bluuebunny/crossref_metadata_2025 huggingface dataset:
Glacial Expansion or Interglacial Expansion? Contrasting Demographic Models of Four Cold-Adapted Fir Species in North America and East Asia
Authors: Shao Yi-Zhen , Yuan Zhi-Liang , Liu Yan-Yan , Liu Feng-Qin , Xiang Rui-Chen , Zhang Yuan-Yuan , Ye Yong-Zhong , Chen Yun , Wen Qian
Published: March 2022

Understanding and forecasting species’ response to climate change is a critical need for future conservation and management. Two expansion hypotheses, the glacial expansion versus the interglacial expansion, have been proposed to interpret how cold-adapted organisms in the northern hemisphere respond to Quaternary climatic fluctuations. To test these two hypotheses, we originally used two pairs of high-low elevation firs from North America (Abies lasiocarpa and Abies balsamea) and East Asia (Abies chensiensis and Abies nephrolepis). Abies lasiocarpa and Abies chensiensis are widely distributed in high-elevation regions of western North America and central China. Abies balsamea and Abies nephrolepis occur in central North America and northeast China, with much lower elevations. These fir species are typical cold-adapted species and sensitive to climate fluctuations. Here, we integrated the mtDNA and cpDNA polymorphisms involving 44 populations and 585 individuals. Based on phylogeographic analyses, recent historical range expansions were indicated in two high-elevation firs (Abies lasiocarpa and Abies chensiensis) during the last glaciation (43.8–28.4 or 21.9–14.2 kya, 53.1–34.5 or 26.6–17.2 kya). Such glacial expansions in high-elevation firs were further confirmed by the evidence of species distribution modelling, geographic-driven genetic patterns, palynological records, and current distribution patterns. Unlike the north American firs, the SDM models indicated unremarkable expansion or contraction in East Asia firs for its much more stable conditions during different historical periods. Taken together, our findings highly supported that high-elevation firs experienced glacial expansion during the Quaternary climate change in East Asia and North America, as interglacial expansion within low-elevation firs. Under this situation, the critically endangered fir species distributed in high elevation would have no enough higher elevational space to migrate. Facing the increasing global warming, thus we proposed ex-situ conservation of defining conservation units as the most meaningful strategy.
Birds of a Feather Flock Together: Extent of Long-Term Consistency of Colony-Size Choice in Cliff Swallows
Authors: Brown Charles R. , Hannebaum Stacey L.
Published: March 2022

Explaining why animal groups vary in size is a fundamental problem in behavioral ecology. One hypothesis is that life-history differences among individuals lead to sorting of phenotypes into groups of different sizes where each individual does best. This hypothesis predicts that individuals should be relatively consistent in their use of particular group sizes across time. Little is known about whether animals’ choice of group size is repeatable across their lives, especially in long-lived species. We studied consistency in choice of breeding-colony size in colonially nesting cliff swallows (Petrochelidon pyrrhonota) in western Nebraska, United States, over a 32-year period, following 6,296 birds for at least four breeding seasons. Formal repeatability of size choice for the population was about 0.41. About 45% of individuals were relatively consistent in choice of colony size, while about 40% varied widely in the colony size they occupied. Birds using the smaller and larger colonies appeared more consistent in size use than birds occupying more intermediate sized colonies. Consistency in colony size was also influenced by whether a bird used the same physical colony site each year and whether the site had been fumigated to remove ectoparasites. The difference between the final and initial colony sizes for an individual, a measure of the net change in its colony size over its life, did not significantly depart from 0 for the dataset as a whole. However, different year-cohorts did show significant net change in colony size, both positive and negative, that may have reflected fluctuating selection on colony size among years based on climatic conditions. The results support phenotypic sorting as an explanation for group size variation, although cliff swallows also likely use past experience at a given site and the extent of ectoparasitism to select breeding colonies.
Genetic Basis for Resistance Against Viral Nervous Necrosis: GWAS and Potential of Genomic Prediction Explored in Farmed European Sea Bass (Dicentrarchus labrax)
Authors: Vela-Avitúa Sergio , Thorland Ingunn , Bakopoulos Vasileios , Papanna Kantham , Dimitroglou Arkadios , Kottaras Eleftherios , Leonidas Papaharisis , Guinand Bruno , Tsigenopoulos Costas S. , Aslam Muhammad L.
Published: March 2022

Viral nervous necrosis (VNN) is an infectious disease caused by the red-spotted grouper nervous necrosis virus (RGNNV) in European sea bass and is considered a serious concern for the aquaculture industry with fry and juveniles being highly susceptible. To understand the genetic basis for resistance against VNN, a survival phenotype through the challenge test against the RGNNV was recorded in populations from multiple year classes (YC2016 and YC2017). A total of 4,851 individuals from 181 families were tested, and a subset (n∼1,535) belonging to 122 families was genotyped using a ∼57K Affymetrix Axiom array. The survival against the RGNNV showed low to moderate heritability with observed scale estimates of 0.18 and 0.25 obtained using pedigree vs. genomic information, respectively. The genome-wide association analysis showed a strong signal of quantitative trait loci (QTL) at LG12 which explained ∼33% of the genetic variance. The QTL region contained multiple genes (ITPK1, PLK4, HSPA4L, REEP1, CHMP2, MRPL35, and SCUBE) with HSPA4L and/or REEP1 genes being highly relevant with a likely effect on host response in managing disease-associated symptoms. The results on the accuracy of predicting breeding values presented 20–43% advantage in accuracy using genomic over pedigree-based information which varied across model types and applied validation schemes.
Antibiotic Exposure Aggravates Bacteroides-Linked Uremic Toxicity in the Gut-Kidney Axis
Authors: Ray Navin , Jeong Hoyoung , Kwon Dasom , Kim Juil , Moon Yuseok
Published: March 2022

Epidemiological and experimental evidence has implicated a potent link between antibiotic exposure and susceptibility to various diseases. Clinically, antibiotic treatment during platinum chemotherapy is associated with poor prognosis in patients with malignancy. In the present study, mucosal antibiotic exposure was assessed for its impact on renal distress as a sequela of platinum-based chemotherapy. Clinical transcriptome dataset-based evaluations demonstrated that levels of dysbiosis-responsive genes were elevated during renal distress, indicating pathological communications between gut and kidney. Experimentally, mucosal exposure to streptomycin aggravated platinum-induced renal tubular lesions in a mouse model. Moreover, antibiotic-induced dysbiosis increased susceptibility to gut mucosal inflammation, epithelial disruption, and bacterial exposure in response to cisplatin treatment. Further investigation of the luminal microbes indicated that antibiotic-induced dysbiosis promoted the dominance of Bacteroides species. Moreover, the functional assessment of dysbiotic microbiota predicted tryptophan metabolic pathways. In particular, dysbiosis-responsive Bacteroides acidifaciens was associated with the production of the uremic toxin indoxyl sulfate and renal injuries. The results of this study including bacterial community-based evaluations provide new predictive insights into the interorgan communications and interventions against dysbiosis-associated disorders.
PgtE Enzyme of Salmonella enterica Shares the Similar Biological Roles to Plasminogen Activator (Pla) in Interacting With DEC-205 (CD205), and Enhancing Host Dissemination and Infectivity by Yersinia pestis
Authors: Li Qiao , Ye Chenglin , Zhao Fei , Li Wenjin , Zhu Sizhe , Lv Yin , Park Chae Gyu , Zhang Yingmiao , Jiang Ling-Yu , Yang Kun , He Yingxia , Cai Huahua , Zhang Song , Ding Hong-Hui , Njiri Olivia Adhiambo , Tembo John Mambwe , Alkraiem Ayman Ahmad , Li An-Yi , Sun Zi-Yong , Li Wei , Yan Mei-Ying , Kan Biao , Huo Xixiang , Klena John D. , Skurnik Mikael , Anisimov Andrey P. , Gao Xiaofang , Han Yanping , Yang Rui-Fu , Xiamu Xiding , Wang Yuanzhi , Chen Hongxiang , Chai Bao , Sun Yicheng , Yuan Jingping , Chen Tie
Published: March 2022

Yersinia pestis, the cause of plague, is a newly evolved Gram-negative bacterium. Through the acquisition of the plasminogen activator (Pla), Y. pestis gained the means to rapidly disseminate throughout its mammalian hosts. It was suggested that Y. pestis utilizes Pla to interact with the DEC-205 (CD205) receptor on antigen-presenting cells (APCs) to initiate host dissemination and infection. However, the evolutionary origin of Pla has not been fully elucidated. The PgtE enzyme of Salmonella enterica, involved in host dissemination, shows sequence similarity with the Y. pestis Pla. In this study, we demonstrated that both Escherichia coli K-12 and Y. pestis bacteria expressing the PgtE-protein were able to interact with primary alveolar macrophages and DEC-205-transfected CHO cells. The interaction between PgtE-expressing bacteria and DEC-205-expressing transfectants could be inhibited by the application of an anti-DEC-205 antibody. Moreover, PgtE-expressing Y. pestis partially re-gained the ability to promote host dissemination and infection. In conclusion, the DEC-205-PgtE interaction plays a role in promoting the dissemination and infection of Y. pestis, suggesting that Pla and the PgtE of S. enterica might share a common evolutionary origin.
Functional Profile of CD8+ T-Cells in Response to HLA-A*02:01-Restricted Mutated Epitopes Derived from the Gag Protein of Circulating HIV-1 Strains from Medellín, Colombia
Authors: Sánchez-Martínez Alexandra , Acevedo-Sáenz Liliana , Alzate-Ángel Juan Carlos , Álvarez Cristian M. , Guzmán Fanny , Roman Tanya , Urcuqui-Inchima Silvio , Cardona-Maya Walter D. , Velilla Paula Andrea
Published: March 2022

CD8+ T-cells play a crucial role in the control of HIV replication. HIV-specific CD8+ T-cell responses rapidly expand since the acute phase of the infection, and it has been observed that HIV controllers harbor CD8+ T-cells with potent anti-HIV capacity. The development of CD8+ T-cell-based vaccine against HIV-1 has focused on searching for immunodominant epitopes. However, the strong immune pressure of CD8+ T-cells causes the selection of viral variants with mutations in immunodominant epitopes. Since HIV-1 mutations are selected under the context of a specific HLA-I, the circulation of viral variants with these mutations is highly predictable based on the most prevalent HLA-I within a population. We previously demonstrated the adaptation of circulating strains of HIV-1 to the HLA-A*02 molecule by identifying mutations under positive selection located in GC9 and SL9 epitopes derived from the Gag protein. Also, we used an in silico prediction approach and evaluated whether the mutations found had a higher or lower affinity to the HLA-A*02. Although this strategy allowed predicting the interaction between mutated peptides and HLA-I, the functional response of CD8+ T-cells that these peptides induce is unknown. In the present work, peripheral blood mononuclear cells from 12 HIV-1+ HLA-A*02:01+ individuals were stimulated with the mutated and wild-type peptides derived from the GC9 and SL9 epitopes. The functional profile of CD8+ T-cells was evaluated using flow cytometry, and the frequency of subpopulations was determined according to their number of functions and the polyfunctionality index. The results suggest that the quality of the response (polyfunctionality) could be associated with the binding affinity of the peptide to the HLA molecule, and the functional profile of specific CD8+ T-cells to mutated epitopes in individuals under cART is maintained.
Analysis of Plasma Using Flow Cytometry Reveals Increased Immune Cell-Derived Extracellular Vesicles in Untreated Relapsing-Remitting Multiple Sclerosis
Authors: Blandford Stephanie N. , Fudge Neva J. , Corkum Chris P. , Moore Craig S.
Published: March 2022

Extracellular vesicles (EVs) are secreted from cells under physiological and pathological conditions, and are found in biological fluids while displaying specific surface markers that are indicative of their cell of origin. EVs have emerged as important signaling entities that may serve as putative biomarkers for various neurological conditions, including multiple sclerosis (MS). The objective of this study was to measure and compare immune cell-derived EVs within human plasma between untreated RRMS patients and healthy controls. Using blood plasma and peripheral blood mononuclear cells (PBMCs) collected from RRMS patients and controls, PBMCs and EVs were stained and quantified by flow cytometry using antibodies against CD9, CD61, CD45, CD3, CD4, CD8, CD14, and CD19. While several immune cell-derived EVs, including CD3+, CD4+, CD8+, CD14+, and CD19+ were significantly increased in RRMS vs. controls, no differences in immune cell subsets were observed with the exception of increased circulating CD19+ cells in RRMS patients. Our study demonstrated that plasma-derived EVs secreted from T cells, B cells, and monocytes were elevated in untreated RRMS cases with low disability, despite very limited changes in circulating immune cells, and suggest the utility of circulating EVs as biomarkers in MS.
IgG4 Autoantibodies in Organ-Specific Autoimmunopathies: Reviewing Class Switching, Antibody-Producing Cells, and Specific Immunotherapies
Authors: Koneczny Inga , Tzartos John , Mané-Damas Marina , Yilmaz Vuslat , Huijbers Maartje G. , Lazaridis Konstantinos , Höftberger Romana , Tüzün Erdem , Martinez-Martinez Pilar , Tzartos Socrates , Leypoldt Frank
Published: March 2022

Organ-specific autoimmunity is often characterized by autoantibodies targeting proteins expressed in the affected tissue. A subgroup of autoimmunopathies has recently emerged that is characterized by predominant autoantibodies of the IgG4 subclass (IgG4-autoimmune diseases; IgG4-AID). This group includes pemphigus vulgaris, thrombotic thrombocytopenic purpura, subtypes of autoimmune encephalitis, inflammatory neuropathies, myasthenia gravis and membranous nephropathy. Although the associated autoantibodies target specific antigens in different organs and thus cause diverse syndromes and diseases, they share surprising similarities in genetic predisposition, disease mechanisms, clinical course and response to therapies. IgG4-AID appear to be distinct from another group of rare immune diseases associated with IgG4, which are the IgG4-related diseases (IgG4-RLD), such as IgG4-related which have distinct clinical and serological properties and are not characterized by antigen-specific IgG4. Importantly, IgG4-AID differ significantly from diseases associated with IgG1 autoantibodies targeting the same organ. This may be due to the unique functional characteristics of IgG4 autoantibodies (e.g. anti-inflammatory and functionally monovalent) that affect how the antibodies cause disease, and the differential response to immunotherapies of the IgG4 producing B cells/plasmablasts. These clinical and pathophysiological clues give important insight in the immunopathogenesis of IgG4-AID. Understanding IgG4 immunobiology is a key step towards the development of novel, IgG4 specific treatments. In this review we therefore summarize current knowledge on IgG4 regulation, the relevance of class switching in the context of health and disease, describe the cellular mechanisms involved in IgG4 production and provide an overview of treatment responses in IgG4-AID.
Human B Cells Mediate Innate Anti-Cancer Cytotoxicity Through Concurrent Engagement of Multiple TNF Superfamily Ligands
Authors: Janjic Bratislav M. , Kulkarni Aditi , Ferris Robert L. , Vujanovic Lazar , Vujanovic Nikola L.
Published: March 2022

The essential innate immunity effector cells, natural killer and dendritic cells, express multiple plasma membrane-associated tumor necrosis factor (TNF) superfamily (TNFSF) ligands that, through simultaneous and synergistic engagement, mediate anti-cancer cytotoxicity. Here, we report that circulating B cells, mediators of adaptive humoral immunity, also mediate this innate anti-cancer immune mechanism. We show that resting human B cells isolated from peripheral blood induce apoptosis of, and efficiently kill a large variety of leukemia and solid tumor cell types. Single-cell RNA sequencing analyses indicate, and flow cytometry data confirm that B cells from circulation express transmembrane TNF, Fas ligand (FasL), lymphotoxin (LT) α1β2 and TNF-related apoptosis-inducing ligand (TRAIL). The cytotoxic activity can be inhibited by individual and, especially, combined blockade of the four transmembrane TNFSF ligands. B cells from tumor-bearing head and neck squamous cell carcinoma patients express lower levels of TNFSF ligands and are less cytotoxic than those isolated from healthy individuals. In conclusion, we demonstrate that B cells have the innate capacity to mediate anti-cancer cytotoxicity through concurrent activity of multiple plasma membrane-associated TNFSF ligands, that this mechanism is deficient in cancer patients and that it may be part of a general cancer immunosurveillance mechanism.
Local Innate Markers and Vaginal Microbiota Composition Are Influenced by Hormonal Cycle Phases
Authors: Adapen Cindy , Réot Louis , Nunez Natalia , Cannou Claude , Marlin Romain , Lemaître Julien , d’Agata Léo , Gilson Emmanuel , Ginoux Eric , Le Grand Roger , Nugeyre Marie-Thérèse , Menu Elisabeth
Published: March 2022

Background

The female reproductive tract (FRT) mucosa is the first line of defense against sexually transmitted infection (STI). FRT environmental factors, including immune-cell composition and the vaginal microbiota, interact with each other to modulate susceptibility to STIs. Moreover, the menstrual cycle induces important modifications within the FRT mucosa. Cynomolgus macaques are used as a model for the pathogenesis and prophylaxis of STIs. In addition, their menstrual cycle and FRT morphology are similar to women. The cynomolgus macaque vaginal microbiota is highly diverse and similar to dysbiotic vaginal microbiota observed in women. However, the impact of the menstrual cycle on immune markers and the vaginal microbiota in female cynomolgus macaques is unknown. We conducted a longitudinal study covering three menstrual cycles in cynomolgus macaques. The evolution of the composition of the vaginal microbiota and inflammation (cytokine/chemokine profile and neutrophil phenotype) in the FRT and blood was determined throughout the menstrual cycle.

Results

Cervicovaginal cytokine/chemokine concentrations were affected by the menstrual cycle, with a peak of production during menstruation. We observed three main cervicovaginal neutrophil subpopulations: CD11bhigh CD101+ CD10+ CD32a+, CD11bhigh CD101+ CD10- CD32a+, and CD11blow CD101low CD10- CD32a-, of which the proportion varied during the menstrual cycle. During menstruation, there was an increase in the CD11bhigh CD101+ CD10+ CD32a+ subset of neutrophils, which expressed higher levels of CD62L. Various bacterial taxa in the vaginal microbiota showed differential abundance depending on the phase of the menstrual cycle. Compilation of the factors that vary according to hormonal phase showed the clustering of samples collected during menstruation, characterized by a high concentration of cytokines and an elevated abundance of the CD11bhigh CD101+ CD10+ CD32a+ CD62L+ neutrophil subpopulation.

Conclusions

We show a significant impact of menstruation on the local environment (cytokine production, neutrophil phenotype, and vaginal microbiota composition) in female cynomolgus macaques. Menstruation triggers increased production of cytokines, shift of the vaginal microbiota composition and the recruitment of mature/activated neutrophils from the blood to the FRT. These results support the need to monitor the menstrual cycle and a longitudinal sampling schedule for further studies in female animals and/or women focusing on the mucosal FRT environment.
Oncogenic Mutations and Tumor Microenvironment Alterations of Older Patients With Diffuse Large B-Cell Lymphoma
Authors: Zhu Yue , Fu Di , Shi Qing , Shi Ziyang , Dong Lei , Yi Hongmei , Liu Zhenhua , Feng Yan , Liu Qian , Fang Hai , Cheng Shu , Wang Li , Tian Qiang , Xu Pengpeng , Zhao Weili
Published: March 2022

The incidence of diffuse large B-cell lymphoma (DLBCL) increases by age and older DLBCL are commonly related to poor prognosis. However, the clinical and biological features of older DLBCL patients remain to be determined. A total of 2,445 patients with newly diagnosed DLBCL were enrolled for clinical data analysis according to age at diagnosis, with tumor samples of 1,150 patients assessed by DNA sequencing and 385 patients by RNA sequencing. Older DLBCL presented advanced disease stage, elevated serum lactate dehydrogenase, poor performance status, multiple extranodal involvement, high percentage of double expressor subtype, and adverse clinical outcome. According to molecular features, age was positively correlated with the oncogenic mutations of PIM1, MYD88, BTG2, CD79B, TET2, BTG1, CREBBP, TBL1XR1, and with the MYD88-like genetic subtype. These oncogenic mutations were involved in B-cell receptor/NF-κB signaling, B-cell differentiation, and histone acetylation based on biological functions. Older DLBCL also manifested reduction in CD4+ naïve T and CD8+ naïve T cells, and also increased recruitment of exhausted T cells and macrophages, leading to immunosuppressive tumor microenvironment. Our work thus contributes to the understanding of aging-related oncogenic mutations and tumor microenvironment alterations in lymphoma progression, and may provide new insights to mechanism-based targeted therapy in DLBCL.
Differential Transcriptomics Analysis of IPEC-J2 Cells Single or Coinfected With Porcine Epidemic Diarrhea Virus and Transmissible Gastroenteritis Virus
Authors: Song Lina , Chen Jing , Hao Pengfei , Jiang Yuhang , Xu Wang , Li Letian , Chen Si , Gao Zihan , Jin Ningyi , Ren Linzhu , Li Chang
Published: March 2022

Porcine epidemic diarrhea (PED) and transmissible gastroenteritis (TGE) caused by porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV) are two highly contagious intestinal diseases in the swine industry worldwide. Notably, coinfection of TGEV and PEDV is common in piglets with diarrhea-related diseases. In this study, intestinal porcine epithelial cells (IPEC-J2) were single or coinfected with PEDV and/or TGEV, followed by the comparison of differentially expressed genes (DEGs), especially interferon-stimulated genes (ISGs), between different groups via transcriptomics analysis and real-time qPCR. The antiviral activity of swine interferon-induced transmembrane protein 3 (sIFITM3) on PEDV and TGEV infection was also evaluated. The results showed that DEGs can be detected in the cells infected with PEDV, TGEV, and PEDV+TGEV at 12, 24, and 48 hpi, and the number of DEGs was the highest at 24 hpi. The DEGs are mainly annotated to the GO terms of protein binding, immune system process, organelle part, and intracellular organelle part. Furthermore, 90 ISGs were upregulated during PEDV or TGEV infection, 27 of which were associated with antiviral activity, including ISG15, OASL, IFITM1, and IFITM3. Furthermore, sIFITM3 can significantly inhibit PEDV and TGEV infection in porcine IPEC-J2 cells and/or monkey Vero cells. Besides, sIFITM3 can also inhibit vesicular stomatitis virus (VSV) replication in Vero cells. These results indicate that sIFITM3 has broad-spectrum antiviral activity.
An Oral Microencapsulated Vaccine Loaded by Sodium Alginate Effectively Enhances Protection Against GCRV Infection in Grass Carp (Ctenopharyngodon idella)
Authors: Xu Chuang , Qiao Meihua , Huo Xingchen , Liao Zhiwei , Su Jianguo
Published: March 2022

Grass carp reovirus (GCRV) is highly infectious and lethal to grass carp, causing huge economic losses to the aquaculture industry annually. Currently, vaccination is the most effective method against viral infections. Among the various vaccination methods, the oral vaccination is an ideal way in aquaculture. However, low protective efficiency is the major problem for oral vaccination owing to some reasons, such as antigen degradation and low immunogenicity. In our study, we screened the antigenic epitopes of GCRV-II and prepared an oral microencapsulated vaccine using sodium alginate (SA) as a carrier and flagellin B (FlaB) as an adjuvant, and evaluated its protective effects against GCRV-II infection in grass carp. The full length and three potential antigenic epitope regions of GCRV-II VP56 gene were expressed in Escherichia coli and purified by glutathione affinity column respectively. The optimal antigen (VP56-3) was screened by enzyme-linked immunosorbent assay (ELISA). Adjuvant FlaB was also expressed in E. coli and purified by Ni2+ affinity column. Subsequently, we prepared the oral vaccines using sodium alginate as a carrier. The vaccine (SA-VP56-3/FlaB) forms microsphere (1.24 ± 0.22 μm), examined by transmission electron microscopy, scanning electron microscopy, and dynamic light scattering assay. SA-VP56-3/FlaB vaccine has excellent stability, slow-release, and low toxicity by dynamic light scattering assay, release dynamic assay, in vivo fluorescence imaging system, hemolytic activity and cytotoxicity. Then we vaccinated grass carp orally with SA-VP56-3/FlaB and measured immune-related parameters (serum neutralizing antibody titer, serum enzyme activity (TSOD, LZM, C3), immune-related genes ((IgM, IFN1, MHC-II, CD8 in head kidney and spleen), IgZ in hindgut)). The results showed that SA-VP56-3/FlaB significantly induced strong immune responses, compared to other groups. The highest survival rate achieved in SA-VP56-3/FlaB microencapsulated vaccine (56%) in 2 weeks post GCRV challenge, while 10% for the control group. Meanwhile, the tissue virus load in survival grass carp is lowest in SA-VP56-3/FlaB group. These results indicated that SA-VP56-3/FlaB could be a candidate oral vaccine against GCRV-II infection in aquaculture.
Investigating Hypoxic and Euxinic Area Changes Based on Various Datasets From the Baltic Sea
Authors: Krapf Karina , Naumann Michael , Dutheil Cyril , Meier H. E. Markus
Published: March 2022

The Baltic Sea is a coastal sea with the world’s largest anthropogenically induced hypoxic bottom area. Although hypoxia has periodically occurred during the sea’s 8,000-year history, the rapid rise in the population and intensified agriculture after World War II have led to nutrient input levels that have made hypoxia a permanent, widespread phenomenon. Efforts since the 1980s considerably reduced nutrient inputs in the Baltic Sea, but an improved ecological status in the deep basins of the Baltic Sea has yet to be achieved. In fact, hypoxic areas in those basins have reached record size and in some cases large euxinic areas have emerged. This study was based on a novel observational dataset comprising maps of hypoxic and euxinic areas of the Baltic Sea. The seasonal cycles of hypoxia and euxinia in the various sub-basins were investigated. The comparison of those maps with other observational and reanalysis datasets of hypoxia and euxinia revealed some discrepancies. Those discrepancies together with a pronounced interannual variability prevent the detection of robust trends in hypoxic and euxinic areas that would indicate an influence of decreasing nutrient inputs from the land and the atmosphere since the 1980s. A correlation analysis of physical drivers and hypoxic and euxinic areas suggests that climate change has already played an important role by enhancing oxygen depletion.
Nitrate Regeneration and Loss in the Central Yellow Sea Bottom Water Revealed by Nitrogen Isotopes
Authors: Tian Shichao , Gaye Birgit , Tang Jianhui , Luo Yongming , Lahajnar Niko , Dähnke Kirstin , Sanders Tina , Xiong Tianqi , Zhai Weidong , Emeis Kay-Christian
Published: March 2022

The Yellow Sea (YS) is an epicontinental sea framed by the densely populated mainland of China and the Korean peninsula. Human activities over the last decades resulted in heavily increasing discharge of reactive nitrogen into the YS, which created numerous ecological problems. To elucidate the role of central YS in the cycling of reactive nitrogen, specifically the Yellow Sea Cold Water Mass (YSCWM), we determined nutrient concentrations, dual stable isotopes of nitrate (δ15N-NO3- and δ18O-NO3-), and stable isotopes of particulate and sedimentary nitrogen in spring and summer, i.e., in biologically inactive and active periods. The nitrate concentration in spring was higher than that in summer in the northern part of the YSCWM, Nitrate increased in the southern part accompanied by a decrease in δ15N-NO3- and δ18O-NO3-, which are indicative of nitrification that was a significant source of recycled nitrate in the south part of YSCWM. To quantify this regenerated nitrate, we use a mixing model with end members of preformed nitrate in spring and regenerated nitrate in summer, both with their distinct dual isotope values. The results suggest that only 35% nitrate was a residual of nitrate preformed in spring and 65% in summer in the southern branch of YSCWM was regenerated. The northern part of YSCWM has low concentrations of dissolved inorganic nitrogen, mainly because of denitrification in sediments. In contrast, the southern pool of YSCWM is a growing reservoir of regenerated terrestrial reactive nitrogen, the addition of which compensates the removal by co-occurring sediment denitrification. In consequence, the southern branch of YSCWM is facing a higher ecological risk than the northern branch, when excess reactive nitrogen discharge from Changjiang River continues at present levels or even increases.
Synchronous Shifts in Nutrients and Organic Carbon Responses Over the Diatom-to-Dinoflagellate Succession
Authors: Wang Xiaolu , Jiang Shan , Wu Ying , Wang Yanna
Published: March 2022

Phytoplankton blooms, including the diatom-to-dinoflagellate succession in coastal regions, are frequently observed by researchers through incubation experiments, albeit mainly in nutrient-enrichment conditions. This study, complementary to such previous experiments, aims at the dynamics of nutrients and organic matter during the natural community shift in a nutrient-constraint condition. A nutrient-constraint incubation experiment is conducted herein to investigate nutrient dynamics during a diatom-to-dinoflagellate succession and evaluate its effects on carbon cycling. The incubation successfully induced a transition from a diatom bloom dominated by Skeletonema costatum to a dinoflagellate bloom dominated by Prorocentrum donghaiense. Results showed that the DIP limitation triggers the succession. This experiment provides an excellent opportunity to examine how senescent bloom under nutrient stress affects the amount and bioavailability of dissolved organic matter (DOM) that is produced. Under the nutrient limitation, organic carbon production was significantly influenced by nutrient availability. Particulate organic carbon (POC) production is closely related to phytoplankton growth phases, while dissolved organic carbon (DOC) is related to nutrient structure. The relative partitioning of net production to POC is higher in the dinoflagellate-dominant stage than that in the diatom-dominant stage, which is driven by quick turnover of DOM related to nutrient structure in different stages. In terms of C:Chl a ratio, it was strongly dependent on growth phases and nutrient conditions. From the signatures of chromophoric dissolved organic matter (CDOM), the bioavailability of DOM decreased during the succession. In different phases, DOM composition varied, containing more protein-like components in the degradation phase than in the growth phases. Differences of DOM composition among varying community dominance were far smaller than different growth phases during this succession. Such an observation of a diatom-to-dinoflagellate succession and the related dynamics of nutrients and organic matter benefits the prediction of organic carbon export during community shifts in ecological models.
Microplastic Contamination on the Beaches of South China
Authors: Chai Bingwen , Li Yanping , Wang Li , Zhang Xiao-Tan , Wan Yi-Ping , Chen Fengyuan , Ma Jie , Lan Wenlu , Pan Ke
Published: March 2022

Microplastics (MPs) have emerged as a pollutant of significant global concern. The sandy beach is a fragile environment that deserves our special attention with regard to MP contamination, as this area is a hotspot that accumulates large quantities of plastic waste. Notably, our current understanding of the MP distribution on beaches and the scale of contamination is far from sufficient. Hence, this study investigated the occurrence and characteristics of MPs on 14 beaches along the coast of South China. The MPs were ubiquitously distributed in the sand, most were small, less than 1 mm. A total of 18 types of polymers were identified in the sand, suggesting that diverse types of MPs are present on the beaches. Polyethylene, polypropylene, and polystyrene were the dominant types of MPs in most of our sampling sites. The MP abundance was higher in the upper layers (0–20 cm) of the beach than in the deeper layers (20–40 cm) of the sampling site when characterized by depth (Yangjiang beach). Our study demonstrates the extent and severity of MP pollution on the beaches of South China and provides implications for future remediation measures. More effort is needed to clarify the vertical distribution of MPs on beaches, especially for those MPs less than 1 μm.
Light Chain Restriction in Proximal Tubules—Implications for Light Chain Proximal Tubulopathy
Authors: Büttner-Herold Maike , Krieglstein Nathalie , Chuva Teresa , Minuth Kaija , Pfister Frederick , Daniel Christoph , Klewer Monika , Büttner Anke , Ferrazzi Fulvia , Bertz Simone , Amann Kerstin
Published: March 2022

Monoclonal gammopathy (MG) causes various nephropathies, which may suffice for cytoreductive therapy even in the absence of diagnostic criteria for multiple myeloma or B-cell non-Hodgkin lymphoma. The aim of this study was to better understand the significance of light chain (LC) restriction or crystals (LC-R/C) in proximal tubules in the spectrum of LC-induced nephropathies. A consecutive cohort of 320 renal specimens with a history of B-cell dyscrasia was characterized. Special attention was paid to immunohistochemical LC restriction in proximal tubules, tubular crystals or constipation, and ultrastructural findings. Complementary cell culture experiments were performed to assess the role of LC concentrations in generating LC restriction. Light chain restriction or crystals in proximal tubules was found in a quarter of analyzed cases (81/316) and was associated with another LC-induced disease in 70.4% (57/81), especially LC cast-nephropathy (cast-NP) and interstitial myeloma infiltration. LC restriction without significant signs of acute tubular injury was observed in 11.1% (9/81). LC-R/C was not associated with inferior renal function compared to the remainder of cases, when cases with accompanying cast-NP were excluded. Besides crystals, cloudy lysosomes were significantly associated with LC-R/C on an ultrastructural level. In summary, LC-R/C is frequent and strongly associated with cast-NP, possibly indicating that a high load of clonal LC is responsible for this phenomenon, supported by the observation that LC restriction can artificially be generated in cell culture. This and the lack of significant tubular injury in a subgroup imply that in part LC-R/C is a tubular trafficking phenomenon rather than an independent disease process.
Use of Artificial Intelligence to Identify New Mechanisms and Approaches to Therapy of Bone Disorders Associated With Chronic Kidney Disease
Authors: Gaweda Adam E. , Lederer Eleanor D. , Brier Michael E.
Published: March 2022

Chronic kidney disease (CKD) leads to clinically severe bone loss, resulting from the deranged mineral metabolism that accompanies CKD. Each individual patient presents a unique combination of risk factors, pathologies, and complications of bone disease. The complexity of the disorder coupled with our incomplete understanding of the pathophysiology has significantly hampered the ability of nephrologists to prevent fractures, a leading comorbidity of CKD. Much has been learned from animal models; however, we propose in this review that application of multiple techniques of mathematical modeling and artificial intelligence can accelerate our ability to develop relevant and impactful clinical trials and can lead to better understanding of the osteoporosis of CKD. We highlight the foundational work that informed our current model development and discuss the potential applications of our approach combining principles of quantitative systems pharmacology, model predictive control, and reinforcement learning to deliver individualized precision medical therapy of this highly complex disorder.
Case Report: Intraocular Hemorrhage in a Primary Vitreoretinal Lymphoma Patient Treated With Zanubrutinib
Authors: Zhang Xiao , Dai Rongping , Zhao Chan , Zhang Meifen
Published: March 2022

Purpose

To report a case of primary vitreoretinal lymphoma (PVRL) treated with oral zanubrutinib, who had bilateral intraocular hemorrhage after intravitreal injection of methotrexate (MTX).

Case report

A 69-year-old Chinese female presented with vision decrease in both eyes. After diagnostic vitrectomy, the patient was diagnosed as PVRL in both eyes, and was treated with intravenous rituximab, oral zanubrutinib and bilateral intravitreal MTX. There were bilateral anterior chamber and vitreous hemorrhage after the fourth intravitreal MTX combined with paracentesis. After discontinuation of zanubrutinib, vitrectomy and silicon oil tamponade were performed on the left eye, and the blood in the right eye was absorbed.

Conclusion

Bleeding is a major concern in the use of zanubrutinib. It is suggested that drugs be held for a few days prior to procedures and surgeries.
The Role of Human Epididymis Protein 4 in the Diagnosis and Prognosis of Diseases: An Umbrella Review of Systematic Reviews and Meta-Analyses of Observational Studies
Authors: Sun Ming-Li , Yang Zhi-Yong , Wu Qi-Jun , Li Yi-Zi , Li Xin-Yu , Liu Fang-Hua , Wei Yi-Fan , Wen Zhao-Yan , Lin Bei , Gong Ting-Ting
Published: March 2022

Background

The application of human epididymis protein 4 (HE4) in diverse health diseases, especially in cancers, has been extensively studied in recent decades. To summarize the existing evidence of the aforementioned topic, we conducted an umbrella review to systematically evaluate the reliability and strength of evidence regarding the role of HE4 in the diagnostic and prognostic estimate of diverse diseases.

Methods

Electronic searches in PubMed, Web of Science, and Embase databases were conducted from inception to September 16, 2021, for meta-analyses, which focus on the role of HE4 in the diagnosis and prognosis of diseases. This study protocol has been registered at PROSPERO (CRD42021284737). We collected the meta-analysis effect size of sensitivity, specificity, positive predictive value, and negative predictive value from diagnostic studies and gathered the hazard ratio (HR) of disease-free survival, overall survival, and progression-free survival from prognostic studies. For each systematic review and meta-analysis, we used a measurable tool for evaluating systematic reviews and meta-analysis (AMSTAR) to evaluate the methodological quality. Additionally, we assessed the quality of evidence on estimating the ability of HE4 in the diagnosis and prognosis of diverse diseases by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guideline.

Results

Overall, 20 meta-analyses including a total of 331 primary studies of different diseases were examined, mainly including ovarian cancer (OC) (n = 9), endometrial cancer (EC) (n = 6), and lung cancer (LC) (n = 4). The methodological qualities of all studies were rated as moderate (45%) or high (55%) by the AMSTAR. According to the GRADE, the certainties of 18 diagnostic pieces of evidence (9 for sensitivity and 9 for specificity) were rated as moderate (34%), low (33%), and very low (33%). Moreover, outcomes from prognosis studies showed evidence (1 for disease-free survival) with high certainty in regard to cancers (such as EC, OC, and LC) with the remaining three being moderate.

Conclusion

This umbrella review suggested that HE4 was a favored biomarker in the prognosis of cancers, which was supported by high certainty of evidence. Additionally, HE4 could provide a suitable method for the diagnosis of EC, OC, and LC with moderate certainty evidence. Further large prospective cohort studies are needed to better elucidate the diagnostic and prognostic role of HE4 in diseases.
The Effect of General Anesthesia vs. Regional Anesthesia on Postoperative Delirium—A Systematic Review and Meta-Analysis
Authors: Zhu Xianlin , Yang Min , Mu Junying , Wang Zaiping , Zhang Liang , Wang Hongbai , Yan Fuxia
Published: March 2022

Background

Postoperative delirium (POD) commonly occurs in patients following major surgeries and is associated with adverse prognosis. The modes of anesthesia may be associated with POD occurrence. General anesthesia (GA) causes loss of consciousness in the patient by altering the levels of some neurotransmitters as well as signaling pathways. We conducted this meta-analysis to investigate the effect of GA vs. regional anesthesia (RA) on POD incidence in surgical patients.

Methods

The databases of Pubmed, Embase, and Cochrane Library were searched till October 22, 2021. The eligible criteria were participants aged 18 years or older, patients undergoing surgery under GA and RA, and articles reporting the effect of GA vs. RA on POD incidence. RevMan 5.3 was used to perform statistical analyses.

Results

A total of 21 relevant trials with a total of 1,702,151 patients were included. The pooled result using random-effects model with OR demonstrated significant difference in POD incidence between patients with GA and RA (OR = 1.15, 95% CI: [1.02, 1.31], I2 = 83%, p for effect = 0.02). We did not obtain the consistent pooled result after sensitivity analysis (OR = 0.95, 95% CI: [0.83, 1.08], I2 =13%, p for effect = 0.44) and excluded the articles without the information on preoperative cognitive or neuropsychological assessment (OR = 1.12, 95% CI: [1.00, 1.25], I2 =80%, p for effect = 0.05), respectively.

Conclusion

This meta-analysis could not identify that GA was significantly associated with POD occurrence in surgical patients compared with RA.
Susceptibility-Guided Therapy vs. Bismuth-Containing Quadruple Therapy as the First-Line Treatment for Helicobacter pylori Infection: A Systematic Review and Meta-Analysis
Authors: Ouyang Yaobin , Zhang Wenjing , He Chen , Zhu Yin , Lu Nonghua , Hu Yi
Published: March 2022

Background

The increased antibiotic resistance of Helicobacter pylori (H. pylori) has led to the decreased efficacy of H. pylori regimens.

Aim

To evaluate the efficacy, safety, and compliance of susceptibility-guided therapy (SGT) vs. bismuth-containing quadruple therapy (BQT) as the first-line treatment for H. pylori infection.

Materials and Methods

This meta-analysis was performed in accordance with the PRISMA 2009 guidelines. A systematic search in PubMed, Embase, and Cochrane databases was conducted using the combination of “H. pylori or H. pylori or Hp,” “bismuth quadruple,” and “tailored eradication OR tailored therapy OR susceptibility-guided therapy OR personalized therapy OR antibiotic susceptibility testing.”

Results

Five studies with 2,110 H. pylori-infected patients were enrolled. The pooled eradication rates of SGT and BQT were 86 vs. 78% (p < 0.05) and 92 vs. 86% (p > 0.05) by intention-to-treat (ITT) and per-protocol (PP) analyses, respectively. SGT has a significantly superior efficacy than BQT [pooled risk ratio (RR) = 1.14, p < 0.05] in a subgroup of cultures with the susceptibility test. The pooled side effect rate was 20% in SGT and 22% in BQT, which showed no significant difference (p > 0.05). The compliances of SGT and BQT were 95 and 92%, respectively.

Conclusion

Compared with BQT, SGT showed a higher efficacy and similar safety as the first-line treatment of H. pylori infection in areas with high antibiotic resistance. The decision-making of first-line regimens for H. pylori infection should depend on the availability and cost-effectiveness of susceptibility tests and bismuth in local areas.
Osteoradionecrosis of the Hip, a Troublesome Complication of Radiation Therapy: Case Series and Systematic Review
Authors: Xu Sheng-hao , Tang Jin-shuo , Shen Xian-yue , Niu Zhi-xin , Xiao Jian-lin
Published: March 2022

Background

Osteoradionecrosis of the hip is a serious complication of radiotherapy that is easily overlooked by physicians and patients in the early stages. There are relatively few reports on this subject, so there is no clear scientific consensus for the pathogenesis, early diagnosis, and clinical treatment of hip osteoradionecrosis. In this paper, we report two cases of hip osteoradionecrosis and systematically review the related literature.

Case Presentation

We report two cases of hip osteoradionecrosis. One patient successfully underwent total hip arthroplasty in our hospital and recovered well postoperatively. Another patient although we offered a variety of surgical options for this patient, the patient was worried that the bone loss would lead to poor prosthesis fixation, resulting in prosthesis loosening and infection, and therefore ultimately refused surgical treatment.

Conclusion

With the development of radiological techniques, the incidence of hip osteoradionecrosis is decreasing year by year, but early diagnosis and rational treatment remain challenging. The effects of non-surgical treatment are limited. Early prevention, early detection, and early intervention are crucial to delay or prevent the emergence of more serious complications.
Therapeutic Strategies for Dystrophin Replacement in Duchenne Muscular Dystrophy
Authors: Happi Mbakam Cedric , Lamothe Gabriel , Tremblay Jacques P.
Published: March 2022

Duchenne muscular dystrophy (DMD) is an X-linked hereditary disease characterized by progressive muscle wasting due to modifications in the DMD gene (exon deletions, nonsense mutations, intra-exonic insertions or deletions, exon duplications, splice site defects, and deep intronic mutations) that result in a lack of functional dystrophin expression. Many therapeutic approaches have so far been attempted to induce dystrophin expression and improve the patient phenotype. In this manuscript, we describe the relevant updates for some therapeutic strategies for DMD aiming to restore dystrophin expression. We also present and analyze in vitro and in vivo ongoing experimental approaches to treat the disease.
Case Report: Potential Applications of Using a 3D-Ring CZT SPECT for Lymphoscintigraphic Exploration of Lower Limb Edema
Authors: Besse Hélène , Bailly Matthieu
Published: March 2022

Lymphoscintigraphy is still considered the gold standard imaging modality for diagnosing lymphedema, due to ineffective lymphatic transport resulting in edema and skin damage. However, protocol variability and poor image resolution can make the interpretation challenging. Up to now, 99 mTc-labeled colloid lymphatic travel is monitored with dual-head cameras, but single-photon emission CT (SPECT) has proved its interest. Here, we present the case of a 59-year-old-man with bilateral asymmetric lower limb edema which was explored using dual-head and new 3D-ring cadmium -zinc-telluride (CZT) SPECT cameras, confirming bilateral lower limb lymphatic dysfunction. In line with other recently published reports, this case report promotes the use of SPECT/CT in the lymphoscintigraphic exploration of lower limb edema. The recognition of the clinicopathologic features of lower limb edema is required to prevent missed diagnoses, such as compressive disease, tumors, etc., as well as to better influence the management of patients.