bluuebunny/crossref_metadata_2025 huggingface dataset:
Gill and Liver Transcript Expression Changes Associated With Gill Damage in Atlantic Salmon (Salmo salar)
Authors: Emam Mohamed , Caballero-Solares Albert , Xue Xi , Umasuthan Navaneethaiyer , Milligan Barry , Taylor Richard G. , Balder Rachel , Rise Matthew L.
Published: March 2022

Gill damage represents a significant challenge in the teleost fish aquaculture industry globally, due to the gill’s involvement in several vital functions and direct contact with the surrounding environment. To examine the local and systemic effects accompanying gill damage (which is likely to negatively affect gill function) of Atlantic salmon, we performed a field sampling to collect gill and liver tissue after several environmental insults (e.g., harmful algal blooms). Before sampling, gills were visually inspected and gill damage was scored; gill scores were assigned from pristine [gill score 0 (GS0)] to severely damaged gills (GS3). Using a 44K salmonid microarray platform, we aimed to compare the transcriptomes of pristine and moderately damaged (i.e., GS2) gill tissue. Rank Products analysis (5% percentage of false-positives) identified 254 and 34 upregulated and downregulated probes, respectively, in GS2 compared with GS0. Differentially expressed probes represented genes associated with functions including gill remodeling, wound healing, and stress and immune responses. We performed gill and liver qPCR for all four gill damage scores using microarray-identified and other damage-associated biomarker genes. Transcripts related to wound healing (e.g., neb and klhl41b) were significantly upregulated in GS2 compared with GS0 in the gills. Also, transcripts associated with immune and stress-relevant pathways were dysregulated (e.g., downregulation of snaclec 1-like and upregulation of igkv3) in GS2 compared with GS0 gills. The livers of salmon with moderate gill damage (i.e., GS2) showed significant upregulation of transcripts related to wound healing (i.e., chtop), apoptosis (e.g., bnip3l), blood coagulation (e.g., f2 and serpind1b), transcription regulation (i.e., pparg), and stress-responses (e.g., cyp3a27) compared with livers of GS0 fish. We performed principal component analysis (PCA) using transcript levels for gill and liver separately. The gill PCA showed that PC1 significantly separated GS2 from all other gill scores. The genes contributing most to this separation were pgam2, des, neb, tnnt2, and myom1. The liver PCA showed that PC1 significantly separated GS2 from GS0; levels of hsp70, cyp3a27, pparg, chtop, and serpind1b were the highest contributors to this separation. Also, hepatic acute phase biomarkers (e.g., serpind1b and f2) were positively correlated to each other and to gill damage. Gill damage-responsive biomarker genes and associated qPCR assays arising from this study will be valuable in future research aimed at developing therapeutic diets to improve farmed salmon welfare.
Ficolin-2 Lectin Complement Pathway Mediates Capsule-Specific Innate Immunity Against Invasive Pneumococcal Disease
Authors: Nahm Moon H. , Yu Jigui , Calix Juan J. , Ganaie Feroze
Published: March 2022

Reports conflict regarding which lectin-microbial ligand interactions elicit a protective response from the lectin pathway (LP) of complement. Using fluorescent microscopy, we demonstrate the human lectin ficolin-2 binds to Streptococcus pneumoniae serotype 11A capsule polysaccharide dependent on the O-acetyltransferase gene wcjE. This triggers complement deposition and promotes opsonophagocytosis of encapsulated pneumococci. Even partial loss of ficolin-2 ligand expression through wcjE mutation abrogated bacterial killing. Ficolin-2 did not interact with any pneumococcal non-capsule structures, including teichoic acid. We describe multiple 11A clonal derivatives expressing varying degrees of wcjE-dependent epitopes co-isolated from single blood specimens, likely representing microevolutionary shifts towards wcjE-deficient populations during invasive pneumococcal disease (IPD). We find epidemiological evidence of wcjE impairing pneumococcal invasiveness, supporting that the LP’s ficolin-2 axis provides innate, serotype-specific serological protection against IPD. The fact that the LP is triggered by only a few discrete carbohydrate ligands emphasizes the need to reevaluate its impact in a glycopolymer-specific manner.
A SIRPαFc Fusion Protein Conjugated With the Collagen-Binding Domain for Targeted Immunotherapy of Non-Small Cell Lung Cancer
Authors: Liu Jiayang , Meng Zhefeng , Xu Tongyang , Kuerban Kudelaidi , Wang Songna , Zhang Xuyao , Fan Jiajun , Ju Dianwen , Tian Wenzhi , Huang Xuan , Huang Xiting , Pan Danjie , Chen Huaning , Zhao Weili , Ye Li
Published: March 2022

The SIRPαFc fusion protein can block the immunosuppressive CD47-SIRPα signal between macrophages and tumor cells as a decoy receptor and has demonstrated its immunotherapeutic efficacy in various tumors. However, its clinical application was limited because of the potential hematologic toxicity. The heptapeptide “TKKTLRT” is a collagen-binding domain (CBD) which can bind collagen specifically. Herein, we aim to improve the tumor targeting of SIRPαFc and therefore avoid its unnecessary exposure to normal cells through synthesizing a TKKTLRT–SIRPαFc conjugate. Experiments at molecular and cellular levels indicate that the TKKTLRT–SIRPαFc conjugate-derived collagen-binding affinity and the introduction of CBD did not impact the CD47-binding affinity as well as its phagocytosis-promoting effect on NSCLC cells. In vivo distribution experiments showed that CBD–SIRPαFc accumulated in tumor tissue more effectively compared to unmodified SIRPαFc, probably due to the exposed collagen in the tumor vascular endothelium and stroma resulting from the abnormal vessel structure. On an A549 NSCLC nude mouse xenograft model, CBD–SIRPαFc presented more stable and effective antitumor efficacy than SIRPαFc, along with significantly increased CD11b+F4/80+ macrophages especially MHC II+ M1 macrophages within tumors. All of these results revealed that CBD brought a tumor-targeting ability to the SIRPαFc fusion protein, which contributed to the enhanced antitumor immune response. Altogether, the CBD–SIRPαFc conjugate may have the potential to be an effective tumor immunotherapy with improved antitumor efficacy but less non-tumor-targeted side effect.
What's Race Got to Do With It? CRP Levels in Immune Mediated Skin Diseases: Considerations for Hidradenitis Suppurativa
Authors: Okeke Chidubem A. V. , Williams Jonathan P. , Iwuala Callyn U. , Igwe Pearl K. , Khanna Raveena , Perry Jessica D. , Okoye Ginette A. , Byrd Angel S.
Published: March 2022

Currently, there is a lack of racial/ethnic heterogeneity in research databases, exposing a systematic issue in studies exploring inflammation-mediated diseases, such as hidradenitis suppurativa (HS). HS is a chronic inflammatory skin condition that disrupts normal structure and functioning of terminal hair follicles, resulting in the formation of recurrent abscesses, nodules, and sinus tracts within intertriginous regions. Studies have described higher serum levels of inflammation-mediated C-reactive protein (CRP) in patients with HS, a disease that predominantly affects skin of color (SOC) populations. Herein, we explore the role of CRP levels in the context of HS disease presentation, management, and psychosocial implications in SOC patients to determine existing disparities in research studies.
Navigate Towards the Immunotherapy Era: Value of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer Patients With Brain Metastases
Authors: Yang Guanqun , Xing Ligang , Sun Xiaorong
Published: March 2022

Brain metastases (BMs) in non-small-cell lung cancer (NSCLC) patients are associated with significant morbidity and poor prognosis. Immune checkpoint inhibitors (ICIs) have resulted in a paradigm shift in the management of advanced NSCLC. However, the value of ICIs in NSCLC patients with BMs remains unclear because patients with BMs are routinely excluded in numerous prospective trials on ICIs. Here, starting from the mechanisms of ICIs for BMs, we will reveal the value of ICIs by reviewing the efficacy and adverse effects of ICIs monotherapy as well as promising combination strategies, such as combinations with chemotherapy, radiotherapy, and anti-angiogenic drugs, etc. In addition, the methods of patient selection and response assessment will be summarized to assist clinical practice and further studies.
Natural Killer Cells in Hepatic Ischemia-Reperfusion Injury
Authors: Huang Miao , Cai Hao , Han Bing , Xia Yuhan , Kong Xiaoni , Gu Jinyang
Published: March 2022

Ischemia-reperfusion injury can be divided into two phases, including insufficient supply of oxygen and nutrients in the first stage and then organ injury caused by immune inflammation after blood flow recovery. Hepatic ischemia-reperfusion is an important cause of liver injury post-surgery, consisting of partial hepatectomy and liver transplantation, and a central driver of graft dysfunction, which greatly leads to complications and mortality after liver transplantation. Natural killer (NK) cells are the lymphocyte population mainly involved in innate immune response in the human liver. In addition to their well-known role in anti-virus and anti-tumor defense, NK cells are also considered to regulate the pathogenesis of liver ischemia-reperfusion injury under the support of more and more evidence recently. The infiltration of NK cells into the liver exacerbates the hepatic ischemia-reperfusion injury, which could be significantly alleviated after depletion of NK cells. Interestingly, NK cells may contribute to both liver graft rejection and tolerance according to their origins. In this article, we discussed the development of liver NK cells, their role in ischemia-reperfusion injury, and strategies of inhibiting NK cell activation in order to provide potential possibilities for translation application in future clinical practice.
GPR105-Targeted Therapy Promotes Gout Resolution as a Switch Between NETosis and Apoptosis of Neutrophils
Authors: Liu Chunxiao , Zhou Mengze , Jiang Wenjiao , Ye Shumin , Tian Sheng , Jiang Cheng , Hao Kun , Li Huanqiu , Hu Qinghua
Published: March 2022

The fate of infiltrating neutrophils in inflamed joints determines the development of acute gouty arthritis (AGA). GPR105 highly expressed in human neutrophils is sensitive to monosodium urate crystals (MSU); nevertheless, the roles of GPR105 in AGA remain unclear. Here, we show that GPR105 is significantly upregulated in peripheral polymorphonuclear neutrophils of AGA patients. GPR105 knockout (GPR105−/−) prevented NETosis and induced apoptosis of neutrophils under MSU exposure, as well as attenuating inflammatory cascades in AGA. Mechanistically, GPR105 deletion activated cAMP-PKA signals, thereby disrupting Raf-Mek1/2-Erk1/2 pathway-mediated NADPH oxidase activation, contributing to inhibition of NETosis. Whereas, cAMP-PKA activation resulting in GPR105 deficiency modulated PI3K-Akt pathway to regulate apoptosis. More importantly, suppression of cAMP-PKA pathway by SQ22536 and H-89 restored NETosis instead of apoptosis in GPR105−/− neutrophils, promoting MSU-induced gout flares. Interestingly, lobetyolin was screened out as a potent GPR105 antagonist using molecular docking-based virtual screening and in vitro activity test, which efficiently attenuated MSU-induced inflammatory response interacting with GPR105. Taken together, our study implicated that modulating cell death patterns between NETosis and apoptosis through targeting GPR105 could be a potential therapeutic strategy for the treatment of AGA.
CARD9 Signaling, Inflammation, and Diseases
Authors: Liu Xuanyou , Jiang Bimei , Hao Hong , Liu Zhenguo
Published: March 2022

Caspase-recruitment domain 9 (CARD9) protein is expressed in many cells especially in immune cells, and is critically involved in the function of the innate and adaptive immune systems through extensive interactions between CARD9 and other signaling molecules including NF-κB and MAPK. CARD9-mediated signaling plays a central role in regulating inflammatory responses and oxidative stress through the productions of important cytokines and chemokines. Abnormalities of CARD9 and CARD9 signaling or CARD9 mutations or polymorphism are associated with a variety of pathological conditions including infections, inflammation, and autoimmune disorders. This review focuses on the function of CARD9 and CARD9-mediated signaling pathways, as well as interactions with other important signaling molecules in different cell types and the relations to specific disease conditions including inflammatory diseases, infections, tumorigenesis, and cardiovascular pathologies.
A Typology for Reef Passages
Authors: Breckwoldt Annette , Nozik Alexandra , Moosdorf Nils , Bierwirth Jan , Fache Elodie , Ferse Sebastian , Ford Amanda , Mangubhai Sangeeta , Pelletier Dominique , Piovano Susanna
Published: March 2022

Coral reefs host exceptionally diverse and abundant marine life. Connecting coasts and sheltered lagoons to the open ocean, reef passages are important yet poorly studied components of these ecosystems. Abiotic and biotic elements ‘pass’ through these reef passages, supporting critical ecological processes (e.g. fish spawning). Reef passages provide multiple social and ecological benefits for islands and their peoples, but are so far neither characterized nor recognized for their multifaceted significance. This study investigated 113 reef passages across nine Pacific islands (Fiji, New Caledonia, Vanuatu). GIS-based visual interpretations of satellite imagery were used to develop criteria to define three distinct types, mainly based on distance to coastline and presence/absence of an enclosed water body. The discussion identifies ways to refine and augment this preliminary typology as part of a research agenda for reef passages. With these next steps, this typology will be extendable to other regions to better document reef passages and their various roles, supporting biodiversity conservation and sustainable fisheries management.
Non-stationary Natural Mortality Influencing the Stock Assessment of Atlantic Cod (Gadus morhua) in a Changing Gulf of Maine
Authors: Chen Ning , Sun Ming , Zhang Chongliang , Ren Yiping , Chen Yong
Published: March 2022

Climate changes have increasingly driven diverse biological processes of fish and lead to non-stationary dynamics of populations. The Gulf of Maine (GOM) is vulnerable to climate change, which should be considered in fishery stock assessment and management. This study focuses on the effects of possible non-stationary natural mortality (M) on the stock assessment of Atlantic cod (Gadus morhua) in GOM. We evaluated different assumptions about stationary and non-stationary M driven by sea surface temperature (SST) using a simulation approach. We found that adopting non-stationary M could effectively improve the quality of stock assessment compared to the commonly used stationary assumption for the GOM cod. Non-stationary scenario assuming a non-linear relationship between SST and M had the lowest estimation errors of spawning stock biomass (SSB) and fishing mortality, and the younger and the older age groups tended to be less accurately estimated. Different assumptions in M led to diverged estimates of biological reference points and yielded large differences in the determination of stock status and development of management advices. This study highlights the importance of including non-stationary vital rates in fisheries assessment and management in response to changing ecosystems.
The Portuguese Man-of-War Has Always Entered the Mediterranean Sea—Strandings, Sightings, and Museum Collections
Authors: Tiralongo Francesco , Badalamenti Rosario , Arizza Vincenzo , Prieto Laura , Lo Brutto Sabrina
Published: March 2022

A search of records from different kinds of sources namely, scientific and grey literature, social media, and zoological museum collections, has been carried out to review the incidence of Physalia physalis (Linnaeus, 1758), the Portuguese man-of-war, in the Mediterranean Sea. The temporal frame of the records, considered valid if documented with images or collected specimens, ranged from the second half of the eighteenth century to the year 2021. Thanks to colonies preserved in some Italian historical museum collections, originating from the western basin, it was possible to date the putative first documented record of P. physalis of the Mediterranean Sea in 1850. The dataset shows some massive strandings that occurred in localities of the Strait of Gibraltar and Alboran Sea, the area of the entrance, from the Atlantic toward the Mediterranean waters, and the starting point from where the species spread toward the western and central basin. Physalia physalis does not reach the eastern area of the Mediterranean Sea. As the records of this species from the Italian maritime regions were abundant in the summertime and considering the danger related to contact with humans, they were subdivided into three categories of risk according to the months of occurrence. These categories were created to assign a level of danger for swimmers. The increasing sightings of such a poisonous cnidarian in coastal waters can represent a risk to human health, and a threat to all those activities linked to the marine tourism sector. The overview given goes beyond scientific purposes and aims to reach society and public administrators. The involvement of citizens and touristic structures for the early detection of P. physalis can play a key role in preventing encounters with the species, allowing marine tourist facilities to operate within a range of reasonable security.
Bioactives From Marine Animals: Potential Benefits for Human Reproductive Health
Authors: Hoang Thanh H. , Liang Qi , Luo Xuan , Tang Youhong , Qin Jian G. , Zhang Wei
Published: March 2022

Reproductive and sexual health issues, including infertility and sexual dysfunctions (SD), are common concerns affecting millions of reproductive age worldwide. Scattered literature reports that marine animals such as oysters, sea cucumbers, seahorses and spoon worms have unique bioactive compounds like saponins, steroids, seahorse-derived hydrolysates, polypeptide, oligopeptides and essential trace elements that significantly improve infertility, hormonal imbalance, SD, and impotence. In addition, these compounds have exhibited pharmacological properties against reproductive problems due to diabetes and exposure to electromagnetic fields, cyclophosphamide, or a high exercise load. This review presents the first critical assessment of the advances in understanding and applying bioactives from marine organisms to support human reproductive health. Key knowledge and technical gaps have been identified for future research to improve the lack of in-depth understanding of the mechanism and action of these bioactives in human clinical studies. There is a need to develop simple, selective, low-cost, and scalable processes to isolate and purify individual bioactive compounds for industrial applications. The optimizing culturing and farming conditions for specific bioactive compounds from targeted species are suggested for sustainable production. The review indicates a promising future of extracts and marine-derived bioactives as functional foods in preventing and managing human reproductive health issues, but mechanistic studies and further clinical trials are urgently required to evaluate their efficacy and safety.
Research on Void Signal Recognition Algorithm of 3D Ground-Penetrating Radar Based on the Digital Image
Authors: Huang Zhiyong , Xu Guoyuan , Tang Jiaming , Yu Huayang , Wang Duanyi
Published: March 2022

The three-dimensional ground-penetrating radar system is an effective method to detect road void disease. Ground penetrating radar image interpretation has the characteristics of multi-solution, long interpretation period, and high professional requirements of processors. In recent years, researchers have put forward solutions for automatic interpretation of ground-penetrating radar images, including automatic detection algorithm for subgrade diseases based on support vector machines, etc., but there are still some shortcomings such as training models with a large amount of data or setting parameters. In this article, a three-dimensional ground-penetrating radar void signal recognition algorithm based on the digital image is proposed, and the algorithm uses digital images to characterize radar signals. With the help of digital image processing methods, the images are processed by binarization, corrosion, expansion, connected area inspection, fine length index inspection, and three-dimensional matching inspection, so as to identify and determine the void signals and extract the void area volume index. The algorithm has been verified by laboratory tests and engineering projects, and the results show that the void identification algorithm can accurately identify the void area position; the error level between the measured values and the measured values of length, width, buried depth, and area is between 2.2 and 17.3%, and the error is generally within the engineering acceptance range. The volume index calculated by the algorithm has a certain engineering application value; compared with the support vector machine, the regressive convolution neural network, and other recognition methods, it has the advantage of not needing a large amount of data to train or modify parameters.
A Mini Review on the Microvia Filling Technology Based on Printed Metal Nano/Microparticles
Authors: Yang Guannan , Luo Shaogen , Li Zhen , Zhang Yu , Cui Chengqiang
Published: March 2022

Microvia filling is a core interconnection technique in electronic manufacturing. Electroplating is the primary method used in the industry for filling microvias but also has the drawbacks of cumbersome procedures and toxic by-products. New microvia filling technology through printing of metal particle–based conductive fillers was then developed, with the advantages of simpler process, higher efficiency, better compatibility, and eco-friendliness. Here, we review the up-to-date research findings on the microvia filling technology based on printed metal nano/microparticles from the perspectives of material development and filling performance. Some key questions about this technology are also discussed. We hope the outlook presented by this review could help the further studies on this topic. The review also identifies some key remaining issues to be resolved.
Tropisetron Preconditioning Decreases Myocardial Biomarkers in Patients Undergoing Heart Valve Replacement Surgery
Authors: Yu Di , Gong Xingrui , Zhang Yufei , Li Qing , Zhang Mazhang
Published: March 2022

Background

Cardioplegic arrest during the heart valve replacement surgery frequently leads to myocardial damage. Tropisetron (TRP) has been demonstrated to reduce myocardial ischemia-reperfusion injury and inflammation in animals. We examined the efficacy of TRP in lowering myocardial biomarkers in patients undergoing heart valve replacement surgery.

Methods

A total of seventy-five patients, scheduled for elective heart valve replacement surgery, were randomly chosen to receive either 10 ml of normal saline or 10 mg/10 ml of TRP immediately after anesthesia induction. Blood samples for the measurement of cardiac troponin I (cTnI), creatine kinase (CK-MB), lactate dehydrogenase (LDH), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-10 (IL-10) were taken before anesthesia, as well as 4, 12, and 24 h after aortic cross-clamp release to evaluate myocardial injury using two-way ANOVA for repeated measurements. The study was registered at www.chictr.org.cn (number, ChiCTR-1800018681).

Results

Treatment with TRP decreased the increment of cTnI (Fgroup = 4.911, p = 0.030; Ftime = 55.356, p = 0.001; Fgroup × time = 5.340, p = 0.002) at 12 and 24 h; of CK-MB (Fgroup = 6.552, p = 0.013; Ftime = 49.276, p = 0.001; Fgroup × time = 7.627, p = 0.003) at 4, 12, and 24 h; of TNF-α (Fgroup = 4.153, p = 0.046; Ftime = 28.244, p = 0.002; Fgroup × time = 4.692, p = 0.006) at 4 and 12 h; and of LDH (Fgroup = 4.275, p = 0.043; Ftime = 63.225, p = 0.001; Fgroup × time = 2.501, p = 0.083) at 24 h after the release of the aortic cross-clamp. It increased IL-10 (Fgroup = 5.958, p = 0.018; Ftime = 31.226, p = 0.002; Fgroup × time = 1.464, p = 0.236) at 12 h after the release of the aortic cross-clamp. Multiple linear regression analysis showed that cardiopulmonary bypass (CPB) time was a risk factor, and that TRP treatment was a protective factor for postoperative cTNI change (β = 4.449, 95% CI [0.97–7.92], p = 0.013 for CPB time; and β = −381, 95% CI [−613.4 to −148.5], p = 0.002 for TRP treatment).

Conclusions

Tropisetron had cardioprotective and anti-inflammatory effects in patients undergoing heart valve replacement surgery with cardioplegic arrest. The addition of TRP and reduction of CPB time should be considered for myocardial protection in heart valve replacement surgery.

Clinical Trial Registration

[www.chictr.org.cn/index.aspx], identifier [ChiCTR1800018681].
The Value of the Frog Lateral View Radiograph for Detecting Collapse of Femur Head Necrosis: A Retrospective Study of 1001 Cases
Authors: Yang Fan , Deng Xiaoqiang , Xin Pengfei , Hong Zhinan , Pang Fengxiang , He Wei , Wei Qiushi , Li Ziqi
Published: March 2022

Aims

The collapse in femur head necrosis is generally detected by CT or MRI which are not primary routine examination at every follow-up in developing countries. The purpose of this study was to verify the reliability of the frog lateral view radiograph in detecting the collapse of femoral head.

Methods

We retrospectively included 1001 hips of 620 patients with femur head necrosis. The anteroposterior view and frog lateral view of X-ray standard radiographs, CT and MRI of patients were collected and simultaneously evaluated by three orthopedists to evaluate the condition of collapse according to the unified standard. The inter-observer reliability of each view of X-ray for detecting the collapse were analyzed through the weighted Cohen's kappa index. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of each evaluation method were also calculated.

Results

A moderate or substantial reliability was indicated in the evaluation of frog lateral view radiograph, whereas the anteroposterior view only showed fair or poor reliability. Using the CT or MRI results of collapse as the gold standard, the frog lateral view indicated higher sensitivity and accuracy than the anteroposterior view (sensitivity: 82.8 vs. 64.9%; accuracy: 87.1 vs. 73.9%). The combination of the anteroposterior view and frog lateral view indicated higher reliability than individual views.

Conclusion

The frog lateral view radiograph has higher sensitivity and accuracy than anteroposterior view. It is a complementary method to AP view for detecting the collapse in femur head necrosis during the follow-up, which has moderate or substantial inter-observer reliability.
Hyperinflammatory State and Low T1 Adaptive Immune Response in Severe and Critical Acute COVID-19 Patients
Authors: Garcia-Gasalla Mercedes , Berman-Riu María , Pons Jaime , Rodríguez Adrián , Iglesias Amanda , Martínez-Pomar Natalia , Llompart-Alabern Isabel , Riera Melchor , Ferré Beltrán Adrián , Figueras-Castilla Albert , Murillas Javier , Ferrer Joana M.
Published: March 2022

Background

A better understanding of COVID-19 immunopathology is needed to identify the most vulnerable patients and improve treatment options.

Objective

We aimed to identify immune system cell populations, cytokines, and inflammatory markers related to severity in COVID-19.

Methods

139 hospitalized patients with COVID-19−58 mild/moderate and 81 severe/critical—and 74 recovered patients were included in a prospective longitudinal study. Clinical data and blood samples were obtained on admission for laboratory markers, cytokines, and lymphocyte subsets study. In the recovered patients, lymphocyte subsets were analyzed 8–12 weeks after discharge.

Results

A National Early Warning Score 2 >2 (OR:41.4; CI:10.38–167.0), ferritin >583 pg/mL (OR:16.3; CI: 3.88–69.9), neutrophil/lymphocyte ratio >3 (OR: 3.5; CI: 1.08–12.0), sIL-2rα (sCD25) >512 pg/mL (OR: 3.3; CI: 1.48–7.9), IL-1Ra >94 pg/mL (OR: 3.2; IC: 1.4–7.3), and IL-18 >125 pg/mL (OR: 2.4; CI: 1.1–5.0) were associated with severe/critical COVID-19 in the multivariate models used. Lower absolute values of CD3, CD4, CD8, and CD19 lymphocytes together with higher frequencies of NK cells, a CD4 and CD8 activated (CD38+HLA-DR+) memory T cell and effector memory CD45RA+ (EMRA) phenotype, and lower T regulatory cell frequencies were found in severe/critical patients relative to mild/moderate and recovered COVID-19 patients. A significant reduction in Th1, Tfh1, and Tc1 with higher Th2, Tfh2, Tc2, and plasma cell frequencies was found in the most severe cases.

Conclusion

A characteristic hyperinflammatory state with significantly elevated neutrophil/lymphocyte ratio and ferritin, IL-1Ra, sIL-2rα, and IL-18 levels together with a “low T1 lymphocyte signature” was found in severe/critical COVID-19 patients.
The Value of the Antibody Detection in the Diagnosis of Ocular Toxocariasis and the Aqueous Cytokine Profile Associated With the Condition
Authors: Zhang Xiang , Yang Yuan , Zheng Yan , Hu Yiqian , Rao Yuqing , Li Jiakai , Zhao Peiquan , Li Jing
Published: March 2022

Introduction

To evaluate and compare the specificity of Toxocara canis-specific antibody detection in the serum and aqueous samples for the diagnosis of ocular toxocariasis (OT) and explore the cytokine profiles associated with the condition in children.

Materials and Methods

This is a prospective cohort study. The inclusion criteria were the clinical presentations of OT, which included unilateral vision reduction, typical peripheral or posterior pole granuloma with variable degrees of vitritis, and exclusion of other diagnoses. The titer of antibody against the excretory-secretory antigen of Toxocara canis [T-immunoglobulin G (IgG)] was measured in serum and aqueous samples that were taken from the affected eyes. The diagnosis of OT was made upon positive detection of T-IgG either in the serum or aqueous. The rest with typical clinical presentations as described above but a positive serum or aqueous T-IgG could not be confirmed were diagnosed as suspected OT. Cytokines were measured using multiplexed cytometric bead array system.

Results

Two hundred and eleven eyes of 211 patients had participated in the study. One hundred and twenty-eight eyes were diagnosed as OT. The median age of the cohort was 7.7 years with a male to female ratio of 2.5:1. Major initial symptoms were decreased vision (74%) and strabismus (22%). The percentages of eyes with peripheral granuloma, posterior granuloma, and endophthalmitis were 40, 18, and 41%, respectively. Vitritis (100%), vitreous strands (64%), retinal fibrotic bands (57%), and retinal detachment (42%) were the most common signs. T-IgG was positive in 66.7% of the aqueous and 57.2% of the serum samples. Forty-four patients were diagnosed T-IgG negative in both serum and aqueous of the affected eyes. Interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, IL-8, eosinophil chemotactic protein (Eotaxin), MCP-1β, and vascular endothelial growth factor (VEGF) were higher in T-IgG negative eyes when compared to controls and further increased in T-IgG positive eyes. However, only T-IgG positive eyes showed increased IL-5, IL-13, and IL-10. IL-1β, tumor necrosis factor-alpha (TNF-α), IL-12, IL-2, interferon-gamma (IFN-γ), and IL-4 were undetectable in all eyes.

Conclusions

Pediatric OT is often present with severe retinal complications. Polarized intraocular Th2 response was only found in aqueous T-IgG positive eyes. Our results supported an aqueous sample-based antibody test for the more specific diagnosis of OT.
Vitamin D Status in Relation to the Clinical Outcome of Hospitalized COVID-19 Patients
Authors: Hafez Wael , Saleh Husam , Arya Arun , Alzouhbi Mouhamad , Fdl Alla Osman , Lal Kumar , Kishk Samy , Ali Sara , Raghu Srinivasa , Elgaili Walaa , Abdul Hadi Wissam
Published: March 2022

Coronavirus Disease (COVID-19) is a newly emerged infectious disease that first appeared in China. Vitamin D is a steroid hormone with an anti-inflammatory protective role during viral infections, including SARS-CoV-2 infection, via regulating the innate and adaptive immune responses. The study aimed to investigate the correlation between serum 25-hydroxyvitamin D (25[OH]D) levels and clinical outcomes of COVID-19. This was a retrospective study of 126 COVID-19 patients treated in NMC Royal Hospital, UAE. The mean age of patients was 43 ± 12 years. Eighty three percentage of patients were males, 51% patients were with sufficient (> 20 ng/mL), 41% with insufficient (12–20 ng/mL), and 8% with deficient (<12 ng/mL) serum 25(OH)D levels. There was a statistically significant correlation between vitamin D deficiency and mortality (p = 0.04). There was a statistically significant correlation between 25(OH)D levels and ICU admission (p = 0.03), but not with the need for mechanical ventilation (p = 0.07). The results showed increased severity and mortality by 9 and 13%, respectively, for each one-year increase in age. This effect was maintained after adjustment for age and gender (Model-1) and age, gender, race, and co-morbidities (Models-2,3). 25(OH)D levels (<12 ng/mL) showed a significant increase in mortality by eight folds before adjustments (p = 0.01), by 12 folds in Model-1 (p = 0.04), and by 62 folds in the Model-2. 25(OH)D levels (< 20 ng/mL) showed no association with mortality before adjustment and in Model-1. However, it showed a significant increase in mortality by 29 folds in Model-3. Neither 25(OH)D levels (<12 ng/mL) nor (< 20 ng/mL) were risk factors for severity. Radiological findings were not significantly different among patients with different 25(OH)D levels. Despite observed shorter time till viral clearance and time from cytokine release storm to recovery among patients with sufficient 25(OH)D levels, the findings were statistically insignificant. In conclusion, we demonstrated a significant correlation between vitamin D deficiency and poor COVID-19 outcomes.
Incidence Trend and Competing Risk Analysis of Patients With Intrahepatic Cholangiocarcinoma: A Population-Based Study
Authors: Xing Huiwu , Tan Bingqian , Yang Chenyu , Zhang Mingman
Published: March 2022

Background

Intrahepatic cholangiocarcinoma (ICCA) is a primary liver cancer characterized by rapid progression and poor prognosis. There are few effective tools for evaluating the prognosis of ICCA patients, and the use of liver transplantation (LT) of the treatment for ICCA is still controversial.

Methods

We analyzed ICCA incidence data and clinicopathological data from the Surveillance, Epidemiology, and End Results database. Prognostic predictors were identified by univariate and multivariate Cox regression analyses and then used to establish a nomogram. The prediction performance of the nomogram was evaluated with receiver operating characteristic (ROC) curves, calibration plots and decision curve analysis (DCA) plots. Propensity score matching (PSM) was used to balance the baseline data of patients undergoing LT and other operations, and then, univariate Cox regression analysis was used to evaluate the therapeutic value of LT for ICCA.

Results

The incidence of ICCA increased significantly, from 0.6 per 100,000 in 2,000 to 1.3 per 100,000 in 2018. The median overall survival (OS) of the patients was 13 months, and the 1-, 3-, and 5-year OS rates were 51.40, 22.14, and 13.79%, respectively. Cox regression analysis showed that age under 60 years old, female, tumor size ≤ 50 mm, better differentiation, smaller range of tumor invasion, lack of distant metastasis, regional lymph node surgery and treatment were associated with a better prognosis. The ROC curves, calibration plots, and DCA plots showed that the nomogram had good discrimination and calibration power, as well as clinical utility. After PSM, the univariate Cox regression analysis showed no significant difference in OS between patients treated with LT and patients treated with other operations.

Conclusion

The incidence of ICCA increased significantly. A nomogram with good predictive performance was developed to predict the OS of ICCA patients. LT might be considered as a potential option for some ICCA patients.
Metagenomic Next-Generation Sequencing to Investigate Infectious Endophthalmitis of Brucella: A Case Report
Authors: Xi Huiyu , Zhang Lishuai , Xu Bo , Liu Haiyang , Li Suyan
Published: March 2022

Introduction

Brucellosis is a systemic disease that exists prevalently in clinical manifestations. The symptoms present in organs such as the eyes (in ocular brucellosis) can lead to misdiagnosis or even failure to diagnose. Metagenomic Next-Generation Sequencing (mNGS), a high-throughput sequencing approach, could be applied for the detection of microorganisms.

Case Presentation

A 57-year-old female with acute right-eye vision loss, treated with clindamycin and dexamethasone sodium phosphate for 1.5 months, was difficult to diagnose using regular methods. mNGS was utilized for the aqueous fluid from the patient, and Brucella melitensis was identified. The inflammation was treated with 3 months of antibiotherapy. However, even with specific medicine and surgery, the vision remained poor because severe ocular conditions last for a long time.

Conclusion

It suggests that brucella should still be a probable pathogen in endophthalmitis despite its low incidence in non-epidemic areas. Moreover, mNGS can achieve early diagnosis and timely treatment for difficult-to-diagnose ocular infections.
RDHCformer: Fusing ResDCN and Transformers for Fetal Head Circumference Automatic Measurement in 2D Ultrasound Images
Authors: Yang Chaoran , Liao Shanshan , Yang Zeyu , Guo Jiaqi , Zhang Zhichao , Yang Yingjian , Guo Yingwei , Yin Shaowei , Liu Caixia , Kang Yan
Published: March 2022

Fetal head circumference (HC) is an important biological parameter to monitor the healthy development of the fetus. Since there are some HC measurement errors that affected by the skill and experience of the sonographers, a rapid, accurate and automatic measurement for fetal HC in prenatal ultrasound is of great significance. We proposed a new one-stage network for rotating elliptic object detection based on anchor-free method, which is also an end-to-end network for fetal HC auto-measurement that no need for any post-processing. The network structure used simple transformer structure combined with convolutional neural network (CNN) for a lightweight design, meanwhile, made full use of powerful global feature extraction ability of transformer and local feature extraction ability of CNN to extract continuous and complete skull edge information. The two complement each other for promoting detection precision of fetal HC without significantly increasing the amount of computation. In order to reduce the large variation of intersection over union (IOU) in rotating elliptic object detection caused by slight angle deviation, we used soft stage-wise regression (SSR) strategy for angle regression and added KLD that is approximate to IOU loss into total loss function. The proposed method achieved good results on the HC18 dataset to prove its effectiveness. This study is expected to help less experienced sonographers, provide help for precision medicine, and relieve the shortage of sonographers for prenatal ultrasound in worldwide.
The Role of Inorganics in Preeclampsia Assessed by Multiscale Multimodal Characterization of Placentae
Authors: Rduch Thomas , Tsolaki Elena , El Baz Yassir , Leschka Sebastian , Born Diana , Kinkel Janis , Anthis Alexandre H. C. , Fischer Tina , Jochum Wolfram , Hornung René , Gogos Alexander , Herrmann Inge K.
Published: March 2022

Preeclampsia is one of the most dangerous diseases in pregnancy. Because of the hypertensive nature of preeclampsia, placental calcifications are believed to be a predictor for its occurrence, analogous to their role in cardiovascular diseases. However, the prevalence and the relevance of calcifications for the clinical outcome with respect to preeclampsia remains controversial. In addition, the role of other inorganic components present in the placental tissue in the development of preeclampsia has rarely been investigated. In this work, we therefore characterized inorganic constituents in placental tissue in groups of both normotensive and preeclamptic patients (N = 20 each) using a multi-scale and multi-modal approach. Examinations included elemental analysis (metallomics), sonography, computed tomography (CT), histology, scanning electron microscopy, X-ray fluorescence and energy dispersive X-ray spectroscopy. Our data show that tissue contents of several heavy metals (Al, Cd, Ni, Co, Mn, Pb, and As) were elevated whereas the Rb content was decreased in preeclamptic compared to normotensive placentae. However, the median mineral content (Ca, P, Mg, Na, K) was remarkably comparable between the two groups and CT showed lower calcified volumes and fewer crystalline deposits in preeclamptic placentae. Electron microscopy investigations revealed four distinct types of calcifications, all predominantly composed of calcium, phosphorus and oxygen with variable contents of magnesium in tissues of both maternal and fetal origin in both preeclamptic and normotensive placentae. In conclusion our study suggests that heavy metals, combined with other factors, can be associated with the development of preeclampsia, however, with no obvious correlation between calcifications and preeclampsia.
Occupational Therapy for People Living With Human T-Lymphotropic Virus 1: Importance and Effectiveness of an Intervention Plan at the Level of Prevention and Rehabilitation
Authors: Sampaio Edilson Coelho , Aben-Athar Cintia Yolette Urbano Pauxis , Pinto Denise da Silva , Vallinoto Antonio Carlos Rosário , Cayres Vallinoto Izaura Maria Vieira
Published: March 2022

Introduction

Human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy (HAM) restricts activities of daily living (ADLs), affecting health and quality of life. Occupational therapy is used to promote independence during ADL in people living with HTLV (PLHTLV).

Objective

To quantify the clinical aspects, levels of functionality, performance in ADLs and occupational roles of PLHTLV and propose an occupational therapeutic intervention.

Method

A cross-sectional, descriptive, observational study was designed with 40 PLHTLV monitored at two referral laboratories of the Federal University of Pará. The Evandro Chagas Research Institute Neurological Disability Scale (EIPEC-2), the Barthel Index and the Occupational Roles Identification List were applied. The G test and Fisher’s exact test (to identify associations between qualitative variables), the Mann–Whitney test (to identify associations between quantitative variables) and Pearson correlation analysis (to identify associations between the total Barthel Index and EIPEC-2 scores) were performed with Microsoft Excel and BioEstat 5.0, and the significance level was set atp≤ 0.05.

Results

Motor aspects, the presence of spasticity, sensory aspects, and pain in the lumbar region and lower limbs were significantly (p= 0.0002) higher among symptomatic individuals, who also had more difficulties urinating, traveling up and down stairs and transferring from a chair to a bed. Being a worker, performing housework and socializing (with friends or family members) were the most affected activities among HAM patients.

Conclusion

The impact of HAM on PLHTLV should include an intervention plan with occupational therapists in rehabilitation programs to create an important third-level prevention initiative, which may help achieve short-, medium-, and long-term goals. Asymptomatic PLHTLV should also be able to prevent future ADL impairment.
Improved Precision-Cut Liver Slice Cultures for Testing Drug-Induced Liver Fibrosis
Authors: Dewyse Liza , De Smet Vincent , Verhulst Stefaan , Eysackers Nathalie , Kunda Rastislav , Messaoudi Nouredin , Reynaert Hendrik , van Grunsven Leo A.
Published: March 2022

In vitro models of human liver disease often fail to mimic the complex 3D structures and cellular organizations found in vivo. Precision cut liver slices (PCLS) retain the complex physiological architecture of the native liver and therefore could be an exceptional in vitro liver model. However, the production of PCLS induces a spontaneous culture-induced fibrogenic reaction, limiting the application of PCLS to anti-fibrotic compounds. Our aim was to improve PCLS cultures to allow compound-induced fibrosis induction. Hepatotoxicity in PCLS cultures was analyzed by lactate dehydrogenase leakage and albumin secretion, while fibrogenesis was analyzed by qRT-PCR and western blot for hepatic stellate cell (HSC) activation markers and collagen 6 secretion by enzyme-linked immunosorbent assays (ELISA). We demonstrate that supplementation of 3 mm mouse PCLS cultures with valproate strongly reduces fibrosis and improves cell viability in our PCLS cultures for up to 5 days. Fibrogenesis can still be induced both directly and indirectly through exposure to TGFβ and the hepatotoxin acetaminophen, respectively. Finally, human PCLS cultures showed similar but less robust results. In conclusion, we optimized PCLS cultures to allow for drug-induced liver fibrosis modeling.
Identification of 1, 2, 4-Triazine and Its Derivatives Against Lanosterol 14-Demethylase (CYP51) Property of Candida albicans: Influence on the Development of New Antifungal Therapeutic Strategies
Authors: Verma Abhishek Kumar , Majid Aarfah , Hossain Md. Shahadat , Ahmed SK. Faisal , Ashid Mohammad , Bhojiya Ali Asger , Upadhyay Sudhir K. , Vishvakarma Naveen Kumar , Alam Mudassir
Published: March 2022

This research aims to find out whether the 1, 2, 4-triazine and its derivatives have antifungal effects and can protect humans from infection with Candida albicans. Molecular docking and molecular dynamic simulation are widely used in modern drug design to target a particular protein with a ligand. We are interested in using molecular docking and molecular dynamics modeling to investigate the interaction between the derivatives of 1, 2, 4-triazine with enzyme Lanosterol 14-demethylase (CYP51) of Candida albicans. The inhibition of Candida albicans CYP51 is the main goal of our research. The 1, 2, 4-triazine and its derivatives have been docked to the CYP51 enzyme, which is involved in Candida albicans Multidrug Drug Resistance (MDR). Autodock tools were used to identify the binding affinities of molecules against the target proteins. Compared to conventional fluconazole, the molecular docking results indicated that each drug has a high binding affinity for CYP51 proteins and forms unbound interactions and hydrogen bonds with their active residues and surrounding allosteric residues. The docking contacts were made using a 10 ns MD simulation with nine molecules. RMSD, RMSF, hydrogen bonds, and the Rg all confirm these conclusions. In addition, these compounds were expected to have a favorable pharmacological profile and low toxicity. The compounds are being offered as scaffolds for the development of new antifungal drugs and as candidates for future in vitro testing.