA) by the gut microbiota. TMA is then oxidized to TMAO, which has been associated with atherosclerosis. Our aim was to investigate whether TMAO modulates the expression of the miR-17/92 cluster, along with the impact of this modulation on the expression of target genes related to atherosclerosis and inflammation. We treated HepG-2 cells, THP-1 cells, murine liver organoids, and human peripheral mononuclear cells with 6 µM of TMAO at different timepoints. TMAO increased the expression of all analyzed members of the cluster, except for miR-20a-5p in murine liver organoids and primary human macrophages. Genes and protein levels of SERPINE1 and IL-12A increased. Both have been associated with atherosclerosis and cardiovascular disease (CDVD) and are indirectly modulated by the miR-17-92 cluster. We concluded that TMAO modulates the expression of the miR-17/92 cluster and that such modulation could promote inflammation through IL-12A and blood clotting through SERPINE1 expression, which could ultimately promote atherosclerosis and CVD.
Dominant and Priming Role of Waterlogging in Tomato at e[CO2] by Multivariate Analysis
Authors: Zhou Rong , Jiang Fangling , Yu Xiaqing , Abdelhakim Lamis , Li Xiangnan , Rosenqvist Eva , Ottosen Carl-Otto , Wu Zhen
Published: October 2022

The frequency of waterlogging episodes has increased due to unpredictable and intense rainfalls. However, less is known about waterlogging memory and its interaction with other climate change events, such as elevated CO2 concentration (e[CO2]). This study investigated the combined effects of e[CO2] and two rounds of waterlogging stress on the growth of cultivated tomato (Solanum lycopersicum) and wild tomato (S. pimpinellifolium). The aim is to elucidate the interaction between genotypes and environmental factors and thereby to improve crop resilience to climate change. We found that two rounds of treatments appeared to induce different acclimation strategies of the two tomato genotypes. S. pimpinellifolium responded more negatively to the first-time waterlogging than S. lycopersicum, as indicated by decreased photosynthesis and biomass loss. Nevertheless, the two genotypes respond similarly when waterlogging stress recurred, showing that they could maintain a higher leaf photosynthesis compared to single stress, especially for the wild genotype. This showed that waterlogging priming played a positive role in stress memory in both tomato genotypes. Multivariate analysis showed that waterlogging played a dominant role when combined with [CO2] for both the cultivated and wild tomato genotypes. This work will benefit agricultural production strategies by pinpointing the positive effects of e[CO2] and waterlogging memory.
Characterization of Copper/Zinc Superoxide Dismutase Activity on Phascolosoma esculenta (Sipuncula: Phascolosomatidea) and Its Protection from Oxidative Stress Induced by Cadmium
Authors: Liu Yang , Du Chen , Lin Chenwen , Gao Xinming , Zhu Junquan , Zhang Chundan
Published: October 2022

Phascolosoma esculenta, an economically important species inhabiting the high tide areas of the intertidal zone, is particularly sensitive to water pollution. Considering its potential as a bioindicator, studies on the ecotoxicology of P. esculenta are imperative. The toxic effects of cadmium (Cd) were analyzed by exposing P. esculenta to different concentrations of Cd (6, 24, 96 mg/L). In this study, the changes in the antioxidative indexes of total superoxide dismutase (T-SOD), glutathione s-transferase (GST), reduced glutathione (GSH), and microscale malondialdehyde (MDA) were recorded. Copper/zinc superoxide dismutase (Cu/Zn SOD) is one of the most important free radical scavenging members. To reveal the antioxidative function of P. esculenta, an important member of the antioxidative system, designated Pe-Cu/Zn SOD, was cloned and analyzed. Phylogenic analysis revealed that Pe-Cu/Zn SOD was located in the invertebrate evolutionary branch of intracellular Cu/Zn SOD (icCu/Zn SOD). The quantitative real-time polymerase chain reaction results showed that Pe-Cu/Zn SOD messenger ribonucleic acid was widely expressed in all tissues examined. The highest expression levels in coelomic fluid after Cd exposure indicated its function in the stress response. Using a prokaryotic expression system, we obtained a Pe-Cu/Zn SOD recombinant protein, which enhanced the heavy metal tolerance of Escherichia coli. In vivo assays also confirmed that the Pe-Cu/Zn SOD recombinant protein had an antioxidative and free radical scavenging ability. A Cd toxicity experiment, in which purified Pe-Cu/Zn SOD protein was injected into the body cavities of P. esculenta, showed that the reactive oxygen species content in the coelomic fluid of the experimental group was significantly lower compared with the control group. These results suggest that Pe-Cu/Zn SOD played a role in Cd detoxification by chelating heavy metal ions and scavenging reactive oxygen free radicals, and that P. esculenta could be used as a bioindicator to evaluate heavy metal pollution.
Pathogenesis of Port-Wine Stains: Directions for Future Therapies
Authors: Liu Lian , Li Xiaoxue , Zhao Qian , Yang Lihua , Jiang Xian
Published: October 2022

Port-wine stains (PWSs) are congenital vascular malformations that involve the skin and mucosa. To date, the mechanisms underlying the pathogenesis and progression of PWSs are yet to be clearly elucidated. The potential reasons for dilated vessels are as follows: (1) somatic GNAQ (R183Q) mutations that form enlarged capillary malformation-like vessels through angiopoietin-2, (2) decreased perivascular nerve elements, (3) the coexistence of Eph receptor B1 and ephrin B2, and (4) the deficiency of αSMA expression in pericytes. In addition, ERK, c-JNK, P70S6K, AKT, PI3K, and PKC are assumed to be involved in PWS development. Although pulsed-dye laser (PDL) remains the gold standard for treating PWSs, the recurrence rate is high. Topical drugs, including imiquimod, axitinib, and rapamycin, combined with PDL treatments, are expected to alter the recurrence rate and reduce the number of PDL sessions for PWSs. For the deep vascular plexus, photosensitizers or photothermal transduction agents encapsulated by nanocarriers conjugated to surface markers (CD133/CD166/VEGFR-2) possess a promising therapeutic potential in photodynamic therapy or photothermal therapy for PWSs. The pathogenesis, progression, and treatment of PWSs should be extensively investigated.
Single-Cell Analysis to Better Understand the Mechanisms Involved in MS
Authors: Dugast Emilie , Shah Sita , Laplaud David-Axel
Published: October 2022

Multiple sclerosis is a chronic and inflammatory disease of the central nervous system. Although this disease is widely studied, many of the precise mechanisms involved are still not well known. Numerous studies currently focusing on multiple sclerosis highlight the involvement of many major immune cell subsets, such as CD4+ T cells, CD8+ T cells and more recently B cells. However, our vision of its pathology has remained too broad to allow the proper use of targeted therapeutics. This past decade, new technologies have emerged, enabling deeper research into the different cell subsets at the single-cell level both in the periphery and in the central nervous system. These technologies could allow us to identify new cell populations involved in the disease process and new therapeutic targets. In this review, we briefly introduce the major single-cell technologies currently used in studies before diving into the major findings from the multiple sclerosis research from the past 5 years. We focus on results that were obtained using single-cell technologies to study immune cells and cells from the central nervous system.
Addition of MPS-II to the Recommended Uniform Screening Panel in the United States
Authors: Millington David , Ficicioglu Can
Published: October 2022

It has recently been announced that the Secretary of the U.S. Department of Health and Human Services has approved the recommendation by the Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) to add mucopolysaccharidosis type II (MPS-II, Hunter Syndrome) to the recommended uniform screening panel (RUSP) in the United States [...]
Judd-Ofelt Analysis of High Erbium Content Yttrium-Aluminum and Yttrium-Scandium-Aluminum Garnet Ceramics
Authors: Zhmykhov Vadim , Dobretsova Elena , Tsvetkov Vladimir S. , Nikova Marina , Chikulina Irina , Vakalov Dmitry , Tarala Vitaly , Pyrkov Yurii , Kuznetsov Sergey , Tsvetkov Vladimir
Published: October 2022

The Er1.5Y1.5Al5O12 (Er:YAG) and (Er1.43Y1.43Sc0.14)(Sc0.24Al1.76)Al3O12 (Er:YSAG) ceramics have been characterized using the Judd-Ofelt (JO) theory. The line strengths and oscillator strengths of several transitions from the ground state 4I15/2 to excited state manifolds have been evaluated from transmittance spectra measured at room temperature (300 K). The JO parameters have been calculated, and the values of the radiative decays rate and the radiative lifetimes for the 4I13/2 excited state, and the luminescence cross-section of 4I15/2 → 4I13/2 in Er-doped ceramic samples have been established. We have traced the influence of Sc3+ inclusion on spectroscopic properties and crystal quality and estimate prospects of application in laser systems.
Clinical and Laboratory Characteristics of Pediatric COVID-19 Population—A Bibliometric Analysis
Authors: Maniu Ionela , Maniu George , Totan Maria
Published: October 2022

The literature on the COVID-19 landscape has rapidly expanded in the pandemic period. The current study undertakes a bibliometric analysis of research in the topic of the clinical and laboratory characteristics of pediatric COVID-19 cases. Our aim is to perform a comprehensive bibliometric review of current research trends and patterns of this research domain. Publications retrieved from the Web of Science Core Collection and VOSviewer were used for analysis and network visualization. We analyzed geographical distribution and temporal trends, collaboration and citation patterns of authors, institutions, and countries, and core research themes from co-occurrence of keywords and terms. The analysis showed that contributions in the research field were from 302 publications, 1104 institutions, 62 countries, and 172 journals. Many publications were authored by American and Chinese authors, and many were published in the Pediatric Infectious Disease Journal, Pediatric Pulmonology, and Frontiers in Pediatrics. The top cited and co-cited journals were the New England Journal of Medicine, Nature, JAMA, Lancet Infectious Diseases, and BMJ. The network visualization maps of keywords and terms offered a global overview of the clinical and laboratory characteristics of pediatric COVID-19 patients. The bibliometric profile of the researched domain, based on analyzing a large collection of publications/data, could (i) enrich the researchers and non-researchers understanding of the field existing patterns and trends, and (ii) be useful in clinical practice (diagnostic and management) and public health policy.
Mesh Graft Urethroplasty—Still a Safe and Promising Technique in Mostly Unpromising Complex Urethral Strictures
Authors: Reichert Mathias , Aragona Maurizio , Soukkar Ahmad , Olianas Roberto
Published: October 2022

Long urethral strictures or even recurrent urethral strictures, mostly with scar tissue showing insufficient healing tendencies, are defined as complex and represent a big challenge in modern reconstructive urology. Initially, the treatment of complicated urethral strictures was associated with a high failure rate (20–40%) due to the growth of hair in the neourethra and a lack of sufficient suitable epithelium when scrotal skin was used. Although much effort was put into tissue engineering recently, harvesting and transplanting autologous tissue represent the standard of care for urethral substitution or augmentation. Since 1977, two-staged urethroplasty with the usage of free foreskin or 0.1 mm thick meshed skin from the upper leg was performed in complicated cases and was initially described in 1984 and 1989 by Schreiter and Schreiter and Noll, respectively. In stage 1, the graft is harvested by cutting the skin thinly above the hair follicles and transplanted as a plate around the opened urethra. In stage 2, after 8–12 weeks, the neourethra is formed. Success rates of up to 84% are described. Considering the complexity of the strictures in which mesh graft urethroplasty is usually performed, the reachable success rates are outstanding, especially considering that this surgery is most likely the last opportunity to prevent perineostomy or even urinary diversion. This article describes the surgical technique and embeds the mesh graft urethroplasty in today’s literature to underline its importance in the surgical management of complex urethral strictures.
Use of CytoSorb© Hemoadsorption in Patients on Veno-Venous ECMO Support for Severe Acute Respiratory Distress Syndrome: A Systematic Review
Authors: Akil Ali , Napp L. Christian , Rao Cristina , Klaus Teresa , Scheier Joerg , Pappalardo Federico
Published: October 2022

Acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality. Adjunct hemoadsorption is increasingly utilized to target underlying hyperinflammation derived from ARDS. This article aims to review available data on the use of CytoSorb© therapy in combination with V-V ECMO in severe ARDS, and to assess the effects on inflammatory, laboratory and clinical parameters, as well as on patient outcomes. A systematic literature review was conducted and reported in compliance with principles derived from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. When applicable, a before-and-after analysis for relevant biomarkers and clinical parameters was carried out. CytoSorb© use was associated with significant reductions in circulating levels of C-reactive protein and interleukin-6 (p = 0.039 and p = 0.049, respectively). Increases in PaO2/FiO2 reached significance as well (p = 0.028), while norepinephrine dosage reductions showed a non-significant trend (p = 0.067). Mortality rates in CytoSorb© patients tended to be lower than those of control groups of most included studies, which, however, were characterized by high heterogeneity and low power. In an exploratory analysis on 90-day mortality in COVID-19 patients supported with V-V ECMO, the therapy was associated with a significantly reduced risk of death. Based on the reviewed data, CytoSorb© therapy is able to reduce inflammation and potentially improves survival in ARDS patients treated with V-V ECMO. Early initiation of CytoSorb© in conjunction with ECMO might offer a new approach to enhance lung rest and promote recovery in patients with severe ARDS.
Expression Pattern of Tenascin-C, Matrilin-2, and Aggrecan in Diseases Affecting the Corneal Endothelium
Authors: Varkoly Gréta , Hortobágyi Tibor G. , Gebri Enikő , Bencze János , Hortobágyi Tibor , Módis László
Published: October 2022

Purpose: The aim of this study was to examine the expression pattern of tenascin-C, matrilin-2, and aggrecan in irreversible corneal endothelial pathology such as pseudophakic bullous keratopathy (PBK) and Fuchs’ endothelial corneal dystrophy (FECD), which most frequently require corneal transplantation. Materials and methods: Histological specimens of corneal buttons removed during keratoplasty were investigated in PBK (n = 20) and FECD (n = 9) and compared to healthy control corneas (n = 10). The sections were studied by chromogenic immunohistochemistry (CHR-IHC) and submitted for evaluation by two investigators. Semiquantitative scoring (0 to 3+) was applied according to standardized methods at high magnification (400x). Each layer of the cornea was investigated; in addition, the stroma was subdivided into anterior, middle, and posterior parts for more precise analysis. In case of non-parametric distribution Mann–Whitney test was applied to compare two groups. Kruskal–Wallis and Dunn’s multiple comparisons tests have been applied for comparison of the chromogenic IHC signal intensity among corneal layers within the control and patient groups. Differences of p < 0.05 were considered as significant. Results: Significantly elevated tenascin-C immunopositivity was present in the epithelium and every layer of the stroma in both pathologic conditions as compared to normal controls. In addition, also significantly stronger matrilin-2 positivity was detected in the epithelium; however, weaker reaction was present in the endothelium in PBK cases. Minimal, but significantly elevated immunopositivity could be observed in the anterior and posterior stroma in the FECD group. Additionally, minimally, but significantly higher aggrecan immunoreaction was present in the anterior stroma in PBK and in the posterior stroma in both endothelial disorders. All three antibodies disclosed the strongest reaction in the posterior stroma either in PBK or in FECD cases. Conclusions: These extracellular matrix molecules disclosed up to moderate immunopositivity in the corneal layers in varying extents. Through their networking, bridging, and adhesive abilities these proteins are involved in corneal regeneration and tissue reorganization in endothelial dysfunction.
Bivalirudin vs. Enoxaparin in Intubated COVID-19 Patients: A Pilot Multicenter Randomized Controlled Trial
Authors: Garofalo Eugenio , Cammarota Gianmaria , Neri Giuseppe , Macheda Sebastiano , Biamonte Eugenio , Pasqua Pino , Guzzo Maria Laura , Longhini Federico , Bruni Andrea
Published: October 2022

(1) Background: In COVID-19 patients, the occurrence of thromboembolic complications contributes to disease progression and mortality. In patients at increased risk for thrombotic complications, therapeutic enoxaparin should be considered. However, critically ill COVID-19 patients could develop resistance to enoxaparin. Bivalirudin, a thrombin inhibitor, may be an alternative. This pilot multicenter randomized controlled trial aims to ascertain if bivalirudin may reduce the time spent under invasive mechanical ventilation, as compared to enoxaparin. (2) Methods: Intubated COVID-19 patients at risk for thrombo-embolic complications were randomized to receive therapeutic doses of enoxaparin or bivalirudin. We ascertained the time spent under invasive mechanical ventilation during the first 28 days from Intensive Care Unit (ICU) admission. A standardized weaning protocol was implemented in all centers. In addition, we assessed the occurrence of thromboembolic complications, the number of patients requiring percutaneous tracheostomy, the gas exchange, the reintubation rate, the ICU length of stay, the ICU and 28-days mortalities. (3) Results: We enrolled 58 consecutive patients. Bivalirudin did not reduce the time spent under invasive mechanical ventilation as compared to enoxaparin (12 [8; 13] vs. 13 [10; 15] days, respectively; p = 0.078). Thrombotic (p = 0.056) and embolic (p = 0.423) complications, need for tracheostomy (p = 0.423) or reintubation (p = 0.999), the ICU length of stay (p = 0.076) and mortality (p = 0.777) were also similar between treatments. Patients randomized to bivalirudin showed a higher oxygenation at day 7 and 15 after randomization, when compared to enoxaparin group. (4) Conclusions: In intubated COVID-19 patients at increased risk for thromboembolic complications, bivalirudin did not reduce the time spent under invasive mechanical ventilation, nor improved any other clinical outcomes.
Are Cirrhotic Patients Receiving Invasive Mechanical Ventilation at Risk of Abundant Microaspiration
Authors: Levy Clementine , Gaudet Alexandre , Jaillette Emmanuelle , Reignier Jean , Lassailly Guillaume , Balduyck Malika , Cailliau Emeline , Rouze Anahita , Nseir Saad ,   on behalf of the Micro Cirrhosis Study Group
Published: October 2022

Previous studies have identified cirrhosis as a risk factor for ventilator-associated pneumonia (VAP). The aim of our study was to determine the relationship between cirrhosis and abundant gastric-content microaspiration in intubated critically ill patients. We performed a matched cohort study using data from three randomized controlled trials on abundant microaspiration in patients under mechanical ventilation. Each cirrhotic patient was matched with three to four controls for gender, age ± 5 years and simplified acute physiology score II (SAPS II) ± 5 points. Abundant microaspiration was defined by significant levels of pepsin and alpha-amylase in >30% of tracheal aspirates. All tracheal aspirates were collected for the first 48 h of the study period. The percentage of patients with abundant gastric-content microaspiration was the primary outcome. The abundant microaspiration of oropharyngeal secretions, VAP incidence, the duration of mechanical ventilation, length of intensive care unit (ICU) stay and mortality were the secondary outcomes. A. total of 39 cirrhotic patients were matched to 138 controls. The percentage of patients with abundant gastric-content microaspiration did not differ between the two groups (relative risk: 0.91 (95% CI: 0.75 to 1.10)). There was no significant difference between the two groups in terms of the abundant microaspiration of oropharyngeal secretions, VAP, the duration of mechanical ventilation, the length of ICU stay and mortality. Our results suggest that cirrhosis is not associated with abundant gastric-content microaspiration.
The Time-Based Effects of Kinesio Taping on Acute-Onset Muscle Soreness and Calf Muscle Extensibility among Endurance Athletes: A Randomized Cross-Over Trial
Authors: Malhotra Deepak , Sharma Shruti , Chachra Ashima , Dhingra Meenu , Alghadir Ahmad H. , Nuhmani Shibili , Jaleel Ghufran , Alqhtani Raee S. , Alshehri Mohammed M. , Beg Rashid Ali , Shaphe Mohammad Abu , Iqbal Amir
Published: October 2022

Background: This study aims to determine the effects of kinesio tape (KT) application on acute-onset muscle soreness and the extensibility of the calf muscles in endurance athletes. Methods: A one-arm repeated-measures randomized cross-over controlled study design investigated 55 endurance athletes, including 10 cyclists, 30 badminton players, and 15 long-distance runners (mean age 16.40 ± 2.69) from different stadia in Delhi NCR, India. KT and sham tapes (ST) were applied randomly to right and left legs (prone position) in a cross-over manner with a gap of 72 h. Ankle dorsiflexion range of motion (ADFROM) and pain due to acute-onset muscle soreness were assessed immediately and 10 min and 30 min after treadmill running, using a universal goniometer and numeric pain rating scale (NPRS), respectively, along with the time to fatigue. Results: A statistically significant difference was observed for the NPRS when the mean scores obtained for the KT and ST groups were compared immediately after cessation of running; however, the difference was not statistically significant in the NPRS score that was recorded ten or thirty minutes after. The range of motion increased significantly after the application of both the KT and the ST. After running on a treadmill, the range of motion decreased significantly with both the KT and ST, and the decrease was similar. Conclusion: KT was more effective in reducing the pain intensity immediately after running and increased the time spent running on the treadmill before fatigue set in among endurance athletes. In addition, the two taping methods (KT or ST) were equally effective in enhancing calf muscle extensibility (for both right and left legs) immediately after application. However, both taping methods failed in limiting the decrease in ankle ADFROM after treadmill running.
Practical Recommendations for Optimal Thromboprophylaxis in Patients with COVID-19: A Consensus Statement Based on Available Clinical Trials
Authors: Kyriakoulis Konstantinos , Dimakakos Evangelos , Kyriakoulis Ioannis , Catalano Mariella , Spyropoulos Alex , Schulman Sam , Douketis James , Falanga Anna , Maraveyas Anthony , Olinic Dan-Mircea , Belch Jill , Gerotziafas Grigorios , Syrigos Konstantinos , Kollias Anastasios ,   COVID-19 Thrombosis Collaborative Group, Endorsed by VAS-European Independent Foundation in Angiology/Vascular Medicine, UEMS Division of Angiology/Vascular Medicine/and ESVM-European Society of Vascular Medicine and Supported by the Balkan Working Group
Published: October 2022

Coronavirus disease 2019 (COVID-19) has been shown to be strongly associated with increased risk for venous thromboembolism events (VTE) mainly in the inpatient but also in the outpatient setting. Pharmacologic thromboprophylaxis has been shown to offer significant benefits in terms of reducing not only VTE events but also mortality, especially in acutely ill patients with COVID-19. Although the main source of evidence is derived from observational studies with several limitations, thromboprophylaxis is currently recommended for all hospitalized patients with acceptable bleeding risk by all national and international guidelines. Recently, high quality data from randomized controlled trials (RCTs) further support the role of thromboprophylaxis and provide insights into the optimal thromboprophylaxis strategy. The aim of this statement is to systematically review all the available evidence derived from RCTs regarding thromboprophylaxis strategies in patients with COVID-19 in different settings (either inpatient or outpatient) and provide evidence-based guidance to practical questions in everyday clinical practice. Clinical questions accompanied by practical recommendations are provided based on data derived from 20 RCTs that were identified and included in the present study. Overall, the main conclusions are: (i) thromboprophylaxis should be administered in all hospitalized patients with COVID-19, (ii) an optimal dose of inpatient thromboprophylaxis is dependent upon the severity of COVID-19, (iii) thromboprophylaxis should be administered on an individualized basis in post-discharge patients with COVID-19 with high thrombotic risk, and (iv) thromboprophylaxis should not be routinely administered in outpatients. Changes regarding the dominant SARS-CoV-2 variants, the wide immunization status (increasing rates of vaccination and reinfections), and the availability of antiviral therapies and monoclonal antibodies might affect the characteristics of patients with COVID-19; thus, future studies will inform us about the thrombotic risk and the optimal therapeutic strategies for these patients.