bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of cancer-related fibroblasts (CAF) in hepatocellular carcinoma and construction of CAF-based risk signature based on single-cell RNA-seq and bulk RNA-seq data
Authors: Yu Lianghe , Shen Ningjia , Shi Yan , Shi Xintong , Fu Xiaohui , Li Shuang , Zhu Bin , Yu Wenlong , Zhang Yongjie
Published: September 2022

Background

Cancer-associated fibroblasts (CAFs) are involved in tumor growth, angiogenesis, metastasis, and resistance to therapy. We sought to explore the CAFs characteristics in hepatocellular carcinoma (HCC) and establish a CAF-based risk signature for predicting the prognosis of HCC patients.

Methods

The signal-cell RNA sequencing (scRNA-seq) data was obtained from the GEO database. Bulk RNA-seq data and microarray data of HCC were obtained from the TCGA and GEO databases respectively. Seurat R package was applied to process scRNA-seq data and identify CAF clusters according to the CAF markers. Differential expression analysis was performed to screen differentially expressed genes (DEGs) between normal and tumor samples in TCGA dataset. Then Pearson correlation analysis was used to determine the DEGs associated with CAF clusters, followed by the univariate Cox regression analysis to identify CAF-related prognostic genes. Lasso regression was implemented to construct a risk signature based on CAF-related prognostic genes. Finally, a nomogram model based on the risk signature and clinicopathological characteristics was developed.

Results

Based on scRNA-seq data, we identified 4 CAF clusters in HCC, 3 of which were associated with prognosis in HCC. A total of 423 genes were identified from 2811 DEGs to be significantly correlated with CAF clusters, and were narrowed down to generate a risk signature with 6 genes. These six genes were primarily connected with 39 pathways, such as angiogenesis, apoptosis, and hypoxia. Meanwhile, the risk signature was significantly associated with stromal and immune scores, as well as some immune cells. Multivariate analysis revealed that risk signature was an independent prognostic factor for HCC, and its value in predicting immunotherapeutic outcomes was confirmed. A novel nomogram integrating the stage and CAF-based risk signature was constructed, which exhibited favorable predictability and reliability in the prognosis prediction of HCC.

Conclusion

CAF-based risk signatures can effectively predict the prognosis of HCC, and comprehensive characterization of the CAF signature of HCC may help to interpret the response of HCC to immunotherapy and provide new strategies for cancer treatment.
Recent advances to enhance the immunomodulatory potential of mesenchymal stem cells
Authors: Sarsenova Madina , Kim Yevgeniy , Raziyeva Kamila , Kazybay Bexultan , Ogay Vyacheslav , Saparov Arman
Published: September 2022

Considering the unique therapeutic potential of mesenchymal stem cells (MSCs), including their immunosuppressive and immunomodulatory properties as well as their ability to improve tissue regeneration, these cells have attracted the attention of scientists and clinicians for the treatment of different inflammatory and immune system mediated disorders. However, various clinical trials using MSCs for the therapeutic purpose are conflicting and differ from the results of promising preclinical studies. This inconsistency is caused by several factors such as poor migration and homing capacities, low survival rate, low level of proliferation and differentiation, and donor-dependent variation of the cells. Enhancement and retention of persistent therapeutic effects of the cells remain a challenge to overcome in MSC-based therapy. In this review, we summarized various approaches to enhance the clinical outcomes of MSC-based therapy as well as revised current and future perspectives for the creation of cellular products with improved potential for diverse clinical applications.
Regulation of gut microbiota-bile acids axis by probiotics in inflammatory bowel disease
Authors: Li Lingfeng , Liu Tianyu , Gu Yu , Wang Xinyu , Xie Runxiang , Sun Yue , Wang Bangmao , Cao Hailong
Published: September 2022

Inflammatory bowel disease (IBD) is characterized by chronic and relapsing inflammation of gastrointestinal tract, with steadily increased incidence and prevalence worldwide. Although the precise pathogenesis remains unclear, gut microbiota, bile acids (BAs), and aberrant immune response play essential roles in the development of IBD. Lately, gut dysbiosis including certain decreased beneficial bacteria and increased pathogens and aberrant BAs metabolism have been reported in IBD. The bacteria inhabited in human gut have critical functions in BA biotransformation. Patients with active IBD have elevated primary and conjugated BAs and decreased secondary BAs, accompanied by the impaired transformation activities (mainly deconjugation and 7α-dehydroxylation) of gut microbiota. Probiotics have exhibited certain positive effects by different mechanisms in the therapy of IBD. This review discussed the effectiveness of probiotics in certain clinical and animal model studies that might involve in gut microbiota-BAs axis. More importantly, the possible mechanisms of probiotics on regulating gut microbiota-BAs axis in IBD were elucidated, which we focused on the elevated gut bacteria containing bile salt hydrolase or BA-inducible enzymes at genus/species level that might participate in the BA biotransformation. Furthermore, beneficial effects exerted by activation of BA-activated receptors on intestinal immunity were also summarized, which might partially explain the protect effects and mechanisms of probiotics on IBD. Therefore, this review will provide new insights into a better understanding of probiotics in the therapy targeting gut microbiota-BAs axis of IBD.
Role of Aerosols in Spring Blooms in the Central Yellow Sea During the COVID-19 Lockdown by China
Authors: Baek Ji-Yeon , Park Jinku , Kim Dae-Won , Lee Jong-Seok , Lee Jae-Yong , Lee Seung-Jae , Jo Young-Heon
Published: September 2022

Reduced amounts of aerosols blowing into the Yellow Sea (YS), owing to the temporary lockdown of factories in China during COVID-19, resulted in a 15% decrease in spring chlorophyll-aconcentration (CHL) in March 2020 compared to its mean March values from 2003 to 2021. Particularly, the effect of land-based AOD is insignificant compared with that of atmospheric aerosols flowing into the YS, as indicated by the currents and wind directions. Hence, the main objective of this study was to understand the relationship between atmospheric aerosols and CHL by quantitatively considering relevant environmental changes using a Random Forest (RF) algorithm. Various input physical forcing variables to RF were employed, including aerosol optical depth (AOD), sea surface temperature (SST), mixed layer depth (MLD), wind divergence (WD), and total precipitation (TP). From the RF-based analysis, we estimated the relative contribution of each physical forcing variable to the difference in CHL during and after the COVID-19 lockdown period. The sensitivity of the RF model to changes in aerosol levels indicated positive effects of increased amounts of aerosols during spring blooms. Additionally, we calculated the quantitative contribution of aerosols to CHL changes. When SST was warmer and TP was lower than their climatology in March 2020, CHL increased by 0.22 mg m-3and 0.02 mg m-3, respectively. Conversely, when MLD became shallower and AOD was lower than their climatology, CHL decreased as much as 0.01 mg m-3and 0.20 mg m-3. Variations in WD caused no significant change in CHL. Overall, the specific estimations for reduced spring blooms were caused by a reduction in aerosols during the COVID-19 lockdown period. Furthermore, the RF developed in this study can be used to examine CHL changes and the relative role of significant environmental changes in biological blooms in the ocean for any normal year.
Filtering out false Sargassum detections using context features
Authors: Podlejski Witold , Descloitres Jacques , Chevalier Cristèle , Minghelli Audrey , Lett Christophe , Berline Léo
Published: September 2022

Since 2011, the distribution extent of pelagic Sargassum algae has substantially increased and now covers the whole Tropical North Atlantic Ocean, with significant inter-annual variability. The ocean colour imagery has been used as the only way to monitor regularly such a vast area. However, the detection is hampered by cloud masking, sunglint, coastal contamination and other phenomena. All together, they lead to false detections that can hardly be discriminated by classic radiometric analysis, but may be overcome by considering the shape and the context of the detections. Here, we built a machine learning model base exclusively on spatial features to filter out false detections after the detection process. Moderate-Resolution Imaging Spectroradiometer (MODIS, 1 km) data from Aqua and Terra satellites were used to generate daily map of Alternative Floating Algae Index (AFAI). Based on this radiometric index, Sargassum presence in the Tropical Atlantic North Ocean was inferred. For every Sargassum aggregations, five contextual indices were extracted (number of neighbours, surface of neighbours, temporal persistence, distance to the coast and aggregation texture) then used by a random forest binary classifier. Contextual features at large-scale were most important in the classifier. Trained with a multi-annual (2016-2020) learning set, the model performs the filtering of daily false detections with an accuracy of ~ 90%. This leads to a reduction of detected Sargassum pixels of ~ 50% over the domain. The method provides reliable data while preserving high spatial and temporal resolutions (1 km, daily). The resulting distribution is consistent with the literature for seasonal and inter-annual fluctuations, with maximum coverage in 2018 and minimum in 2016. This dataset will be useful for understanding the drivers of Sargassum dynamics at fine and large scale and validate future models. The methodology used here demonstrates the usefulness of contextual features for complementing classical remote sensing approaches. Our model could easily be adapted to other datasets containing erroneous detections.
Citizen science and machine learning: Interdisciplinary approach to non-invasively monitoring a northern marine ecosystem
Authors: Westphal Ashleigh M. , Breiter C-Jae C. , Falconer Sarah , Saffar Najmeh , Ashraf Ahmed B. , McCall Alysa G. , McIver Kieran , Petersen Stephen D.
Published: September 2022

Successful conservation efforts often require novel tactics to achieve the desired goals of protecting species and habitats. One such tactic is to develop an interdisciplinary, collaborative approach to ensure that conservation initiatives are science-based, scalable, and goal-oriented. This approach may be particularly beneficial to wildlife monitoring, as there is often a mismatch between where monitoring is required and where resources are available. We can bridge that gap by bringing together diverse partners, technologies, and global resources to expand monitoring efforts and use tools where they are needed most. Here, we describe a successful interdisciplinary, collaborative approach to long-term monitoring of beluga whales (Delphinapterus leucas) and their marine ecosystem. Our approach includes extracting images from video data collected through partnerships with other organizations who live-stream educational nature content worldwide. This video has resulted in an average of 96,000 underwater images annually. However, due to the frame extraction process, many images show only water. We have therefore incorporated an automated data filtering step using machine learning models to identify frames that include beluga, which filtered out an annual average of 67.9% of frames labelled as “empty” (no beluga) with a classification accuracy of 97%. The final image datasets were then classified by citizen scientists on the Beluga Bits project on Zooniverse (https://www.zooniverse.org). Since 2016, more than 20,000 registered users have provided nearly 5 million classifications on our Zooniverse workflows. Classified images are then used in various researcher-led projects. The benefits of this approach have been multifold. The combination of machine learning tools followed by citizen science participation has increased our analysis capabilities and the utilization of hundreds of hours of video collected each year. Our successes to date include the photo-documentation of a previously tagged beluga and of the common northern comb jellyfish (Bolinopsis infundibulum), an unreported species in Hudson Bay. Given the success of this program, we recommend other conservation initiatives adopt an interdisciplinary, collaborative approach to increase the success of their monitoring programs.
Assessment of the variation of failure probability of upgraded rubble-mound breakwaters due to climate change
Authors: Stagnitti Martina , Lara Javier L. , Musumeci Rosaria E. , Foti Enrico
Published: September 2022

The effects of climate change on coastal areas are expected to significantly influence the risk for port operations. In the present work, a novel methodology for the quantitative assessment of the performances of upgraded rubble-mound breakwaters under a changing climate is proposed. For each considered upgrading option, the failure probability related to a certain limit state is calculated through the implementation of Monte Carlo (MC) simulations, using the factor of change (FoC) method to include the projected future climate. Three indexes are defined for the immediate and intuitive interpretation of the results: i) the ratio between the calculated and the maximum acceptable failure probability during lifetime (r); ii) the rate of the growth of the failure probability during lifetime (s); iii) the coefficient of variation of the failure probability due to both the intrinsic uncertainty of the MC simulation and the variability of future climate (v). The methodology was applied to the case study of the Catania harbor breakwater, considering the failure of different upgrading solutions due to the collapse of the outer armor layer and to excessive mean overtopping discharge. The results revealed the acceptability of the structural and hydraulic performances of all the tested configurations, under both present and future climate. Moreover, a high climate-related variability of the future failure probability was found. The usefulness of the proposed indexes for designer and decision-makers was also demonstrated. In particular, r gives direct information about the acceptability of the structure performances, enabling the immediate comparison between different configurations and climate scenarios. The index s is fundamental to calculate the appropriate times to implement repair interventions during the structure lifetime. Finally, v allows the identification of those situations which requires the design of highly flexible maintenance plans, able to adapt to a very variable climate avoiding excessive costs.
Use of valvometry as an alert tool to signal the presence of toxic algae Alexandrium catenella by Mytilus edulis
Authors: Durier Guillaume , Nadalini Jean-Bruno , Comeau Luc A. , Starr Michel , Michaud Sonia , Tran Damien , St-Louis Richard , Babarro José M. F. , Clements Jeff C. , Tremblay Réjean
Published: September 2022

Valvometry is a non-invasive technique used to continuously monitor gaping behaviour of bivalves at high frequency. In previous laboratory studies, valvometry has revealed a behavioural sensitivity of bivalves to the presence of toxic microalgae in seawater. However, the application of valvometry as an early-warning system for detecting natural occurrences of toxic microalgae and their resulting toxicity in bivalves remains largely unexplored. In this study, valvometry was used to characterise changes in blue mussels (Mytilus edulis) gaping behaviour during gradual exposure to the toxic dinoflagellate, Alexandrium catenella, which produces paralytic shellfish toxins (PST). Laboratory experiments were first performed to identify specific gaping behaviour changes and these responses were subsequently validated in natural seawater conditions in a second experiment. Under both laboratory and natural seawater conditions, mussels exposed to A. catenella tended to remain open (yawning) longer than non-exposed mussels. This change in gaping behaviour was observed at PST concentration as low as 30 μg STXeq 100 g–1 of mussel tissue. We suggest that increased opening is likely related to temporary muscular paralysis induced by toxic algae, as this mechanism has been previously reported in other bivalve species. Furthermore, we observed that biological rhythms of valve behaviour related to tidal and daily rhythms were modified when mussels were intoxicated by PSP (Paralytic Shellfish Poisoning). In conclusion, the effects of toxic algae on mussel gaping behaviour reveals that valvometry could be used as an early-warning tool for the presence of toxic Alexandrium sp. in the environment prior to mussels reaching the regulatory threshold (80 μg STXeq 100 g–1) for harvest interdiction.
Benthic nitrogen cycling in the deep ocean of the Kuroshio Extension region
Authors: Xu Haoming , Song Guodong , Yang Siqi , Zhu Ruosi , Zhang Guiling , Liu Sumei
Published: September 2022

Benthic nitrogen cycling, including nitrification, N-loss, and other nitrogen transformations, plays a crucial role in the marine nitrogen budget. However, studies on benthic nitrogen cycling mainly focus on marginal seas, while attention to the deep ocean, which occupies the largest area of the seafloor, is severely lacking. In this study, we investigate the benthic nitrogen cycling in the Kuroshio Extension region (KE) of the northwest Pacific Ocean at water depths greater than 5,000 m through 15N enrichment slurry incubation and pore-water dissolved oxygen and inorganic nitrogen profiles. The slurry incubation indicates nitrification is the predominant process in benthic nitrogen cycling. The potential nitrification rates are nearly an order of magnitude higher than dissimilatory nitrate reduction. Nitrification and total N-loss flux estimated from pore-water nitrate and ammonium profiles are 6–42 and 5–30 μmol N m−2 d−1, respectively. Generally, anammox is the predominant N-loss process in KE sediment. The temperature gradient experiment indicates that the optimum temperature for anammox and denitrification is 13 and 41°C, respectively, partially explaining anammox as the dominant process for deep-ocean benthic N-loss. Both the low concentration of ammonium in pore-water and the discrepant results between anoxic incubation amended with 15NO3− and 15NH4++14NO3− suggest that ammonium is another limiting factor for benthic anammox. N-loss activity gradually declines with the distance from the Oyashio–Kuroshio transition zone. However, nitrification has the opposite trend roughly. This reveals that the sediment in KE transfers from nitrate sink to source from north to south. This trend is mainly caused by the variation of primary production and the supplement of active organic matter, which is the energy source for microbes and the potential source for ammonium through remineralization. Overall, our results highlight temperature and ammonium as two limiting factors for deep-ocean benthic N-loss and also exhibit a tight coupling relationship between pelagic primary production and the benthic nitrogen cycle in KE.
Laser-induced breakdown spectroscopy of aqueous silicone rubber in an argon environment
Authors: Deng Yu , Peng Bo , Hao Yuguo , Du Yijun , Zhou Songsong , Gu Chen , Zhou Jun
Published: September 2022

In a high humidity environment, the absorption of water in silicone rubber results in a significant decline or even loss in insulation performance, and the detection of the moisture content of silicone rubber is conducive to timely measuring the water absorption of silicone rubbers. Currently, the moisture content of silicone rubber can only be detected through manual sampling and laboratory analysis, which lack electric field analysis methods. Therefore, this paper proposes using laser-induced breakdown spectroscopy for the rapid qualitative and quantitative analysis of the moisture content of silicone rubber. Experiments were conducted on 50 silicone rubber samples with different moisture contents, with argon gas sprayed onto the sample surfaces to eliminate the interference of H and O elements in the air; a better argon gas flow rate of 3 L/min was determined. The information comprising the intensity and intensity ratio of the elemental spectral lines in the LIBS spectra of silicone rubber with moisture content was analyzed, with the results indicating that H elemental intensity increased as moisture content increased. Compared with the dry silicone rubber, the variation range of H/O and Al/H elements in the samples with different moisture contents was larger. Multivariate analysis was performed using a partial least squares regression model for the aqueous silicone rubber samples, and the model fit was obtained as 0.8088. The model prediction was better for the samples with moisture contents greater than 0.4%. The results indicated that the LIBS technique quantitatively analyzes the moisture content of silicone rubber, which is significant for improving the operation and maintenance of electric transmission lines.
Whole genome sequencing analysis of SARS-CoV-2 from Malaysia: From alpha to Omicron
Authors: Yu Choo Yee , Wong Sie Yeng , Liew Nancy Woan Charn , Joseph Narcisse , Zakaria Zunita , Nurulfiza Isa , Soe Hui Jen , Kairon Rachna , Amin-Nordin Syafinaz , Chee Hui Yee
Published: September 2022

Countries around the world are gearing for the transition of the coronavirus disease 2019 (COVID-19) from pandemic to endemic phase but the emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants could lead to a prolonged pandemic. SARS-CoV-2 has continued to evolve as it optimizes its adaptation to the human host and the successive waves of COVID-19 have been linked to the explosion of particular variant of concern. As the genetic diversity and epidemiological landscape of SARS-CoV-2 differ from country to country, this study aims to provide insights into the variants that are circulating in Malaysia. Whole genome sequencing was performed for 204 SARS-CoV-2 from COVID-19 cases and an additional 18,667 SARS-CoV-2 genome sequences were retrieved from the GISAID EpiCoV database for clade, lineage and genetic variation analyses. Complete genome sequences with high coverage were then used for phylogeny investigation and the resulting phylogenetic tree was constructed from 8,716 sequences. We found that the different waves of COVID-19 in Malaysia were dominated by different clades with the L and O clade for first and second wave, respectively, whereas the progressive replacement by G, GH, and GK of the GRA clade were observed in the subsequence waves. Continuous monitoring of the genetic diversity of SARS-CoV-2 is important to identify the emergence and dominance of new variant in different locality so that the appropriate countermeasures can be taken to effectively contain the spread of SARS-CoV-2.
Case report: Treatment of long COVID with a SARS-CoV-2 antiviral and IL-6 blockade in a patient with rheumatoid arthritis and SARS-CoV-2 antigen persistence
Authors: Visvabharathy Lavanya , Orban Zachary S. , Koralnik Igor J.
Published: September 2022

Introduction

Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC) in ∼30% of all infected individuals. Here, we present a case of PASC in a patient with rheumatoid arthritis characterized by viral persistence in the nasopharynx for 6 months after acute infection. We demonstrate transient disappearance of antigen persistence and decreased antiviral and autoimmune T cell responses after nirmatrelvir/ritonavir and tocilizumab treatment.

Case presentation

A 37-year-old female with a 7-year history of rheumatoid arthritis enrolled in a COVID-19 research study was found to continuously test SARS-CoV-2 antigen positive in the nasopharynx for 6 months after acute infection. She simultaneously presented with new-onset PASC symptoms including chronic occipital headache and periods of intense fatigue 8 weeks after acute infection. The patient was prescribed nirmatrelvir/ritonavir to treat SARS-CoV-2 persistence at 3.5 months post-acute infection and observed a reduction in PASC symptoms 3 weeks after completing antiviral treatment. After resurgence of PASC symptoms, she stopped treatment with tocilizumab for rheumatoid arthritis to attempt complete SARS-CoV-2 viral clearance. The severity of the patient’s PASC symptoms subsequently increased, and she developed new-onset brain fog in addition to previous symptoms, which resolved after resumption of tocilizumab treatment. Assessment of adaptive immune responses demonstrated that nirmatrelvir/ritonavir and tocilizumab treatment decreased antiviral and autoreactive T cell activation. After resuming tocilizumab treatment, the patient’s PASC symptoms were significantly reduced, but nasopharyngeal antigen positivity remained.

Conclusion

These data suggest that nirmatrelvir/ritonavir should be considered in the treatment of PASC in patients who have SARS-CoV-2 antigen persistence, though care must be taken to monitor the patient for symptom resurgence or viral reactivation. In addition, the IL-6 inhibitor tocilizumab may ameliorate PASC symptoms in patients with persistent headache, fatigue, and brain fog.
A lymph node mediastinal foreign body reaction mimicking nodal metastasis: A case series
Authors: Zuccatosta Lina , Latini Maria Agnese , Mei Federico , Bonifazi Martina , Barisione Emanuela , Salio Mario , Gasparini Stefano , Gonnelli Francesca
Published: September 2022

Introduction

In the last decades, many haemostatic substances included oxidized cellulose topically applied have been used during surgery and their use have become a common practice. Oxidized cellulose (OC) is one of the most used haemostatic substances. However, different studies have shown the persistence of OC deposits after surgical procedures that may simulate recurrent malignancies and abscesses. We present a case series of patients with enlarged on CT and PET-FDG positive lymphadenopathies due to foreign body inflammatory reaction to OC after lung surgery for pulmonary malignancies.

Methods

Retrospective chart review of patients from 2021 to 2022 who underwent EBUS-TBNA for the characterization of hilar and/or mediastinal lymphadenopathies and a histopathological diagnosis of foreign body inflammatory reaction to OC.

Results

Eightpatients were referred to “Ospedali Riuniti di Ancona” (n= 7) and “Ospedale San Martino” (Genoa) (n= 1) Interventional Pulmonology Units for the characterization of hilar and/or mediastinal lymphadenopathies. All the evaluated patients underwent surgical procedures for lung cancers within the previous 12 months. EBUS-TBNA was performed in all the patients to rule out nodal metastasis. The cyto-pathological evaluation revealed amorphous acellular eosinofilic material surrounded by inflammatory reaction. As no other apparent causes might explain this finding and considering the temporal relationship between the lymphadenopathy and the lung surgery, foreign body inflammatory reaction to OC is the most likely cause of the phenomenon.

Conclusion

In patients who underwent surgery for lung cancer, especially within few months, the development of lymph node foreign body reaction due to surgical material retention should always be considered.
Association between fat mass and obesity-related variant and osteoarthritis risk: Integrated meta-analysis with bioinformatics
Authors: Zhao Kun , Nie Liuyan , Chin Grace Min Jun , Ye Xiangming , Sun Peng
Published: September 2022

Objective

The association of fat mass and obesity-related (FTO) gene with osteoarthritis (OA) risk has been investigated in multiple genome-wide association studies but showed inconsistent results. Our study aimed to assess FTO expression in different OA sequencing datasets and to meta-analyze whether FTO polymorphism was associated with the risk of osteoarthritis.

Method

Gene expression profiles were obtained from ArrayExpress, Gene Expression Omnibus (GEO), and BioProject databases. Three electronic databases including PubMed and EMBASE were systematically retrieved to identify articles exploring the association between FTO polymorphisms and OA risk published before September 2022. Summary odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were calculated to perform the result. Stata software was utilized to conduct analyses on predetermined ethnicity and gender subgroups and sensitivity.

Results

FTO gene was differentially expressed in the datasets from the UK. This systematic review and meta-analysis encompasses eight studies that revealed a significant association between FTO polymorphisms and OA risk [OR 1.07, 95% CI (1.03, 1.11), P < 0.001] in the overall population. In subgroup analysis, a marked association was observed in European Caucasian [OR 1.08, 95% CI (1.04–1.12), P < 0.001] and North American Caucasian with the Asian subgroups [OR 0.98, 95% CI (0.83–1. 6), P = 0.83] as an exception. Among the studies, four of them demonstrated attenuation in their OA risk after body mass index (BMI) adjustment in Caucasian populations.

Conclusion

FTO significant differential expression was associated with the increased risk of OA in Caucasian populations. Nevertheless, the causality between FTO polymorphisms and OA risk remains largely elusive. Hence, further studies with larger sample size are necessary to validate whether FTO gene polymorphism contributes to OA susceptibility.
Clinicopathological Implications of the BRAFV600E Mutation in Papillary Thyroid Carcinoma of Ukrainian Patients Exposed to the Chernobyl Radiation in Childhood: A Study for 30 Years After the Accident
Authors: Zurnadzhy Liudmyla , Bogdanova Tetiana , Rogounovitch Tatiana I. , Ito Masahiro , Tronko Mykola , Yamashita Shunichi , Mitsutake Norisato , Bolgov Michael , Chernyshov Serhii , Masiuk Sergii , Saenko Vladimir A.
Published: September 2022

With time after the Chernobyl accident, the number of papillary thyroid carcinomas (PTCs) driven by the BRAFV600E oncoprotein is growing in patients exposed to radiation at a young age. Clinicopathological associations of BRAFV600E in PTCs from patients with internal radiation history have not been sufficiently studied so far. This work analyzes the structural characteristics, proliferative activity, invasive features, clinical information, and dosimetric data in the BRAFV600E-positive and BRAFV600E-negative PTCs from the Ukrainian patients exposed to Chernobyl radiation and treated over 30 years after the accident. The study included 428 PTCs from patients aged 4–49 years at surgery who lived in the six northern regions of Ukraine most contaminated by 131I, were ≤18 years of age at the time of exposure, and were operated on from 1990 to 2017. Immunohistochemical staining for BRAFV600E was performed with the VE1 antibody. The probability of causation (POC) of a tumor due to radiation was determined using an interactive online NIH/NCI software. BRAFV600E was detected in 136/428 (31.8%) PTCs. In comparison with the BRAFV600E-negative PTCs, the BRAFV600E-positivity was associated with older patient age at the accident and at surgery, a longer period of latency, and lower POC. The BRAFV600E-positive PTCs were characterized by smaller tumor size, higher Ki67 labeling index, more frequent oncocytic changes, multifocality, and dominant papillary growth pattern. Tumor invasive features were less frequent in the BRAFV600E-positive PTCs and did not change with POC level. Despite a less aggressive tumor phenotype, BRAFV600E was a risk factor for recurrence, namely radioiodine-refractory (RAI-R) recurrent metastases. Multivariate models of RAI-R included BRAFV600E and/or histopathological parameters closely correlating with BRAFV600E such as tumor size, multifocality, dominant papillary growth pattern, or oncocytic changes. Thus, the BRAFV600E-positive PTCs from patients from a high-risk group for radiogenic thyroid cancer diagnosed in the 30 years after the Chernobyl accident did not display higher invasiveness regardless of POC level, but in view of the prognostic impact of this genetic alteration, knowledge of the BRAF status may be beneficial for middle-aged patients with radiogenic PTC considered for RAI therapy, and suggests more careful follow-up of patients with the BRAFV600E-positive tumors.
Association between inflammatory cytokines in the aqueous humor and hyperreflective foci on optical coherence tomography in patients with neovascular age-related macular degeneration and polypoidal choroidal vasculopathy
Authors: Mao Jianbo , Chen Nuo , Zhang Shian , Fang Yuyan , Zheng Zicheng , Wu Sulan , Ye Xin , Chen Yijing , Chen Yiqi , Shen Lijun
Published: September 2022

Purpose

To investigate the associations between cytokine levels in the aqueous humor (AH) and hyperreflective foci (HF) on spectral-domain optical coherence tomography (SD-OCT) in neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV).

Methods

The prospective study included 63 eyes with nAMD, 44 with PCV, and 43 with cataracts (Controls). AH samples were obtained before anti-vascular endothelial growth factor (VEGF) therapy or cataract surgery. Cytokines interleukin 6 (IL-6), IL-8, IL-10, interferon-inducible protein 10 (IP-10), monocyte chemotactic protein 1 (MCP-1), and VEGF were measured by multiplex bead assay. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and the number of HF were evaluated at baseline and 1 month after anti-VEGF treatment.

Results

No significances difference in IL-6 and IL-8 levels were noted among the three groups (P = 0.370 and P = 0.067). VEGF, IP-10, and IL-10 levels were significantly higher in nAMD and PCV groups than in Controls (all P < 0.05). In nAMD, HF was positively correlated with VEGF (rs = 0.300, P = 0.025) and in eyes with HF group, VEGF and IL-10 were significantly higher than those without HF (P = 0.008 and P = 0.022). In PCV, no correlation was observed between HF and cytokines (all P > 0.05). After anti-VEGF treatment, patients with HF in nAMD and PCV were predisposed to worse visual outcomes (P = 0.022 and P = 0.015) and a significantly greater reduction in CMT (P = 0.001 and P = 0.057). And nAMD patients with HF were more sensitive to anti-VEGF treatment than those without HF (P = 0.029).

Conclusions

In the nAMD group, HF was positively correlated with VEGF. Patients in nAMD with HF had elevated levels of VEGF and IL-10 and responded favorably to anti-VEGF. HF might serve as an inflammatory biomarker and a predictive factor for therapeutic efficacy in patients with nAMD.
Causal association of epigenetic aging and COVID-19 severity and susceptibility: A bidirectional Mendelian randomization study
Authors: Xu Wenchang , Zhang Fengjun , Shi Yingzhou , Chen Yuanzhen , Shi Bin , Yu Gongchang
Published: September 2022

Observational data from China, the United States, France, and Italy suggest that chronological age is an adverse COVID-19 outcome risk factor, with older patients having a higher severity and mortality rate than younger patients. Most studies have gotten the same view. However, the role of aging in COVID-19 adverse effects is unclear. To more accurately assess the effect of aging on adverse COVID-19, we conducted this bidirectional Mendelian randomization (MR) study. Epigenetic clocks and telomere length were used as biological indicators of aging. Data on epigenetic age (PhenoAge, GrimAge, Intrinsic HorvathAge, and HannumAge) were derived from an analysis of biological aging based on genome-wide association studies (GWAS) data. The telomere length data are derived from GWAS and the susceptibility and severity data are derived from the COVID-19 Host Genetics Initiative (HGI). Firstly, epigenetic age and telomere length were used as exposures, and following a screen for appropriate instrumental variables, we used random-effects inverse variance weighting (IVW) for the main analysis, and combined it with other analysis methods (e.g., MR Egger, Weighted median, simple mode, Weighted mode) and multiple sensitivity analysis (heterogeneity analysis, horizontal multiplicity analysis, “leave-one-out” analysis). For reducing false-positive rates, Bonferroni corrected significance thresholds were used. A reverse Mendelian randomization analysis was subsequently performed with COVID-19 susceptibility and severity as the exposure. The results of the MR analysis showed no significant differences in susceptibility to aging and COVID-19. It might suggest that aging is not a risk factor for COVID-19 infection (P-values are in the range of 0.05–0.94). According to the results of our analysis, we found that aging was not a risk factor for the increased severity of COVID-19 (P > 0.05). However, severe COVID-19 can cause telomere lengths to become shorter (beta = −0.01; se = 0.01; P = 0.02779). In addition to this, severe COVID-19 infection can slow the acceleration of the epigenetic clock “GrimAge” (beta = −0.24, se = 0.07, P = 0.00122), which may be related to the closely correlation of rs35081325 and COVID-19 severity. Our study provides partial evidence for the causal effects of aging on the susceptibility and severity of COVID-19.
Transfer learning approach based on computed tomography images for predicting late xerostomia after radiotherapy in patients with oropharyngeal cancer
Authors: Fanizzi Annarita , Scognamillo Giovanni , Nestola Alessandra , Bambace Santa , Bove Samantha , Comes Maria Colomba , Cristofaro Cristian , Didonna Vittorio , Di Rito Alessia , Errico Angelo , Palermo Loredana , Tamborra Pasquale , Troiano Michele , Parisi Salvatore , Villani Rossella , Zito Alfredo , Lioce Marco , Massafra Raffaella
Published: September 2022

Background and purpose

Although the latest breakthroughs in radiotherapy (RT) techniques have led to a decrease in adverse event rates, these techniques are still associated with substantial toxicity, including xerostomia. Imaging biomarkers could be useful to predict the toxicity risk related to each individual patient. Our preliminary work aims to develop a radiomic-based support tool exploiting pre-treatment CT images to predict late xerostomia risk in 3 months after RT in patients with oropharyngeal cancer (OPC).

Materials and methods

We performed a multicenter data collection. We enrolled 61 patients referred to three care centers in Apulia, Italy, out of which 22 patients experienced at least mild xerostomia 3 months after the end of the RT cycle. Pre-treatment CT images, clinical and dose features, and alcohol-smoking habits were collected. We proposed a transfer learning approach to extract quantitative imaging features from CT images by means of a pre-trained convolutional neural network (CNN) architecture. An optimal feature subset was then identified to train an SVM classifier. To evaluate the robustness of the proposed model with respect to different manual contouring practices on CTs, we repeated the same image analysis pipeline on “fake” parotid contours.

Results

The best performances were achieved by the model exploiting the radiomic features alone. On the independent test, the model reached median AUC, accuracy, sensitivity, and specificity values of 81.17, 83.33, 71.43, and 90.91%, respectively. The model was robust with respect to diverse manual parotid contouring procedures.

Conclusion

Radiomic analysis could help to develop a valid support tool for clinicians in planning radiotherapy treatment, by providing a risk score of the toxicity development for each individual patient, thus improving the quality of life of the same patient, without compromising patient care.
Body shape and risk of glaucoma: A Mendelian randomization
Authors: Yuan Ruolan , Liu Kangcheng , Cai Yingjun , He Fei , Xiao Xiaoxiong , Zou Jing
Published: September 2022

Background

Body size (BS) is one of the risk factors for the development of many clinical diseases, but the relationship between BS and glaucoma is controversial. Herein, we try to use Mendelian randomization (MR) method to study BS causal association with glaucoma risk from the genetic level.

Methods

The Body Size was determined through anthropometric traits (ATs), such as body mass index (BMI), waist-to-hip ratio adjusted by body mass index (WHRadjBMI), waist-to-hip ratio (WHR), and waist circumference (WC). Association of single nucleotide polymorphisms (SNPs) with each AT and glaucoma were determined individually from the aggregated data of the Genetic Investigation of Anthropometric Traits (GIANT) consortium and the FinnGen study summary data (8,591 cases with glaucoma and 210,201 controls). To explore the role of BS and glaucoma, a two-sample MR analysis was performed on genome-wide association study (GWAS) data. Besides, three MR methods [inverse variance weighted (IVW), Weighted median, and MR-Egger regression] were used to get the whole causal estimate for multiple instrumental SNPs.

Results

BMI (OR = 1.20; 95% CI = 1.02–1.41; P = 0.03) and WC (OR = 1.32; 95% CI =1.04–1.69; P = 0.03) were associated with a risk of glaucoma. Besides, genetically predicted WHRadjBMI (OR = 1.10; 95% CI = 0.88–1.35; P = 0.43) and WHR (OR = 1.22; 95% CI = 0.93–1,572; P = 0.14) were not associated with glaucoma. No heterogeneity and directional pleiotropy were detected.

Conclusion

The data of this study revealed that increased BMI and WC are potential risk factors for glaucoma, and WHRadjBMI and WHR are not associated with the occurrence of glaucoma.
Simulated seasonal diets alter yak rumen microbiota structure and metabolic function
Authors: Yang Xugang , Fan Xueni , Jiang Hui , Zhang Qiang , Basangwangdui  , Zhang Qunying , Dang Siqi , Long Ruijun , Huang Xiaodan
Published: September 2022

Yak is the only ruminant on the Qinghai-Tibetan Plateau that grazes year-round. Although previous research has shown that yak rumen microbiota fluctuates in robust patterns with seasonal foraging, it remains unclear whether these dynamic shifts are driven by changes in environment or nutrient availability. The study examines the response of yak rumen microbiota (bacteria, fungi, and archaea) to simulated seasonal diets, excluding the contribution of environmental factors. A total of 18 adult male yaks were randomly divided into three groups, including a nutrition stress group (NSG, simulating winter pasture), a grazing simulation group (GSG, simulating warm season pasture), and a supplementation group (SG, simulating winter pasture supplemented with feed concentrates). Volatile fatty acids (VFAs) profiling showed that ruminal acetate, propionate and total VFA contents were significantly higher (p < 0.05) in GSG rumen. Metagenomic analysis showed that Bacteroidetes (53.9%) and Firmicutes (37.1%) were the dominant bacterial phyla in yak rumen across dietary treatments. In GSG samples, Actinobacteriota, Succinivibrionaceae_UCG-002, and Ruminococcus albus were the most abundant, while Bacteroides was significantly more abundant in NSG samples (p < 0.05) than that in GSG. The known fiber-degrading fungus, Neocallimastix, was significantly more abundant in NSG and SG samples, while Cyllamyces were more prevalent in NSG rumen than in the SG rumen. These findings imply that a diverse consortium of microbes may cooperate in response to fluctuating nutrient availability, with depletion of known rumen taxa under nutrient deficiency. Archaeal community composition showed less variation between treatments than bacterial and fungal communities. Additionally, Orpinomyces was significantly positively correlated with acetate levels, both of which are prevalent in GSG compared with other groups. Correlation analysis between microbial taxa and VFA production or between specific rumen microbes further illustrated a collective response to nutrient availability by gut microbiota and rumen VFA metabolism. PICRUSt and FUNGuild functional prediction analysis indicated fluctuation response of the function of microbial communities among groups. These results provide a framework for understanding how microbiota participate in seasonal adaptations to forage availability in high-altitude ruminants, and form a basis for future development of probiotic supplements to enhance nutrient utilization in livestock.
Distribution pattern of endophytic bacteria and fungi in tea plants
Authors: Lin Haiyan , Liu Changwei , Peng Zhong , Tan Bin , Wang Kunbo , Liu Zhonghua
Published: September 2022

Endophytes are critical for plant growth and health. Tea is an economically important crop in China. However, little is known about the distribution pattern and potential functions of endophytic communities in tea trees. In this study, two genotypes (BXZ and MF) cultivated under the same conditions were selected, and endophytic bacteria and fungi were analyzed through 16S rRNA and ITS high-throughput sequencing technologies, respectively. For endophytic bacteria, root tissues harbored the most diverse endophytes, followed by stems and old leaves, and new leaves possessed the lowest diversity. In contrast, old leave tissues harbored more diverse endophytic fungi than did root and stem tissues. Most of the dominant endophytes showed obvious cultivar and tissue preferences. Tissue type played a more important role in shaping community structure than did cultivar. Nevertheless, some endophytic bacterial groups, which mainly affiliated to Chryseobacterium, Sphingomonas, Rhizobium, Morganella, Methylobacterium and Comamonadaceae, could parasitize different tissues, and the average relative abundance of endophytic bacteria was as high as 72.57%. Some endophytic fungal populations, such as Colletotrichum, Uwebraunia, Cladosporium, and Devriesia, could also parasitize tea, and the relative abundance accounted for approximately 25.70–97.26%. The cooperative relationship between endophytic bacteria and fungi in the new leaves was stronger than that in the old leaves, which can better participate in the metabolism of tea material.
Seagrass Colonization Alters Diversity, Abundance, Taxonomic, and Functional Community Structure of Benthic Microbial Eukaryotes
Authors: Pan Ying , Li Guihao , Su Lei , Zheng Pengfei , Wang Yaping , Shen Zhuo , Chen Zigui , Han Qiuying , Gong Jun
Published: September 2022

Seagrass form high productive ecosystems in coastal environments. However, the effects of these coastal plants on the structure and function of the belowground eukaryotic microbiome remain elusive. In this study, we characterized the community of microbial eukaryotes (microeukaryotes) in both vegetated and unvegetated sediments using 18S rRNA gene amplicon sequencing and quantitative PCR. Analysis of sequencing data showed that the eelgrass (Zostera marina) colonization decreased the alpha diversity indices of benthic microeukaryotes. Apicomplexa represented an average of 83% of reads across all samples, with a higher proportion at the vegetated sites. The taxonomic community structure was significantly different between these two types of sediments, for which the concentration of NH4+ in sediment porewater and salinity could account. Phylogenetic analyses of long 18S rRNA genes (around 1,030 bp) indicated these apicomplexan parasites are closely related to gregarine Lecudina polymorpha. Determination of 18S rRNA gene abundances provided evidence that the eelgrass markedly promoted the biomass of the gregarine and all microeukaryotes in the seagrass-colonized sediments and confirmed that the gregarine was hosted by a polychaete species. Significantly higher gene abundances of heterotrophs and mixotrophs were found at the vegetated sites, which could be explained by the finer sediments and short supply of dissolved inorganic nitrogen, respectively. The pigmented protists were more abundant in 18S rRNA gene copies at the lower and higher pH levels than at the intermediate. Nevertheless, the fractions of heterotrophs and phototrophs in the community were significantly related to porewater N:P ratio. These results indicate that seagrass colonization significantly induces an increase in overall biomass and a decrease in diversity of benthic microeukaryotes, making them more heterotrophic. This study also highlights that the hotspot of eukaryotic parasites could be linked with the high productivity of a natural ecosystem.