bluuebunny/crossref_metadata_2025 huggingface dataset:
Etiology and Treatment of Growth Delay in Noonan Syndrome
Authors: Rodríguez Fernando , Gaete Ximena , Cassorla Fernando
Published: June 2021

Noonan syndrome is characterized by multiple phenotypic features, including growth retardation, which represents the main cause of consultation to the clinician. Longitudinal growth during childhood and adolescence depends on several factors, among them an intact somatotrophic axis, which is characterized by an adequate growth hormone (GH) secretion by the pituitary, subsequent binding to its receptor, proper function of the post-receptor signaling pathway for this hormone (JAK-STAT5b and RAS/MAPK), and ultimately by the production of its main effector, insulin like growth factor 1 (IGF-1). Several studies regarding the function of the somatotrophic axis in patients with Noonan syndrome and data from murine models, suggest that partial GH insensitivity at a post-receptor level, as well as possible derangements in the RAS/MAPK pathway, are the most likely causes for the growth failure in these patients. Treatment with recombinant human growth hormone (rhGH) has been used extensively to promote linear growth in these patients. Numerous treatment protocols have been employed so far, but the published studies are quite heterogeneous regarding patient selection, length of treatment, and dose of rhGH utilized, so the true benefit of GH therapy is somewhat difficult to establish. This review will discuss the possible etiologies for the growth delay, as well as the outcomes following rhGH treatment in patients with Noonan syndrome.
Overexpression of SHMT2 Predicts a Poor Prognosis and Promotes Tumor Cell Growth in Bladder Cancer
Authors: Zhang Peng , Yang Qian
Published: June 2021

SHMT2 was overexpressed in many tumors, however, the role of SHMT2 in bladder cancer (BLCA) remains unclear. We first analyzed the expression pattern of SHMT2 in BLCA using the TNMplot, Oncomine, the Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO) databases. Next, the association between SHMT2 expression and overall survival (OS)/disease-free survival (DFS) in BLCA patients were analyzed using TCGA and PrognoScan database. The correlation between SHMT2 expression and clinicopathology was determined using TCGA database. Furthermore, the genes co-expressed with SHMT2 and their underlying molecular function in BLCA were explored based on the Oncomine database, Metascape and gene set enrichment analysis (GSEA). Finally, the effects of SHMT2 on cell proliferation, cell cycle, and apoptosis were assessed using in vitro experiments. As a results, SHMT2 was significantly overexpressed in BLCA tissues and cells compared to normal bladder tissues and cells. A high SHMT2 expression predicts a poor OS of BLCA patients. In addition, SHMT2 expression was higher in patients with a high tumor grade and in those who were older than 60 years. However, the expression of SHMT2 was not correlated with gender, tumor stage, lymph node stage, and distant metastasis stage. Finally, overexpression of SHMT2 promoted BLCA cell proliferation and suppressed apoptosis, the silencing of SHMT2 significantly inhibited BLCA cell proliferation by impairing the cell cycle, and promoting apoptosis. SHMT2 mediates BLCA cells growth by regulating STAT3 signaling. In summary, SHMT2 regulates the proliferation, cell cycle and apoptosis of BLCA cells, and may act as a candidate therapeutic target for BLCA.
GRMT: Generative Reconstruction of Mutation Tree From Scratch Using Single-Cell Sequencing Data
Authors: Yu Zhenhua , Liu Huidong , Du Fang , Tang Xiaofen
Published: June 2021

Single-cell sequencing (SCS) now promises the landscape of genetic diversity at single cell level, and is particularly useful to reconstruct the evolutionary history of tumor. There are multiple types of noise that make the SCS data notoriously error-prone, and significantly complicate tumor tree reconstruction. Existing methods for tumor phylogeny estimation suffer from either high computational intensity or low-resolution indication of clonal architecture, giving a necessity of developing new methods for efficient and accurate reconstruction of tumor trees. We introduce GRMT (GenerativeReconstruction ofMutationTree from scratch), a method for inferring tumor mutation tree from SCS data. GRMT exploits thek-Dollo parsimony model to allow each mutation to be gained once and lost at mostktimes. Under this constraint on mutation evolution, GRMT searches for mutation tree structures from a perspective of tree generation from scratch, and implements it to an iterative process that gradually increases the tree size by introducing a new mutation per time until a complete tree structure that contains all mutations is obtained. This enables GRMT to efficiently recover the chronological order of mutations and scale well to large datasets. Extensive evaluations on simulated and real datasets suggest GRMT outperforms the state-of-the-arts in multiple performance metrics. The GRMT software is freely available athttps://github.com/qasimyu/grmt.
Sleep Disruption and Depression, Stress and Anxiety Levels in Women With Polycystic Ovary Syndrome (PCOS) During the Lockdown Measures for COVID-19 in the UK
Authors: Kite Chris , Atkinson Lou , McGregor Gordon , Clark Cain C. T. , Brown James E. , Kyrou Ioannis , Randeva Harpal S.
Published: June 2021

Background: Lockdown measures have been enforced globally in response to the COVID-19 pandemic. Given the comorbidity burden in women with polycystic ovary syndrome (PCOS), these lockdown measures may have a particularly negative impact on sleep health, quality of life (QoL), and depression/stress levels in this population. The aim of this study was to explore whether such potential problems were present in women with PCOS during the COVID-19 lockdown in the UK.

Methods: UK women with PCOS were recruited through social media into a cross-sectional study during the COVID-19 lockdown. The study survey was delivered online, and included demographic and COVID-19 relevant questions, as well as validated questionnaires/scales, namely the Insomnia Severity Index (ISI), Depression Anxiety and Stress Scale (DASS-21), and PCOSQOL questionnaire.

Results: Three hundred and thirty-three women with PCOS [median age: 30.0 (9.0) years] were recruited. Participants were dichotomized based on responses regarding the impact of COVID-19 restrictions on their sleep [negative (N = 242) vs. no/positive (N = 91) impact]. No differences were noted between groups regarding age, time since PCOS diagnosis, body mass index, or number of comorbidities. Based on the ISI, 44.2% of participants reporting a negative impact on sleep exhibited at least moderately severe clinical insomnia. Compared to those who reported no/positive effect on sleep, the participants reporting a negative impact on sleep also reported poorer QoL, based on the total PCOSQOL score, with a greater impact of PCOS and poorer mood in the corresponding PCOSQOL domains. Based on the DASS-21, the latter also had statistically higher depression and stress levels compared to the former. Finally, for this cohort significant inverse correlations were noted between the ISI and PCOSQOL scores (total and domain scores), whilst the DASS-21 and ISI scores were positively correlated (all p-values <0.001).

Conclusion: The majority of recruited UK women with PCOS reported that the COVID-19 lockdown had a negative impact on their sleep, which was also associated with impaired QoL and higher depression/stress levels. Whilst further research is required, women with PCOS should be considered a vulnerable population that may experience an adverse impact on sleep, QoL and mental health well-being due to lockdown measures during the COVID-19 pandemic.
Effects of Vaccination Against Coccidiosis on Gut Microbiota and Immunity in Broiler Fed Bacitracin and Berry Pomace
Authors: Das Quail , Shay Julie , Gauthier Martin , Yin Xianhua , Hasted Teri-Lyn , Ross Kelly , Julien Carl , Yacini Hassina , Kennes Yan Martel , Warriner Keith , Marcone Massimo F. , Diarra Moussa S.
Published: June 2021

Feeding practices have been found to influence gut microbiota which play a major role in immunity of poultry. In the present study, changes in cecal microbiota and humoral responses resulting in the 55 ppm bacitracin (BACI), 1% each of cranberry (CP1) and wild blueberry (BP1) pomace alone or in combination (CP+BP) feeding in broiler Cobb 500 vaccinated or not against coccidiosis were investigated. In the non-vaccinated group, no significant treatment effects were observed on performance parameters. Vaccination significantly affected bird’s performance parameters particularly during the growing phase from 10 to 20 days of age. In general, the prevalence of coccidiosis and necrotic enteritis (NE) was reduced by vaccination (P < 0.05). BACI-treated birds showed low intestinal lesion scores, and both CP1 and BP1 feed supplementations reduced Eimeria acervulina and Clostridium perfringens incidences similar to BACI. Vaccination induced change in serum enzymes, minerals, and lipid levels in 21-day old birds while, levels of triglyceride (TRIG) and non-esterified fatty acids (NEFA) were higher (P < 0.05) in CP1 treated non–vaccinated group than in the control. The levels of NEFA were lower in BACI- and CP1-fed birds than in the control in non-vaccinated day 28 old birds. The highest levels of all estimated three immunoglobulins (IgY, IgM, and IgA) were found in the vaccinated birds. Metagenomics analysis of the cecal bacterial community in 21-day old birds showed the presence of Firmicutes (90%), Proteobacteria (5%), Actinobacteria (2%), and Bacteroidetes (2%). In the vaccinated group, an effect of BACI was noted on Proteobacteria (P = 0.03). Vaccination and/or dietary treatments influenced the population of Lactobacillaceae, Enterobacteriaceae, Clostridiaceae, and Streptococcaceae which were among the most abundant families. Overall, this study revealed that besides their beneficial effects on performance, alike bacitracin, berry pomaces in poultry feed have profound impacts on the chicken cecal microbiota and blood metabolites that could be influenced by vaccination against coccidiosis.
The Macrophage Response Is Driven by Mesenchymal Stem Cell-Mediated Metabolic Reprogramming
Authors: Luque-Campos Noymar , Bustamante-Barrientos Felipe A. , Pradenas Carolina , García Cynthia , Araya María Jesús , Bohaud Candice , Contreras-López Rafael , Elizondo-Vega Roberto , Djouad Farida , Luz-Crawford Patricia , Vega-Letter Ana María
Published: June 2021

Mesenchymal stem cells (MSCs) are multipotent adult stromal cells widely studied for their regenerative and immunomodulatory properties. They are capable of modulating macrophage plasticity depending on various microenvironmental signals. Current studies have shown that metabolic changes can also affect macrophage fate and function. Indeed, changes in the environment prompt phenotype change. Therefore, in this review, we will discuss how MSCs orchestrate macrophage’s metabolic plasticity and the impact on their function. An improved understanding of the crosstalk between macrophages and MSCs will improve our knowledge of MSC’s therapeutic potential in the context of inflammatory diseases, cancer, and tissue repair processes in which macrophages are pivotal.
Epigenetic Features of HIV-Induced T-Cell Exhaustion Persist Despite Early Antiretroviral Therapy
Authors: Martin Genevieve E. , Sen Debattama R. , Pace Matthew , Robinson Nicola , Meyerowitz Jodi , Adland Emily , Thornhill John P. , Jones Mathew , Ogbe Ane , Parolini Lucia , Olejniczak Natalia , Zacharopoulou Panagiota , Brown Helen , Willberg Christian B. , Nwokolo Nneka , Fox Julie , Fidler Sarah , Haining W. Nicholas , Frater John
Published: June 2021

T cell dysfunction occurs early following HIV infection, impacting the emergence of non-AIDS morbidities and limiting curative efforts. ART initiated during primary HIV infection (PHI) can reverse this dysfunction, but the extent of recovery is unknown. We studied 66 HIV-infected individuals treated from early PHI with up to three years of ART. Compared with HIV-uninfected controls, CD4 and CD8 T cells from early HIV infection were characterised by T cell activation and increased expression of the immune checkpoint receptors (ICRs) PD1, Tim-3 and TIGIT. Three years of ART lead to partial – but not complete – normalisation of ICR expression, the dynamics of which varied for individual ICRs. For HIV-specific cells, epigenetic profiling of tetramer-sorted CD8 T cells revealed that epigenetic features of exhaustion typically seen in chronic HIV infection were already present early in PHI, and that ART initiation during PHI resulted in only a partial shift of the epigenome to one with more favourable memory characteristics. These findings suggest that although ART initiation during PHI results in significant immune reconstitution, there may be only partial resolution of HIV-related phenotypic and epigenetic changes.
RUVBL1/2 Complex Regulates Pro-Inflammatory Responses in Macrophages via Regulating Histone H3K4 Trimethylation
Authors: Zhang Rui , Cheung Chris Y. , Seo Sang-Uk , Liu Hang , Pardeshi Lakhansing , Wong Koon Ho , Chow Larry M. C. , Chau Mary P. , Wang Yixiang , Lee Ah Ra , Kwon Woon Yong , Chen Sheng , Chan Bill Kwan-wai , Wong Kenneth , Choy Richard K. W. , Ko Ben C. B.
Published: June 2021

Macrophages play an important role in the host defense mechanism. In response to infection, macrophages activate a genetic program of pro-inflammatory response to kill any invading pathogen, and initiate an adaptive immune response. We have identified RUVBL2 - an ATP-binding protein belonging to the AAA+ (ATPase associated with diverse cellular activities) superfamily of ATPases - as a novel regulator in pro-inflammatory response of macrophages. Gene knockdown of Ruvbl2, or pharmacological inhibition of RUVBL1/2 activity, compromises type-2 nitric oxide synthase (Nos2) gene expression, nitric oxide production and anti-bacterial activity of mouse macrophages in response to lipopolysaccharides (LPS). RUVBL1/2 inhibitor similarly inhibits pro-inflammatory response in human monocytes, suggesting functional conservation of RUVBL1/2 in humans. Transcriptome analysis further revealed that major LPS-induced pro-inflammatory pathways in macrophages are regulated in a RUVBL1/2-dependent manner. Furthermore, RUVBL1/2 inhibition significantly reduced the level of histone H3K4me3 at the promoter region of Nos2 and Il6, two prototypical pro-inflammatory genes, and diminished the recruitment of NF-kappaB to the corresponding enhancers. Our study reveals RUVBL1/2 as an integral component of macrophage pro-inflammatory responses through epigenetic regulations, and the therapeutic potentials of RUVBL1/2 inhibitors in the treatment of diseases caused by aberrant activation of pro-inflammatory pathways.
IFN-β Acts on Monocytes to Ameliorate CNS Autoimmunity by Inhibiting Proinflammatory Cross-Talk Between Monocytes and Th Cells
Authors: Rasouli Javad , Casella Giacomo , Ishikawa Larissa L. W. , Thome Rodolfo , Boehm Alexandra , Ertel Adam , Melo-Silva Carolina R. , Mari Elisabeth R. , Porazzi Patrizia , Zhang Weifeng , Xiao Dan , Sigal Luis J. , Fortina Paolo , Zhang Guang-Xian , Rostami Abdolmohamad , Ciric Bogoljub
Published: June 2021

IFN-β has been the treatment for multiple sclerosis (MS) for almost three decades, but understanding the mechanisms underlying its beneficial effects remains incomplete. We have shown that MS patients have increased numbers of GM-CSF+Th cells in circulation, and that IFN-β therapy reduces their numbers. GM-CSF expression by myelin-specific Th cells is essential for the development of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. These findings suggested that IFN-β therapy may functionviasuppression of GM-CSF production by Th cells. In the current study, we elucidated a feedback loop between monocytes and Th cells that amplifies autoimmune neuroinflammation, and found that IFN-β therapy ameliorates central nervous system (CNS) autoimmunity by inhibiting this proinflammatory loop. IFN-β suppressed GM-CSF production in Th cells indirectly by acting on monocytes, and IFN-β signaling in monocytes was required for EAE suppression. IFN-β increased IL-10 expression by monocytes, and IL-10 was required for the suppressive effects of IFN-β. IFN-β treatment suppressed IL-1β expression by monocytes in the CNS of mice with EAE. GM-CSF from Th cells induced IL-1β production by monocytes, and, in a positive feedback loop, IL-1β augmented GM-CSF production by Th cells. In addition to GM-CSF, TNF and FASL expression by Th cells was also necessary for IL-1β production by monocyte. IFN-β inhibited GM-CSF, TNF, and FASL expression by Th cells to suppress IL-1β secretion by monocytes. Overall, our study describes a positive feedback loop involving several Th cell- and monocyte-derived molecules, and IFN-β actions on monocytes disrupting this proinflammatory loop.
Circulating and Tumor-Infiltrating NK Cells From Clear Cell Renal Cell Carcinoma Patients Exhibit a Predominantly Inhibitory Phenotype Characterized by Overexpression of CD85j, CD45, CD48 and PD-1
Authors: Ziblat Andrea , Iraolagoitia Ximena Lucía Raffo , Nuñez Sol Yanel , Torres Nicolás Ignacio , Secchiari Florencia , Sierra Jessica Mariel , Spallanzani Raúl Germán , Rovegno Agustín , Secin Fernando Pablo , Fuertes Mercedes Beatriz , Domaica Carolina Inés , Zwirner Norberto Walter
Published: June 2021

Although natural killer (NK) cells infiltrate clear cell renal cell carcinomas (ccRCC), the most frequent malignancy of the kidney, tumor progression suggests that they become dysfunctional. As ccRCC-driven subversion of NK cell effector functions is usually accompanied by phenotypic changes, analysis of such alterations might lead to the identification of novel biomarkers and/or targets in immuno-oncology. Consequently, we performed a phenotypic analysis of peripheral blood NK cells (PBNK) and tumor-infiltrating NK cells (TINK) from ccRCC patients. Compared to HD, PBNK from ccRCC patients exhibited features of activated cells as shown by CD25, CD69 and CD62L expression. They also displayed increased expression of DNAM-1, CD48, CD45, MHC-I, reduced expression of NKG2D, and higher frequencies of CD85j+ and PD-1+ cells. In addition, compared to PBNK from ccRCC patients, TINK exhibited higher expression of activation markers, tissue residency features and decreased expression of the activating receptors DNAM-1, NKp30, NKp46, NKp80 and CD16, suggesting a more inhibitory phenotype. Analysis of The Cancer Genome Atlas (TCGA) revealed that CD48, CD45, CD85j and PD-1 are significantly overexpressed in ccRCC and that their expression is associated with an NK cell infiltration signature. Calculation of z-scores revealed that their expression on PBNK, alone or combined, distinguished ccRCC patients from HD. Therefore, these molecules emerge as novel potential biomarkers and our results suggest that they might constitute possible targets for immunotherapy in ccRCC patients.
Engineered Cytokine Signaling to Improve CAR T Cell Effector Function
Authors: Bell Matthew , Gottschalk Stephen
Published: June 2021

Adoptive immunotherapy with T cells genetically modified to express chimeric antigen receptors (CARs) is a promising approach to improve outcomes for cancer patients. While CAR T cell therapy is effective for hematological malignancies, there is a need to improve the efficacy of this therapeutic approach for patients with solid tumors and brain tumors. At present, several approaches are being pursued to improve the antitumor activity of CAR T cells including i) targeting multiple antigens, ii) improving T cell expansion/persistence, iii) enhancing homing to tumor sites, and iv) rendering CAR T cells resistant to the immunosuppressive tumor microenvironment (TME). Augmenting signal 3 of T cell activation by transgenic expression of cytokines or engineered cytokine receptors has emerged as a promising strategy since it not only improves CAR T cell expansion/persistence but also their ability to function in the immunosuppressive TME. In this review, we will provide an overview of cytokine biology and highlight genetic approaches that are actively being pursued to augment cytokine signaling in CAR T cells.
Evaluating Uncertainties in Reconstructing the Pre-eutrophic State of the North Sea
Authors: Stegert Christoph , Lenhart Hermann-Josef , Blauw Anouk , Friedland René , Leujak Wera , Kerimoglu Onur
Published: June 2021

The North Sea is affected by eutrophication problems despite the decreasing riverine nutrient fluxes since the late 1980s. Formally, assessment of the eutrophication state of European marine environments is based on their historical state. Model estimates are increasingly used to support monitoring data that often do not encompass such pre-eutrophic conditions. However, various sources of uncertainties emerge when producing these estimates. In this study, we systematically quantify various sources of uncertainties in terms of variability, and assess their importance for the North Sea. For the reconstruction of the historical state, we use two coupled physical-biogeochemical model systems: ECOHAM on a 20-km grid for the European shelf and GPM on a high-resolution (1.5–4.5 km) grid for the Southern North Sea. To gain insights into the impacts due to the uncertainty in riverine loadings, we consider the historical nutrient inputs from two alternative watershed-models (MONERIS and E-HYPE). Overall, the modeled historic state based on E-HYPE shows higher nutrient concentrations compared to the state based on MONERIS, especially in the coastal regions. Assessing the degree of methodological uncertainties by an inter-comparison of different sources and against natural variabilities provides insight into the reliability of the model-based reconstruction of the historical state. We find that in regions influenced by freshwater from major rivers uncertainties owed to riverine loading scenarios exceed the natural sources of variability. For the offshore regions, natural sources of variability dominate over those caused by model- and scenario-related uncertainties. These findings are expected to assist decision makers and researchers in gaining insight into the degree of confidence in evaluating the model results, and prioritizing the need for refinement of models and scenarios for the production of reliable projections.
Understanding the Impact of Bathymetric Changes in the German Bight on Coastal Hydrodynamics: One Step Toward Realistic Morphodynamic Modeling
Authors: Jacob Benjamin , Stanev Emil V.
Published: June 2021

The hydrodynamic response to morphodynamic variability in the coastal areas of the German Bight was analyzed via numerical experiments using time-referenced bathymetric data for the period 1982–2012. Time-slice experiments were conducted for each year with the Semi-implicit Cross-scale Hydroscience Integrated System Model (SCHISM). This unstructured-grid model resolves small-scale bathymetric features in the coastal zone, which are well-resolved in the high-resolution time-referenced bathymetric data (50 m resolution). Their analysis reveals the continuous migration of tidal channels, as well as rather complex change of the depths of tidal flats in different periods. The almost linear relationship between the cross-sectional inlet areas and the tidal prisms of the intertidal basins in the East Frisian Wadden Sea demonstrates that these bathymetric data describe a consistent morphodynamic evolutionary trend. The numerical experiment results are streamlined to explain the hydrodynamic evolution from 1982 to 2012. Although the bathymetric changes were mostly located in a relatively small part of the model area, they resulted in substantial changes in the M2 tidal amplitudes, i.e., larger than 5 cm in some areas. The hydrodynamic response to bathymetric changes largely exceeded the response to sea level rise. The tidal asymmetry estimated from the model appeared very sensitive to bathymetric evolution, particularly between the southern tip of Sylt Island and the Eider Estuary along the eastern coast. The peak current asymmetry weakened from 1982 to 1995 and even reversed within some tidal basins to become flood-dominant. This would suggest that the flushing trend in the 1980s was reduced or reversed in the second half of the studied period. Salinity also appeared sensitive to bathymetric changes; the deviations in the individual years reached ~22 psu in the tidal channels and tidal flats. One practical conclusion from the present numerical simulations is that wherever possible, the numerical modeling of near-coastal zones must employ time-referenced bathymetry data. The second, perhaps even more important conclusion, is that the progress of morphodynamic modeling in realistic ocean settings with multiple scales and varying bottom forms is strongly dependent on the availability of bathymetric data with appropriate temporal and spatial resolution.
Influence of Pre-Oxidation on High Temperature Oxidation and Corrosion Behavior of Ni-Based Aluminide Coating in Na2SO4 Salt at 1050°C
Authors: Li Qing , Zhang Defeng , Song Peng , Li Zhenhua , Zhai Ruixiong , Hua Chen , Lu Jiansheng
Published: June 2021

Aluminide coating is prepared on K438 Ni-based superalloy by pack cementation. The hot corrosion test of as-received and pre-oxidation aluminide coating in Na2SO4 salt are carried out at 1050°C. The coating morphologies, phase composition, and corrosion products are characterized by XRD, SEM, EDS, and TEM. The conclusion is that the pre-oxidation aluminide coating has excellent hot corrosion properties. After hot corrosion, the oxide scale of pre-oxidation aluminide coating is the thinnest and maintains good integrity. However, the oxide scale of as-received aluminide coating fluctuates greatly and there are corrosion cavities. CrS is formed in the alloy immediately below the oxide scale for the two coating systems.
Improving the Flame Retardancy of Bamboo Slices by Coating With Melamine–Phytate via Layer-by-Layer Assembly
Authors: Lin Peng , Xu Yuchen , Hou Junfeng , Zhang Xiaochun , Ma Lingfei , Che Wenbo , Yu Youming
Published: June 2021

Bamboo is a rich natural resource in the Asia Pacific, and it is widely used in the construction and decoration industry. Meanwhile, bamboo is an extremely combustible natural polymer material. Herein, the bamboo slices were treated with melamine and phytic acid using layer-by-layer (LBL) assembly technology to improve their flame retardancy properties. The morphology and chemical composition of untreated and treated bamboo slices were measured by scanning electron microscopy equipped with energy dispersive X-ray analysis and Fourier transform infrared spectra. The results showed that two-dimensional melamine–phytate (MP) nanoflakes were successfully formed and deposited on the bamboo surface. The deposition of the MP coating caused the earlier degradation of the bamboo to form char, according to thermogravimetric analysis. The peak heat release rates of the treated bamboo slices were reduced by more than 28% compared to those of the untreated ones. The MP coating promoted the formation of thermally stable char, which was responsible for the significant improvement in flame retardancy. Besides, the char layer with excellent thermal resistance performed a vital role in suppressing flame spread.
Acupuncture Point Stimulation Treatments Combined With Conventional Treatment in Chronic Obstructive Pulmonary Disease: A Systematic Review and Network Meta-Analysis
Authors: Tsai Cheng-Lin , Lan Chou-Chin , Wu Chih-Wei , Wu Yun-Chun , Kuo Chan-Yen , Tzeng I-Shiang , Hsu Pei-Shan , Lee Chang-Ti , Hsieh Po-Chun
Published: June 2021

Background: Chronic obstructive pulmonary disease (COPD), which is a disease characterized by dyspnea, cough, and respiratory symptoms, leading to impaired health-related quality of life (HRQL) and exercise capacity, is highly prevalent worldwide. Some studies demonstrated that acupuncture point stimulation treatments (APSTs) are effective and safe in treating patients with COPD. The aim of this systematic review and network meta-analysis is to analyze the effects on HRQL and FEV1% predicted of diverse APSTs in treating patients with COPD.

Materials and Methods: We searched seven electronic databases. Randomized controlled trials (RCTs) with stable COPD patients comparing APSTs and conventional treatment (Tx) were included. The primary outcome was HRQL measured by COPD Assessment Test or St. George's Respiratory Questionnaire. The secondary outcome was FEV1% predicted. We performed random effect network meta-analysis using a consistency model.

Results: This network meta-analysis analyzed 21 RCTs with 1,577 stable COPD participants. In comparison with Tx, acupressure massage (AM) + Tx [−5.11; 95% confidence interval (CI), −6.65 to −3.57] was the most effective intervention in improving HRQL, followed by moxibustion (Mx) + Tx (−2.86; 95% CI, −3.86 to −1.86). Moreover, in comparison with Tx, Mx + Tx (7.79; 95% CI, 2.16 to 13.42) was the most effective intervention in improving FEV1% predicted, followed by acupuncture (A) + Tx (5.79; 95% CI, 2.90 to 8.68).

Conclusions: Combined interventions (APSTs + Tx) are more effective than single intervention in improving both HRQL and FEV1% predicted. AM, Mx, and A can be considered effective non-pharmacological complementary interventions in treating patients with COPD under Tx.
Comparison Between Cultivation and Sequencing Based Approaches for Microbiota Analysis in Swabs and Biopsies of Chronic Wounds
Authors: Mahnic Aleksander , Breznik Vesna , Bombek Ihan Maja , Rupnik Maja
Published: June 2021

Chronic wounds are a prominent health concern affecting 0.2% of individuals in the Western population. Microbial colonization and the consequent infection contribute significantly to the healing process. We have compared two methods, cultivation and 16S amplicon sequencing (16S-AS), for the characterization of bacterial populations in both swabs and biopsy tissues obtained from 45 chronic wounds. Using cultivation approach, we detected a total of 39 bacterial species, on average 2.89 per sample (SD = 1.93), compared to 5.9 (SD = 7.1) operational taxonomic units per sample obtained with 16S-AS. The concordance in detected bacteria between swab and biopsy specimens obtained from the same CWs was greater when using cultivation (58.4%) as compared to 16S-AS (25%). In the entire group of 45 biopsy samples concordance in detected bacterial genera between 16S-AS and cultivation-based approach was 36.4% and in swab samples 28.7%. Sequencing proved advantageous in comparison to the cultivation mainly in case of highly diverse microbial communities, where we could additionally detect numerous obligate and facultative anaerobic bacteria from genera Anaerococcus, Finegoldia, Porphyromonas, Morganella, and Providencia. Comparing swabs and biopsy tissues we concluded, that neither sampling method shows significant advantage over the other regardless of the method used (16S-AS or cultivation). In this study, chronic wound microbiota could be distributed into three groups based on the bacterial community diversity. The chronic wound surface area was positively correlated with bacterial diversity in swab specimens but not in biopsy tissues. Larger chronic wound surface area was also associated with the presence of Pseudomonas in both biopsy and swab specimens. The presence of Corynebacterium species at the initial visit was the microbial marker most predictive of the unfavorable clinical outcome after one-year follow-up visit.
Nanomedicine: A Diagnostic and Therapeutic Approach to COVID-19
Authors: Sharma Arjun , Kontodimas Konstantinos , Bosmann Markus
Published: June 2021

The SARS-CoV-2 virus is causing devastating morbidity and mortality worldwide. Nanomedicine approaches have a high potential to enhance conventional diagnostics, drugs and vaccines. In fact, lipid nanoparticle/mRNA vaccines are already widely used to protect from COVID-19. In this review, we present an overview of the taxonomy, structure, variants of concern, epidemiology, pathophysiology and detection methods of SARS-CoV-2. The efforts of repurposing, tailoring, and adapting pre-existing medications to battle COVID-19 and the state of vaccine developments are presented. Next, we discuss the broad concepts and limitations of how nanomedicine could address the COVID-19 threat. Nanomaterials are particles in the nanometer scale (10–100 nm) which possess unique properties related to their size, polarity, structural and chemical composition. Nanoparticles can be composed of precious metals (copper, silver, gold), inorganic materials (graphene, silicon), proteins, carbohydrates, lipids, RNA/DNA, or conjugates, combinations and polymers of all of the aforementioned. The advanced biochemical features of these nanoscale particles allow them to directly interact with virions and irreversibly disrupt their structure, which can render a virus incapable of replicating within the host. Virus-neutralizing coats and surfaces impregnated with nanomaterials can enhance personal protective equipment, hand sanitizers and air filter systems. Nanoparticles can enhance drug-based therapies by optimizing uptake, stability, target cell-specific delivery, and magnetic properties. In fact, recent studies have highlighted the potential of nanoparticles in different aspects of the fight against SARS-CoV-2, such as enhancing biosensors and diagnostic tests, drug therapies, designing new delivery mechanisms, and optimizing vaccines. This article summarizes the ongoing research on diagnostic strategies, treatments, and vaccines for COVID-19, while emphasizing the potential of nanoparticle-based pharmaceuticals and vaccines.
Risk of Herpes Zoster Among Psoriasis Patients Taking Biologics: A Network Meta-Analysis of Cohort Studies
Authors: Tang Zhenwei , Shen Minxue , Chen Xiang
Published: June 2021

Background: Herpes zoster (HZ) has raised public concern. An increasing incidence of HZ can be seen in the immunocompromised population, such as the psoriasis patients taking biologics. Real-world evidences are still needed to investigate the risks of HZ among patients receiving different biologics treatments. This study aims to summarize the findings from cohort studies.

Methods: Herein, we performed a meta-analysis of cohort studies. We included studies referred to seven biologics (adalimumab, alefacept, efalizumab, etanercept, infliximab, rituximab, and ustekinumab) as well as methotrexate for psoriasis. We estimated summary relative risks (RRs) for HZ using pairwise and network meta-analysis.

Results: Overall, five studies were included for analysis. A total of 32827.6 patient-years were observed. The result of the meta-analysis showed that the pooled HZ incidence rate of adalimumab, which accounts for the most patient-years in our analysis, is 2.6 per 1,000 patient-years. Our analysis based on several cohorts showed an insignificant difference among the patients receiving adalimumab, alefacept, efalizumab, etanercept, infliximab, rituximab, ustekinumab, and methotrexate.

Conclusions: Based on this analysis, the type of mono-biologic treatment contributes little to the risk of HZ among psoriasis patients. Of note, the negative findings of our study do not mean the unnecessity of vaccination. More efforts must be taken to further determine HZ risk of different therapeutic strategies.
Identification and Prediction of Novel Clinical Phenotypes for Intensive Care Patients With SARS-CoV-2 Pneumonia: An Observational Cohort Study
Authors: Chen Hui , Zhu Zhu , Su Nan , Wang Jun , Gu Jun , Lu Shu , Zhang Li , Chen Xuesong , Xu Lei , Shao Xiangrong , Yin Jiangtao , Yang Jinghui , Sun Baodi , Li Yongsheng
Published: June 2021

Background: Phenotypes have been identified within heterogeneous disease, such as acute respiratory distress syndrome and sepsis, which are associated with important prognostic and therapeutic implications. The present study sought to assess whether phenotypes can be derived from intensive care patients with coronavirus disease 2019 (COVID-19), to assess the correlation with prognosis, and to develop a parsimonious model for phenotype identification.

Methods: Adult patients with COVID-19 from Tongji hospital between January 2020 and March 2020 were included. The consensus k means clustering and latent class analysis (LCA) were applied to identify phenotypes using 26 clinical variables. We then employed machine learning algorithms to select a maximum of five important classifier variables, which were further used to establish a nested logistic regression model for phenotype identification.

Results: Both consensus k means clustering and LCA showed that a two-phenotype model was the best fit for the present cohort (N = 504). A total of 182 patients (36.1%) were classified as hyperactive phenotype, who exhibited a higher 28-day mortality and higher rates of organ dysfunction than did those in hypoactive phenotype. The top five variables used to assign phenotypes were neutrophil-to-lymphocyte ratio (NLR), ratio of pulse oxygen saturation to the fractional concentration of oxygen in inspired air (Spo2/Fio2) ratio, lactate dehydrogenase (LDH), tumor necrosis factor α (TNF-α), and urea nitrogen. From the nested logistic models, three-variable (NLR, Spo2/Fio2 ratio, and LDH) and four-variable (three-variable plus TNF-α) models were adjudicated to be the best performing, with the area under the curve of 0.95 [95% confidence interval (CI) = 0.94–0.97] and 0.97 (95% CI = 0.96–0.98), respectively.

Conclusion: We identified two phenotypes within COVID-19, with different host responses and outcomes. The phenotypes can be accurately identified with parsimonious classifier models using three or four variables.
Non-invasive Diagnosis and Prognosis Values of 3D Pseudocontinuous Arterial Spin Labeling and Optical Coherence Tomography Angiography in Proliferative Diabetic Retinopathy
Authors: Hou Yanli , Song Shuai , Sun Jiao , Wang Huihui , Wang Yanling , Wang Zhenchang , Li Jing , Li Hongyang
Published: June 2021

Background: 3D Pseudocontinuous Arterial Spin Labeling (3D-PCASL) MRI and optical coherence tomography angiography (OCTA) have been applied to detect ocular blood flow (BF). We aim to characterize the ocular BF in diabetic retinopathy (DR) using 3D-PCASL and OCTA, to discuss the relationship between ocular and cerebral BF, and to evaluate their potential utility to assess the severity of DR.

Methods: A total of 66 participants (132 eyes) were included. Seventy-two eyes were classified in the proliferative diabetic retinopathy (PDR) group, and 60 were in the non-proliferative diabetic retinopathy NPDR group. Ocular and cerebral BF values were detected by 3D-PCASL using a 3.0T MRI scanner with two post-labeling delays (PLDs). Vessel density (VD)/perfusion density (PD) of the macular or peripapillary area were detected by OCTA. Parameters and clinical characteristics were compared between the PDR and NPDR eyes utilizing two-sample t-tests and chi-square tests. Spearman's rank correlation analysis, logistic regression analysis, and receiver operating characteristic curves (ROC) analyses were performed to evaluate the factors' role in DR severity.

Results: The perfusions of the retinal/choroidal plexus (RCP), optic nerve head (ONH)/optic nerve (ON), and VD/PD of macular/peripapillary area in the PDR group were significantly lower compared to the NPDR group (p < 0.05). They were protective factors for PDR [ORs = 0.842 for RCP (1.5 s PLD), 0.910 for ONH (1.5 s PLD), 0.905 for ON (both 1.5 and 2.5 s PLD), 0.707 for macular VD, 0.652 for peripapillary VD, p < 0.05, respectively]. Ocular BF had a positive correlation with BF of the occipital lobe (OL) and temporal lobe (TL) in the cerebrum. The BF of RCP (lower than 7.825 mL/min/100 g at 1.5 s PLD) indicated PDR [areas under the curve (AUCs) = 0.682, 95% CI: 0.588–0.777, sensitivity: 70.7% specificity: 63.9%]. The AUC of RCP (PLD = 1.5 s) BF combined with peripapillary VD was 0.841 (95% CI: 0.588–0.777, sensitivity: 75.9% specificity: 82.9%).

Conclusions: 3D-pcASL and OCTA may be effective non-invasive methods to measure ocular blood flow in DR patients and assess the severity of DR.
Molecular Epidemiology, Genetic Diversity, and Antifungal Susceptibility of Major Pathogenic Dermatophytes Isolated From Human Dermatophytosis
Authors: Salehi Zahra , Shams-Ghahfarokhi Masoomeh , Razzaghi-Abyaneh Mehdi
Published: June 2021

Background

Dermatophytes are a homogeneous group of species with low genetic diversity, and there are still many uncertainties about the boundaries among species.

Objectives

Aiming at clarifying the relationships among species in the genus and introducing suitable genes for multilocus sequence typing (MLST), a new MLST scheme approach was developed to characterize the major pathogenic dermatophytes.

Methods

We performed maximum parsimony (MP), MrBayes, RAxML, and eBURST analyses, based on the MLST scheme to scrutinize the evolution within 95 clinical isolates and four reference strains belonging to the four major dermatophytes species. Then, the discriminatory power, pairwise genetic distances, ratio dN/dS, and sequence types (STs) of these isolates were determined. Also, to study taxonomy, sequences of the internal transcribed spacer (ITS), Beta-tubulin (BT2), and translation elongation factor 1-α (TEF-1α) genes of other dermatophytes species available in the GenBank were analyzed.

Results

Findings of the present study indicated that three genes: BT2, ITS, and TEF−1α, which showed the greatest diversity among dermatophyte species, were suitable for MLST. The most prevalent STs were seen among the species of Trichophyton interdigitale. Also, two new genotypes, i.e., XXVII and XXVIII, were introduced for T. interdigitale and Trichophyton mentagrophytes. The least informative sites were found in Epidermophyton floccosum, Trichophyton rubrum, and T. mentagrophytes, while the most informative sites were observed in T. interdigitale. Furthermore, the most informative locus was TEF-1α. The phylogenetic tree, constructed by the combination of the three genes, shows a new topological pattern that confirms the derivation of the anthropophilic and zoophilic genera from the geophilic genus. Also, the phylogenetic analyses and pairwise distances of the combination of the three loci showed that Trichophyton tonsurans and Trichophyton equinum were a species complex, where T. equinum is derived from T. tonsurans.

Conclusions

Results of this study showed that MLST is very effective in determining the boundaries between species and taxonomy. Considering that there is no database for MLST dermatophytes, further studies are needed to determine the suitable genes for MLST. Also, the determination of STs in epidemiological studies and raising epidemiological information are helpful. This study was a new starting point to determine the ST and a foundation for a dermatophyte MLST database.
Autophagy Receptor Protein Tax1-Binding Protein 1/TRAF6-Binding Protein Is a Cellular Substrate of Enteroviral Proteinase
Authors: Mohamud Yasir , Xue Yuan Chao , Liu Huitao , Ng Chen Seng , Bahreyni Amirhossein , Luo Honglin
Published: June 2021

Enteroviruses (EVs) usurp the host autophagy pathway for pro-viral functions; however, the consequence of EV-induced diversion of autophagy on organelle quality control is poorly defined. Using coxsackievirus B3 (CVB3) as a model EV, we explored the interplay between EV infection and selective autophagy receptors, i.e., Tax1-binding protein 1/TRAF6-binding protein (T6BP), optineurin (OPTN), and nuclear dot 10 protein 52 (NDP52), known to be involved in regulating the clearance of damaged mitochondria, a process termed as mitophagy. Following CVB3 infection, we showed significant perturbations of the mitochondrial network coincident with degradation of the autophagy receptor protein T6BP, similar phenomenon to what we previously observed on NDP52. Notably, protein levels of OPTN are not altered during early infection and slightly reduced upon late infection. Cell culture studies revealed that T6BP degradation occurs independent of the function of host caspases and viral proteinase 3C, but requires the proteolytic activity of viral proteinase 2A. Further investigation identified the cleavage site on T6BP after the amino acid 621 that separates the C-terminal ubiquitin-binding domain from the other functional domains at the N-terminus. Genetic silencing of T6BP and OPTN results in the attenuation of CVB3 replication, suggesting a pro-viral activity for these two proteins. Finally, functional assessment of cleaved fragments from NDP52 and T6BP revealed abnormal binding affinity and impaired capacity to be recruited to depolarized mitochondria. Collectively, these results suggest that CVB3 targets autophagy receptors to impair selective autophagy.
Behavior of Vibrio spp. in Table Olives
Authors: Posada-Izquierdo Guiomar Denisse , Valero Antonio , Arroyo-López Francisco Noé , González-Serrano Miriam , Ramos-Benítez Alfonso M. , Benítez-Cabello Antonio , Rodríguez-Gómez Francisco , Jimenez-Diaz Rufino , García-Gimeno Rosa M.
Published: June 2021

The presence of Vibrio species in table olive fermentations has been confirmed by molecular biology techniques in recent studies. However, there has been no report of any foodborne outbreak caused by Vibrio due to the consumption of table olives, and their role as well as the environmental conditions allowing their survival in table olives has not been elucidated so far. The aims of this work were to model the behavior of an inoculated Vibrio cocktail in diverse table olive environments and study the possible behavior of an inoculated Vibrio cocktail in table olives. First, an in vitro study has been performed where the microbial behavior of a Vibrio cocktail was evaluated in a laboratory medium and in olive brines using predictive models at different NaCl concentrations (2–12%) and pH levels (4.0–9.0). Afterward, a challenge testing was done in lye-treated olives inoculated at the beginning of fermentation with the Vibrio cocktail for 22 days. The Vibrio cocktail inoculated in table olives has not been detected in olive brines during fermentation at different pH levels. However, it was observed that this microorganism in a laboratory medium could reach an optimal growth at pH 9 and 2% salt, without time of constant absorbance (tA), and the maximum absorbance value (yend) observed was at pH 8 and 2% salt conditions. The statistical analysis demonstrated that the effect of salt concentration was higher than pH for the kinetic growth parameters (μmax, tA, and yend). On the other hand, it was confirmed that no growth of the Vibrio cocktail on any sample was noticed in lye-treated olive fermentations. Thus, it was concluded that the presence of olive compounds (unknown) did not allow the development of Vibrio strains, so it is a very safety product as it has a natural antimicrobial compound, but the possibility that a native Vibrio sp. is able to acquire the capacity to adapt to this compound should be considered in further studies.