bluuebunny/crossref_metadata_2025 huggingface dataset:
Breast implant – Associated Anaplastic large cell lymphoma
Authors: Ioannidis Charilaos
Published: October 2021

Breast Implant –Associated Anaplastic Large Cell Lymphoma is a newly recognized malignant neoplasm presenting in breasts of women who have had breast implants for cosmetic or reconstructive purposes. A review of the literature showed thatit is an uncommon, slow growing T-cell lymphoma with morphology and immunophenotype similar to anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma. Its clinicopathologic features and treatment, however, are unique. It usually follows an indolent clinical course, but it has the potential to form a mass, to invade locally through the periimplant breast capsule into the breast parenchyma or soft tissues and/or to spread to regional lymph nodes. Surgical removal of the implant en bloc with the whole of the capsule (explantation plus complete capsulectomy) is the treatment of choice and confers an excellent disease free and overall survival. In the few cases with metastatic disease, chemotherapy is used as an adjuvant therapy. Early detection and management convey the best prognosis; therefore clinicians, gynecologists among others, ought to be aware of this new entity and refer suspicious cases for further evaluation and treatment. Change in attitudes towards implant based surgery does not seem necessary, as long as patients are properly informed about the risk of breast implant –associated anaplastic large cell lymphoma.
Ovarian hyperstimulation syndrome and the risk of internal jugular vein thrombosis
Authors: Kanellopoulou Theoni
Published: October 2021

Introduction: Thromboembolic events are a rare complication of severe ovarian hyperstimulation syndrome (OHSS). In contrast to the classical left ilio-femoral deep vein thrombosis casesduring pregnancy,atypical localization in upper extremity, including internal jugular vein (IJV)is also reported. Review of the literature: We reviewed 39 cases of IJV thrombosis associated with OHSS mostly during assisted reproductive treatment. The diagnosis was made during first trimester, mainly with Doppler ultrasound, and treatment with heparin was initiated in all cases. In 14 patients another risk factor for thromboembolic event was reported (50% had FV-Leiden mutation). The IJV was extended in upper extremityincluding axillary, subclavian or superior vena cava in 46%, whereas pulmonary embolism was reported in 10% of cases. Discussion: Obstetricians should be aware of the rare complication of deep vein thrombosis in upper extremity including thrombosis of IJV, even weeks after OHSS symptoms have resolved.Patients with OHSS after assisted reproductive treatmentshould be prescribed heparin in prophylactic dose during the first trimester.
Relationship of soluble Fms-like tyrosine kinase 1, soluble endoglin, placental growth factor blood levels with the severity of late onset preeclampsia
Authors: Yalvac Ethem Serdar , Kara Mustafa , Baser Emre , Onat Taylan , Caltekin Melike Demir , Ercan Müjgan , Kirmizi1 Demet Aydogan
Published: October 2021

Purpose: Preeclampsia (PE) is a pregnancy-specific syndrome characterized by placentation disorder that increases maternal and fetal morbidity and mortality. Overproduction of anti-angiogenic factors such as soluble fms-like tyrosine kinase receptor 1 (sFlt-1) and soluble endoglin (sEng) and low production of placental growth factor (Pgf) from angiogenic factors contribute to preeclampsia pathogenesis. In this study, factors involved in angiogenesis including sEng, Pgf and sFlt1 were investigated for pre-recognition of preeclampsia. Methods: A total of 54 pregnant women were included in the study and the patients were divided into normotensive (n = 25) and preeclampsia groups (n = 29). Both groups demographic characteristics, laboratory parameters, sEng, sFlt1 and placental growth factor levels were compared. Results: While AST, uric acid, LDH mean values were significantly higher in the study group compared to the control group (p<0.05), there was no significant difference between the groups in terms of ALT, creatinin, hemoglobin, leucocyte, and platelet values. sEng, sFlt1 values were significantly lover in the preeclampsia group compared to the control group (p<0.05). Conclusion: it is thought that Pgf may have a place in the prediction of preeclampsia in advanced pregnancy weeks, but sFlt-1 and sEng are weak in predicting preeclampsia in advanced pregnancy weeks as well.
Rendimientos del capital humano en las microempresas de la frontera norte de México
Authors: Osorio-Novela Germán , Martínez-Sidón Gilberto , Saavedra-Leyva Rafael
Published: October 2021

This paper aims to calculate and analyze the human capital returns of micro-enterprises on Mexico’s northern border by examining the education levels of the micro-entrepreneurs in charge of the production unit. Analyzing data from the National Survey of Occupation and Employment from 2010 to 2019, we estimated econometric cross-section models based on Mincer equations. The results suggest that elementary education is not sufficient to achieve high monetary income in micro-enterprises, even its rates are negative, generating losses systematically. The turning point starts in high school, where positive rates are beginning to be observed. However, it highlights that undergraduate and postgraduate education doubles their positive returns, although the number of business owners with this education level is lower.
A SEGURANÇA PÚBLICA COMO UM PROBLEMA SOCIOCULTURAL
Authors:   GAECO – Grupo de Atuação Especial de Combate ao Crime Organizado, VIEIRA Álvaro de Souza , PESSOA Marcelo ,   Universidade do Estado de Minas Gerais - Unidade Frutal
Published: October 2021

The present study falls within the scope of Urban Public Security, to the extent that ostensive and preventive policing actions - motorized, on foot or in prison - tend to better meet the social needs provided for by the demand for the crime prevention and protection service provided. by the State. A study like ours justifies the fact that, in times of the COVID-19 Pandemic, with the almost compulsory impediment of the citizen to come and go by legal instrument, there was a robust increase in the rates of family disagreements, minor bodily injuries, subversions to order and discipline, and other major unlawful conduct. As main research results, it was possible to understand to what extent society tends or not to actively participate in the processes that involve its own mental, physical or social well-being. We also note that there is a certain resistance from this same society regarding the presence of State apparatus, especially in less privileged layers of the community, since citizenship, on the one hand, manifests itself against police actions, in the face of less positive past experiences. R - 01-04 Revista AKEDIA – Versões, Negligências e Outros Mundos p - ISSN 2447-7656 e – ISSN 2674-2561 DOI 10.33726 – Volume 12 – Ano VII – 2º Sem. de 2021 On the other hand, it is seen that part of this same community tends to act, voluntarily or involuntarily, as a passive accomplice, keeping active contexts of high crime, a condition that, in the eyes of the State, appears paradoxical, but which, from a cultural perspective, maybe it's a sophisticated survival strategy.
DETERMINATION OF THE VERTICAL GRADIENT OF GRAVITY FROM GRAVITY ANOMALIES
Authors: Inzhevatov Ivan A.
Published: October 2021

In connection with the need to use the vertical gradient in the processing of the results of gravimetric measurements and their interpretation when solving problems of geology, geophysics, geodesy, geodynamics and navigation, in addition to the urgent problems of improvement, socalled indirect methods of measuring the vertical gradient, there is an equally urgent task of developing methods for determining the vertical gradient of gravity, using dependencies between different physical fields. The article presents the development and study of a method for determining the vertical gradient from gravity anomalies using the relationship between gravity anomalies and altitude based on field data obtained in the area of the Tashtagol field on Mount Boulanger in 2019 and 2020.
RESEARCH OF THE METHOD OF ORTHOPHOTOMAP DECIVED FROM UAV IMAGES WITH LARGE TILT ANGLES
Authors: Arutyunov Denis V.
Published: October 2021

The article reflects the method of orthophotomap decivetion. The flow diagram of UAV data processing in Photomod is presented. The final processing results are presented in the form of an orthophotomap. The technology for constructing point objects for further error analysis is presented. The calculation of the plotted points in Excel for further error analysis was performed. Errors based on the tolerances that are proposed in the instructions for topographic survey are analyzed.
SOFTWARE FOR AUTOMATION OF SPACE IMAGE RECOGNITION
Authors: Myasoedov Sergey A.
Published: October 2021

The article discusses the main universal systems for working with remote sensing data - services that provide software for automated recognition of urban infrastructure objects in space images. The functions that these products can perform and their structure are considered.
ANALYSIS OF CRYPROCURRENCIES AND PROBLEMS OF BLOCKCHAIN DEVELOPMENT
Authors: Nedobezhkin Maxim I. , Fionov Andrew N.
Published: October 2021

This article examines the history of the emergence of cryptocurrencies, their advantages and disadvantages, and also considers the blockchains, where special attention is paid to the problem of the development of this technology.
ANALYSIS OF THE IMPACT OF OIL PRODUCT SPILLS ON NATURAL OBJECTS BASED ON SENTINEL-2 REMOTE SENSING DATA IN EASTERN SIBERIA
Authors: Baikin Dmitry A.
Published: October 2021

The article analyzes the impact of oil spills on natural objects according to the remote sensing system Sentinel-2 in Eastern Siberia. Remote sensing data analysis is used to detect traces of oil products in the accident area. Conclusions about the usage of Sentinel-2 data for detecting traces of oil products were made.
COMPETENCE APPROACH IN TRAINING SPECIALISTS IN THE FIELD OF INFORMATION SECURITY
Authors: Yazovski Alexander M. , Shaburova Aelita V. , Gavrilenko Nadezhda L.
Published: October 2021

The relevance of the topic, the training of specialists in the field of information security from the standpoint of the competence-based approach and proposals for improving this approach are considered.
TECHNOLOGICAL FEATURES OF MANUFACTURING COMPLEX PARTS OF THE MECHANICAL PART OF OPTICAL DEVICES AT MACHINING CENTERS
Authors: Gavrichenko Nikolay E.
Published: October 2021

The article defines the concept of "technological features". Examples of technological features of modern manufacturing by cutting complex parts of the mechanical part of optical devices are considered and analyzed. The examples contain fragments of manufacturing parts only on CNC machines of the "machining center" type. This type of metal-cutting equipment is accepted as the main one in the conditions of automation of processing by cutting metal products. The necessity of systematization of the features of manufacturing products in optical and assembly technology is stated. Attention is drawn to the practical and theoretical significance of this work.
LIGHT DISTRIBUTION IN WIDE-ANGLE LENSES
Authors: Deeva Daria E.
Published: October 2021

The article considers a two methods for determining light distribution in wide-angle lenses: the direct calculation method a lot of rays and the analytical method. Formulas for calculating the light distribution in lenses with different image construction laws are given. The results of computer simulation of light distribution in lenses with fields of view equal to 150 and 190 °are presented. The efficiency of the use of nondeterministic ray tracing for the analysis of light distribution in lenses with fields of view close to the hemisphere is shown.
TECHNOLOGIES OF QUANTUM CRYPTOGRAPHY
Authors: Dolgochub Evgeniy A.
Published: October 2021

The article discusses the main classical algorithms of quantum cryptography, explaining the principle of operation of the mechanism for ensuring information security in the transmission of messages with the analysis of the polarization of photons. Conclusions are made about the most optimal variants of the combination of algorithms.
The Truth about Vitamin C Enriched Plants and Vegetables Used in Nigeria for the Management of COVID-19
Authors: Uchejeso M Obeta , Goodluck AK Ohanube , Muhammad Akram
Published: October 2021

The COVID-19 pandemic has shown the dexterity and wits of Nigerians in the face of dire challenges. The low fatality recorded by Nigeria during the ongoing COVID-19 pandemic attests to this. A minimal death rate bewilders experts, despite the speculation that Nigeria might experience a high death rate. Nigerians resorted to home remedies for prophylaxis and curative measures using available vitamin C enriched plants and vegetables. This brief review explored various plants and vegetables reported to have been utilized during the COVID-19 pandemic in Nigeria. The obvious is that many Nigerians use one or more plants and vegetables as a home remedy. This spurred the interest of Nigerian scientists in more researches in Nigeria with the aim of standardization and registration for use.
Intracellular Lipid Accumulation and Mitochondrial Dysfunction Accompanies Endoplasmic Reticulum Stress Caused by Loss of the Co-chaperone DNAJC3
Authors: Jennings Matthew J. , Hathazi Denisa , Nguyen Chi D. L. , Munro Benjamin , Münchberg Ute , Ahrends Robert , Schenck Annette , Eidhof Ilse , Freier Erik , Synofzik Matthis , Horvath Rita , Roos Andreas
Published: October 2021

Recessive mutations in DNAJC3, an endoplasmic reticulum (ER)-resident BiP co-chaperone, have been identified in patients with multisystemic neurodegeneration and diabetes mellitus. To further unravel these pathomechanisms, we employed a non-biased proteomic approach and identified dysregulation of several key cellular pathways, suggesting a pathophysiological interplay of perturbed lipid metabolism, mitochondrial bioenergetics, ER-Golgi function, and amyloid-beta processing. Further functional investigations in fibroblasts of patients with DNAJC3 mutations detected cellular accumulation of lipids and an increased sensitivity to cholesterol stress, which led to activation of the unfolded protein response (UPR), alterations of the ER-Golgi machinery, and a defect of amyloid precursor protein. In line with the results of previous studies, we describe here alterations in mitochondrial morphology and function, as a major contributor to the DNAJC3 pathophysiology. Hence, we propose that the loss of DNAJC3 affects lipid/cholesterol homeostasis, leading to UPR activation, β-amyloid accumulation, and impairment of mitochondrial oxidative phosphorylation.
Roles of the Mesenchymal Stromal/Stem Cell Marker Meflin/Islr in Cancer Fibrosis
Authors: Takahashi Masahide , Kobayashi Hiroki , Mizutani Yasuyuki , Hara Akitoshi , Iida Tadashi , Miyai Yuki , Asai Naoya , Enomoto Atsushi
Published: October 2021

Fibroblasts synthesise the extracellular matrix (ECM) such as collagen and elastin, the excessive accumulation of which can lead to fibrosis and organ dysfunction under pathological conditions. Cancer-associated fibroblasts (CAFs) are major constituents of the tumour microenvironment (TME) that accompany the desmoplastic reaction responsible for anti-cancer treatment resistance. Thus, it is important to dissect the roles of CAFs in the TME to develop new therapeutic strategies for refractory cancers. Recent progress in the studies of CAF biology suggests that the functions of CAFs are complicated and that they are composed of functionally distinct populations, including cancer-promoting CAFs (pCAFs) and cancer-restraining CAFs (rCAFs). We recently identified a new cell surface marker for rCAFs in pancreatic and colon cancers, designated as Meflin (mesenchymal stromal cell- and fibroblast-expressing Linx paralogue)/Islr (immunoglobulin super family containing leucine-rich repeat). Based on the distribution of Meflin/Islr-positive cells, we also considered it a specific candidate marker for mesenchymal stroma/stem cells. Meflin/Islr-positive CAFs have been shown to suppress cancer progression by being involved in regulating collagen structures and BMP signalling in the TME. This review describes the function of Meflin/Islr in cancer fibrosis as well as in cardiac and lung fibrosis and its potential in the development of new cancer therapeutics.
Molecular Characterization of Dengue Virus Type 1 in Zhejiang in 2019
Authors: Yao Wenwu , Yang Zhangnv , Lou Xiuyu , Mao Haiyan , Yan Hao , Zhang Yanjun
Published: October 2021

Dengue fever (DF) is a mosquito-borne viral disease caused by the dengue virus (DENV), which is considered one of the most important arboviruses in the world. This study aimed to determine the molecular, epidemiological, and phylogenetic characterization of 174 DENV-1 (132 indigenous cases and 42 imported cases) isolated from nine municipalities of Zhejiang province in 2019. The analyses of phylogenetics, haplotypes, and amino acid substitutions were conducted based on the full envelope (E) gene sequences. Sixty-four haplotypes were clustered into two main clades, with isolates from Wenzhou and Taizhou mainly clustered into clade I and Hangzhou and Ningbo cases clustered into clade II. Six sites of amino acid substitutions including A88T, F96L, M297V, T339S, I378L, and V436I were only observed in strains isolated from Ningbo and Hangzhou, while two sites of amino acid substitutions including V312L and V380I were observed in strains from Taizhou and Wenzhou. In our study, strains were in high homology with the strains from Southeast Asian countries, thus cases in Zhejiang were probably imported from Southeast Asian countries. The strains from different regions in Zhejiang were clustered in the same branch which may be caused by the continuous import of cases in the same country at different time periods. After the continuous outbreak in Zhejiang province, some sites of the dengue gene have mutated, and the effects need further study.
The Long-Term Effect of a Nine Amino-Acid Antimicrobial Peptide AS-hepc3(48-56) Against Pseudomonas aeruginosa With No Detectable Resistance
Authors: Zhu Depeng , Chen Fangyi , Chen Yan-Chao , Peng Hui , Wang Ke-Jian
Published: October 2021

The emergence of multidrug-resistant (MDR) pathogens has become a global public health crisis. Among them, MDR Pseudomonas aeruginosa is the main cause of nosocomial infections and deaths. Antimicrobial peptides (AMPs) are considered as competitive drug candidates to address this threat. In the study, we characterized two AMPs (AS-hepc3(41-71) and AS-hepc3(48-56)) that had potent activity against 5 new clinical isolates of MDR P. aeruginosa. Both AMPs destroyed the integrity of the cell membrane, induced leakage of intracellular components, and ultimately led to cell death. A long-term comparative study on the bacterial resistance treated with AS-hepc3(41-71), AS-hepc3(48-56) and 12 commonly used antibiotics showed that P. aeruginosa quickly developed resistance to the nine antibiotics tested (including aztreonam, ceftazidime, cefepime, imipenem, meropenem, ciprofloxacin, levofloxacin, gentamicin, and piperacillin) as early as 12 days after 150 days of successive culture generations. The initial effective concentration of 9 antibiotics against P. aeruginosa was greatly increased to a different high level at 150 days, however, both AS-hepc3(41-71) and AS-hepc3(48-56) maintained their initial MIC unchangeable through 150 days, indicating that P. aeruginosa did not produce any significant resistance to both AMPs. Furthermore, AS-hepc3(48-56) did not show any toxic effect on mammalian cells in vitro and mice in vivo. AS-hepc3(48-56) had a therapeutic effect on MDR P. aeruginosa infection using a mouse lung infection model and could effectively increase the survival rate of mice by inhibiting bacterial proliferation and attenuating lung inflammation. Taken together, the short peptide AS-hepc3(48-56) would be a promising agent for clinical treatment of MDR P. aeruginosa infections.
Matrix Metalloproteinase 2 Is Associated With Secondary Caries Independent From the Restorative Material
Authors: Benli Merve , Frota de Souza Luiza Arieta , Deeley Kathleen , Modesto Adriana , Vieira Alexandre R.
Published: October 2021

Certain patients, despite receiving proper treatment, still show higher failure rates of restorative dental treatments. The aim of this work was to test if MMP2 and MMP3 alleles are overrepresented in individuals with secondary caries. A total of 1,089 individuals from the University of Pittsburgh School of Dental Medicine Dental Registry and DNA Repository project were selected for this study. From this total, 341 individuals were selected for having a record of secondary caries in any type of restoration and were matched with 748 individuals by sex, age, ethnicity, and restorative work in the same teeth that did not fail. Genomic DNA extracted from saliva was used to obtain genotypes in five markers of MMP2 and MMP3 using TaqMan chemistry and end-point analysis. Chi-square was used to test if differences in allele and genotype distributions were statistically different at an alpha of 0.05. The less common allele and homozygote genotype of MMP2 rs9923304 were less commonly found among individuals with secondary caries. The less common allele of MMP2 rs2287074 was also less frequent among individuals with secondary caries. These results provide statistical evidence for the role of MMP2 in failure of restorations due to secondary caries. We can conclude that MMP2 variation impacts the risk of having secondary caries, independent of the restorative material.
The Roles of Genetic and Early-Life Environmental Factors in the Association Between Overweight or Obesity and Hypertension: A Population-Based Twin Study
Authors: Xi Yu’e , Gao Wenjing , Zheng Ke , Lv Jun , Yu Canqing , Wang Shengfeng , Huang Tao , Sun Dianjianyi , Liao Chunxiao , Pang Yuanjie , Pang Zengchang , Yu Min , Wang Hua , Wu Xianping , Dong Zhong , Wu Fan , Jiang Guohong , Wang Xiaojie , Liu Yu , Deng Jian , Lu Lin , Cao Weihua , Li Liming
Published: October 2021

Aims/Hypothesis

We aimed to explore whether and to what extent overweight or obesity could increase the risk of hypertension, and further to estimate the roles of genetic and early-life familial environmental factors in their association.

Methods

This prospective twin study was based on the Chinese National Twin Registry (CNTR), which collected information from self-report questionnaires. We conducted unmatched case-control analysis to examine the association between overweight or obesity and hypertension. And further to explore whether genetics and familiar environments shared within a twin pair, accounted for their association via co-twin matched case-control design. Generalized estimating equation (GEE) models and conditional logistic regressions were used in the unmatched and matched analyses, respectively. Then, we used logistic regressions to test the difference in odds ratios (ORs) between the unmatched and matched analyses. Finally, through bivariate twin model, the roles of genetic and environmental factors in the body mass index (BMI)- hypertension association were estimated.

Results

Overall, we included a total of 30,617 twin individuals, of which 7533 (24.6%) twin participants were overweight or obesity and 757 (2.5%) developed hypertension during a median follow-up time of 4.4 years. In the GEE model, overweight or obesity was associated with a 94% increased risk of hypertension (OR=1.94, 95% confidence interval (CI): 1.64~2.30). In the conditional logistic regression, the multi-adjusted OR was 1.80 (95% CI: 1.18~2.74). The difference in OR between unmatched and matched analyses was significant (P=0.016). Specifically, overweight or obesity was not associated with hypertension risk in the co-twin design when we full controlled genetic and familiar environmental factors (OR=0.89, 95 CI: 0.46~1.72). After controlling for age and sex, we found the positive BMI-hypertension association was mainly explained by a genetic correlation between them (rA= 0.59, 95% CI: 0.44~1.00).

Conclusions/Interpretation

Genetics and early-life environments shared by participants within a twin pair appear to account for the association between overweight or obesity and hypertension risk.
Study on Hydrate Phase Equilibrium Diagram of Methane Containing System Based on Thermodynamic Model
Authors: Liang Hao , Duan Yonggang , Pei Jun , Wei Na
Published: October 2021

Natural gas hydrate is a potential energy source in the future, which widely occurs in nature and industrial activities, and its formation and decomposition are identified by phase equilibrium. The calculation of multicomponent gas phase equilibrium is more complex than that of single component gas, which depends on the accurate model characterized by enthalpy and free energy. Based on the Kvamme-Tanaka statistical thermodynamic model, theoretical and experimental methods were used to predict and verify the phase equilibrium of pure methane hydrate and carbon dioxide hydrate in the temperature range of 273.17–289.05 K. The phase equilibrium curves of methane-containing gases such as CH4+CO2,CH4+C2H6,CH4+H2S and CH4+CO2+H2S under different mole fractions were drawn and analyzed, and the decomposition or formation enthalpy and free energy of hydrate were calculated. The results show that, the phase equilibrium curves of the methane containing systems is mainly related to the guest molecule type and the composition of gas. The evolution law of phase equilibrium pressure of different gases varies with composition and temperature, and the phase splitting of CO2at the quadruple point affects the phase equilibrium conditions. Due to the consideration of the interaction between the motion of guest molecules and the vibration of crystal lattice, the model exhibits a good performance, which is quantified in terms of mean square error (MSE) with respect to the experimental data. The magnitudes of MSE percent are respectively 1.2, 4.8, 15.12 and 9.20 MPa2for CH4+CO2, CH4+C2H6, CH4+H2S and CH4+CO2+H2S systems, and the values are as low as 3.57 and 1.32 MPa2for pure methane and carbon dioxide, respectively. This study provides engineers and researchers who want to consult the diagrams at any time with some new and accurate experimental data, calculated results and phase equilibrium curves. The research results are of great significance to the development and utilization of gas hydrate and the flow safety prediction of gas gathering and transportation.
Germination Characteristics Is More Associated With Phylogeny-Related Traits of Species in a Salinized Grassland of Northeastern China
Authors: Zhao Ming , Liu Zhaogang , Zhang Hongxiang , Wang Yuanyuan , Yan Hong
Published: October 2021

Knowing the determinants of seed germination helps us understand plant adaptive strategies to the environment and predict population and community regeneration under climate change. However, multiple factors, including plant and seed traits that influence germination and their relative importance, have received little attention. Here, seed germination experiments were conducted on newly collected seeds for 89 herbaceous species from salinized Songnen grassland. We tested the effects of multiple phylogeny-related plant traits and seed morphological and physiological traits on germination percentage and initial germination time and their relative contribution to shaping germination variation. We found that biennials had higher germination percentages and rates than annuals and perennials. Species with brown seeds had higher germination percentages than those with yellow and black seeds. Eudicots germinated faster than monocots, and seeds with morphophysiological dormancy required more time to initiate germination than those with other kinds of dormancy. Phylogeny-related factors explained more of the variation in germination than seed traits. Seed mass and volume of the large-seeded, but not small-seeded group species were positively correlated with germination percentage. Our findings provide important information for understanding germination variation across species and local adaptation for species in the salinized Songnen grassland.
Multiallelic Rare Variants in BBS Genes Support an Oligogenic Ciliopathy in a Non-obese Juvenile-Onset Syndromic Diabetic Patient: A Case Report
Authors: Dallali Hamza , Kheriji Nadia , Kammoun Wafa , Mrad Mehdi , Soltani Manel , Trabelsi Hajer , Hamdi Walid , Bahlous Afef , Ben Ahmed Melika , Mahjoub Faten , Jamoussi Henda , Abdelhak Sonia , Kefi Rym
Published: October 2021

Juvenile-onset diabetes may occur in the context of a rare syndromic presentation, suggesting a monogenic etiology rather than a common multifactorial diabetes. In the present study, we report the case of a young diabetic Tunisian patient presenting learning problems, speech deficits, short stature, brachydactyly, and a normal weight. Whole exome sequencing analysis revealed five heterozygous genetic variants in BBS1, BBS4, BBS8, MKS1, and CEP290. These genes are involved in the regulation of cilium biogenesis and function. We analyzed variant combinations pathogenicity using the recently developed ORVAL tool, and we hypothesized that cumulative synergetic effects of these variants could explain the syndromic phenotype observed in our patient. Therefore, our investigation suggested a genetic diagnosis of Bardet–Biedl syndrome with an oligogenic inheritance pattern rather than a monogenic diabetes. Although there is no curative therapy for this ciliopathy at the moment, a genetic diagnosis may offer other supportive care options, including the prevention of other possible clinical manifestations of this syndrome, mainly renal abnormalities, obesity, liver fibrosis, and hypertension, as well as the genetic counseling for family members.
Teriflunomide Treatment of Multiple Sclerosis Selectively Modulates CD8 Memory T Cells
Authors: Tilly Gaëlle , Cadoux Marion , Garcia Alexandra , Morille Jérémy , Wiertlewski Sandrine , Pecqueur Claire , Brouard Sophie , Laplaud David , Degauque Nicolas
Published: October 2021

Background and Objectives

Inhibition ofde novopyrimidine synthesis in proliferating T and B lymphocytes by teriflunomide, a pharmacological inhibitor of dihydroorotate dehydrogenase (DHODH), has been shown to be an effective therapy to treat patients with MS in placebo-controlled phase 3 trials. Nevertheless, the underlying mechanism contributing to the efficacy of DHODH inhibition has been only partially elucidated. Here, we aimed to determine the impact of teriflunomide on the immune compartment in a longitudinal high-dimensional follow-up of patients with relapse-remitting MS (RRMS) treated with teriflunomide.

Methods

High-dimensional spectral flow cytometry was used to analyze the phenotype and the function of innate and adaptive immune system of patients with RRMS before and 12 months after teriflunomide treatment. In addition, we assessed the impact of teriflunomide on the migration of memory CD8 T cells in patients with RRMS, and we defined patient immune metabolic profiles.

Results

We found that 12 months of treatment with teriflunomide in patients with RRMS does not affect the B cell or CD4 T cell compartments, including regulatory TREGfollicular helper TFHcell and helper THcell subsets. In contrast, we observed a specific impact of teriflunomide on the CD8 T cell compartment, which was characterized by decreased homeostatic proliferation and reduced production of TNFα and IFNγ. Furthermore, we showed that DHODH inhibition also had a negative impact on the migratory velocity of memory CD8 T cells in patients with RRMS. Finally, we showed that the susceptibility of memory CD8 T cells to DHODH inhibition was not related to impaired metabolism.

Discussion

Overall, these findings demonstrate that the clinical efficacy of teriflunomide results partially in the specific susceptibility of memory CD8 T cells to DHODH inhibition in patients with RRMS and strengthens active roles for these T cells in the pathophysiological process of MS.
The Dynamics of B Cell Aging in Health and Disease
Authors: de Mol Jill , Kuiper Johan , Tsiantoulas Dimitrios , Foks Amanda C.
Published: October 2021

Aging is considered to be an important risk factor for several inflammatory diseases. B cells play a major role in chronic inflammatory diseases by antibody secretion, antigen presentation and T cell regulation. Different B cell subsets have been implicated in infections and multiple autoimmune diseases. Since aging decreases B cell numbers, affects B cell subsets and impairs antibody responses, the aged B cell is expected to have major impacts on the development and progression of these diseases. In this review, we summarize the role of B cells in health and disease settings, such as atherosclerotic disease. Furthermore, we provide an overview of age-related changes in B cell development and function with respect to their impact in chronic inflammatory diseases.
Changes in Functional Glucocorticoid Sensitivity of Isolated Splenocytes Induced by Chronic Psychosocial Stress – A Time Course Study
Authors: Kempter Elena , Amoroso Mattia , Duffner Hannah L. , Werner Andrea M. , Langgartner Dominik , Kupfer Sandra , Reber Stefan O.
Published: October 2021

Chronic psychosocial stress is a risk factor for the development of numerous disorders, of which most are associated with chronic low-grade inflammation. Given the immunosuppressive effects of glucocorticoids (GC), one underlying mechanism might be the development of stress-induced GC resistance in certain immune cell subpopulations. In line with this hypothesis, male mice exposed to the chronic subordinate colony housing (CSC, 19 days) model develop GC resistance of in vitro lipopolysaccharide (LPS)-stimulated splenocytes, splenomegaly and an increased percentage of splenic CD11b+ cells. Here male C57BL/6N mice were euthanized at different days during CSC, and following 30 days of single housing after stressor termination to assess when CSC-induced splenic GC resistance starts to develop and whether this is a transient effect. Moreover, splenic CD11b, GC receptor (GR) and/or macrophage migration inhibiting factor (MIF) protein levels were quantified at respective days. While mild forms of CSC-induced GC resistance, increased splenic CD11b expression and/or splenomegaly were detectable on days 8 and 9 of CSC, more severe forms took until days 15 and 16 to develop, but normalized almost completely within 30 days following stressor termination (day 51). In contrast, splenic GR expression was decreased in CSC versus single-housed control (SHC) mice at all days assessed. While MIF expression was increased on days 15 and 16 of CSC, it was decreased in CSC versus SHC mice on day 20 despite persisting splenomegaly, increased CD11b expression and functional GC resistance. In summary, our data indicate that GC resistance and CD11b+ cell-mediated splenomegaly develop gradually and in parallel over time during CSC exposure and are transient in nature. Moreover, while we can exclude that CSC-induced reduction in splenic GR expression is sufficient to induce functional GC resistance, the role of MIF in CD11b+ cell-mediated splenomegaly and GC resistance requires further investigation.
Characteristics of Anti-Contactin1 Antibody-Associated Autoimmune Nodopathies With Concomitant Membranous Nephropathy
Authors: Xu Qianhui , Liu Shuhu , Zhang Peng , Wang Zhen , Chang Xin , Liu Yulu , Yan Jiahe , He Ruirong , Luo Xiaoguang , Zou Liang-Yu , Chu Xiaofan , Guo Yi , Huang Suli , Fu Xuejun , Huang Ying
Published: October 2021

Background

The concurrence of anti-contactin 1 (CNTN1) antibody-associated chronic inflammatory demyelinating polyneuropathy (CIDP) and membranous nephropathy (MN) has previously been reported in the literature. CIDP with autoantibodies against paranodal proteins are defined as autoimmune nodopathies (AN) in the latest research. In view of the unclear relationship between CIDP and MN, we performed a case study and literature review to investigate the clinical characteristics of anti-CNTN antibody-associated AN with MN.

Methods

We detected antibodies against NF155, NF186, CNTN1, CNTN2, CASPR1 and PLA2R in blood samples of a patient with clinically manifested MN and concomitant peripheral neuropathyviadouble immunofluorescence staining and conducted a quantitative measurement of anti-PLA2R IgG antibodiesviaenzyme-linked immunosorbent assay (ELISA). Case reports of anti-CNTN1 antibody-associated AN, anti-CNTN1 antibody-associated AN with MN, and CIDP with MN were retrieved through a literature search for a comparative analysis of clinical characteristics. The cases were grouped according to the chronological order of CIDP and MN onset for the comparison of clinical characteristics.

Results

A 57-year-old man with anti-PLA2R positive MN was admitted to the hospital due to limb numbness, weakness, and proprioceptive sensory disorder. He was diagnosed with anti-CNTN1 antibody-associated AN and recovered well after immunotherapy. Our literature search returned 22 cases of CIDP with MN that occurred before, after, or concurrently with CIDP. Good responses were achieved with early single-agent or combination immunotherapy, but eight out of the 22 patients with CIDP and concomitant MN ultimately developed different motor sequelae. Five patients had anti-CNTN1 antibody-associated AN with MN. Among these patients, males accounted for the majority of cases (male:female=4:1), the mean age at onset was late (60.2 ± 15.7 years, range 43–78 years), and 40% had acute to subacute onset. Clinical manifestations included sensory-motor neuropathy, sensory ataxia caused by proprioceptive impairment, and elevated cerebrospinal fluid protein levels.

Conclusion

The age at onset of CIDP with MN was earlier than that of anti-CNTN1 antibody-associated AN. MN may occur before, after or concurrently with CIDP. The early detection and isotyping of anti-CNTN1 and anti-PLA2R antibodies and the monitoring of isotype switching may be essential for suspected CIDP patients.
T Cell Subsets in Graft Versus Host Disease and Graft Versus Tumor
Authors: Jiang Hua , Fu Denggang , Bidgoli Alan , Paczesny Sophie
Published: October 2021

Allogeneic hematopoietic cell transplantation (allo-HCT) is an essential therapeutic modality for patients with hematological malignancies and other blood disorders. Unfortunately, acute graft-versus-host disease (aGVHD) remains a major source of morbidity and mortality following allo-HCT, which limits its use in a broader spectrum of patients. Chronic graft-versus-host disease (cGVHD) also remains the most common long-term complication of allo-HCT, occurring in reportedly 30-70% of patients surviving more than 100 days. Chronic GVHD is also the leading cause of non-relapse mortality (NRM) occurring more than 2 years after HCT for malignant disease. Graft versus tumor (GVT) is a major component of the overall beneficial effects of allogeneic HCT in the treatment of hematological malignancies. Better understanding of GVHD pathogenesis is important to identify new therapeutic targets for GVHD prevention and therapy. Emerging data suggest opposing roles for different T cell subsets, e.g., IFN-γ producing CD4+ and CD8+ T cells (Th1 and Tc1), IL-4 producing T cells (Th2 and Tc2), IL-17 producing T cells (Th17 and Tc17), IL-9 producing T cells (Th9 and Tc9), IL-22 producing T cells (Th22), T follicular helper cells (Tfh), regulatory T-cells (Treg) and tissue resident memory T cells (Trm) in GVHD and GVT etiology. In this review, we first summarize the general description of the cytokine signals that promote the differentiation of T cell subsets and the roles of these T cell subsets in the pathogenesis of GVHD. Next, we extensively explore preclinical findings of T cell subsets in both GVHD/GVT animal models and humans. Finally, we address recent findings about the roles of T-cell subsets in clinical GVHD and current strategies to modulate T-cell differentiation for treating and preventing GVHD in patients. Further exploring and outlining the immune biology of T-cell differentiation in GVHD that will provide more therapeutic options for maintaining success of allo-HCT.
Dyspnea Measurement in Acute Heart Failure: A Systematic Review and Evidence Map of Randomized Controlled Trials
Authors: Zhang Xiaoyu , Zhao Chen , Zhang Houjun , Liu Wenjing , Zhang Jingjing , Chen Zhao , You Liangzhen , Wu Yuzhuo , Zhou Kehua , Zhang Lijing , Liu Yan , Chen Jianxin , Shang Hongcai
Published: October 2021

Background: Dyspnea is the most common presenting symptom among patients hospitalized for acute heart failure (AHF). Dyspnea relief constitutes a clinically relevant therapeutic target and endpoint for clinical trials and regulatory approval. However, there have been no widely accepted dyspnea measurement standards in AHF. By systematic review and mapping the current evidence of the applied scales, timing, and results of measurement, we hope to provide some new insights and recommendations for dyspnea measurement.

Methods: PubMed, Embase, Cochrane Library, and Web of Science were searched from inception until August 27, 2020. Randomized controlled trials (RCTs) with dyspnea severity measured as the endpoint in patients with AHF were included.

Results: Out of a total of 63 studies, 28 had dyspnea as the primary endpoint. The Likert scale (34, 54%) and visual analog scale (VAS) (22, 35%) were most widely used for dyspnea assessment. Among the 43 studies with detailed results, dyspnea was assessed most frequently on days 1, 2, 3, and 6 h after randomization or drug administration. Compared with control groups, better dyspnea relief was observed in the experimental groups in 21 studies. Only four studies that assessed tolvaptan compared with control on the proportion of dyspnea improvement met the criteria for meta-analyses, which did not indicate beneficial effect of dyspnea improvement on day 1 (RR: 1.16; 95% CI: 0.99–1.37; p = 0.07; I2 = 61%).

Conclusion: The applied scales, analytical approaches, and timing of measurement are in diversity, which has impeded the comprehensive evaluation of clinical efficacy of potential therapies managing dyspnea in patients with AHF. Developing a more general measurement tool established on the unified unidimensional scales, standardized operation protocol to record the continuation, and clinically significant difference of dyspnea variation may be a promising approach. In addition, to evaluate the effect of experimental therapies on dyspnea more precisely, the screening time and blinded assessment are factors that need to be considered.
Genomic Analysis of Ciprofloxacin-Resistant Salmonella enterica Serovar Kentucky ST198 From Spanish Hospitals
Authors: Vázquez Xenia , Fernández Javier , Bances Margarita , Lumbreras Pilar , Alkorta Miriam , Hernáez Silvia , Prieto Elizabeth , de la Iglesia Pedro , de Toro María , Rodicio M. Rosario , Rodicio Rosaura
Published: October 2021

Salmonella enterica serovar Kentucky (S. Kentucky) with sequence type (ST) 198 and highly resistant to ciprofloxacin (ST198-CipR) has emerged as a global MDR clone, posing a threat to public health. In the present study, whole genome sequencing (WGS) was applied to characterize all CipRS. Kentucky detected in five Spanish hospitals during 2009–2018. All CipR isolates (n = 13) were ST198 and carried point mutations in the quinolone resistance-determining regions (QRDRs) of both gyrA (resulting in Ser83Phe and Asp87Gly, Asp87Asn, or Asp87Tyr substitutions in GyrA) and parC (with Thr57Ser and Ser80Ile substitutions in ParC). Resistances to other antibiotics (ampicillin, chloramphenicol, gentamicin, streptomycin, sulfonamides, and tetracycline), mediated by the blaTEM–1B, catA1, aacA5, aadA7, strA, strB, sul1, and tet(A) genes, and arranged in different combinations, were also observed. Analysis of the genetic environment of the latter resistance genes revealed the presence of multiple variants of SGI1 (Salmonella genomic island 1)-K and SGI1-P, where all these resistance genes except catA1 were placed. IS26 elements, found at multiple locations within the SGI1 variants, have probably played a crucial role in their generation. Despite the wide diversity of SGI1-K- and SGI1-P-like structures, phylogenetic analysis revealed a close relationship between isolates from different hospitals, which were separated by a minimum of two and a maximum of 160 single nucleotide polymorphisms. Considering that S. enterica isolates resistant to fluoroquinolones belong to the high priority list of antibiotic-resistant bacteria compiled by the World Health Organization, continuous surveillance of the S. Kentucky ST198-CIPR clone is required.
Bacteriophages in Biological Wastewater Treatment Systems: Occurrence, Characterization, and Function
Authors: Runa Viviane , Wenk Jannis , Bengtsson Simon , Jones Brian V. , Lanham Ana B.
Published: October 2021

Phage bacteria interactions can affect structure, dynamics, and function of microbial communities. In the context of biological wastewater treatment (BWT), the presence of phages can alter the efficiency of the treatment process and influence the quality of the treated effluent. The active role of phages in BWT has been demonstrated, but many questions remain unanswered regarding the diversity of phages in these engineered environments, the dynamics of infection, the determination of bacterial hosts, and the impact of their activity in full-scale processes. A deeper understanding of the phage ecology in BWT can lead the improvement of process monitoring and control, promote higher influent quality, and potentiate the use of phages as biocontrol agents. In this review, we highlight suitable methods for studying phages in wastewater adapted from other research fields, provide a critical overview on the current state of knowledge on the effect of phages on structure and function of BWT bacterial communities, and highlight gaps, opportunities, and priority questions to be addressed in future research.
Integrative Analysis of Metallothioneins Identifies MT1H as Candidate Prognostic Biomarker in Hepatocellular Carcinoma
Authors: Zhang Feng , Guo Shuijiao , Zhong Wenhui , Huang Kaijun , Liu Yubin
Published: October 2021

Background: Metallothioneins (MTs) play crucial roles in the modulation of zinc/copper homeostasis, regulation of neoplastic growth and proliferation, and protection against apoptosis. The present study attempted to visualize the prognostic landscape of MT functional isoforms and identify potential prognostic biomarkers in hepatocellular carcinoma (HCC).

Methods: The transcriptional expression, comprehensive prognostic performances, and gene–gene interaction network of MT isoforms in HCC were evaluated via Oncomine, GEPIA, Kaplan–Meier plotter, and GeneMANIA databases. Characterized by good prognostic value in three external cohorts, MT1H was specifically selected as a potential prognostic biomarker in HCC with various clinicopathological features. Functional and pathway enrichment analyses of MT1H status were performed using cBioPortal, the Database for Annotation, Visualization, and Integrated Discovery (DAVID), and ssGSVA method.

Results:MT1E/1F/1G/1H/1M/1X/2A was greatly downregulated in HCC. Prognostic analyses elucidated the essential correlations between MT1A/1B/1H/1X/2A/4 attenuation and poor overall survival, between MT1B/1H/4 downregulation and worse relapse-free survival, and between MT1A/1B/1E/1H/1M/2A/4 downregulation and diminished progression-free survival in HCC. Taken together, these results indicated the powerful prognostic value of MT1H among MTs in HCC. In-depth analyses suggested that MT1H may be more applicable to alcohol-derived HCC and involved in the downregulation of the inflammatory pathway, Jak–STAT pathway, TNF pathway, and Wnt signaling pathway.

Conclusion: MT-specific isoforms displayed aberrant expression and varying prognostic value in HCC. MT1H repression in HCC was multi-dimensionally detrimental to patient outcomes. Therefore, MT1H was possibly associated with carcinogenesis and exploited as a novel prognostic biomarker and candidate therapeutic target for HCC.