bluuebunny/crossref_metadata_2025 huggingface dataset:
Zygmunt Bauman Sosyolojisi: Akışkan Modernite Özgür Olduğunu Zanneden Köleler mi Üretiyor?
Authors: ALPDOĞAN Fatih Furkan
Published: April 2023

Zygmunt Bauman çağdaş sosyoloji literatürünün önde gelen isimlerinden biridir. Bu çalışmada Bauman’ın modern dünyaya yönelik görüşleri esas alınmıştır. Bauman moderniteye dair görüşlerini katı ve akışkan olarak iki ayrı durum üzerine temellendirmiştir. O, katı modernitenin kutsanan yönlerine eleştirel bir bakış açısı getirirken, akışkan modern durumda değişen tek şeyin yapısal unsurlar olduğuna dikkat çekmiştir. Bu çalışmanın amacı sosyolojinin önemli bir boyutunu oluşturan toplumsal olanı “özgürleştirme” misyonuna katkı sağlamaktır. Bu ana hedef doğrultusunda akışkan modern dünyanın bireyi nasıl baskıladığına ve toplumsal alanı gözetlerken katı moderniteden farklı olarak hangi yöntemlere başvurduğuna dikkat çekilmiştir. Böylelikle makalenin asıl sorguladığı konu olan güncel gözetimin ve sosyal baskının doğru şekilde anlaşılabilmesi için akışkan modern köleliğin, tüketimin, küresel siyasetin ve kapitalizmin ontolojik ve epistemolojik boyutlarına vurgu yapılmıştır. Bu noktada akışkan modern dünyada akışkan köleliğin eski köle prangalarından farklı olarak, bireylerin zihinlerine nakşettiği yeni prangalara dikkat çekilmiştir. Ayrıca katı modern dünyadan miras kalan köle prangalarının farklı şekillerde devam edip etmediği sorgulanmıştır.
THE DOUBLE CHARGE ON THE SURFACE OF THE SUN
Authors: Svanbayev Yeldos
Published: April 2023

We propose a model for the double charged layer on the surface of the Sun's spicules. Thermal energy of the star leads to the emission of electrons, and strong gravity leads to the retention of ions and formation of a self-regulating positive charge on the surface of the star. The charge value is affected by parameters of the star: mass, radius, temperature, rotation speed, and composition. The positive surface charge is shielded by an electrons from plasma cloud and a double charged layer is formed. Electrons are accelerated in the Coulomb field and ionize atoms on the spicule surface. Ions are accelerated by the binary field and form a high-temperature corona and a fast solar wind. The hot temperature of corona of the star, the multi charged ions, the EUF and X-ray radiation, and the solar wind are all due to the electric double layer on the star's surface.
The effect of terminal impedance on aortic morphology and hemodynamics: an in vitro phantom study using flow field visualization
Authors: Chen Huimin , Wang Wenjun , Liu Dengji , Cao Zhen , Yang Yi , He Ying , Chi Qingzhuo
Published: April 2023

To investigate the risk factors for aortic dissection tearing, we fabricated a simplified patient-specific aortic silicone phantom using the brush-spin-coating method. The aortic phantom only includes the aorta from the ascending aorta to the descending aorta, without other branches. We designed two experiments to investigate the alteration of aortic morphology and intravascular hemodynamics using the particle image velocimetry method. The results revealed dilation and elongation of the aortic phantom, especially the ascending aorta, after the phantom’s terminal resistance was increased. Additionally, the particle image velocimetry results demonstrated an increased vortex region, which caused the inner side of the aortic wall to become scoured by blood. This study suggests that the deformation of the inner side aortic wall and the change in hemodynamics in response to the increased terminal resistance may be a risk factor for aortic tearing and should be monitored.
Anoikis-related genes combined with single cell sequencing: Insights into model specification of lung adenocarcinoma and applicability for prognosis and therapy
Authors: Zhou Yiyi , Hu Zhenli
Published: April 2023

Background: Anoikis has therapeutic potential against different malignancies including lung adenocarcinoma. This study used anoikis and bioinformatics to construct a prognostic model for lung adenocarcinoma and explore new therapeutic strategies.

Methods: Several bioinformatic algorithms (co-expression analysis, univariate Cox analysis, multivariate Cox analysis, and cross-validation) were used to screen anoikis-related genes (ARGs) to construct a risk model. Lung adenocarcinoma patients were divided into training and testing groups at a ratio of 1:1. The prognostic model was validated by risk score comparison between high- and low-risk groups using receiver operating characteristic curve (ROC), nomograms, independent prognostic analysis and principal component analysis. In addition, two anoikis-related genes patterns were classified utilizing consensus clustering method and were compared with each other in survival time, immune microenvironment, and regulation in pathway. Single cell sequencing was applied to analyze anoikis-related genes constructed the model.

Results: This study demonstrated the feasibility of the model based on seven anoikis-related genes, as well as identifying axitinib, nibtinib and sorafenib as potential therapeutic strategies for LUAD. Risk score based on this model had could be used as an independent prognostic factor for lung adenocarcinoma (HR > 1; p < 0.001) and had the highest accuracy to predict survival compared with the clinical characteristics. Single cell sequencing analysis discovered Keratin 14 (KRT14, one of the seven anoikis-related genes) was mainly expressed in malignant cells in various cancers.

Conclusion: We identified seven anoikis-related genes and constructed an accurate risk model based on bioinformatics analysis that can be used for prognostic prediction and for the design of therapeutic strategies in clinical practice.
Working a second job: Cell adhesion proteins that moonlight in the nucleus
Authors: Haage Amanda , Dhasarathy Archana
Published: April 2023

Cells are adept at sensing changes in their environment, transmitting signals internally to coordinate responses to external stimuli, and thereby influencing adaptive changes in cell states and behavior. Often, this response involves modulation of gene expression in the nucleus, which is seen largely as a physically separated process from the rest of the cell. Mechanosensing, whereby a cell senses physical stimuli, and integrates and converts these inputs into downstream responses including signaling cascades and gene regulatory changes, involves the participation of several macromolecular structures. Of note, the extracellular matrix (ECM) and its constituent macromolecules comprise an essential part of the cellular microenvironment, allowing cells to interact with each other, and providing both structural and biochemical stimuli sensed by adhesion transmembrane receptors. This highway of information between the ECM, cell adhesion proteins, and the cytoskeleton regulates cellular behavior, the disruption of which results in disease. Emerging evidence suggests a more direct role for some of these adhesion proteins in chromatin structure and gene regulation, RNA maturation and other non-canonical functions. While many of these discoveries were previously limited to observations of cytoplasmic-nuclear transport, recent advances in microscopy, and biochemical, proteomic and genomic technologies have begun to significantly enhance our understanding of the impact of nuclear localization of these proteins. This review will briefly cover known cell adhesion proteins that migrate to the nucleus, and their downstream functions. We will outline recent advances in this very exciting yet still emerging field, with impact ranging from basic biology to disease states like cancer.
The function and regulation of heat shock transcription factor in Cryptococcus
Authors: Suo Chenhao , Gao Yiru , Ding Chen , Sun Tianshu
Published: April 2023

Cryptococcus species are opportunistic human fungal pathogens. Survival in a hostile environment, such as the elevated body temperatures of transmitting animals and humans, is crucial for Cryptococcus infection. Numerous intriguing investigations have shown that the Hsf family of thermotolerance transcription regulators plays a crucial role in the pathogen-host axis of Cryptococcus. Although Hsf1 is known to be a master regulator of the heat shock response through the activation of gene expression of heat shock proteins (Hsps). Hsf1 and other Hsfs are multifaceted transcription regulators that regulate the expression of genes involved in protein chaperones, metabolism, cell signal transduction, and the electron transfer chain. In Saccharomyces cerevisiae, a model organism, Hsf1’s working mechanism has been intensively examined. Nonetheless, the link between Hsfs and Cryptococcus pathogenicity remains poorly understood. This review will focus on the transcriptional regulation of Hsf function in Cryptococcus, as well as potential antifungal treatments targeting Hsf proteins.
Looking towards the future: patient-specific computational modeling to optimize outcomes for transcatheter mitral valve repair
Authors: Wong Paul , Wisneski Andrew D. , Sandhu Amitoj , Wang Zhongjie , Mahadevan Vaikom S. , Nguyen Tom C. , Guccione Julius M.
Published: April 2023

Severe mitral valve regurgitation (MR) is a heart valve disease that progresses to end-stage congestive heart failure and death if left untreated. Surgical repair or replacement of the mitral valve (MV) remains the gold standard for treatment of severe MR, with repair techniques aiming to restore the native geometry of the MV. However, patients with extensive co-morbidities may be ineligible for surgical intervention. With the emergence of transcatheter MV repair (TMVR) treatment paradigms for MR will evolve. The longer-term outcomes of TMVR and its effectiveness compared to surgical repair remain unknown given the differing patient eligibility for either treatment at this time. Advances in computational modeling will elucidate answers to these questions, employing techniques such as finite element method and fluid structure interactions. Use of clinical imaging will permit patient-specific MV models to be created with high accuracy and replicate MV pathophysiology. It is anticipated that TMVR technology will gradually expand to treat lower-risk patient groups, thus pre-procedural computational modeling will play a crucial role guiding clinicians towards the optimal intervention. Additionally, concerted efforts to create MV models will establish atlases of pathologies and biomechanics profiles which could delineate which patient populations would best benefit from specific surgical vs. TMVR options. In this review, we describe recent literature on MV computational modeling, its relevance to MV repair techniques, and future directions for translational application of computational modeling for treatment of MR.
Retrospective content analysis of consumer product reviews related to chronic pain
Authors: Fan Jungwei W. , Wang Wanjing , Huang Ming , Liu Hongfang , Hooten W. Michael
Published: April 2023

Chronic pain (CP) lasts for more than 3 months, causing prolonged physical and mental burdens to patients. According to the US Centers for Disease Control and Prevention, CP contributes to more than 500 billion US dollars yearly in direct medical cost plus the associated productivity loss. CP is complex in etiology and can occur anywhere in the body, making it difficult to treat and manage. There is a pressing need for research to better summarize the common health issues faced by consumers living with CP and their experience in accessing over-the-counter analgesics or therapeutic devices. Modern online shopping platforms offer a broad array of opportunities for the secondary use of consumer-generated data in CP research. In this study, we performed an exploratory data mining study that analyzed CP-related Amazon product reviews. Our descriptive analyses characterized the review language, the reviewed products, the representative topics, and the network of comorbidities mentioned in the reviews. The results indicated that most of the reviews were concise yet rich in terms of representing the various health issues faced by people with CP. Despite the noise in the online reviews, we see potential in leveraging the data to capture certain consumer-reported outcomes or to identify shortcomings of the available products.
Impact of ENSO events on meteorological drought in the Weihe River basin, China
Authors: Fan Jingjing , Wei Shibo , Liu Dengfeng , Qin Tianling , Xu Fanfan , Wu Chenyu , Liu Guanpeng , Cheng Yao
Published: April 2023

El Niño–Southern Oscillation (ENSO) events influence elements of the terrestrial water cycle such as precipitation and temperature, which in turn have a significant impact on drought. This work assessed the impact of El Niño and La Niña on droughts from 1970 to 2020 in the Weihe River basin (WRB) in China. This study used a standardized precipitation index (SPI) to characterize meteorological drought. The regional drought response to extreme events in El Niño/La Niña was analyzed using principal component analysis (PCA), Wilcoxon and Mann–Whitney tests, and other methods. The results showed that, based on PCA, the WRB is divided into two regions, with the northwest region (67%) comprising more area than the southeast region (33%). El Niño/La Niña significantly impacted drought in the WRB. Droughts mainly occurred in the El Niño year and the year following La Niña. El Niño had the highest number of drought years (44%), followed by the year following La Niña (43%). The number of droughts was lowest in the year following El Niño (22%). At 1-, 3-, and 6-month timescales, significant droughts mainly occurred from July to December in El Niño years and the summer following La Niña. On a 12-month timescale, significant droughts mainly occurred from January to April in El Niño years, while no droughts occurred in La Niña years. The longer the timescale of the SPI, the more months of significant drought in El Niño years; however, the intensity of drought in the basin was reduced. In the year following La Niña, summer droughts intensified on a 6-month timescale compared to a 3-month timescale. El Niño and La Niña had greater impacts on the drought index in the northwest region of the WRB. In the northwest region, 60% of the months showed significant drought, compared to only 2% of the months in the southeast region. The drought intensity was higher in the northwest region. The results of this study provide a reference for drought management and early warning systems in the WRB and support solutions to water shortage.
The impact of product and process innovation on abandoning fossil fuel energy consumption in low and middle income countries: consent towards carbon neutrality
Authors: Taqqadus Hafsa , Khan Alam , Khan Dilawar , Magda Robert
Published: April 2023

The study used a sample of 43 low and middle-income countries for the time span of 14 years, i.e., from 2005 to 2018 with the objective to analyze the global fossil fuel market. The novelty of the study lies in its variable product and process innovation, study sample as well as the methodology adopted by the System GMM model. The fossil fuels demand in terms of Domestic material consumption of fossil fuel is regressed against 4 Energy and innovation, social and economic variables. The study employed System GMM model for estimation of results and FMOLS for robustness check. The results reveal that estimates for lag fossil fuels consumption, fossil fuel price and GDP are statistically significant and positive while estimates for patents are negative. The study suggests that low and middle income countries’ Government should focus on product and process innovation as a critical element while structuring their policy for climate change mitigation.
Asymmetric warming among elevations may homogenize plant α-diversity and aboveground net primary production of alpine grasslands
Authors: Han Fusong , Yu Chengqun , Fu Gang
Published: April 2023

It is well known that asymmetric warming among elevations (i.e., warming magnitude increases with increasing elevation) will weaken the difference of air temperature among elevations. However, it remains controversial on whether asymmetric warming among elevations can homogenize plant α-diversity and above-ground net primary production (ANPP) in alpine regions. In the present study, we conducted an experiment of asymmetric warming among elevations in alpine grasslands, Northern Tibet since 2010. There were four experiment treatments, including a treatment under natural conditions at elevation 4,313 m (C4313), a treatment under natural conditions at elevation 4,513 m (C4513), a treatment under warming conditions at elevation 4,513 m (W4513) and a treatment under warming conditions at elevation 4,693 m (W4693). We investigated ANPP, taxonomic α-diversity (i.e., species richness, Shannon, Simpson and Pielou) and phylogenetic α-diversity (mean nearest taxon distance, MNTD; phylogenetic diversity, PD) in 2011–2019. There were no significant differences of mean air temperature between C4313 and W4513, or between C4513 and W4693 in 2011–2019, indicating the differences of air temperature were eliminated among elevations. Then we found that the differences of plant α-diversity and ANPP were also eliminated among elevations: (1) there were no significant differences of ANPP, Pielou and MNTD between C4313 and W4513, or between C4513 and W4693 in 2011–2019. (2) There were also no significant differences of mean species richness, Shannon and Simpson between C4513 and W4693 in 2011–2019. (3) There were also no significant differences of ANPP, species richness, Shannon, Simpson, Pielou, PD and MNTD between C4313 and W4513, or C4513 and W4693 in 2019. Therefore, asymmetric warming among elevations may homogenize plant α-diversity and aboveground net primary production in alpine grasslands, at least in Northern Tibet.
Role of dispersal in the altitudinal migration of Pinus hartwegii and Abies religiosa in mountain systems
Authors: Guzmán-Vázquez Itzel , León-Cruz José Francisco , Galicia Leopoldo
Published: April 2023

Seed long-distance dispersal (LDD) is essential to explain plant migration. However, few studies have addressed the magnitude and frequency of LDD events given the difficulty of measuring them in situ. Computational simulation offers an alternative to the in situ methods. In this study we proposed a simulation model of seed dispersal for two anemochoric conifers, which includes wind patterns, seed and tree traits. We proposed and measured 18 dispersal traits for Abies religiosa and Pinus hartwegii and analyzed variation between traits and species through a principal component analysis. We used the Weather Research and Forecasting (WRF) atmospheric simulation model to obtain wind speed and direction data at the study zone (Iztaccihuatl volcano, central Mexico). We performed linear regression models to simulated seed dispersal events considering horizontal wind speed, seed traits and seed release height, and using a mechanistic model, we integrated vertical wind speed and wind direction. Seeds of both species presented similar morphology but were sorted into two groups. The relationship between wing size and seed weight may be a key element to dispersal, as it influences the interaction of the seed with the wind. Although we expected that P. hartwegii, seed traits and higher distribution would promote more and longer LDD events, A. religiosa presented more and longer LDD. The maximum dispersal distance was 105 m for A. religiosa and 64 m for P. hartwegii. Both species showed differences in dispersal capacity, which may be related to their seed traits. The frequency of LDD events indicates that a low proportion of seeds would travel more than 20 m away from the parent tree. This suggests that, under migration scenarios, new trees movement up would take place gradually.
Disentangling multiproxy temperature reconstructions from the subtropical North Atlantic
Authors: Repschläger Janne , Weinelt Mara , Schneider Ralph , Blanz Thomas , Leduc Guillaume , Schiebel Ralf , Haug Gerald H.
Published: April 2023

Reliable reconstruction of past sea surface temperature (SST) is of prime importance for understanding the Earth’s sensitivity to external forcing. Yet, it remains a major challenge in paleoceanography because comparison between SST estimates from different proxies reveals mismatches and raise the question as to what the contrasting proxies actually record. A better understanding of these mismatches in the light of seasonal occurrence of the proxy bearing organisms (archives) and water mass changes help to assess climate models. Here, we analyze data from the last deglaciation using a sediment core site situated at the northern boundary of the North Atlantic subtropical gyre influenced by fast latitudinal migrations of the subtropical Azores Front (AF) and resulting changes in water masses that may affect the SST records. Differences between the SST estimates from different deglacial SST reconstructions obtained from (1) Mg/Ca in planktic foraminifer tests, (2) alkenone UK′37, and (3) planktic foraminifer assemblages (SIMMAX), are assumed to result from the ecology of the proxy bearing organisms, and are assessed for the impact on different SST reconstructions from local seawater δ18O (δ18Ow) reconstructions. The general trends of SSTs from all four proxies confirm the well-known deglacial succession of warm and cold events. Mismatches between amplitudes of temperature changes are explained by differences in the phenology of the proxy-bearing organisms and local changes in hydrography. The combination of δ18O SST from the three different archives of δ18Ow reconstructions may cause offsets that exceed the climate driven signals.
Decoding the microbial universe with metagenomics: a brief insight
Authors: Chaudhari Hiral G. , Prajapati Shobha , Wardah Zuhour Hussein , Raol Gopal , Prajapati Vimalkumar , Patel Rajesh , Shati Ali A. , Alfaifi Mohammad Y. , Elbehairi Serag Eldin I. , Sayyed R. Z.
Published: April 2023

A major part of any biological system on earth involves microorganisms, of which the majority are yet to be cultured. The conventional methods of culturing microbes have given fruitful outcomes yet have limitations. The curiosity for better understanding has led to the development of culture-independent molecular methods that help push aside the roadblocks of earlier methods. Metagenomics unifies the scientific community in search of a better understanding of the functioning of the ecosystem and its component organisms. This approach has opened a new paradigm in advanced research. It has brought to light the vast diversity and novelty among microbial communities and their genomes. This review focuses on the development of this field over time, the techniques and analysis of data generated through sequencing platforms, and its prominent interpretation and representation.
How autophagy, a potential therapeutic target, regulates intestinal inflammation
Authors: Chen Shuang-Lan , Li Chun-Meng , Li Wei , Liu Qing-Song , Hu Shuang-Yuan , Zhao Mao-Yuan , Hu Dong-Sen , Hao Yan-Wei , Zeng Jin-Hao , Zhang Yi
Published: April 2023

Inflammatory bowel disease (IBD) is a group of disorders that cause chronic inflammation in the intestines, with the primary types including ulcerative colitis and Crohn’s disease. The link between autophagy, a catabolic mechanism in which cells clear protein aggregates and damaged organelles, and intestinal health has been widely studied. Experimental animal studies and human clinical studies have revealed that autophagy is pivotal for intestinal homeostasis maintenance, gut ecology regulation and other aspects. However, few articles have summarized and discussed the pathways by which autophagy improves or exacerbates IBD. Here, we review how autophagy alleviates IBD through the specific genes (e.g., ATG16L1, IRGM, NOD2 and LRRK2), crosstalk of multiple phenotypes with autophagy (e.g., Interaction of autophagy with endoplasmic reticulum stress, intestinal antimicrobial defense and apoptosis) and autophagy-associated signaling pathways. Moreover, we briefly discuss the role of autophagy in colorectal cancer and current status of autophagy-based drug research for IBD. It should be emphasized that autophagy has cell-specific and environment-specific effects on the gut. One of the problems of IBD research is to understand how autophagy plays a role in intestinal tract under specific environmental factors. A better understanding of the mechanism of autophagy in the occurrence and progression of IBD will provide references for the development of therapeutic drugs and disease management for IBD in the future.
Research-based flow cytometry assays for pathogenic assessment in the human B-cell biology of gene variants revealed in the diagnosis of inborn errors of immunity: a Bruton’s tyrosine kinase case-study
Authors: del Pino-Molina L. , Bravo Gallego L. Y. , Soto Serrano Y. , Reche Yebra K. , Marty Lobo J. , González Martínez B. , Bravo García-Morato M. , Rodríguez Pena R. , van der Burg M. , López Granados E.
Published: April 2023

Introduction

Inborn errors of immunity (IEI) are an expanding group of rare diseases whose field has been boosted by next-generation sequencing (NGS), revealing several new entities, accelerating routine diagnoses, expanding the number of atypical presentations and generating uncertainties regarding the pathogenic relevance of several novel variants.

Methods

Research laboratories that diagnose and provide support for IEI require accurate, reproducible and sustainable phenotypic, cellular and molecular functional assays to explore the pathogenic consequences of human leukocyte gene variants and contribute to their assessment. We have implemented a set of advanced flow cytometry-based assays to better dissect human B-cell biology in a translational research laboratory. We illustrate the utility of these techniques for the in-depth characterization of a novel (c.1685G>A, p.R562Q) de novo gene variant predicted as probably pathogenic but with no previous insights into the protein and cellular effects, located in the tyrosine kinase domain of the Bruton’s tyrosine kinase (BTK) gene, in an apparently healthy 14-year-old male patient referred to our clinic for an incidental finding of low immunoglobulin (Ig) M levels with no history of recurrent infections.

Results and discussion

A phenotypic analysis of bone marrow (BM) revealed a slightly high percentage of pre-B-I subset in BM, with no blockage at this stage, as typically observed in classical X-linked agammaglobulinemia (XLA) patients. The phenotypic analysis in peripheral blood also revealed reduced absolute numbers of B cells, all pre-germinal center maturation stages, together with reduced but detectable numbers of different memory and plasma cell isotypes. The R562Q variant allows Btk expression and normal activation of anti-IgM-induced phosphorylation of Y551 but diminished autophosphorylation at Y223 after anti IgM and CXCL12 stimulation. Lastly, we explored the potential impact of the variant protein for downstream Btk signaling in B cells. Within the canonical nuclear factor kappa B (NF-κB) activation pathway, normal IκBα degradation occurs after CD40L stimulation in patient and control cells. In contrast, disturbed IκBα degradation and reduced calcium ion (Ca2+) influx occurs on anti-IgM stimulation in the patient’s B cells, suggesting an enzymatic impairment of the mutated tyrosine kinase domain.
ATRA treatment slowed P-selectin-mediated rolling of flowing HL60 cells in a mechano-chemical-dependent manner
Authors: Dong Xiaoting , Peng Shiping , Ling Yingchen , Huang Bing , Tu Wenjian , Sun Xiaoxi , Li Quhuan , Fang Ying , Wu Jianhua
Published: April 2023

All-trans retinoic acid (ATRA)-induced differentiation of acute promyelocytic leukemia (APL) toward granulocytes may trigger APL differentiation syndrome (DS), but there is less knowledge about the mechano-chemical regulation mechanism of APL DS under the mechano-microenvironment. We found that ATRA-induced changes in proliferation, morphology, and adhesive molecule expression levels were either dose or stimulus time dependent. An optimal ATRA stimulus condition for differentiating HL60 cells toward neutrophils consisted of 1 × 10-6 M dose and 120 h of stimulus time. Under wall shear stresses, catch–slip bond transition governs P-selectin-mediated rolling for neutrophils and untreated or ATRA-treated (1 × 10-6 M, 120 h) HL60 cells. The ATRA stimuli slowed down the rolling of HL60 cells on immobilized P-selectin no matter whether ICAM-1 was engaged. The β2 integrin near the PSGL-1/P-selectin axis would be activated within sub-seconds for each cell group mentioned above, thus contributing to slow rolling. A faster β2 integrin activation rate and the higher expression levels of PSGL-1 and LFA-1 were assigned to induce the over-enhancement of ATRA-treated HL60 adhesion in flow, causing APL DS development. These findings provided an insight into the mechanical–chemical regulation for APL DS development via ATRA treatment of leukemia and a novel therapeutic strategy for APL DS through targeting the relevant adhesion molecules.
Kidney allograft rejection is associated with an imbalance of B cells, regulatory T cells and differentiated CD28-CD8+ T cells: analysis of a cohort of 1095 graft biopsies
Authors: Mai Hoa Le , Degauque Nicolas , Lorent Marine , Rimbert Marie , Renaudin Karine , Danger Richard , Kerleau Clarisse , Tilly Gaelle , Vivet Anaïs , Le Bot Sabine , Delbos Florent , Walencik Alexandre , Giral Magali , Brouard Sophie
Published: April 2023

Introduction

The human immune system contains cells with either effector/memory or regulatory functions. Besides the well-established CD4+CD25hiCD127lo regulatory T cells (Tregs), we and others have shown that B cells can also have regulatory functions since their frequency and number are increased in kidney graft tolerance and B cell depletion as induction therapy may lead to acute rejection. On the other hand, we have shown that CD28-CD8+ T cells represent a subpopulation with potent effector/memory functions. In the current study, we tested the hypothesis that kidney allograft rejection may be linked to an imbalance of effector/memory and regulatory immune cells.

Methods

Based on a large cohort of more than 1000 kidney graft biopsies with concomitant peripheral blood lymphocyte phenotyping, we investigated the association between kidney graft rejection and the percentage and absolute number of circulating B cells, Tregs, as well as the ratio of B cells to CD28-CD8+ T cells and the ratio of CD28-CD8+ T cells to Tregs. Kidney graft biopsies were interpreted according to the Banff classification and divided into 5 biopsies groups: 1) normal/subnormal, 2) interstitial fibrosis and tubular atrophy grade 2/3 (IFTA), 3) antibody-mediated rejection (ABMR), 4) T cell mediated-rejection (TCMR), and 5) borderline rejection. We compared group 1 with the other groups as well as with a combined group 3, 4, and 5 (rejection of all types) using multivariable linear mixed models.

Results and discussion

We found that compared to normal/subnormal biopsies, rejection of all types was marginally associated with a decrease in the percentage of circulating B cells (p=0.06) and significantly associated with an increase in the ratio of CD28-CD8+ T cells to Tregs (p=0.01). Moreover, ABMR, TCMR (p=0.007), and rejection of all types (p=0.0003) were significantly associated with a decrease in the ratio of B cells to CD28-CD8+ T cells compared to normal/subnormal biopsies. Taken together, our results show that kidney allograft rejection is associated with an imbalance between immune cells with effector/memory functions and those with regulatory properties.
Cry1Ba1-mediated toxicity of transgenic Bergera koenigii and Citrus sinensis to the Asian citrus psyllid Diaphorina citri
Authors: Orbović Vladimir , Ravanfar Seyed Ali , Achor Diann S. , Shilts Turksen , Ibanez-Carrasco Freddy , Banerjee Rahul , El-Mohtar Choaa , Stelinski Lukasz L. , Bonning Bryony C.
Published: April 2023

The Asian citrus psyllid, Diaphorina citri, vectors the bacterial causative agent of citrus greening disease, which has severely impacted citrus production on a global scale. As the current repeated application of chemical insecticides is unsustainable for management of this insect and subsequent protection of groves, we investigated the potential use of the bacteria-derived pesticidal protein, Cry1Ba1, when delivered via transgenic citrus plants. Having demonstrated transformation of the Indian curry leaf tree, Bergera koenigii, for Cry1Ba1 expression for use as a trap plant, we produced transgenic plants of Duncan grapefruit, Citrus paridisi, Valencia sweet orange, Citrus sinensis, and Carrizo citrange, C. sinensis x Poncirus trifoliata, for expression of Cry1Ba1. The presence of the cry1ba1 gene, and cry1ba1 transcription were confirmed. Western blot detection of Cry1Ba1 was confirmed in most cases. When compared to those from wild-type plants, leaf discs from transgenic Duncan and Valencia expressing Cry1Ba1 exhibited a “delayed senescence” phenotype, similar to observations made for transgenic B. koenigii. In bioassays, significant reductions in the survival of adult psyllids were noted on transgenic B. koenigii and Valencia sweet orange plants expressing Cry1Ba1, but not on transgenic Duncan grapefruit or Carrizo citrange. In contrast to psyllids fed on wild type plants, the gut epithelium of psyllids fed on transgenic plants was damaged, consistent with the mode of action of Cry1Ba1. These results indicate that the transgenic expression of a bacterial pesticidal protein in B. koenigii and Valencia sweet orange offers a viable option for management of D. citri, that may contribute to solutions that counter citrus greening disease.
A new Merluccius polli reference genome to investigate the effects of global change in West African waters
Authors: Mateo Juan L. , Blanco-Fernandez Carmen , Garcia-Vazquez Eva , Machado-Schiaffino Gonzalo
Published: April 2023

Genome resources have become crucial to assess genome-wide level of variation as well as to detect adaptive variation. This is particularly important for studying diversity in marine species inhabiting regions highly affected by accelerated climate warming and pollution, also known as global change. A greater awareness of the impacts of global change is urgently needed to ensure sustainable marine fisheries. Despite recent efforts, there are still many gaps in fish reference genomes, both geographical and taxonomic. Here, we sequence, assemble and annotate the genome of Merluccius polli. The total length of this new assembly (~582 Kb, N50 = 168Kb) is approximately 40% longer and much less fragmented than a previous version. Even though it might not be intrinsic of this species, low level of heterozygosity (1.16 SNPs/Kb) and low proportion of repeat content (9.21%) was found in this genome. This hake species has a wide latitudinal distribution; therefore, it is exposed to a changing temperature gradient and to a variety of contaminants in part of its distribution along West African coast. Special emphasis was laid on the identification and characterization of candidate genes known to respond to different stressors (depth, temperature, hypoxia, and heavy metals) happening along its geographical distribution. A total of 68 of the selected candidate genes known to be associated with responses to these stressors were found in the current assembly of the genome, and their predicted sequence can be considered as full-length. Therefore, it is expected that this genome would serve as a tool to further investigations of global change in one of the most stressed marine regions in the planet.
Sources, pathways, and abatement strategies of macroplastic pollution: an interdisciplinary approach for the southern North Sea
Authors: Meyerjürgens Jens , Ricker Marcel , Aden Christian , Albinus Michelle , Barrelet Johna , Freund Holger , Hahner Florian , Lettmann Karsten A. , Mose Ingo , Schaal Peter , Schöneich-Argent Rosanna I. , Stanev Emil V. , Wolff Jörg-Olaf , Zielinski Oliver , Badewien Thomas H.
Published: April 2023

The issue of marine plastic pollution has been extensively studied by various scientific disciplines in recent decades due to its global threat. However, owing to its complexity, it requires an interdisciplinary approach to develop effective management strategies. The multidisciplinary scientific approach presented here focuses on understanding the sources and pathways of macroplastic litter and developing abatement strategies in the southern North Sea region. Over 2.5 years, more than 63,400 biodegradable wooden drifters were deployed with the help of citizen science to study the sources, pathways, and accumulation areas of floating marine litter. Rivers act as sinks of most of the floating marine litter released within their waterways. Short-term field experiments were also conducted to analyse the hydrodynamic and atmospheric processes that govern the transport of floating litter particles at the sea surface. Numerical models were used to examine the transport of virtual litter particles in the entire North Sea and in coastal regions. It was found that there are no permanent accumulation areas in the North Sea, and the Skagerrak and fronts can increase the residence times of floating marine litter and favour sinking. Field surveys revealed that the majority of litter objects originate from fisheries and consumer waste. To develop effective abatement strategies, the key stakeholder landscape was analysed on a regional level. The interdisciplinary approach developed in this study highlights the importance of synergizing scientific resources from multiple disciplines for a better understanding of marine plastic pollution and the development of effective management strategies.
Hydroxychloroquine improves pregnancy outcomes of women with positive antinuclear antibody spectrum test results
Authors: Ye Shenglong , Liu Yuanying , Zhao Xueqing , Ma Yue , Wang Yongqing
Published: April 2023

Background:

Empirical use of Hydroxychloroquine (HCQ) in patients with positive antinuclear antibody spectrum (ANAs) test result is controversial regarding its impact on improving perinatal outcomes. This study aimed to investigate the effect of HCQ on adverse pregnancy outcomes associated with placental dysfunction in ANAs-positive patients.

Methods:

The study included pregnant women with positive ANAs test result from 2016 to 2020 in our center, and divided into a weakly positive and a positive group in just ANA positive patients among them. Univariate and multivariate analyses were conducted to determine the effect of HCQ on pregnancy outcomes in each subgroup. Stratified and interactive analyses were performed to assess the value of HCQ in improving pregnancy outcomes.

Results:

(i) A total of 261 cases were included, accounting for 30.60% of pregnancy complicated with autoimmune abnormalities, and 65.12% of them used HCQ during pregnancy. (ii) The application of HCQ significantly reduced the incidence of early-onset preeclampsia (1.18% vs. 12.09%, p = 0.040) and small-for-gestational-age infants (10.06% vs. 25.84%, p = 0.003) in the ANAs-positive population, increased birth weight (3075.87 ± 603.91 g vs. 2847.53 ± 773.73 g, p = 0.025), and prolonged gestation (38.43 ± 2.31 vs. 36.34 ± 5.45 weeks, p < 0.001). (iii) A total of 185 just ANA-positive patients were stratified according to titers. Among them, the rate of HCQ usage was significantly higher than that in the weakly positive group (81.03% vs. 58.27%, p = 0.003). (vi) Stratified univariate analysis showed that HCQ usage in the ANA-positive group could reduce the incidence of preeclampsia (2.13% vs. 27.27%, p = 0.019) and prolong gestation (38.29 ± 2.54 vs. 34.48 ± 7.68 weeks, p = 0.006). In the ANA-weakly positive group, HCQ significantly reduced the incidence of preeclampsia (6.76% vs. 28.30%, p = 0.002), early-onset preeclampsia (1.35% vs. 13.21%, p = 0.027), and small-for-gestational-age infants (7.89% vs. 35.19%, p < 0.001). Multivariate regression analysis showed that HCQ significantly reduced the incidence of preeclampsia in both groups. Intergroup interaction analysis showed no significant difference in the value of HCQ in reducing the incidence of preeclampsia between the two groups.

Conclusion:

ANAs positivity is an important abnormal autoimmunity type in pregnancy. HCQ can be considered as a choice for improving adverse pregnancy outcomes related to placental dysfunction, such as preeclampsia, in this population.
Immunological fingerprint in coronavirus disease-19 convalescents with and without post-COVID syndrome
Authors: Augustin Max , Heyn Ferdinand , Ullrich Stella , Sandaradura de Silva Ute , Albert Marie-Christine , Linne Viktoria , Schlotz Maike , Schommers Philipp , Pracht Elisabeth , Horn Carola , Suarez Isabelle , Simonis Alexander , Picard Lea Katharina , Zoufaly Alexander , Wenisch Christoph , Fätkenheuer Gerd , Gruell Henning , Klein Florian , Hallek Michael , Walczak Henning , Rybniker Jan , Theobald Sebastian J. , Lehmann Clara
Published: April 2023

Background

Symptoms lasting longer than 12  weeks after severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection are called post-coronavirus disease (COVID) syndrome (PCS). The identification of new biomarkers that predict the occurrence or course of PCS in terms of a post-viral syndrome is vital. T-cell dysfunction, cytokine imbalance, and impaired autoimmunity have been reported in PCS. Nevertheless, there is still a lack of conclusive information on the underlying mechanisms due to, among other things, a lack of controlled study designs.

Methods

Here, we conducted a prospective, controlled study to characterize the humoral and cellular immune response in unvaccinated patients with and without PCS following SARS-CoV-2 infection over 7 months and unexposed donors.

Results

Patients with PCS showed as early as 6 weeks and 7 months after symptom onset significantly increased frequencies of SARS-CoV-2-specific CD4+ and CD8+ T-cells secreting IFNγ, TNF, and expressing CD40L, as well as plasmacytoid dendritic cells (pDC) with an activated phenotype. Remarkably, the immunosuppressive counterparts type 1 regulatory T-cells (TR1: CD49b/LAG-3+) and IL-4 were more abundant in PCS+.

Conclusion

This work describes immunological alterations between inflammation and immunosuppression in COVID-19 convalescents with and without PCS, which may provide potential directions for future epidemiological investigations and targeted treatments.
Assessment of the competence in electrocardiographic interpretation among Arabic resident doctors at the emergency medicine and internal medicine departments: A multi-center online cross-sectional study
Authors: Rakab Amine , Swed Sarya , Alibrahim Hidar , Bohsas Haidara , Abouainain Yasmeen , Abbas Kirellos Said , Khair Eldien Jabban Yazan , Sawaf Bisher , Rageh Bushra , Alkhawaldeh Majd , Al-Fayyadh Israa , Rakab Mohamad Saad , Fathey Sherihan , Hafez Wael , Gerbil Amr , El-Shafei Emad Hassan Hassan
Published: April 2023

Background

This study aims to assess the electrocardiographic interpretation abilities of resident doctors at internal medicine and emergency medicine departments in eight Arabic countries.

Methods

An online cross-sectional study was conducted between October 7, 2022 and October 21, 2022 in eight Arabic countries. The questionnaire consisted of two main sections: the first section included sociodemographic information, while the second section contained 12 clinical case questions of the most severe cardiac abnormalities with their electrocardiography (ECG) recordings.

Results

Out of 2,509 responses, 630 were eligible for the data analysis. More than half of the participants were males (52.4%). Internal medicine residents were (n = 530, 84.1%), whereas emergency medicine residents were (n = 100, 15.9%). Almost participants were in their first or second years of residency (79.8%). Only 36.2% of the inquired resident doctors had attended an ECG course. Most participants, 85.6%, recognized the ECG wave order correctly, and 50.5% of the participants scored above 7.5/10 on the ECG interpretation scale. The proportions of participants who were properly diagnosed with atrial fibrillation, third-degree heart block, and atrial tachycardia were 71.1, 76.7, and 56.6%, respectively. No statistically significant difference was defined between the internal and emergency medicine residents regarding their knowledge of ECG interpretation (p value = 0.42). However, there was a significant correlation between ECG interpretation and medical residency year (p value < 0.001); the fourth-year resident doctors had the highest scores (mean = 9.24, SD = 1.6). As well, participants in the third and second years of postgraduate medical residency have a probability of adequate knowledge of ECG interpretation more than participants in the first year of residency (OR = 2.1, p value = 0.001) and (OR = 1.88, p value = 0.002), respectively.

Conclusion

According to our research findings, resident doctors in departments of internal medicine and emergency medicine in Arabic nations have adequate ECG interpretation abilities; nevertheless, additional development is required to avoid misconceptions about critical cardiac conditions.
One assay to test them all: Multiplex assays for expansion of respiratory virus surveillance
Authors: Boukli Narjis , Flamand Claude , Chea Kim Lay , Heng Leangyi , Keo Seangmai , Sour Kimhoung , In Sophea , Chhim Panha , Chhor Bunthea , Kruy Lomor , Feenstra Jelena D. M. , Gandhi Manoj , Okafor Obiageli , Ulekleiv Camilla , Auerswald Heidi , Horm Viseth Srey , Karlsson Erik A.
Published: April 2023

Molecular multiplex assays (MPAs) for simultaneous detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza and respiratory syncytial virus (RSV) in a single RT-PCR reaction reduce time and increase efficiency to identify multiple pathogens with overlapping clinical presentation but different treatments or public health implications. Clinical performance of XpertXpress® SARS-CoV-2/Flu/RSV (Cepheid, GX), TaqPath™ COVID−19, FluA/B, RSV Combo kit (Thermo Fisher Scientific, TP), and PowerChek™ SARS-CoV-2/Influenza A&B/RSV Multiplex RT-PCR kit II (KogeneBiotech, PC) was compared to individual Standards of Care (SoC). Thirteen isolates of SARS-CoV-2, human seasonal influenza, and avian influenza served to assess limit of detection (LoD). Then, positive and negative residual nasopharyngeal specimens, collected under public health surveillance and pandemic response served for evaluation. Subsequently, comparison of effectiveness was assessed. The three MPAs confidently detect all lineages of SARS-CoV-2 and influenza viruses. MPA-LoDs vary from 1 to 2 Log10 differences from SoC depending on assay and strain. Clinical evaluation resulted in overall agreement between 97 and 100%, demonstrating a high accuracy to detect all targets. Existing differences in costs, testing burden and implementation constraints influence the choice in primary or community settings. TP, PC and GX, reliably detect SARS-CoV-2, influenza and RSV simultaneously, with reduced time-to-results and simplified workflows. MPAs have the potential to enhance diagnostics, surveillance system, and epidemic response to drive policy on prevention and control of viral respiratory infections.