bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Optical Coherence Tomography and Intravascular Ultrasound Imaging to Quantify Coronary Plaque Cap Stress/Strain and Progression: A Follow-Up Study Using 3D Thin-Layer Models
Authors: Lv Rui , Maehara Akiko , Matsumura Mitsuaki , Wang Liang , Zhang Caining , Huang Mengde , Guo Xiaoya , Samady Habib , Giddens Don. P. , Zheng Jie , Mintz Gary S. , Tang Dalin
Published: August 2021

Accurate plaque cap thickness quantification and cap stress/strain calculations are of fundamental importance for vulnerable plaque research. To overcome uncertainties due to intravascular ultrasound (IVUS) resolution limitation, IVUS and optical coherence tomography (OCT) coronary plaque image data were combined together to obtain accurate and reliable cap thickness data, stress/strain calculations, and reliable plaque progression predictions. IVUS, OCT, and angiography baseline and follow-up data were collected from nine patients (mean age: 69; m: 5) at Cardiovascular Research Foundation with informed consent obtained. IVUS and OCT slices were coregistered and merged to form IVUS + OCT (IO) slices. A total of 114 matched slices (IVUS and OCT, baseline and follow-up) were obtained, and 3D thin-layer models were constructed to obtain stress and strain values. A generalized linear mixed model (GLMM) and least squares support vector machine (LSSVM) method were used to predict cap thickness change using nine morphological and mechanical risk factors. Prediction accuracies by all combinations (511) of those predictors with both IVUS and IO data were compared to identify optimal predictor(s) with their best accuracies. For the nine patients, the average of minimum cap thickness from IVUS was 0.17 mm, which was 26.08% lower than that from IO data (average = 0.23 mm). Patient variations of the individual errors ranged from ‒58.11 to 20.37%. For maximum cap stress between IO and IVUS, patient variations of the individual errors ranged from ‒30.40 to 46.17%. Patient variations of the individual errors of maximum cap strain values ranged from ‒19.90 to 17.65%. For the GLMM method, the optimal combination predictor using IO data had AUC (area under the ROC curve) = 0.926 and highest accuracy = 90.8%, vs. AUC = 0.783 and accuracy = 74.6% using IVUS data. For the LSSVM method, the best combination predictor using IO data had AUC = 0.838 and accuracy = 75.7%, vs. AUC = 0.780 and accuracy = 69.6% using IVUS data. This preliminary study demonstrated improved plaque cap progression prediction accuracy using accurate cap thickness data from IO slices and the differences in cap thickness, stress/strain values, and prediction results between IVUS and IO data. Large-scale studies are needed to verify our findings.
Global Epidemiology, Health Outcomes, and Treatment Options for Patients With Type 2 Diabetes and Kidney Failure
Authors: Phillips Jessica , Chen Jenny H. C. , Ooi Esther , Prunster Janelle , Lim Wai H.
Published: August 2021

The burden of type 2 diabetes and related complications has steadily increased over the last few decades and is one of the foremost global public health threats in the 21st century. Diabetes is one of the leading causes of chronic kidney disease and kidney failure and is an important contributor to the cardiovascular morbidity and mortality in this population. In addition, up to one in three patients who have received kidney transplants develop post-transplant diabetes, but the management of this common complication continues to pose a significant challenge for clinicians. In this review, we will describe the global prevalence and temporal trend of kidney failure attributed to diabetes mellitus in both developing and developed countries. We will examine the survival differences between treated kidney failure patients with and without type 2 diabetes, focusing on the survival differences in those on maintenance dialysis or have received kidney transplants. With the increased availability of novel hypoglycemic agents, we will address the potential impacts of these novel agents in patients with diabetes and kidney failure and in those who have developed post-transplant diabetes.
Identification and Characteristics of Fusion Peptides Derived From Enveloped Viruses
Authors: Lozada Camille , Barlow Thomas M. A. , Gonzalez Simon , Lubin-Germain Nadège , Ballet Steven
Published: August 2021

Membrane fusion events allow enveloped viruses to enter and infect cells. The study of these processes has led to the identification of a number of proteins that mediate this process. These proteins are classified according to their structure, which vary according to the viral genealogy. To date, three classes of fusion proteins have been defined, but current evidence points to the existence of additional classes. Despite their structural differences, viral fusion processes follow a common mechanism through which they exert their actions. Additional studies of the viral fusion proteins have demonstrated the key role of specific proteinogenic subsequences within these proteins, termed fusion peptides. Such peptides are able to interact and insert into membranes for which they hold interest from a pharmacological or therapeutic viewpoint. Here, the different characteristics of fusion peptides derived from viral fusion proteins are described. These criteria are useful to identify new fusion peptides. Moreover, this review describes the requirements of synthetic fusion peptides derived from fusion proteins to induce fusion by themselves. Several sequences of the viral glycoproteins E1 and E2 of HCV were, for example, identified to be able to induce fusion, which are reviewed here.
Short-Term Prediction of Preeclampsia in Chinese Women Using the Soluble fms-Like Tyrosine Kinase 1/Placental Growth Factor Ratio: A Sub-Analysis of the PROGNOSIS Asia Study
Authors: Gao Jinsong , Huang Xianghua , Di Wen , Dong Xiaojing , Gou Wenli , Shi Hong , Wang Zilian , Dietl Angela , Grill Sonja , Hund Martin
Published: August 2021

The diagnosis of preeclampsia in China currently relies on limited clinical signs and unspecific laboratory findings. These are inadequate predictors of preeclampsia development, limiting early diagnosis and appropriate management. Previously, the Prediction of Short-Term Outcome in Pregnant Women with Suspected Preeclampsia Study (PROGNOSIS) and PROGNOSIS Asia demonstrated that a soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio of ≤38 can be used to rule out preeclampsia within 1 week, with negative predictive values of 99.3 and 98.6%, respectively. This is an exploratory sub-analysis of the Chinese cohort (n= 225) of the PROGNOSIS Asia study. The primary objectives were to assess the predictive performance of using the sFlt-1/PlGF ratio to rule out preeclampsia within 1 week and to rule in preeclampsia within 4 weeks. The sFlt-1/PlGF ratio was also examined for short-term prediction of fetal adverse outcomes, maternal adverse outcomes, and time to delivery. The overall prevalence of preeclampsia was 17.3%. With the use of an sFlt-1/PlGF ratio of ≤38, the negative predictive value for ruling out preeclampsia within 1 week was 97.3% [95% confidence interval (CI), 93.8–99.1], with a sensitivity of 64.3% and specificity of 85.3%. With the use of an sFlt-1/PlGF ratio of >38, the positive predictive value for ruling in preeclampsia within 4 weeks was 35.0% (95% CI, 20.6–51.7), with a sensitivity of 50.0% and specificity of 86.8%. In the analyses of the sFlt-1/PlGF ratio and fetal adverse outcomes, the area under the receiver operating characteristic curve was 92.8% (95% CI, 83.5–98.7) for ruling out fetal adverse outcomes within 1 week and 79.9% (95% CI, 68.1–90.3) for ruling in fetal adverse outcomes within 4 weeks. An sFlt-1/PlGF ratio of >38 increased the likelihood of imminent delivery 3.3-fold compared with a ratio of ≤38 [hazard ratio, 3.3 (95% CI, 2.1–5.1)]. This sub-analysis confirms the high predictive performance of the sFlt-1/PlGF ratio cutoff of 38 for short-term prediction of preeclampsia in Chinese women, which may help prevent unnecessary hospitalization of women with low risk of developing preeclampsia.
Catheter-based Closure of a Post-infective Aortic Paravalvular Pseudoaneurysm Fistula With Severe Regurgitation After Two Valve Replacement Surgeries: A Case Report
Authors: Onorato Eustaquio Maria , Vercellino Matteo , Masoero Giovanni , Monizzi Giovanni , Sanchez Federico , Muratori Manuela , Bartorelli Antonio L.
Published: August 2021

Backgsround: Infective endocarditis (IE) of prosthetic valves is a dire complication of cardiac valve replacement surgery and is associated with high rates of morbidity and mortality.

Case Summary: A 72-year-old woman with multiple comorbidities underwent surgical replacement of the aortic valve with a mechanical prosthetic valve after recurrent IE. After nine months, IE recurred and the mechanical valve was surgically replaced with a bioprosthetic valve. Three years later, severe heart failure developed due to severe paravalvular leak (PVL) caused by an aortic annulus abscess complicated by a paravalvular pseudoaneurysm fistula (PPF). The patient was deemed at prohibitive surgical risk and a catheter-based PVL closure procedure was planned. However, the interventional procedure was delayed several months due to the Covid-19 pandemic with progressive heart failure worsening. Despite an acute satisfactory result of the PPF transcatheter closure and a significant clinical improvement, the patient died 10 months later due to multiorgan failure. It is likely that this was due, at least in part, to the long treatment delay caused by the unprecedented strain on the healthcare system.

Discussion: In patients at high surgical risk, early diagnosis and prompt interventional treatment of severe PVL are crucial for improving expectancy and quality of life. However, the recent outbreak of COVID-19 caused deferral of elective and semi-elective structural heart disease procedures (SHD) as in our case. Thus, a proactive and vigilant stance on managing SHD should be a priority even in the context of the COVID-19 pandemic.
Monsoon Surges Enhance Extreme Rainfall by Maintaining the Circulation of Landfalling Tropical Cyclones and Slowing Down Their Movement
Authors: Zhao Dajun , Chen Lianshou , Yu Yubin
Published: August 2021

Extreme rainfall induced by landfalling tropical cyclones (ERLTCs) in China can cause flash floods and other disastrous impacts, so investigating their genesis and mechanism of enhancement has been attracting considerable attention. This study demonstrates that the extreme rainfall of landfalling tropical cyclones (LTCs) possesses two key properties—namely, maintenance of the LTC circulation and a lagging (slowing down or looping) of its movement, and the monsoon surge can provide a positive contribution to these properties. Specifically, diagnostics show that the low-level cyclonic vorticity and upper-level divergence of ERLTCs are significantly stronger than those of NERLTCs (non-extreme-rainfall-producing LTCs). The continuous intensification of the cyclonic rotation in the lower troposphere before the occurrence of extreme rainfall is a significant feature that distinguishes ERLTCs from NERLTCs. Vorticity budget analysis further shows that the relative vorticity advection term contributes the most to the local increase and maintenance of vorticity in the middle and lower troposphere of ERLTCs under the influence of the southwest monsoonal surge, thus demonstrating that the monsoonal surge favors the maintenance of LTC circulation. On the other hand, the activity of the southwest monsoonal surge is mainly manifested in the zonal wind anomaly, and the corresponding strong westerly transport can significantly reduce the zonal component of the steering flow. As a result, the total steering flow can be weakened, which decreases the northwestward translation speed of ERLTCs, and thus the monsoonal surge favors a lagging (slowing down or looping) of LTC movement. These results reveal the mechanism of influence through which the monsoonal surge affects ERLTCs via its direct impacts on the maintenance of their circulation and lagging of their movement—two distinct evolutionary characteristics.
3D Atlas of the Pituitary Gland of the Model Fish Medaka (Oryzias latipes)
Authors: Royan Muhammad Rahmad , Siddique Khadeeja , Csucs Gergely , Puchades Maja A. , Nourizadeh-Lillabadi Rasoul , Bjaalie Jan G. , Henkel Christiaan V. , Weltzien Finn-Arne , Fontaine Romain
Published: August 2021

In vertebrates, the anterior pituitary plays a crucial role in regulating several essential physiological processes via the secretion of at least seven peptide hormones by different endocrine cell types. Comparative and comprehensive knowledge of the spatial distribution of those endocrine cell types is required to better understand their physiological functions. Using medaka as a model and several combinations of multi-color fluorescence in situ hybridization, we present the first 3D atlas revealing the gland-wide distribution of seven endocrine cell populations: lactotropes, thyrotropes, Lh and Fsh gonadotropes, somatotropes, and pomca-expressing cells (corticotropes and melanotropes) in the anterior pituitary of a teleost fish. By combining in situ hybridization and immunofluorescence techniques, we deciphered the location of corticotropes and melanotropes within the pomca-expressing cell population. The 3D localization approach reveals sexual dimorphism of tshba-, pomca-, and lhb-expressing cells in the adult medaka pituitary. Finally, we show the existence of bi-hormonal cells co-expressing lhb-fshb, fshb-tshba and lhb-sl using single-cell transcriptomics analysis and in situ hybridization. This study offers a solid basis for future comparative studies of the teleost pituitary and its functional plasticity.
Detection of Fruit Meals Within Laboratory-Raised and Field-Trapped Adult Drosophila suzukii (Diptera: Drosophilidae) Guts
Authors: Kraft Laura J. , Sit Tim L. , Diepenbrock Lauren M. , Ashrafi Hamid , Aryal Rishi , Fernandez Gina E. , Burrack Hannah J.
Published: August 2021

The feeding habits of adult Brachycera are understudied and may provide important context for understanding invasive pest biology, as with the polyphagous small fruit pestDrosophila suzukii. We developed molecular methods to study adultD. suzukiigut content in order to understand its feeding habits. We designed and verified two primer pairs specific for either blueberries or blackberries and used a qPCR melt curve analysis to determine whether we can detect the presence or absence of berry feeding by adult flies. In a laboratory assay, the blueberry fly meal DNA can be detected for longer periods than the blackberry meal DNA. Generally, female gut contents are less variable than male gut contents. We also tested recently emerged flies that were not fed as adults but developed as larvae in either blueberries or blackberries. Some adult flies from each fruit had detectable fruit DNA in their gut, which could be due to pupal meconium feeding after emergence. Next, we aimed to test the primers in the field to develop techniques to track fruit feeding byD. suzukiiin its natural field environment. First, to identify the most appropriate collection method, we determined how long we could detect fruit DNA, using previously developed primers withinD. suzukiigut preserved in four types of trap fluid in the laboratory. The likelihood of detecting blackberry DNA differed by day, trap fluid, and between sexes. For the blueberry primer, the possibility of detecting blueberry DNA differed by trap fluid only. Based on those results, we used RV antifreeze with a Scentry SWD lure in field trials at two research station locations, one containing blackberries and one with blueberries. We established transects away from each fruit planting and collected up to 120 total flies at each point along transects. There were no significant differences in the number of flies containing berry DNA among collection points along the transect in both locations. These results suggest that adult flies move between crop and non-crop habitats and may not be highly dependent on fruit food resources.
Identification and Functional Characterization of a Low-Density Lipoprotein Receptor Gene Pathogenic Variant in Familial Hypercholesterolemia
Authors: Shu Hong-Yan , Zhang Wei , Zheng Cong-Cong , Gao Man-Yun , Li Yong-Cun , Wang Yan-Gang
Published: August 2021

We report a single-point variant of low-density lipoprotein receptor (LDLR) in a Chinese proband with a clinical diagnosis of familial hypercholesterolemia (FH) with a comprehensive functional analysis. Target exome capture-based next-generation sequencing was used for sequencing and identification of genomic variants in the LDLR gene. The expression, cellular location, and function of the mutant LDLR were analyzed. Sequencing of LDLR in FH patients indicated a point variant of single-base substitution (G < A) at a position of 2389 in the 16th exon, which led to a loss of the 16th exon in the LDLR messenger RNA. This genomic variant was found to cause exon 16 deletion in the mutant LDLR protein. Subsequent functional analyses showed that the mutant LDLR was retained in the Golgi apparatus and rarely expressed in the cellular membranes of HepG2 cells. Accordingly, the intake ability of HepG2 cells with the mutant LDLR was significantly reduced (P < 0.05). In conclusion, our results suggest that a mutant with a single-base substitution (c. 2389G > A) in the 16th exon of the LDLR gene was associated with miscleavage of messenger RNA and the retention of mutant LDLR in the Golgi apparatus, which revealed a pathogenic variant in LDLR underlying the pathogenesis of FH.
Clinical Significance and Immunologic Landscape of a Five-IL(R)-Based Signature in Lung Adenocarcinoma
Authors: Fan Tao , Pan Shize , Yang Shuo , Hao Bo , Zhang Lin , Li Donghang , Geng Qing
Published: August 2021

Interleukins (ILs) and interleukin receptors (ILRs) play important role in the antitumor immune response. However, the expression signature and clinical characteristics of the IL(R) family in lung adenocarcinoma (LUAD) remains unclear. The main purpose of this study was to explore the expression profile of IL(R) family genes and construct an IL(R)-based prognostic signature in LUAD. Five public datasets of 1,312 patients with LUAD were enrolled in this study. Samples from The Cancer Genome Atlas (TCGA) were used as the training set, and samples from the other four cohorts extracted from Gene Expression Omnibus (GEO) database were used as the validation set. Additionally, the profile of IL(R) family signature was explored, and the association between this signature and immunotherapy response was also analyzed. Meanwhile, the prognostic value was compared between this IL(R)-based signature and different immunotherapy markers. A signature based on five identified IL(R)s (IL7R, IL5RA, IL20RB, IL11, IL22RA1) was constructed using the TCGA dataset through univariate/multivariable Cox proportional hazards regression and least absolute shrinkage and selection operator (LASSO) Cox analysis. These cases with LUAD were stratified into high- and low-risk group according to the risk score. This signature showed a strong prognostic ability, which was verified by the five independent cohorts and clinical subtypes. The IL(R)-based models presented unique characteristics in terms of immune cell infiltration and immune inflammation profile in tumor microenvironment (TME). Biological pathway analysis confirmed that high-risk patients showed significant T- and B-cell immunosuppression and rapid tumor cell proliferation. More importantly, we researched the relationship between this IL(R)-based signature and immune checkpoints, tumor mutation burden (TMB), tumor purity and ploidy, and tumor immune dysfunction and exclusion (TIDE) score, which confirmed that this signature gave the best prognostic value. We first provided a robust prognostic IL(R)-based signature, which had the potential as a predictor for immunotherapy response to realize individualized treatment of LUAD.
Siglec-H-Deficient Mice Show Enhanced Type I IFN Responses, but Do Not Develop Autoimmunity After Influenza or LCMV Infections
Authors: Szumilas Nadine , Corneth Odilia B. J. , Lehmann Christian H. K. , Schmitt Heike , Cunz Svenia , Cullen Jolie G. , Chu Talyn , Marosan Anita , Mócsai Attila , Benes Vladimir , Zehn Dietmar , Dudziak Diana , Hendriks Rudi W. , Nitschke Lars
Published: August 2021

Siglec-H is a DAP12-associated receptor on plasmacytoid dendritic cells (pDCs) and microglia. Siglec-H inhibits TLR9-induced IFN-α production by pDCs. Previously, it was found that Siglec-H-deficient mice develop a lupus-like severe autoimmune disease after persistent murine cytomegalovirus (mCMV) infection. This was due to enhanced type I interferon responses, including IFN-α. Here we examined, whether other virus infections can also induce autoimmunity in Siglec-H-deficient mice. To this end we infected Siglec-H-deficient mice with influenza virus or with Lymphocytic Choriomeningitis virus (LCMV) clone 13. With both types of viruses we did not observe induction of autoimmune disease in Siglec-H-deficient mice. This can be explained by the fact that both types of viruses are ssRNA viruses that engage TLR7, rather than TLR9. Also, Influenza causes an acute infection that is rapidly cleared and the chronicity of LCMV clone 13 may not be sufficient and may rather suppress pDC functions. Siglec-H inhibited exclusively TLR-9 driven type I interferon responses, but did not affect type II or type III interferon production by pDCs. Siglec-H-deficient pDCs showed impaired Hck expression, which is a Src-family kinase expressed in myeloid cells, and downmodulation of the chemokine receptor CCR9, that has important functions for pDCs. Accordingly, Siglec-H-deficient pDCs showed impaired migration towards the CCR9 ligand CCL25. Furthermore, autoimmune-related genes such as Klk1 and DNase1l3 are downregulated in Siglec-H-deficient pDCs as well. From these findings we conclude that Siglec-H controls TLR-9-dependent, but not TLR-7 dependent inflammatory responses after virus infections and regulates chemokine responsiveness of pDCs.
Functional Fc Gamma Receptor Gene Polymorphisms and Long-Term Kidney Allograft Survival
Authors: Wahrmann Markus , Döhler Bernd , Arnold Marie-Luise , Scherer Sabine , Mayer Katharina A. , Haindl Susanne , Haslacher Helmuth , Böhmig Georg A. , Süsal Caner
Published: August 2021

The functional Fc gamma receptor (FcγR) IIIA polymorphism FCGR3A-V/F158 was earlier suggested to determine the potential of donor-specific HLA antibodies to trigger microcirculation inflammation, a key lesion of antibody-mediated renal allograft rejection. Associations with long-term transplant outcomes, however, have not been evaluated to date. To clarify the impact of FCGR3A-V/F158 polymorphism on kidney transplant survival, we genotyped a cohort of 1,940 recipient/donor pairs. Analyzing 10-year death-censored allograft survival, we found no significant differences in relation to FCGR3A-V/F158. There was also no independent survival effect in a multivariable Cox model. Similarly, functional polymorphisms in two other activating FcγR, FCGR2A-H/R131 (FcγRIIA) and FCGR3B-NA1/NA2 (FcγRIIIB), were not associated with outcome. There were also no significant survival differences among patient subgroups at increased risk of rejection-related injury, such as pre-sensitized recipients (> 0% panel reactivity; n = 438) or recipients treated for rejection within the first year after transplantation (n = 229). Our study results suggest that the earlier shown association of FcγR polymorphism with microcirculation inflammation may not be strong enough to exert a meaningful effect on graft survival.
The Epithelial Cell Glycocalyx in Ocular Surface Infection
Authors: Argüeso Pablo , Woodward Ashley M. , AbuSamra Dina B.
Published: August 2021

The glycocalyx is the main component of the transcellular barrier located at the interface between the ocular surface epithelia and the external environment. This barrier extends up to 500 nm from the plasma membrane and projects into the tear fluid bathing the surface of the eye. Under homeostatic conditions, defense molecules in the glycocalyx, such as transmembrane mucins, resist infection. However, many pathogenic microorganisms have evolved to exploit components of the glycocalyx in order to gain access to epithelial cells and consequently exert deleterious effects. This manuscript reviews the implications of the ocular surface epithelial glycocalyx to bacterial, viral, fungal and parasitic infection. Moreover, it presents some ongoing controversies surrounding the functional relevance of the epithelial glycocalyx to ocular infectious disease.
Development of a Smartphone-Based Nanozyme-Linked Immunosorbent Assay for Quantitative Detection of SARS-CoV-2 Nucleocapsid Phosphoprotein in Blood
Authors: Liu Bochao , Wu Ze , Liang Chaolan , Lu Jinhui , Li Jinfeng , Zhang Ling , Li Tingting , Zhao Wei , Fu Yongshui , Hou Shuiping , Tang Xi , Li Chengyao
Published: August 2021

Since December 2019, a novel coronavirus (SARS-CoV-2) has resulted in a global pandemic of coronavirus disease (COVID-19). Although viral nucleic acid test (NAT) has been applied predominantly to detect SARS-CoV-2 RNA for confirmation diagnosis of COVID-19, an urgent need for alternative, rapid, and sensitive immunoassays is required for primary screening of virus. In this study, we developed a smartphone-based nanozyme-linked immunosorbent assay (SP-NLISA) for detecting the specific nucleocapsid phosphoprotein (NP) of SARS-CoV-2 in 37 serum samples from 20 COVID-19 patients who were diagnosed by NAT previously. By using SP-NLISA, 28/37 (75.7%) serum samples were detected for NP antigens and no cross-reactivity with blood donors’ control samples collected from different areas of China. In a control assay using the conventional enzyme-linked immunosorbent assay (ELISA), only 7/37 (18.91%) serum samples were detected for NP antigens and no cross-reactivity with control samples. SP-NLISA could be used for rapid detection of SARS-CoV-2 NP antigen in primary screening of SARS-CoV-2 infected individuals.
Prevalence of tet(X4) in Escherichia coli From Duck Farms in Southeast China
Authors: Yu Yang , Cui Chao-Yue , Kuang Xu , Chen Chong , Wang Min-Ge , Liao Xiao-Ping , Sun Jian , Liu Ya-Hong
Published: August 2021

Objectives

Carbapenems, colistin, and tigecycline are critically important antibiotics in clinics. After the global appearance of blaNDM and mcr mediating the resistance to carbapenems and colistin, respectively, tigecycline becomes the last-resort drug against severe human infections caused by multidrug-resistant bacteria. Recently, a mobile tigecycline resistance gene tet(X4) has been identified in Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii that causes high resistance to tigecycline and other tetracyclines. In this study, the prevalence of tet(X4) in E. coli isolates from duck and goose farms in Southeast China was identified and characterized.

Methods

Feces, soil, sewage, and dust samples were collected from duck and goose farms along with the southeast coast provinces of China. Antimicrobial susceptibility testing and polymerase chain reaction screening were performed to investigate the phenotype and genotype of tigecycline resistance. Conjugation, S1 pulsed-field gel electrophoresis (PFGE), and whole-genome sequencing were used to determine the transferability, genetic location, and the genomic characteristics of tet(X4).

Results

In total, 1,716 samples were collected, and 16 isolates (0.9%) recovered from Guangdong, Shandong, and Jiangsu were positive for tet(X4) gene with tigecycline minimum inhibitory concentrations ≥16 mg/L. Notably, among these tet(X4)-positive E. coil isolates, seven of them were from the environment samples (soil and sewage). PFGE and multilocus sequence typing demonstrated that ST3997 was the most prevalent sequence type (eight isolates, 50%) in Jiangsu province. By conjugation assays, 11 isolates were able to transfer tet(X4) plasmid to E. coli C600 recipient, and these plasmids belonged to IncHI1 and IncX1 detected by sequence analysis. tet(X4) was found adjacent to an insertion sequence ISCR2 downstream and a catD gene upstream for all isolates. In addition, multiple-drug resistance to tigecycline, chlortetracycline, ampicillin, florfenicol, ciprofloxacin, gentamicin, trimethoprim/sulfamethoxazole, and fosfomycin was profiled in most of the tet(X4)-positive isolates.

Conclusion

The identification of tet(X4) harboring E. coli strains in duck farms and their surrounding environment enlarges our knowledge of the variety and prevalence of tigecycline resistance. The prevalence of tet(X4) raises concern for the use of tetracyclines in animal farming, and the tet(X4) gene should be listed as primary gene for resistance surveillance.
Anti-inflammatory Effect of Probiotic Limosilactobacillus reuteri KUB-AC5 Against Salmonella Infection in a Mouse Colitis Model
Authors: Buddhasiri Songphon , Sukjoi Chutikarn , Kaewsakhorn Thattawan , Nambunmee Kowit , Nakphaichit Massalin , Nitisinprasert Sunee , Thiennimitr Parameth
Published: August 2021

Acute non-typhoidal salmonellosis (NTS) caused by Salmonella enterica Typhimurium (STM) is among the most prevalent of foodborne diseases. A global rising of antibiotic resistance strains of STM raises an urgent need for alternative methods to control this important pathogen. Major human food animals which harbor STM in their gut are cattle, swine, and poultry. Previous studies showed that the probiotic Limosilactobacillus (Lactobacillus) reuteri KUB-AC5 (AC5) exhibited anti-Salmonella activities in chicken by modulating gut microbiota and the immune response. However, the immunobiotic effect of AC5 in a mammalian host is still not known. Here, we investigated the anti-Salmonella and anti-inflammatory effects of AC5 on STM infection using a mouse colitis model. Three groups of C57BL/6 mice (prophylactic, therapeutic, and combined) were fed with 109 colony-forming units (cfu) AC5 daily for 7, 4, and 11 days, respectively. Then, the mice were challenged with STM compared to the untreated group. By using a specific primer pair, we found that AC5 can transiently colonize mouse gut (colon, cecum, and ileum). Interestingly, AC5 reduced STM gut proliferation and invasion together with attenuated gut inflammation and systemic dissemination in mice. The decreased STM numbers in mouse gut lumen, gut tissues, and spleen possibly came from longer AC5 feeding duration and/or the combinatorial (direct and indirect inhibitory) effect of AC5 on STM. However, AC5 attenuated inflammation (both in the gut and in the spleen) with no difference between these three approaches. This study demonstrated that AC5 confers both direct and indirect inhibitory effects on STM in the inflamed gut.
DeepComplex: A Web Server of Predicting Protein Complex Structures by Deep Learning Inter-chain Contact Prediction and Distance-Based Modelling
Authors: Quadir Farhan , Roy Raj S. , Soltanikazemi Elham , Cheng Jianlin
Published: August 2021

Proteins interact to form complexes. Predicting the quaternary structure of protein complexes is useful for protein function analysis, protein engineering, and drug design. However, few user-friendly tools leveraging the latest deep learning technology for inter-chain contact prediction and the distance-based modelling to predict protein quaternary structures are available. To address this gap, we develop DeepComplex, a web server for predicting structures of dimeric protein complexes. It uses deep learning to predict inter-chain contacts in a homodimer or heterodimer. The predicted contacts are then used to construct a quaternary structure of the dimer by the distance-based modelling, which can be interactively viewed and analysed. The web server is freely accessible and requires no registration. It can be easily used by providing a job name and an email address along with the tertiary structure for one chain of a homodimer or two chains of a heterodimer. The output webpage provides the multiple sequence alignment, predicted inter-chain residue-residue contact map, and predicted quaternary structure of the dimer. DeepComplex web server is freely available at http://tulip.rnet.missouri.edu/deepcomplex/web_index.html
Combined Neuroprotective Strategies Blocked Neurodegeneration and Improved Brain Function in Senescence-Accelerated Mice
Authors: Malerba Helena Nascimento , Pereira Arthur Antonio Ruiz , Pierrobon Marcela Favoretto , Abrao Guilherme Souza , Toricelli Mariana , Akamine Eliana Hiromi , Buck Hudson Sousa , Viel Tania Araujo
Published: August 2021

Increase in the quality of life, combined with drug strategies, has been studied as possibilities for improving memory and delaying the onset of neurodegenerative diseases. A previous study published by the group of the authors has shown that microdose lithium and enriched environment can improve memory in both mice and humans. To elucidate this relationship better, this study aimed to evaluate whether the chronic combination of these two strategies could increase healthy aging in Senescence Accelerated Mouse-Prone 8 (SAMP8). Animals were submitted to either one or both of these strategies until the age of 10 months when they were anesthetized and killed and their hippocampus was extracted. The untreated SAMP-8 group exhibited worse memory and reduced neuronal density with greater neurodegeneration and increased amyloid-β plaque density compared with the control group. Moreover, significant alterations in proteins related to long-term potentiation, such as, synaptophysin and brain-derived neurotrophic factor (BDNF), were observed in this group. The strategies used in the study maintained long-term memory, reduced anxiety, and increased neuroprotection. Both strategies were efficient in reducing neurodegeneration and increasing parameters related to memory maintenance. In many experiments, the combination of the two strategies was more effective in improving healthy aging. This study sheds light on the combination of strategies that choose to improve the quality of life and drugs with low side effects. Moreover, it opens perspectives for a new field of study for healthy aging.
A Short-Term Efficacy of Anlotinib in the Treatment of Refractory Nasopharyngeal Inverted Papilloma: A Case Report
Authors: Yang Pan , Meng Gang , Shu Qiuxia , Dong Yan , Li Chong , Lu Yujiao , Li Jianjun
Published: August 2021

To our knowledge, no studies have reported the use of anlotinib in the treatment of locally cancerous nasopharyngeal inverted papillomas that cannot be operated on or treated with radiotherapy. Here, we report a case of a 53-year-old woman diagnosed with recurrent local canceration of nasopharynx papilloma. Magnetic resonance imaging (MRI) showed that the right parapharyngeal space, nasopharynx, and ethmoid sinus were changed, and recurrence was considered. There was no indication for surgery or radiotherapy. Imaging showed that the tumor had obvious enhancement and abundant blood vessels. Immunohistochemistry showed that vascular endothelial growth factor receptor (VEGFR) 2 expression was positive in papilloma tissue and in local canceration tissue of the papilloma. After the patient’s consent was obtained, anlotinib treatment was started in May and ended in November 2019. Then, the patient was treated with intensity-modulated radiotherapy (IMRT) with planning gross tumor volume (PGTV) 66 Gy, planning clinical tumor volume 1 (PCTV1) 60 Gy, and planning clinical tumor volume 2 (PCTV2) 54 Gy in 33 fractions. No disease recurrence was reported at 4 months after radiotherapy.
Case Report: Autoimmune Pemphigus Vulgaris in a Patient Treated With Cemiplimab for Multiple Locally Advanced Cutaneous Squamous Cell Carcinoma
Authors: Buquicchio Rosalba , Mastrandrea Valentina , Strippoli Sabino , Quaresmini Davide , Guida Michele , Filotico Raffaele
Published: August 2021

Background

Pemphigus vulgaris (PV) is a rare and severe autoimmune blistering disorder affecting the skin and mucous membranes, characterized by the production of autoantibodies against two desmosomal adhesion proteins, desmoglein 1 and 3. In patients with advanced squamous cell carcinoma of the skin unfit for surgery and radiotherapy, immune check-point inhibitors, including the anti-Programmed Death-1 (PD-1) agent cemiplimab have been successfully employed proving relevant clinical outcomes. Cemiplimab is a monoclonal antibody capable of inhibiting PD-1 signalling that has recently been approved for the treatment of patients with metastatic or locally advanced cutaneous squamous cell carcinoma. Although the peculiar setting of advanced CSCC involving elderly patients, rare and unusual skin immune-related adverse events such as PV could be observed in cemiplimab treated patients.

Case Report

A 95-year-old man without a history of autoimmune disease was treated with cemiplimab for multiple and advanced squamous cell carcinomas of the head obtaining a complete response to therapy. After seven cycles of cemiplimab administered every 21 days, the patient developed a mucocutaneous blistering eruption. Clinical diagnosis of PV was suspected on the basis of the diffuse involvement of trunk and extremities with large blisters and necrotic eschar. It was carried out an ELISA test, that showed high level of circulating antibodies against desmoglein 1, thus confirming the diagnosis of PV. For this reason, cemiplimab infusion was discontinued and complete resolution of skin lesions was obtained using oral prednisone 0,8 mg/kg/daily for four weeks. Once remission was achieved, a maintenance dose of 10 mg/day was administered, observing a good control of bullous disease and low value of desmoglein 1. Response to CSCC persisted also during cemiplimab discontinuation, until obtaining a complete remission still persisting at 9 months after the last cycle of therapy.

Conclusion

The case we observed is the first description of PV revealed from cemiplimab therapy, thus suggesting that cemiplimab could allow the arise of underlying autoimmune PV, through a mechanism both T and B-cell-mediated.
Prognostic Relevance of 18F-FDG-PET/CT-Guided Target Volume Delineation in Loco-Regionally Advanced Nasopharyngeal Carcinomas: A Comparative Study
Authors: Yan Ouying , Wang Hui , Han Yaqian , Fu Shengnan , Chen Yanzhu , Liu Feng
Published: August 2021

Introduction

An optimal approach to define tumor volume in locoregionally advanced nasopharyngeal carcinoma (NPC) using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) remains unclear. This retrospective study aimed at comparing the outcomes and toxicities of different FDG-PET/CT-guided techniques for primary tumor volume delineation in locoregionally advanced NPC.

Methods

From August 2015 to February 2018, 292 patients with stage III-IVB NPC received FDG-PET/CT-guided IMRT. Three PET/CT-based techniques were used to determine the gross tumor volume (GTV) as follows: visual criteria (group A; n = 98), a standard uptake value (SUV) threshold of 2.5 (group B; n = 95), and a threshold of 50% maximal intensity (group C, n = 99) combined with a dose-painting technique.

Results

In groups A, B, and C, the 5-year LRFS rates were 89.4%, 90.0%, and 97.8%, respectively (p = 0.043). The 5-year DMFS rates were 75.1%, 76.0%, and 87.7%, respectively (p = 0.043). The 5-year DFS rates were 70.9%, 70.3%, and 82.2%, respectively (p = 0.048). The 5-year OS rates were 73.5%, 73.9%, and 84.9%, respectively (p = 0.038). Group C showed significantly higher 5-year LRFS, LRRFS, DMFS, DFS, and OS than those in groups A and B (p < 0.05). No statistically significant differences were observed between the three study groups in the cumulative incidences of grade 3-4 acute and late toxicities. Multivariate analyses showed that the PET/CT-guided technique for target volume delineation was an independent prognostic factor for 5-year LRFS, DFS, DMFS, and OS (p = 0.039, p = 0.030, p = 0.035 and p = 0.028, respectively), and was marginally significant in predicting LRRFS (p = 0.080).

Conclusions

The 50% SUVmax threshold regimen for GTV delineation with dose-painting appeared to be superior to the visual criteria or SUV2.5 threshold in locoregionally advanced NPC, and there was no increased toxicity.
Integrative Analysis of Gene Expression Data by RNA Sequencing for Differential Diagnosis of Acute Leukemia: Potential Application of Machine Learning
Authors: Lee Jaewoong , Cho Sungmin , Hong Seong-Eui , Kang Dain , Choi Hayoung , Lee Jong-Mi , Yoon Jae-Ho , Cho Byung-Sik , Lee Seok , Kim Hee-Je , Kim Myungshin , Kim Yonggoo
Published: August 2021

BCR-ABL1–positive acute leukemia can be classified into three disease categories: B-lymphoblastic leukemia (B-ALL), acute myeloid leukemia (AML), and mixed-phenotype acute leukemia (MPAL). We conducted an integrative analysis of RNA sequencing (RNA-seq) data obtained from 12 BCR-ABL1–positive B-ALL, AML, and MPAL samples to evaluate its diagnostic utility. RNA-seq facilitated the identification of all p190 BCR-ABL1 with accurate splicing sites and a new gene fusion involving MAP2K2. Most of the clinically significant mutations were also identified including single-nucleotide variations, insertions, and deletions. In addition, RNA-seq yielded differential gene expression profile according to the disease category. Therefore, we selected 368 genes differentially expressed between AML and B-ALL and developed two differential diagnosis models based on the gene expression data using 1) scoring algorithm and 2) machine learning. Both models showed an excellent diagnostic accuracy not only for our 12 BCR-ABL1–positive cases but also for 427 public gene expression datasets from acute leukemias regardless of specific genetic aberration. This is the first trial to develop models of differential diagnosis using RNA-seq, especially to evaluate the potential role of machine learning in identifying the disease category of acute leukemia. The integrative analysis of gene expression data by RNA-seq facilitates the accurate differential diagnosis of acute leukemia with successful detection of significant gene fusion and/or mutations, which warrants further investigation.
N6-Methyladenosine Writer Gene ZC3H13 Predicts Immune Phenotype and Therapeutic Opportunities in Kidney Renal Clear Cell Carcinoma
Authors: Guo Tao , Duan Hongxiang , Chen Jinbo , Liu Jinhui , Othmane Belaydi , Hu Jiao , Li Huihuang , Zu Xiongbing
Published: August 2021

Background

Although the RNA modification N6-methyladenosine ZC3H13 has been found to play vital regulatory roles in many types of cancers, its role in predicting the tumor immune microenvironment (TME) and response to immune checkpoint blockade (ICB) in kidney renal clear cell carcinoma (KIRC) remains unclear.

Methods

We comprehensively analyzed the expression, prognostic significance and immunological role of ZC3H13 in pan-cancers and systematically correlated ZC3H13 with TME cell-infiltration, ICB response and targeted therapy in KIRC. The data were collected from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Genotype-Tissue Expression (GTEx), Broad Institute Cancer Cell Line Encyclopedia (CCLE) and DrugBank database. Also, we performed RNA sequencing (RNA-seq) of 46 renal cell carcinoma tissues and 11 adjacent normal tissues to validate our result. All analyses were implemented using R software, version 3.6.3.

Results

ZC3H13 was significantly differentially expressed in most tumors. However, its expression profiles and prognostic significance were consistent only in KIRC, regardless of overall survival, progression-free survival and cancer-specific survival. Additionally, ZC3H13 expression was correlated with clinicopathological factors in KIRC. Furthermore, we found that ZC3H13 might shape a noninflamed phenotype and could predict a lower response to ICB in KIRC. These results could be validated in our own RNA-seq data. Tumor mutation burden (TMB) was significantly higher in the low ZC3H13 group. Finally, we found that ZC3H13 could predict the sensitivity of targeted therapy for KIRC.

Conclusions

ZC3H13 might shape a noninflamed phenotype in KIRC. Moreover, ZC3H13 could predict the prognosis and clinical response of ICB and the sensitivity to targeted therapies in KIRC.
Clinical Characteristics and Outcomes Until 2 Years of Age in Preterm Infants With Typical Chest Imaging Findings of Bronchopulmonary Dysplasia: A Propensity Score Analysis
Authors: Ruan Qiqi , Wang Jianhui , Shi Yuan
Published: August 2021

Objective: The goal of the current study was to assess the associations of typical chest imaging findings of bronchopulmonary dysplasia (BPD) in preterm infants with clinical characteristics and outcomes until 2 years of age.

Method: This retrospective cohort study enrolled 256 preterm infants with BPD who were admitted between 2014 and 2018. A propensity score analysis was used to adjust for confounding factors. The primary outcomes were the severity of BPD, home oxygen therapy (HOT) at discharge and mortality between 28 days after birth and 2 years of age. A multivariate logistic regression analysis was performed to identify related variables of mortality.

Results: Seventy-eight patients with typical chest imaging findings were enrolled, of which 50 (64.1%) were first found by CXR, while 28 (35.9%) were first found by CT. In addition, 85.9% (67/78) were discovered before 36 weeks postmenstrual age (PMA) (gestational age [GA] < 32 weeks) or before 56 days after birth (GA > 32 weeks). After propensity score matching, the matched groups consisted of 58 pairs of patients. Those with typical imaging findings had a remarkably higher mortality rate (29.3 vs. 12.1%, p = 0.022, OR 3.021), higher proportion of severe BPD (32.8 vs. 12.1%, p = 0.003, OR 4.669) and higher rate of HOT at discharge (74.1 vs. 46.6%, p = 0.002, OR 3.291) than those without typical imaging findings. The multivariate logistic regression analysis showed that typical imaging findings ≤ 7 days and typical typical imaging findings >7 days were independent risk factors for mortality in preterm infants with BPD (OR 7.794, p = 0.004; OR 4.533, p = 0.001).

Conclusions: More attention should be given to chest imaging findings of BPD, especially in the early stage (within 7 days). Early recognition of the development of BPD helps early individualized treatment of BPD.

Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT04163822.
Extracellular HSP90α Interacts With ER Stress to Promote Fibroblasts Activation Through PI3K/AKT Pathway in Pulmonary Fibrosis
Authors: Zhang Jinming , Zhong Wenshan , Liu Yuanyuan , Chen Weimou , Lu Ye , Zeng Zhaojin , Qiao Yujie , Huang Haohua , Wan Xuan , Li Wei , Meng Xiaojing , Zou Fei , Cai Shaoxi , Dong Hangming
Published: August 2021

Pulmonary fibrosis is characterized by alveolar epithelial cell injury, lung fibroblast proliferation, differentiation, and extracellular matrix (ECM) deposition. Our previous study indicated that extracellular HSP90α (eHSP90α) promotes pulmonary fibrosis by activating the MAPK signaling pathway. Thus, treatment with 1G6-D7 (a selective HSP90α monoclonal antibody) to antagonize eHSP90α could effectively ameliorate fibrosis. This study aimed to elucidate the mechanism underlying the effects of eHSP90α in pulmonary fibrosis by focusing on its link with endoplasmic reticulum (ER) stress. Our results showed that eHSP90α promoted lung fibroblast differentiation by activating ER stress. Treatment with the ER stress inhibitor tauroursodeoxycholate (TUDCA) or glucose-regulated protein 78 kDa (GRP78) depletion significantly abrogated the effect of eHSP90α on ER stress and fibroblast activation. In addition, eHSP90α induced ER stress in fibroblasts via the phosphoinositide-4,5-bisphosphate 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway, which could be blocked by the PI3K/AKT inhibitor LY294002, and blockade of eHSP90α by 1G6-D7 markedly inhibited ER stress in the model, indicating preventive and therapeutic applications. Intriguingly, we observed that TUDCA effectively reduced the secretion of eHSP90α in vitro and in vivo. In conclusion, this study shows that the interaction between eHSP90α and ER stress plays a crucial role in pulmonary fibrosis, indicating a positive feedback in lung fibroblasts. Targeting eHSP90α and alleviating fibroblast ER stress may be promising therapeutic approaches for pulmonary fibrosis.