bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Immune-Related Gene Signature in Stanford Type A Aortic Dissection
Authors: Li Zhaoshui , Wang Jumiao , Yu Qiao , Shen Ruxin , Qin Kun , Zhang Yu , Qiao Youjin , Chi Yifan
Published: June 2022

Background: Stanford type A aortic dissection (ATAAD) is a common life-threatening event in the aorta. Recently, immune disorder has been linked to the risk factors that cause ATAAD at the molecular level. However, the specific immune-related gene signature during the progression is unclear.

Methods: The GSE52093 and GSE98770 datasets related to ATAAD from the Gene Expression Omnibus (GEO) database were acquired. The immune gene expression levels were analyzed by single sample gene set enrichment analysis (ssGSEA). The correlations between gene networks and immune scores were determined by weighted gene correlation network analysis (WGCNA). The different immune subgroups were finally divided by consensus clustering. The differentially expressed genes (DEGs) were identified and subsequent functional enrichment analyses were conducted. The hub genes were identified by protein–protein interaction (PPI) network and functional similarities analyses. The immune cell infiltration proportion was determined by the CIBERSORT algorithm.

Results: According to the ssGSEA results, the 13 ATAAD samples from the GEO database were divided into high- and low-immune subgroups according to the ssGSEA, WGCNA, and consensus clustering analysis results. Sixty-eight immune-related DEGs (IRDEGs) between the two subgroups were enriched in inflammatory-immune response biological processes, including leukocyte cell–cell adhesion, mononuclear cell migration, and myeloid leukocyte migration. Among these IRDEGs, 8 genes (CXCR4, LYN, CCL19, CCL3L3, SELL, F11R, DPP4, and VAV3) were identified as hub genes that represented immune-related signatures in ATAAD after the PPI and functional similarities analyses. The proportions of infiltrating CD8 T cells and M1 macrophages were significantly higher in ATAAD patients in the immune-high group than the immune-low group.

Conclusion: Eight immune-related genes were identified as hub genes representing potential biomarkers and therapeutic targets linked to the immune response in ATAAD patients.
The Role of Registers in Increasing Knowledge and Improving Management of Children and Adolescents Affected by Familial Hypercholesterolemia: the LIPIGEN Pediatric Group
Authors: Gazzotti Marta , Casula Manuela , Bertolini Stefano , Capra Maria Elena , Olmastroni Elena , Catapano Alberico Luigi , Pederiva Cristina ,   the LIPIGEN Paediatric Group
Published: June 2022

Pathology registers can be a useful tool to overcome obstacles in the identification and management of familial hypercholesterolemia since childhood. In 2018, the LIPIGEN pediatric group was constituted within the Italian LIPIGEN study to focus on FH subjects under 18 years. This work aimed at discussing its recent progress and early outcomes. Demographic, biochemical, and genetic baseline characteristics were collected, with an in-depth analysis of the genetic defects. The analysis was carried out on 1,602 children and adolescents (mean age at baseline 9.9 ± 4.0 years), and almost the whole cohort underwent the genetic test (93.3%). Overall, the untreated mean value of LDL-C was 220.0 ± 97.2 mg/dl, with an increasing gradient from subjects with a negative (N = 317; mean untreated LDL-C = 159.9 ± 47.7 mg/dl), inconclusive (N = 125; mean untreated LDL-C = 166.4 ± 56.5 mg/dl), or positive (N = 1,053; mean untreated LDL-C = 246.5 ± 102.1 mg/dl) genetic diagnosis of FH. In the latter group, the LDL-C values presented a great variability based on the number and the biological impact of involved causative variants. The LIPIGEN pediatric group represents one of the largest cohorts of children with FH, allowing the deepening of the characterization of their baseline and genetic features, providing the basis for further longitudinal investigations for complete details.
The Accuracy of Sequence-Specific Oligonucleotide and Real-Time Polymerase Chain Reaction HLA Typing in Determining the Presence of Pre-Transplant Donor-Specific Anti-HLA Antibodies and Total Eplet Mismatches for Deceased Donor Kidney Transplantation
Authors: Larkins Nicholas G. , D’Orsogna Lloyd , Taverniti Anne , Sharma Ankit , Chakera Aron , Chan Doris , Krishnan Anoushka , Wong Germaine , Lim Wai H.
Published: June 2022

High resolution human leukocyte antigen (HLA) typing is important in establishing eplet compatibility and the specificity of donor-specific anti-HLA antibodies (DSA). In deceased donor kidney transplantation, high resolution donor HLA typing may not be immediately available, leading to inaccuracies during the organ allocation process. We aimed to determine the concordance and agreement of HLA-Class I and II eplet mismatches calculated using population frequency based allelic haplotype association (linkage disequilibrium, LD) from sequence-specific oligonucleotide (SSO) and real-time polymerase chain reaction (rtPCR) donor HLA typing (available at time of donor kidney allocation) compared to high-resolution Next Generation Sequencing (NGS) donor typing. NGS high resolution HLA typing were available for all recipients prior to donor kidney allocation. A cohort of 94 deceased donor-recipient pairs from a single Western Australian center were included (77 individual donors typed, 55 local and 22 interstate). The number of class I (HLA-A+B+C) and class II (HLA-DRB1+DRB3/4/5+DQB1+DQA1+DPB1+DPA1) eplet mismatches were calculated using HLAMatchmaker, comparing LD- and NGS-HLA typing. The accuracy in assigning pre-transplant DSA was compared between methods. The concordance correlation coefficient (95%CI) for HLA-class I and II eplet mismatches were 0.994 (0.992 to 0.996) and 0.991 (0.986 to 0.993), respectively. The 95% limits of agreement for class I were -1.3 (-1.6 to -1.1) to 1.4 (1.2 to 1.7) and -4.8 (-5.7 to -3.9) to 5.0 (4.1 to 5.9) for Class II. Disagreement between the two methods were present for 11 and 37 of the Class I and II donor/recipient pairs. Of which, 5 had a difference of ≥5 class II eplet mismatches. There were 34 (36%) recipients with potential pre-transplant DSA, of which 8 (24% of recipients with DSA) had indeterminate and ultimately false positive DSA assigned by donor LD-typing. While the concordance between NGS- and LD-typing was high, the limits of agreement suggest meaningful differences between these two techniques. The inaccurate assignment of DSA from donor LD-typing may result in associated HLA being considered unacceptable mismatches, inappropriately precluding candidates’ access to transplantation. Accurate imputation of two-field HLA alleles based on LD from SSO and rtPCR HLA typing remains a substantial challenge in clinical practice in-lieu of widely available, rapid, high-resolution methods.
Innate Immune Responses by Respiratory Viruses, Including Rhinovirus, During Asthma Exacerbation
Authors: Nakagome Kazuyuki , Nagata Makoto
Published: June 2022

Viral infection, especially with rhinovirus (RV), is a major cause of asthma exacerbation. The production of anti-viral cytokines such as interferon (IFN)-β and IFN-α from epithelial cells or dendritic cells is lower in patients with asthma or those with high IgE, which can contribute to viral-induced exacerbated disease in these patients. As for virus-related factors, RV species C (RV-C) induces more exacerbated disease than other RVs, including RV-B. Neutrophils activated by viral infection can induce eosinophilic airway inflammation through different mechanisms. Furthermore, virus-induced or virus-related proteins can directly activate eosinophils. For example, CXCL10, which is upregulated during viral infection, activates eosinophilsin vitro. The role of innate immune responses, especially type-2 innate lymphoid cells (ILC2) and epithelial cell-related cytokines including IL-33, IL-25, and thymic stromal lymphopoietin (TSLP), in the development of viral-induced airway inflammation has recently been established. For example, RV infection induces the expression of IL-33 or IL-25, or increases the ratio of ILC2 in the asthmatic airway, which is correlated with the severity of exacerbation. A mouse model has further demonstrated that virus-induced mucous metaplasia and ILC2 expansion are suppressed by antagonizing or deleting IL-33, IL-25, or TSLP. For treatment, IFNs including IFN-β suppress not only viral replication but also ILC2 activationin vitro. Agonists of toll-like receptor (TLR) 3 or 7 can induce IFNs, which can then suppress viral replication and ILC2 activation. Therefore, if delivered in the airway, IFNs or TLR agonists could become innovative treatments for virus-induced asthma exacerbation.
CD47-SIRPα Controls ADCC Killing of Primary T Cells by PMN Through a Combination of Trogocytosis and NADPH Oxidase Activation
Authors: Gondois-Rey Françoise , Miller Thomas , Laletin Vladimir , Morelli Xavier , Collette Yves , Nunès Jacques , Olive Daniel
Published: June 2022

Immunotherapies targeting the “don’t eat me” myeloid checkpoint constituted by CD47 SIRPα interaction have promising clinical potential but are limited by toxicities associated with the destruction of non-tumor cells. These dose-limiting toxicities demonstrate the need to highlight the mechanisms of anti–CD47-SIRPα therapy effects on non-tumor CD47-bearing cells. Given the increased incidence of lymphopenia in patients receiving anti-CD47 antibodies and the strong ADCC (antibody-dependent cellular cytotoxicity) effector function of polymorphonuclear cells (PMNs), we investigated the behavior of primary PMNs cocultured with primary T cells in the presence of anti-CD47 mAbs. PMNs killed T cells in a CD47-mAb–dependent manner and at a remarkably potent PMN to T cell ratio of 1:1. The observed cytotoxicity was produced by a novel combination of both trogocytosis and a strong respiratory burst induced by classical ADCC and CD47-SIRPα checkpoint blockade. The complex effect of the CD47 blocking mAb could be recapitulated by combining its individual mechanistic elements: ADCC, SIRPα blockade, and ROS induction. Although previous studies had concluded that disruption of SIRPα signaling in PMNs was limited to trogocytosis-specific cytotoxicity, our results suggest that SIRPα also tightly controls activation of NADPH oxidase, a function demonstrated during differentiation of immature PMNs but not so far in mature PMNs. Together, our results highlight the need to integrate PMNs in the development of molecules targeting the CD47-SIRPα immune checkpoint and to design agents able to enhance myeloid cell function while limiting adverse effects on healthy cells able to participate in the anti-tumor immune response.
Gasdermins in Innate Host Defense Against Entamoeba histolytica and Other Protozoan Parasites
Authors: Wang Shanshan , Moreau France , Chadee Kris
Published: June 2022

Gasdermins (GSDMs) are a group of proteins that are cleaved by inflammatory caspases to induce pore formation in the plasma membrane to cause membrane permeabilization and lytic cell death or pyroptosis. All GSDMs share a conserved structure, containing a cytotoxic N-terminal (NT) pore-forming domain and a C-terminal (CT) repressor domain. Entamoeba histolytica (Eh) in contact with macrophages, triggers outside-in signaling to activate inflammatory caspase-4/1 via the noncanonical and canonical pathway to promote cleavage of gasdermin D (GSDMD). Cleavage of GSDMD removes the auto-inhibition that masks the active pore-forming NT domain in the full-length protein by interactions with GSDM-CT. The cleaved NT-GSDMD monomers then oligomerize to form pores in the plasma membrane to facilitate the release of IL-1β and IL-18 with a measured amount of pyroptosis. Pyroptosis is an effective way to counteract intracellular parasites, which exploit replicative niche to avoid killing. To date, most GSDMs have been verified to perform pore-forming activity and GSDMD-induced pyroptosis is rapidly emerging as a mechanism of anti-microbial host defence. Here, we review our comprehensive and current knowledge on the expression, activation, biological functions, and regulation of GSDMD cleavage with emphases on physiological scenario and related dysfunctions of each GSDM member as executioner of cell death, cytokine secretion and inflammation against Eh and other protozoan parasitic infections.
T Cell Extracellular Traps: Tipping the Balance Between Skin Health and Disease
Authors: Ouyang Kelsey , Oparaugo Nicole , Nelson Amanda M. , Agak George W.
Published: June 2022

The role of extracellular traps (ETs) in the innate immune response against pathogens is well established. ETs were first identified in neutrophils and have since been identified in several other immune cells. Although the mechanistic details are not yet fully understood, recent reports have described antigen-specific T cells producing T cell extracellular traps (TETs). Depending on their location within the cutaneous environment, TETs may be beneficial to the host by their ability to limit the spread of pathogens and provide protection against damage to body tissues, and promote early wound healing and degradation of inflammatory mediators, leading to the resolution of inflammatory responses within the skin. However, ETs have also been associated with worse disease outcomes. Here, we consider host-microbe ET interactions by highlighting how cutaneous T cell-derived ETs aid in orchestrating host immune responses againstCutibacterium acnes (C. acnes), a commensal skin bacterium that contributes to skin health, but is also associated with acne vulgaris and surgical infections following joint-replacement procedures. Insights on the role of the skin microbes in regulating T cell ET formation have broad implications not only in novel probiotic design for acne treatment, but also in the treatment for other chronic inflammatory skin disorders and autoimmune diseases.
Case Report: Successful Treatment of Alopecia Universalis With Tofacitinib and Increased Cytokine Levels: Normal Therapeutic Reaction or Danger Signal?
Authors: Yu Ling , Yu Huiqian , Zhang Shuai , Hao Yanzhao , Zhang Shoumin
Published: June 2022

Alopecia universalis (AU) is an autoimmune disorder characterized by non-scarring hair loss in the scalp, eyebrows, beard, and nearly the entire body, negatively affecting patient prognosis. Available treatments are usually unsatisfactory. The autoimmune attacks of hair follicles induced by CD8+ T cells and the collapse of hair follicle immune privilege are believed to be the leading causes of AU. Additionally, interferon (IFN)-γ plays an important role in triggering the collapse of hair follicle immune privilege and impairing hair follicle stem cells. Furthermore, the upregulation of Janus kinase (JAK)3 and phospho-signal transducer and activator of transcription (pSTAT)3/STAT1 in alopecia areata patients suggest that JAK inhibitors can be a potentially promising choice for AU patients for the reason that JAK inhibitors can interfere with JAK-STAT signaling pathways and inhibit IFN-γ. Herein, we report a case of AU successfully treated with tofacitinib. However, this beneficial response in the patient was accompanied by a remarkable increase in peripheral blood cytokine levels during tofacitinib treatment.
A Bibliometric and Knowledge-Map Analysis of Macrophage Polarization in Atherosclerosis From 2001 to 2021
Authors: Song Luxia , Zhang Jie , Ma Dan , Fan Yixuan , Lai Runmin , Tian Wende , Zhang Zihao , Ju Jianqing , Xu Hao
Published: June 2022

In recent years, studies of macrophage polarization in atherosclerosis have become an intense area of research. However, there are few bibliometric analyses regarding this area. In this review, we used CiteSpace 5.8.R3 and VOSviewer 1.6.16 software to perform text mining and knowledge-map analysis. We explored the development process, knowledge structure, research hotspots, and potential trends using a bibliometric and knowledge-map analysis to provide researchers with a macroscopic view of this field. The studies concerning macrophage polarization in atherosclerosis were downloaded from the Web of Science Core Collection. A total of 781 studies were identified and published by 954 institutions from 51 countries/regions. The number of studies of macrophage polarization in atherosclerosis increased over time. Arteriosclerosis Thrombosis and Vascular Biology published the highest number of articles and was the top co-cited journal. De Winther was the most prolific researcher, and Moore had the most co-citations. The author co-occurrence map illustrated that there was active cooperation among researchers. The most productive countries were the United States and China. Amsterdam University, Harvard University, and Maastricht University were the top three productive institutions in the research field. Keyword Co-occurrence, Clusters, and Burst analysis showed that “inflammation,” “monocyte,” “NF kappa B,” “mechanism,” and “foam cell” appeared with the highest frequency in studies. “Oxidative stress,” “coronary heart disease,” and “prevention” were the strongest citation burst keywords from 2019 to 2021.
BNT162b2 Booster Vaccination Elicits Cross-Reactive Immunity Against SARS-CoV-2 Variants B.1.1.529 and B.1.617.2 in Convalescents of All Ages
Authors: Jahrsdörfer Bernd , Proffen Matthias , Scholz Judith , Hägele Janina , Ludwig Carolin , Vieweg Christiane , Grempels Aline , Fabricius Dorit , Lotfi Ramin , Körper Sixten , Adler Guido , Schrezenmeier Hubert
Published: June 2022

In this prospective observational cohort study we analyzed cellular and serological immune response parameters against SARS-CoV-2 and current variants of concern (VOC) in 147 COVID-19-convalescent and 39 COVID-19-naïve individuals before and after BNT162b2 booster vaccination. No significant differences regarding immunological response parameters were observed between younger and older individuals. Booster vaccination induced full recovery of both cellular and serological response parameters including IFN-γ secretion and anti-spike antibody titers with strong neutralization capacities against wild type SARS-COV-2 and Delta. Surprisingly, even serological neutralization capacity against Omicron was detectable one month after second vaccination and four months before it had been first observed in South Africa. As a result, more than 90% of convalescent individuals exhibited detectable and 75% strong Omicron neutralization capacity after booster vaccination, compared with 72% and 46% of COVID-19-naïve individuals. Our results support the notion that broad and cross-reactive immune memory against SARS-CoV-2 including currently known VOCs can be established by booster vaccination with spike-based mRNA vaccines like BNT162b2, particularly in COVID-19-convalescent individuals of all ages. Nevertheless, especially in COVID-19-naïve individuals future variants escaping the memory immune response may require vaccine approaches such as inactivated whole virus vaccines, which include all antigenic components of the virus.
Implementing a One Health Approach to Rabies Surveillance: Lessons From Integrated Bite Case Management
Authors: Swedberg Catherine , Mazeri Stella , Mellanby Richard J. , Hampson Katie , Chng Nai Rui
Published: June 2022

As part of the ‘Zero by 30’ strategy to end human deaths from dog-mediated rabies by 2030, international organizations recommend a One Health framework that includes Integrated Bite Case Management (IBCM). However, little is understood about the implementation of IBCM in practice. This study aims to understand how IBCM is conceptualized, exploring how IBCM has been operationalized in different contexts, as well as barriers and facilitators to implementation. Semi-structured interviews were conducted with seventeen practitioners and researchers with international, national, and local expertise across Africa, Asia, and the Americas. Thematic analysis was undertaken using both inductive and deductive approaches. Four main themes were identified: 1) stakeholders’ and practitioners’ conceptualization of IBCM and its role in rabies elimination; 2) variation in how IBCM operates across different contexts; 3) barriers and facilitators of IBCM implementation in relation to risk assessment, PEP provisioning, animal investigation, One Health collaboration, and data reporting; and 4) the impact of the COVID-19 pandemic on IBCM programs. This study highlights the diversity within experts’ conceptualization of IBCM, and its operationalization. The range of perspectives revealed that there are different ways of organizing IBCM within health systems and it is not a one-size-fits-all approach. The issue of sustainability remains the greatest challenge to implementation. Contextual features of each location influenced the delivery and the potential impact of IBCM. Programs spanned from highly endemic settings with limited access to PEP charged to the patient, to low endemicity settings with a large patient load associated with free PEP policies and sensitization. In practice, IBCM was tailored to meet the demands of the local context and level of rabies control. Thus, experts’ experiences did not necessarily translate across contexts, affecting perceptions about the function, motivation for, and implementation of IBCM. To design and implement future and current programs, guidance should be provided for health workers receiving patients on assessing the history and signs of rabies in the biting animal. The study findings provide insights in relation to implementation of IBCM and how it can support programs aiming to reach the Zero by 30 goal.
Anatomy and Symbiosis of the Digestive System of the Vent Shrimp Rimicaris Exoculata and Rimicaris Chacei Revealed Through Imaging Approaches
Authors: Guéganton Marion , Rouxel Ouafae , Durand Lucile , Cueff-Gauchard Valérie , Gayet Nicolas , Pradillon Florence , Cambon-Bonavita Marie-Anne
Published: June 2022

The shrimp Rimicaris exoculata and Rimicaris chacei are visually dominant fauna co-occurring at deep-sea hydrothermal sites of the Mid-Atlantic Ridge (MAR). Their co-existence was related to contrasted life-history traits, including differences in their diet and reliance on chemoautotrophic symbionts at the adult stage. Both species of shrimp are colonized by diversified chemosynthetic symbiotic microbial communities in their cephalothoracic cavity. Symbiotic association with bacteria was also evidenced in their digestive system, and the major lineages were identified through sequencing (with Mycoplasmatales in the foregut and Deferribacteres in the midgut) but their precise distribution within each host species was not assessed. For the first time, we used Fluorescence in situ Hybridization (FISH) to visualize these lineages and describe their association with digestive structures of their host. The aim of the study was to identify possible differences between host species that could be related to their different life-history traits. For this purpose, we developed new specific FISH probes targeting Deferribacteres and Mycoplasmatales lineages identified in the digestive system of these shrimp. Our FISH results showed a partitioning of the bacterial lineages according to the digestive organ corroborating sequencing data, and highlighted their association with specific anatomical structures. Despite morphological differences between the foreguts of R. exoculata and R. chacei that could be related to the adult diet, our FISH results showed overall similar distribution of digestive symbionts for the two host species. However, a more comprehensive study is needed with specimens at different life or molt stages to reveal potential host specific patterns. Such comparisons are now possible thanks to our newly designed FISH probes. The tools used in our study are valuable for tracking symbiont lineages in the environment, allowing a better understanding of their relationship with their host along its life cycle, including their acquisition mechanisms.
Dissolved Organic Carbon Along a Meridional Transect in the Western North Pacific Ocean: Distribution, Variation and Controlling Processes
Authors: Ge Tiantian , Luo Chunle , Ren Peng , Zhang Hongmei , Chen Hongtao , Chen Zhaohui , Zhang Jing , Wang Xuchen
Published: June 2022

Dissolved organic carbon (DOC) in the ocean is one of the largest reduced and exchangeable organic carbon pools on Earth and plays important roles in carbon cycling and biogeochemical processes in the ocean. Here, we report the concentrations and distributions of DOC in water samples collected along a meridional transect in the western North Pacific (NP) Ocean in November 2019. Concentrations of DOC ranged from 33-102 μM, were higher in surface water, decreased rapidly with depth to 1,000 m, and then remained relatively constant. The labile fraction of DOC accounted for 20-40% of the surface bulk DOC and was respired very rapidly in the upper 200 m depth. The semi-labile fraction of DOC accounted for 15-20% of the surface bulk DOC and was exported downward and turned over at water depths of 200-2,000 m. The formation of NP Intermediate Water (NPIW) in the Kuroshio Extension (KE) region is a major process carrying some surface semi-labile DOC down. The Low concentrations of DOC (33-44 μM) were present in the entire water column below 1,000 m along the transect in the NP. Primary production and microbial consumption played major roles in the concentration and distribution of DOC in the euphotic zone, and hydrodynamic mixing and circulation of different water masses appear to be dominant factors controlling the distribution and dynamics of DOC in the deep water of the western NP.
The Interplay Between Dimethyl Sulfide (DMS) and Methane (CH4) in a Coral Reef Ecosystem
Authors: Deschaseaux Elisabeth S. M. , Swan Hilton B. , Maher Damien T. , Jones Graham B. , Schulz Kai G. , Koveke Edwin P. , Toda Kei , Eyre Bradley D.
Published: June 2022

Earth’s Radiation Budget is partly dictated by the fragile and complex balance between biogenic volatile organic compounds (BVOCs) and greenhouse gases (GHGs), which have the potential to impose cooling or warming once emitted to the atmosphere. Whilst methane (CH4) is strictly associated with global warming due to its solar-radiation absorbing properties, dimethyl sulfide (DMS) is generally considered a cooling gas through the light scattering properties of its atmospheric oxidation products. However, DMS may also partially contribute to the Earth’s warming through a small portion of it being degraded to CH4 in the water column. Coral reefs emit both DMS and CH4 but they have not previously been simultaneously measured. Here, we report DMS and CH4 fluxes as well as aerosol particle counts at Heron Island, southern Great Barrier Reef, during the austral summer of 2016. Sea-to-air DMS and CH4 fluxes were on average 24.9 ± 1.81 and 1.36 ± 0.11 µmol m-2 d-1, whilst intermediate (< 0.5-2.5 um) and large (> 2.5 um) particle number concentrations averaged 5.51 x 106 ± 1.73 x 105 m-3 and 1.15 x 106 ± 4.63 x 104 m-3, respectively. Positive correlations were found between DMS emissions and the abundance of intermediate (R2 = 0.1669, p < 0.001, n = 93) and large (R2 = 0.0869, p = 0.004, n = 93) aerosol particles, suggesting that DMS sea-to-air emissions significantly contribute to the growth of existing particles to the measured size ranges at the Heron Island lagoon. Additionally, a strong positive correlation was found between DMS and CH4 fluxes (R2 = 0.7526, p < 0.00001, n = 93), suggesting that the emission of these volatile compounds from coral reefs is closely linked. The slope of the regression between DMS and CH4 suggests that CH4 emissions at the Heron Island lagoon represent 5% of that of DMS, which is consistent with the average sea-to-air fluxes reported in this study (i.e. 24.9 ± 1.81 µmol m-2 d-1 for DMS and 1.36 ± 0.11 for CH4). These findings provide new insights on the complexity of BVOC and GHG emissions in coral reef systems and their potential role in climate regulation.
A Randomized, Controlled Trial of Treat-and-Extend vs. Pro Re Nata Regimen for Neovascular Age-Related Macular Degeneration
Authors: Jia Huixun , Lu Bing , Yuan Yuanzhi , Yuan Fei , Li Lei , Song Yanping , Rong Ao , Zhou Minwen , Wang Fenghua , Sun Xiaodong
Published: June 2022

Purpose

To compare the efficacy and safety of conbercept using a treat-and-extend (T&E) regimen vs. a pro re nata (PRN) regimen in Chinese patients with neovascular age-related macular degeneration (nAMD).

Methods

This was a randomized, multicenter, non-inferiority study. After an initial loading phase of three consecutive monthly intravitreal injections of 0.5 mg Conbercept, the patients were treated to PRN or T&E regimen. The prespecified retreatment criteria was defined as a more than 5-letter decrease in BCVA from the previous visit or any evidence of new retinal hemorrhages, or the presence of any IRF and any SRF of more than 200 μm in height at the sub-foveal center. The primary outcome was the mean change in best-corrected visual acuity (BCVA) from baseline to 24 months, with a prespecified non-inferiority limit of −5 letters.

Results

From July 2016 through August 2018, 141 participants were allocated and treated (T&E, n = 69; PRN, n = 72). About one fifth of the overall participants were dropped out during the 12-month follow-up (28/141, 19.9%), and about one thirds of the overall participants were lost during the 24-month follow-up (51/141, 36%). At 2 years, mean BCVA letter improvement was + 4.0 in the T&E group vs. + 5.1 in the PRN group, and T&E regimen was not non-inferior to PRN regimen [difference, −1.169 letters; 95% confidence interval (CI): −6.864 ∼ 4.526]. Subgroup analyses also demonstrate the similar results in PCV patients, naive patients and no-naive patients. The mean decrease in central subfield thickness were 180 ± 165 μm in the T&E group and 247 ± 230 μm in the PRN group, respectively. The patients in the PRN group had required significantly fewer injections than those in the T&E group (12.4 vs. 14.6 injections, P = 0.041). The types and rates of adverse events were comparable in the two treatment groups.

Conclusion

These findings suggest that the T&E regimen was not non-inferior to the PRN regimen in patients with nAMD in terms of BCVA outcomes through 24 months.

Clinical Trial Registration

ClinicalTrials.gov, identifier NCT02802657.
Case Report: Kearns Sayre Syndrome Complicated With Postpartum Cardiac Failure
Authors: Han Caixia , Jia Zongyang , Zhao Guangcai , Chen Wenhui , Hu Yue , Liu Haiying
Published: June 2022

Kearns Sayre Syndrome (KSS) is a rare mitochondrial disease characterized by a primary dysfunction of the mitochondrial respiratory chain. Cardiac involvement is a poor prognostic factor of KSS. Pregnancy and delivery in a KSS patient with cardiac involvement is uncommon, and strategies for the supervision and management of this group remain unclear. Herein, we report and discuss pregnancy and delivery complicated with acute cardiopulmonary failure in a woman with KSS.
Association Between the LZTFL1 rs11385942 Polymorphism and COVID-19 Severity in Colombian Population
Authors: Angulo-Aguado Mariana , Corredor-Orlandelli David , Carrillo-Martínez Juan Camilo , Gonzalez-Cornejo Mónica , Pineda-Mateus Eliana , Rojas Carolina , Triana-Fonseca Paula , Contreras Bravo Nora Constanza , Morel Adrien , Parra Abaunza Katherine , Restrepo Carlos M. , Fonseca-Mendoza Dora Janeth , Ortega-Recalde Oscar
Published: June 2022

Genetic and non-genetic factors are responsible for the high interindividual variability in the response to SARS-CoV-2. Although numerous genetic polymorphisms have been identified as risk factors for severe COVID-19, these remain understudied in Latin-American populations. This study evaluated the association of non-genetic factors and three polymorphisms: ACE rs4646994, ACE2 rs2285666, and LZTFL1 rs11385942, with COVID severity and long-term symptoms by using a case-control design. The control group was composed of asymptomatic/mild cases (n = 61) recruited from a private laboratory, while the case group was composed of severe/critical patients (n = 63) hospitalized in the Hospital Universitario Mayor-Méderi, both institutions located in Bogotá, Colombia. Clinical follow up and exhaustive revision of medical records allowed us to assess non-genetic factors. Genotypification of the polymorphism of interest was performed by amplicon size analysis and Sanger sequencing. In agreement with previous reports, we found a statistically significant association between age, male sex, and comorbidities, such as hypertension and type 2 diabetes mellitus (T2DM), and worst outcomes. We identified the polymorphism LZTFL1 rs11385942 as an important risk factor for hospitalization (p < 0.01; OR = 5.73; 95% CI = 1.2–26.5, under the allelic test). Furthermore, long-term symptoms were common among the studied population and associated with disease severity. No association between the polymorphisms examined and long-term symptoms was found. Comparison of allelic frequencies with other populations revealed significant differences for the three polymorphisms investigated. Finally, we used the statistically significant genetic and non-genetic variables to develop a predictive logistic regression model, which was implemented in a Shiny web application. Model discrimination was assessed using the area under the receiver operating characteristic curve (AUC = 0.86; 95% confidence interval 0.79–0.93). These results suggest that LZTFL1 rs11385942 may be a potential biomarker for COVID-19 severity in addition to conventional non-genetic risk factors. A better understanding of the impact of these genetic risk factors may be useful to prioritize high-risk individuals and decrease the morbimortality caused by SARS-CoV2 and future pandemics.
Proliferative Vasculopathy Associated With Antiphospholipid Antibodies in Patients With Neurological Symptoms
Authors: Yeo Jina , Hwang Inpyeong , Sohn Chul-Ho , Lee Eunyoung Emily , Lee Soon-Tae , Lee Eun Bong , Park Jin Kyun
Published: June 2022

Background

Proliferative vasculopathy (PV) associated antiphospholipid syndrome (APS) in the central nervous system is a rare un(der)recognized form of extra-criteria manifestations of APS. This study investigated the angiographic characteristics of cerebral and cervical arteries in patients with PV associated with antiphospholipid antibodies (aPLs).

Methods

Patients with aPLs, neurologic symptoms and diffuse luminal narrowing on brain or neck magnetic resonance angiography were selected from electronic medical records. Vascular wall and intraluminal pathology were examined by high-resolution vessel wall MR imaging (VW-MRI).

Results

A total of 11 patients (six men and five women) with PV-aPL, of median (interquartile range) age 42 (34–61) years, were included. Median anticardiolipin antibodies IgG titer was 78.9 (28.2–134.0) units and anti-beta 2 glycoprotein I antibodies (aB2GPIs) IgG titer was 227.2 (0.0–1012.1) units. All patients had diffuse luminal narrowing in the carotid basilar and/or cerebral arteries, five in the internal carotid artery (ICA); two each in the middle cerebral artery (MCA) and vertebral artery; and one each in the basilar artery (BA) and posterior cerebral artery. On VW-MRI, four patients showed concentric thickening of the vascular walls of the ICA and/or MCA and two showed mild eccentric wall thickening of the ICA or BA. All patients received antithrombotic treatment. In two patients with extremely high aB2GPIs titer, diffuse narrowing progressed despite treatment with antithrombotic agents on follow-up imaging.

Conclusions

This study suggests that PV-aPL might be a distinct extra-criteria manifestation of APS that can manifest as long-segmental diffuse stenosis of cerebral and cervical arteries. It should be considered in relatively young patients with neurologic symptoms and aPLs.
Case Report: Osmotic Demyelination Syndrome After Transcatheter Aortic Valve Replacement: Case Report and Review of Current Literature
Authors: Jin Xinhao , Wang Yonggang
Published: June 2022

Background

Osmotic demyelination syndrome (ODS) has a low incidence but is a life-threatening neurological disorder whose common cause is rapid overcorrection of chronic hyponatremia. Transcatheter aortic valve replacement (TAVR) is a new and important therapy for patients with aortic valve stenosis. In this article, we discuss the case of a 64-year-old woman who developed ODS after TAVR and provide a literature review.

Case Presentation

A 64-year-old female patient was admitted to the hospital with chest tightness, shortness of breath, and fatigue for 2 months, with worsening of symptoms for 3 days prior to presentation. Auscultation revealed crackles in the lung fields, and systolic murmurs could be easily heard in the aortic area. Echocardiography showed severe aortic stenosis. Chest X-ray showed pulmonary oedema. Laboratory examinations showed that her serum sodium was 135 mmol/L. The patient received a diuretic to relieve her symptoms but showed little benefit. Her symptoms worsened, and her blood pressure dropped. Then, she underwent emergency TAVR under extracorporeal membrane oxygenation (ECMO) support. After the operation, her urine output increased markedly, and serum sodium increased sharply from 140 to 172 mmol/L. An MRI scan showed multiple lesions in the pons suggestive of ODS.

Conclusion

To date, this is the first reported case of a patient who developed ODS after receiving TAVR. In current clinical practice, diuretics are often used in aortic stenosis patients because of pulmonary oedema. After a patient receives TAVR, kidney perfusion pressure quickly returns to normal, and with the residual effect of a high-dose diuretic, balances of fluid volume and electrolyte levels in this phase are quite fragile and must be carefully managed. If a patient has neurological symptoms/signs during this phase, ODS should be considered, and MRI might be necessary.
Current Status of Human Papillomavirus Infection and Cervical Cancer in the Philippines
Authors: Lintao Ryan C. V. , Cando Leslie Faye T. , Perias Glenmarie Angelica S. , Tantengco Ourlad Alzeus G. , Tabios Ian Kim B. , Velayo Clarissa L. , de Paz-Silava Sheriah Laine M.
Published: June 2022

Cervical cancer is estimated to cause 341,831 deaths each year, with 9 of 10 deaths occurring in developing countries. Over the past decade, there has been a significant increase in cervical cancer incidence among women in the Philippines. Persistent infection with high-risk human papillomavirus (HPV) is the well-established necessary cause of cervical cancer. Based on limited studies conducted in the Philippines, the prevalence of infection with any HPV genotype was 93.8% for cervical squamous cell carcinoma and 90.9% for cervical adenocarcinomas. HPV types 16 and 18 were the most common HPV genotypes among Filipino patients with cervical cancer. On the other hand, the incidence of HPV infection among Filipino women with normal cervices was 9.2%. The World Health Organization has launched a global agenda of eliminating HPV infection by 2030. One of its key milestones is to vaccinate 90% of girls with the HPV vaccine by 15 years. However, the HPV vaccination rate among Filipino women remains to be unsatisfactory. HPV vaccination has only been included in the Philippine Department of Health's community-based National Immunization Program in 2015. Despite these efforts, the Philippines currently ranks last on HPV program coverage among low-middle income countries, with coverage of only 23% of the target female population for the first dose and 5% for the final dose. The principal reason for the non-acceptance of HPV vaccines was the perceived high cost of vaccination. The low utilization of available cervical cancer screening tests such as Pap smear and visual inspection with acetic acid hampered the Philippines' control and prevention of HPV infection and cervical cancer. Among those diagnosed with cervical cancer in the Philippines, only an estimated 50% to 60% receive some form of treatment. To this end, we summarize the burden of HPV infection and cervical cancer on Filipinos and the risk factors associated with the disease. We present the current screening, diagnostics, treatment, and prevention of HPV-related diseases in the Philippines. Lastly, we also propose solutions on how each building block in health systems can be improved to eliminate HPV infection and reduce the burden of cervical cancer in the Philippines.
In vitro Susceptibility to β-Lactam Antibiotics and Viability of Neisseria gonorrhoeae Strains Producing Plasmid-Mediated Broad- and Extended-Spectrum β-Lactamases
Authors: Kandinov Ilya , Gryadunov Dmitry , Vinokurova Alexandra , Antonova Olga , Kubanov Alexey , Solomka Victoria , Shagabieva Julia , Deryabin Dmitry , Shaskolskiy Boris
Published: June 2022

Neisseria gonorrhoeae plasmids can mediate high-level antimicrobial resistance. The emergence of clinical isolates producing plasmid β-lactamases that can hydrolyze cephalosporins, the mainstay treatment for gonorrhea, may be a serious threat. In this work, N. gonorrhoeae strains producing plasmid-mediated broad- and extended-spectrum β-lactamases (ESBLs) were obtained in vitro, and their viability and β-lactam antibiotic susceptibility were studied. Artificial pblaTEM-1 and pblaTEM-20 plasmids were constructed by site-directed mutagenesis from a pblaTEM-135 plasmid isolated from a clinical isolate. Minimum inhibitory concentration (MIC) values for a series of β-lactam antibiotics, including benzylpenicillin, ampicillin, cefuroxime, ceftriaxone, cefixime, cefotaxime, cefepime, meropenem, imipenem, and doripenem, were determined. The N. gonorrhoeae strain carrying the pblaTEM-20 plasmid exhibited a high level of resistance to penicillins and second–fourth-generation cephalosporins (MIC ≥2 mg/L) but not to carbapenems (MIC ≤0.008 mg/L). However, this strain stopped growing after 6 h of culture. The reduction in viability was not associated with loss of the plasmid but can be explained by the presence of the plasmid itself, which requires additional reproduction costs, and to the expression of ESBLs, which can affect the structure of the peptidoglycan layer in the cell membrane. Cell growth was mathematically modeled using the generalized Verhulst equation, and the reduced viability of the plasmid-carrying strains compared to the non-plasmid-carrying strains was confirmed. The cell death kinetics of N. gonorrhoeae strains without the pblaTEM-20 plasmid in the presence of ceftriaxone can be described by a modified Chick–Watson law. The corresponding kinetics of the N. gonorrhoeae strain carrying the pblaTEM-20 plasmid reflected several processes: the hydrolysis of ceftriaxone by the TEM-20 β-lactamase and the growth and gradual death of cells. The demonstrated reduction in the viability of N. gonorrhoeae strains carrying the pblaTEM-20 plasmid probably explains the absence of clinical isolates of ESBL-producing N. gonorrhoeae.
Identification of a Novel Ceftazidime-Avibactam-Resistant KPC-2 Variant, KPC-123, in Citrobacter koseri Following Ceftazidime-Avibactam Treatment
Authors: Wang Lin , Shen Weiyi , Zhang Rong , Cai Jiachang
Published: June 2022

This study reported the identification of a novel ceftazidime-avibactam-resistant KPC-2 variant, KPC-123, in a Citrobacter koseri isolated from a patient in a Chinese hospital following ceftazidime-avibactam treatment of infection caused by OXA-232-producing Klebsiella pneumoniae. This novel KPC-123 consisting of 302 amino acids differs from KPC-2 by two insertions after positions 179 (ins179_TY) and 270 (ins270_DDKHSEA), respectively. Conjugation and cloning experiments confirmed that KPC-123 was able to confer high-level resistance to ceftazidime and ceftazidime/avibactam (MICs of 128 mg/L and 64/4 mg/L, respectively) and elevated MIC values of cefotaxime, cefepime, and aztreonam (4 mg/L, 2 mg/L, and 4 mg/L, respectively) but retained susceptibility to carbapenems. Whole-genome sequencing and genomic analysis revealed that blaKPC−123 within the “ISKpn27-blaKPC-ISKpn6” structure was located on a 93,814-bp conjugative plasmid that was almost identical to a blaKPC−2-carrying plasmid harbored in a K. pneumoniae isolate from the same sampling site of the patient, suggesting the transfer and in vivo evolution of this blaKPC-carrying plasmid. Hence, active surveillance of ceftazidime/avibactam resistance and the underlying mechanisms, which may facilitate the prevention and control of the dissemination of resistance, is needed.
Extracellular Vesicles and Their Associated miRNAs as Potential Biomarkers in Intracranial Aneurysm
Authors: Li Yuman , Wen Jiahao , Liang Dingyue , Sun Haitao
Published: June 2022

Intracranial aneurysms (IA) are abnormal expansions of the intracranial arteries. Once it ruptures, the mortality and disability rate are high. The cost of imaging examinations is high, and rupture risk cannot be predicted, making it difficult for high-risk groups to be screened and prevented. Thus, clinically effective biomarkers are required to screen high-risk groups, estimate the risk of rupture, and determine the appropriate early intervention step. This article introduces the current research and application of exosome-derived microRNA (miRNA) as biomarkers of intracranial aneurysms and their limitations, which can give researchers a general overview of the research in this field. It can also serve as a reference point for selecting related research directions.
Behavioral Reserve in Behavioral Variant Frontotemporal Dementia
Authors: Kim Su Hong , Kim Yae Ji , Lee Byung Hwa , Lee Peter , Park Ji Hyung , Seo Sang Won , Jeong Yong
Published: June 2022

“Reserve” refers to the individual clinical differences in response to a neuropathological burden. We explored the behavioral reserve (BR) and associated neural substrates in 40 participants with behavioral variant frontotemporal dementia (bvFTD) who were assessed with the frontal behavioral inventory (FBI) and magnetic resonance imaging. Because neuroimaging abnormality showed a high negative correlation with the FBI negative (but not positive) symptom scores, we developed a linear model only to calculate the nBR (BR for negative symptoms) marker using neuroimaging abnormalities and the FBI score. Participants were divided into high nBR and low nBR groups based on the nBR marker. The FBI negative symptom score was lower in the high nBR group than in the low nBR group having the same neuroimaging abnormalities. However, the high nBR group noted a steeper decline in cortical atrophy and showed less atrophy in the left frontotemporal cortices than the low nBR group. In addition, the fractional anisotropy (FA) values were greater in the high nBR than in the low nBR group, except in the sensory-motor and occipital areas. We identified an nBR-related functional network composed of bilateral frontotemporal areas and the left occipital pole. We propose the concept of BR in bvFTD, and these findings can help predict the disease progression.
Selective Brain Cooling: A New Horizon of Neuroprotection
Authors: Hong Ji Man , Choi Eun Sil , Park So Young
Published: June 2022

Therapeutic hypothermia (TH), which prevents irreversible neuronal necrosis and ischemic brain damage, has been proven effective for preventing ischemia-reperfusion injury in post-cardiac arrest syndrome and neonatal encephalopathy in both animal studies and clinical trials. However, lowering the whole-body temperature below 34°C can lead to severe systemic complications such as cardiac, hematologic, immunologic, and metabolic side effects. Although the brain accounts for only 2% of the total body weight, it consumes 20% of the body's total energy at rest and requires a continuous supply of glucose and oxygen to maintain function and structural integrity. As such, theoretically, temperature-controlled selective brain cooling (SBC) may be more beneficial for brain ischemia than systemic pan-ischemia. Various SBC methods have been introduced to selectively cool the brain while minimizing systemic TH-related complications. However, technical setbacks of conventional SBCs, such as insufficient cooling power and relatively expensive coolant and/or irritating effects on skin or mucosal interfaces, limit its application to various clinical settings. This review aimed to integrate current literature on SBC modalities with promising therapeutic potential. Further, future directions were discussed by exploring studies on interesting coping skills in response to environmental or stress-induced hyperthermia among wild animals, including mammals and birds.