bluuebunny/crossref_metadata_2025 huggingface dataset:
The Potential Risk Factors for Mortality in Patients After In-Hospital Cardiac Arrest: A Multicenter Study
Authors: Wang Mei-Tzu , Huang Wei-Chun , Yen David Hung-Tsang , Yeh En-Hui , Wu Shih-Yuan , Liao Hsun-Hsiang
Published: March 2021

Background and Purpose: In-hospital cardiac arrest (IHCA) has high mortality rate, which needs more research. This multi-center study aims to evaluate potential risk factors for mortality in patients after IHCA.

Methods: Data for this study retrospectively enrolled IHCA patients from 14 regional hospitals, two district hospitals, and five medical centers between 2013 June and 2018 December. The study enrolled 5,306 patients and there were 2,871 patients in subgroup of intensive care unit (ICU) and emergency room (ER), and 1,894 patients in subgroup of general wards.

Results: As for overall IHCA patients, odds ratio (OR) for mortality was higher in older patients (OR = 1.69; 95% CI:1.33–2.14), those treated with ventilator (OR = 1.79; 95% CI:1.36–2.38) and vasoactive agents (OR = 1.88; 95% CI:1.45–2.46). Whereas, better survival was reported in IHCA patients with initial rhythm as ventricular tachycardia (OR = 0.32; 95% CI: 0.21–0.50) and ventricular fibrillation (OR = 0.26; 95% CI: 0.16–0.42). With regard to ICU and ER subgroup, there was no mortality difference among different nursing shifts, whereas for patients in general wards, overnight shift (OR = 1.83; 95% CI: 1.07–3.11) leads to poor outcome.

Conclusion: For IHCA patients, old age, receiving ventilator support and vasoactive agents reported poor survival. Overnight shift had poor survival for IHCA patients in general wards, despite no significance in overall and ICU/ER subgroups.
Alcohol Binge Drinking Selectively Stimulates Protein S-Glutathionylation in Aorta and Liver of ApoE−/− Mice
Authors: Seidel Kerstin , Wan Xueping , Zhang Mo , Zhou Yuxiang , Zang Mengwei , Han Jingyan
Published: March 2021

Background: Binge drinking has become the most common and deadly pattern of excessive alcohol use in the United States, especially among younger adults. It is closely related to the increased risk of cardiovascular disease. Oxidative stress as a result of ethanol metabolism is the primary pathogenic factor for alcohol-induced end organ injury, but the role of protein S-glutathionylation—a reversible oxidative modification of protein cysteine thiol groups that mediates cellular actions by oxidants—in binge drinking-associated cardiovascular disease has not been explored. The present study defines the effect of alcohol binge drinking on the formation of protein S-glutathionylation in a mouse model of atherosclerosis.

Methods and Results: To mimic the weekend binge drinking pattern in humans, ApoE deficient (ApoE−/−) mice on the Lieber-DeCarli liquid diet received ethanol or isocaloric maltose (as a control) gavages (5 g/kg/day, 2 consecutive days/week) for 6 weeks. The primary alcohol-targeted organs (liver, brain), and cardiovascular system (heart, aorta, lung) of these two groups of the mice were determined by measuring the protein S-glutathionylation levels and its regulatory enzymes including [Glutaredoxin1(Grx1), glutathione reductase (GR), glutathione-S-transferase Pi (GST-π)], as well as by assessing aortic endothelial function and liver lipid levels. Our results showed that binge drinking selectively stimulated protein S-glutathionylation in aorta, liver, and brain, which coincided with altered glutathionylation regulatory enzyme expression that is downregulated Grx1 and upregulated GST-π in aorta, massive upregulation of GST-π in liver, and no changes in Grx1 and GST-π in brain. Functionally, binge drinking induced aortic endothelial cell function, as reflected by increased aortic permeability and reduced flow-mediated vasodilation.

Conclusions: This study is the first to provide in vivo evidence for differential effects of binge drinking on formation of protein S-glutathionylation and its enzymatic regulation system in major alcohol-target organs and cardiovascular system. The selective induction of protein S-glutathionylation in aorta and liver is associated with aortic endothelial dysfunction and fatty liver, which may be a potential redox mechanism for the increased risk of vascular disease in human binge-drinkers.
A Theoretical Analysis of Mixing Length for Atmospheric Models From Micro to Large Scales
Authors: Honnert Rachel , Masson Valéry , Lac Christine , Nagel Tim
Published: March 2021

A new mixing length adapted to the constraints of the hectometric-scale gray zone of turbulence for neutral and convective boundary layers is proposed. It combines a mixing length for mesoscale simulations, where the turbulence is fully subgrid and a mixing length for Large-Eddy Simulations, where the coarsest turbulent eddies are explicitly resolved. The mixing length is built for isotropic turbulence schemes, as well as schemes using the horizontal homogeneity assumption. This mixing length is tested over three boundary layer cases: a free convective case, a neutral case and a cold air outbreak case. The later combines turbulence from thermal and dynamical origins as well as presence of clouds. With this new mixing length, the turbulence scheme produces the right proportion between subgrid and resolved turbulent exchanges in Large Eddy Simulations, in the gray zone and at the mesoscale. This opens the way of using a single mixing length whatever the grid mesh of the atmospheric model, the evolution stage or the depth of the boundary layer.
Deep-Sea DC Resistivity and Self-Potential Monitoring System for Environmental Evaluation With Hydrothermal Deposit Mining
Authors: Kasaya Takafumi , Iwamoto Hisanori , Kawada Yoshifumi
Published: March 2021

Environmental impact assessment has become an important issue for deep-sea resource mining. The International Seabed Authority has recently developed recommendations for guidelines on environmental assessment of resource mining effects. Several research and development groups have been organized to develop methods for environmental assessment of the seafloor and sub-seafloor under the “Zipangu in the Ocean program,” a part of the Cross-ministerial Strategic Innovation Promotion Program managed by the Cabinet Office of the Japanese government. One attempt planned for long-term environment and sub-seafloor structure monitoring uses a cabled observatory system. To support this observatory plan, we began development of a system to monitor the sub-seafloor resistivity and self-potential reflecting the physicochemical properties of ore deposits and the existence of hydrothermal fluid. The system, which mainly comprises an electro-magnetometer and an electrical transmitter, detects spatio-temporal changes in subseafloor resistivity and in self-potential. Because of the project’s policy changes, cabled observatory system development was canceled. Therefore, we tried to conduct an experimental observation using only a current transmitter and a voltmeter unit. Data obtained during three and a half months show only slight overall apparent resistivity variation: as small as 0.005 Ω-m peak-to-peak. The electrode pair closest to the hydrothermal mound shows exceptionally large electric field variation, with a semidiurnal period related to tidal variation. Results indicate difficulty of explaining electric field variation by seawater mass migration around the hydrothermal mound. One possibility is the streaming potential, i.e., fluid flow below the seafloor, in response to tides. However, we have not been able to perform rigorous quantitative analysis, and further investigation is required to examine whether this mechanism is effective. The system we have developed has proven to be capable of stable data acquisition, which will allow for long-term monitoring including industrial applications.
Tectonic Switch From Triassic Contraction to Jurassic-Cretaceous Extension in the Western Tarim Basin, Northwest China: New Insights Into the Evolution of the Paleo-Tethyan Orogenic Belt
Authors: Wu Hongxiang , Cheng Xiaogan , Chen Hanlin , Chen Cai , Dilek Yildirim , Shi Jun , Zeng Changmin , Li Chunyang , Zhang Wei , Zhang Yuqing , Lin Xiubin , Zhang Fengqi
Published: March 2021

We use stratigraphic, sedimentological, and borehole data and seismic profiles from the western Tarim Basin to document its Mesozoic tectonic evolution. A nearly 60-km-wide, Triassic fold-and-thrust belt along the southwestern margin of Tarim Basin is unconformably overlain by a Jurassic-Cretaceous sedimentary sequence along a regional angular unconformity. The Lower-Middle Jurassic strata consist mainly of an upward-fining sequence ranging from terrestrial conglomerates to turbidite deposits, which represent the products of an initial rift stage. Palaeocurrent analyses show that sediments for these rift deposits were derived from the paleo-Kunlun and paleo-Tienshan Mountains to the southwest and northern, respectively. The overlying Upper Jurassic-Cretaceous series consist of coarse-grained, alluvial fan to braided river deposits in the lower stratigraphic member, and lagoonal mudstones and marine carbonates in the upper member. These finer-grained rocks were deposited in a subsiding basin, indicating that a significant change and reorientation in the drainage system should have occurred within the basin during the Early Cretaceous. The western Tarim Basin evolved from a syn-rift stage to a post-rift stage during the Jurassic-Cretaceous. A post-orogenic stretch developed due to the evolution of the Paleo-Tethyan orogenic belt in Central Asia is a likely geodynamic mechanism for this major tectonic switch from a contractional episode in the Triassic to an extensional deformation phase in the Jurassic-Cretaceous.
Case Report: SARS-CoV-2 Infection in a Child With Suprasellar Tumor and Hypothalamic-Pituitary Failure
Authors: Gaudino Rossella , Orlandi Valentina , Cavarzere Paolo , Chinello Matteo , Antoniazzi Franco , Cesaro Simone , Piacentini Giorgio
Published: March 2021

In early 2020, a novel coronavirus leading to potentially death was discovered. Since then, the 2019 coronavirus disease (COVID-19) has spread to become a worldwide pandemic. Beyond the risks strictly related to the infection, concerns have been expressed for the endocrinological impact that COVID-19 may have, especially in vulnerable individuals with pre-existing endocrinological health conditions. To date new information is emerging regarding severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) in children but the literature is still scarce concerning this infection in patients with intracranial malignant neoplasms. We report a 9-year-old child infected with SARS-CoV-2 and recent diagnosis of suprasellar non-germinomatous germ cell tumor also suffering from diabetes insipidus and hypothalamic-pituitary failure (hypothyroidism, adrenal insufficiency, hypothalamic obesity and growth hormone deficiency) and its clinical course. The patient remained asymptomatic for the duration of the infection without requiring any change in the replacement therapeutic dosages taken before the infection. We then discuss the proposed approach to treat a pediatric patient with SARS-CoV-2 infection and hypothalamic-pituitary failure and we include a review of the literature. Our report suggests that SARS-CoV-2 infection is usually mild and self-limiting in children even those immunocompromised and with multiple endocrinological deficits. Patients are advised to keep any scheduled appointments unless informed otherwise.
Longitudinal Evolution of Bone Microarchitecture and Bone Strength in Type 2 Diabetic Postmenopausal Women With and Without History of Fragility Fractures—A 5-Year Follow-Up Study Using High Resolution Peripheral Quantitative Computed Tomography
Authors: Heilmeier Ursula , Joseph Gabby B. , Pasco Courtney , Dinh Nhan , Torabi Soheyla , Darakananda Karin , Youm Jiwon , Carballido-Gamio Julio , Burghardt Andrew J. , Link Thomas M. , Kazakia Galateia J.
Published: March 2021

Introduction

Diabetic bone disease is characterized by an increased fracture risk which may be partly attributed to deficits in cortical bone quality such as higher cortical porosity. However, the temporal evolution of bone microarchitecture, strength, and particularly of cortical porosity in diabetic bone disease is still unknown. Here, we aimed to prospectively characterize the 5-year changes in bone microarchitecture, strength, and cortical porosity in type 2 diabetic (T2D) postmenopausal women with (DMFx) and without history of fragility fractures (DM) and to compare those to nondiabetic fracture free controls (Co) using high resolution peripheral quantitative computed tomography (HR-pQCT).

Methods

Thirty-two women underwent baseline HR-pQCT scanning of the ultradistal tibia and radius and a FU-scan 5 years later. Bone microarchitectural parameters, including cortical porosity, and bone strength estimates via µFEA were calculated for each timepoint and annualized. Linear regression models (adjusted for race and change in BMI) were used to compare the annualized percent changes in microarchitectural parameters between groups.

Results

At baseline at the tibia, DMFx subjects exhibited the highest porosity of the three groups (66.3% greater Ct.Po, 71.9% higher Ct.Po.Volume than DM subjects, p < 0.022). Longitudinally, porosity increased significantly over time in all three groups and at similar annual rates, while DMFx exhibited the greatest annual decreases in bone strength indices (compared to DM 4.7× and 6.7× greater decreases in failure load [F] and stiffness [K], p < 0.025; compared to Co 14.1× and 22.2× greater decreases in F and K, p < 0.020).

Conclusion

Our data suggest that despite different baseline levels in cortical porosity, T2D women with and without fractures experienced long-term porosity increases at a rate similar to non-diabetics. However, the annual loss in bone strength was greatest in T2D women with a history of a fragility fractures. This suggests a potentially non-linear course of cortical porosity development in T2D bone disease: major porosity may develop early in the course of disease, followed by a smaller steady annual increase in porosity which in turn can still have a detrimental effect on bone strength—depending on the amount of early cortical pre-damage.
Complications and Comorbidities of Acromegaly—Retrospective Study in Polish Center
Authors: Rolla Małgorzata , Jawiarczyk-Przybyłowska Aleksandra , Halupczok-Żyła Jowita , Kałużny Marcin , Konopka Bogumil M. , Błoniecka Izabela , Zieliński Grzegorz , Bolanowski Marek
Published: March 2021

Introduction

In acromegaly, chronic exposure to impaired GH and IGF-I levels leads to the development of typical acromegaly symptoms, and multiple systemic complications as cardiovascular, metabolic, respiratory, endocrine, and bone disorders. Acromegaly comorbidities contribute to decreased life quality and premature mortality. The aim of our study was to assess the frequency of acromegaly complications and to evaluate diagnostic methods performed toward recognition of them.

Materials and Methods

It was a retrospective study and we analyzed data of 179 patients hospitalized in the Department of Endocrinology, Diabetes and Isotope Therapy in Wroclaw Medical University (Poland) in 1976 to 2018 to create a database for statistical analysis.

Results

The study group comprised of 119 women (66%) and 60 men (34%). The median age of acromegaly diagnosis was 50.5 years old for women (age range 20–78) and 46 for men (range 24–76). Metabolic disorders (hyperlipidemia, diabetes, and prediabetes) were the most frequently diagnosed complications in our study, followed by cardiovascular diseases and endocrine disorders (goiter, pituitary insufficiency, osteoporosis). BP measurement, ECG, lipid profile, fasting glucose or OGTT were performed the most often, while colonoscopy and echocardiogram were the least frequent.

Conclusions

In our population we observed female predominance. We revealed a decrease in the number of patients with active acromegaly and an increase in the number of well-controlled patients. More than 50% of patients demonstrated a coexistence of cardiac, metabolic and endocrine disturbances and only 5% of patients did not suffer from any disease from those main groups.
The Role of Estrogen Receptors in Urothelial Cancer
Authors: Goto Takuro , Miyamoto Hiroshi
Published: March 2021

Epidemiological data have indicated that there are some sex-related differences in bladder cancer. Indeed, the incidence of bladder cancer in men has been substantially higher than that in women throughout the world, while women tend to have higher stage disease and poorer prognosis. These gender disparities have prompted to investigate sex hormones and their cognitive receptors in bladder cancer. Specifically, estrogen receptors, including estrogen receptor-α and estrogen receptor-β, have been shown to contribute to urothelial carcinogenesis and cancer progression, as well as to modulating chemosensitivity in bladder cancer, although conflicting findings exist. Meanwhile, immunohistochemical studies in surgical specimens have assessed the expression of estrogen receptors and related proteins as well as its associations with clinicopathologic features of bladder cancer and patient outcomes. This review article summarizes and discusses available data indicating that estrogen receptor signaling plays an important role in urothelial cancer.
Cortisol Co-Secretion and Clinical Usefulness of ACTH Stimulation Test in Primary Aldosteronism: A Systematic Review and Biases in Epidemiological Studies
Authors: Inoue Kosuke , Kitamoto Takumi , Tsurutani Yuya , Saito Jun , Omura Masao , Nishikawa Tetsuo
Published: March 2021

The hypothalamus-pituitary-adrenal (HPA) axis plays an important role in primary aldosteronism. Aldosterone biosynthesis is regulated not only by angiotensin II in the renin-angiotensin-aldosterone system, but also by adrenocorticotropic hormone (ACTH), one of the key components of the HPA axis. Although previous studies have reported cortisol cosecretion in primary aldosteronism, particularly aldosterone-producing adenoma (APA), the clinical relevance of such aldosterone and cortisol cosecretion from APA and hypertension or other metabolic disorders has not been fully established. Several somatic mutations including KCNJ5 and CACNA1D are known to induce autonomous production of aldosterone in APA, and the aldosterone responsiveness to ACTH may vary according to each mutation. The ACTH stimulation test has been reported to be a useful tool to distinguish the subtypes of primary aldosteronism (e.g., unilateral vs bilateral) in some studies, but it has not been commonly applied in clinical practice due to limited evidence. Given the recent advancement of imaging, omics research, and computational approach, it is important to summarize the most updated evidence to disentangle the potential impact of cortisol excess in primary aldosteronism and whether the ACTH stimulation test needs to be considered during the diagnostic process of primary aldosteronism. In this article, we conducted a systematic review of epidemiological studies about (i) cortisol cosecretion in primary aldosteronism and (ii) the ACTH stimulation test for the diagnosis of primary aldosteronism (including subtype diagnosis). Then, we discussed potential biases (e.g., confounding bias, overadjustment, information bias, selection bias, and sampling bias) in the previous studies and introduced some advanced epidemiological/statistical methods to minimize these limitations. A better understanding of biases and epidemiological perspective on this topic would allow us to produce further robust evidence and balanced discussion about the causal mechanisms involving the HPA axis and clinical usefulness of the ACTH stimulation test among patients with primary aldosteronism.
Mixed Conductivity of Hybrid Halide Perovskites: Emerging Opportunities and Challenges
Authors: Futscher Moritz H. , Milić Jovana V.
Published: March 2021

Hybrid halide perovskites feature mixed ionic-electronic conductivities that are enhanced under device operating conditions. This has been extensively investigated over the past years by a wide range of techniques. In particular, the suppression of ionic motion by means of material and device engineering has been of increasing interest, such as through compositional engineering, using molecular modulators as passivation agents, and low-dimensional perovskite materials in conjunction with alternative device architectures to increase the stabilities under ambient and operating conditions of voltage bias and light. While this remains an ongoing challenge for photovoltaics and light-emitting diodes, mixed conductivities offer opportunities for hybrid perovskites to be used in other technologies, such as rechargeable batteries and resistive switches for neuromorphic memory elements. This article provides an overview of the recent developments with a perspective on the emerging utility in the future.
Ant Communities Resist Even in Small and Isolated Gypsum Habitat Remnants in a Mediterranean Agroecosystem
Authors: Azcárate Francisco M. , Alameda-Martín Aitor , Escudero Adrián , Sánchez Ana M.
Published: March 2021

Natural and seminatural habitat remnants play a crucial ecological role in intensified agroecosystems. Assumptions on the conservation value of small and poorly connected fragments in a hostile matrix come from generalization obtained from a limited number of taxa, mostly plants, and vertebrates. To date, few studies have analyzed the effect of fragmentation on ant communities in Mediterranean agroecosystems, despite the importance of this group of animals on several key ecosystem functions and services. Here, we analyze the effects of fragment area and connectivity on ant communities in gypsum outcrops in a large cereal agroecosystem of Central Spain. Ant communities were described by their species composition, abundance (total number of occurrences), and number of species, standardized both by area (species density), and abundance (species richness). Observed number of species was relatively high in comparison with other studies in the Mediterranean, and we found no effects of fragment characteristics on species density, species richness and species composition, which implies that even small and isolated patches do have a value for ant conservation. Moreover, total number of occurrences were higher for smaller and more isolated fragments. This finding contrasts with the results reported for other taxa in similar gypsum habitats and suggests that certain ant traits and strategies make them particularly resistant to fragmentation and capable to take advantage of small habitat patches. Given the important ecological role played by ants, we recommend the preservation of these small habitat fragments in the management plans of agroecosystems in these drylands, especially in those cases in which intensification of agricultural practices greatly diminish natural habitat availability.
Integrating Environmental DNA Results With Diverse Data Sets to Improve Biosurveillance of River Health
Authors: Sepulveda Adam J. , Hoegh Andrew , Gage Joshua A. , Caldwell Eldridge Sara L. , Birch James M. , Stratton Christian , Hutchins Patrick R. , Barnhart Elliott P.
Published: March 2021

Autonomous, robotic environmental (e)DNA samplers now make it possible for biological observations to match the scale and quality of abiotic measurements collected by automated sensor networks. Merging these automated data streams may allow for improved insight into biotic responses to environmental change and stressors. Here, we merged eDNA data collected by robotic samplers installed at three U.S. Geological Survey (USGS) streamgages with gridded daily weather data, and daily water quality and quantity data into a cloud-hosted database. The eDNA targets were a rare fish parasite and a more common salmonid fish. We then used computationally expedient Bayesian hierarchical occupancy models to evaluate associations between abiotic conditions and eDNA detections and to simulate how uncertainty in result interpretation changes with the frequency of autonomous robotic eDNA sample collection. We developed scripts to automate data merging, cleaning and analysis steps into a chained-step, workflow. We found that inclusion of abiotic covariates only provided improved insight for the more common salmonid fish since its DNA was more frequently detected. Rare fish parasite DNA was infrequently detected, which caused occupancy parameter estimates and covariate associations to have high uncertainty. Our simulations found that collecting samples at least once per day resulted in more detections and less parameter uncertainty than less frequent sampling. Our occupancy and simulation results together demonstrate the advantages of robotic eDNA samplers and how these samples can be combined with easy to acquire, publicly available data to foster real-time biosurveillance and forecasting.
Integrated Transcriptomic Analysis of the miRNA–mRNA Interaction Network in Thin Endometrium
Authors: Zong Lu , Zheng Shengxia , Meng Ye , Tang Wenjuan , Li Daojing , Wang Zhenyun , Tong Xianhong , Xu Bo
Published: March 2021

Although the thin endometrium (TE) has been widely recognized as a critical factor in implantation failure, the contribution of miRNA–mRNA regulatory network to the development of disease etiology remains to be further elucidated. This study performed an integrative analysis of the miRNA–mRNA expression profiles in the thin and adjacent normal endometrium of eight patients with intrauterine adhesion to construct the transcriptomic regulatory networks. A total of 1,093 differentially expressed genes (DEGs) and 72 differentially expressed miRNAs (DEMs) were identified in the thin adhesive endometrium of the TE group compared with the control adjacent normal endometrial cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that the DEGs and the target genes of DEM were significantly enriched in angiogenesis, cell growth regulation, and Wnt signaling pathway. Multiple hub genes (CAV1, MET, MAL2, has-mir-138, ARHGAP6, CLIC4, RRAS, AGFG1, has-mir-200, and has-mir-429) were identified by constructing the miRNA–mRNA regulatory networks. Furthermore, a miRNA–mRNA pathway function analysis was conducted, and the hub genes were enriched in the FoxO signaling pathway, cell growth regulation, inflammatory response regulation, and regulation of autophagy pathways. Our study is the first to perform integrated mRNA-seq and miRNA-seq analyses in the thin adhesive endometrium and the control adjacent normal endometrial cells. This study provides new insights into the molecular mechanisms underlying the formation of thin endometrium.
Unraveling the Link Between Mitochondrial Dynamics and Neuroinflammation
Authors: de Oliveira Lilian Gomes , Angelo Yan de Souza , Iglesias Antonio H. , Peron Jean Pierre Schatzmann
Published: March 2021

Neuroinflammatory and neurodegenerative diseases are a major public health problem worldwide, especially with the increase of life-expectancy observed during the last decades. For many of these diseases, we still lack a full understanding of their etiology and pathophysiology. Nonetheless their association with mitochondrial dysfunction highlights this organelle as an important player during CNS homeostasis and disease. Markers of Parkinson (PD) and Alzheimer (AD) diseases are able to induce innate immune pathways induced by alterations in mitochondrial Ca2+ homeostasis leading to neuroinflammation. Additionally, exacerbated type I IFN responses triggered by mitochondrial DNA (mtDNA), failures in mitophagy, ER-mitochondria communication and mtROS production promote neurodegeneration. On the other hand, regulation of mitochondrial dynamics is essential for CNS health maintenance and leading to the induction of IL-10 and reduction of TNF-α secretion, increased cell viability and diminished cell injury in addition to reduced oxidative stress. Thus, although previously solely seen as power suppliers to organelles and molecular processes, it is now well established that mitochondria have many other important roles, including during immune responses. Here, we discuss the importance of these mitochondrial dynamics during neuroinflammation, and how they correlate either with the amelioration or worsening of CNS disease.
Erythropoietin in Lupus: Unanticipated Immune Modulating Effects of a Kidney Hormone
Authors: Eswarappa Meghana , Cantarelli Chiara , Cravedi Paolo
Published: March 2021

Systemic lupus erythematosus (SLE) is a multiorgan autoimmune disease with variable clinical presentation, typically characterized by a relapsing-remitting course. SLE has a multifactorial pathogenesis including genetic, environmental, and hormonal factors that lead to loss of tolerance against self-antigens and autoantibody production. Mortality in SLE patients remains significantly higher than in the general population, in part because of the limited efficacy of available treatments and the associated toxicities. Therefore, novel targeted therapies are urgently needed to improve the outcomes of affected individuals. Erythropoietin (EPO), a kidney-produced hormone that promotes red blood cell production in response to hypoxia, has lately been shown to also possess non-erythropoietic properties, including immunomodulatory effects. In various models of autoimmune diseases, EPO limits cell apoptosis and favors cell clearance, while reducing proinflammatory cytokines and promoting the induction of regulatory T cells. Notably, EPO has been shown to reduce autoimmune response and decrease disease severity in mouse models of SLE. Herein, we review EPO's non-erythropoietic effects, with a special focus on immune modulating effects in SLE and its potential clinical utility.
Effects of Neutrophil-to-Lymphocyte Ratio Combined With Interleukin-6 in Predicting 28-Day Mortality in Patients With Sepsis
Authors: Liu Shuangqing , Wang Xinkun , She Fei , Zhang Wei , Liu Hongsheng , Zhao Xiaodong
Published: March 2021

Background

The current study aimed to evaluate the relationship between the neutrophil-to-lymphocyte ratio (NLR) combined with interleukin (IL)-6 on admission day and the 28-day mortality of septic patients.

Material and Methods

We conducted an observational retrospective study. Patients with presumed sepsis were included. We observed the correlation of studied biomarkers (NLR, IL-6, PCT, and CRP) and the severity scores (APACHE II and SOFA scores) by plotting scatter plots. The relationships of the studied biomarkers and 28-day mortality were evaluated by using Cox regression model, receiver-operating characteristic (ROC) curve, and reclassification analysis.

Results

A total of 264 patients diagnosed with sepsis were enrolled. It was revealed that IL-6 had the strongest correlation with both APACHE II and SOFA scores, followed by the NLR and PCT, and there was no obvious correlation between CRP and the illness severity. NLR and IL-6 were independent predictors of the 28-day mortality in septic patients in the Cox regression model [NLR, odds ratio 1.281 (95% CI 1.159–1.414), P < 0.001; IL-6, odds ratio 1.017 (95% CI 1.005–1.028), P=0.004]. The area under the ROC curve (AUC) of NLR, IL-6 and NLR plus IL-6 (NLR_IL-6) was 0.776, 0.849, and 0.904, respectively.

Conclusion

Our study showed that the levels of NLR and IL-6 were significantly higher in the deceased patients with sepsis. NLR and IL-6 appeared to be independent predictors of 28-day mortality in septic patients. Moreover, NLR combined with IL-6 could dramatically enhance the prediction value of 28-day mortality.
Serum Detection of Anti-thyroid Peroxidase and Anti-thyroglobulin Antibodies in Chinese Patients With Pemphigus Vulgaris and Pemphigus Foliaceus and Literature Review
Authors: Wang He-Xiao , Yang Yang , Hu Jing-Yuan , Zhang Li-Ming , Cai Yun-Fei , Guo Hao , Xiao Ting , Chen Hong-Duo , Gao Xing-Hua , Qiao Shuai
Published: March 2021

Background

Pemphigus is a rare but life-threatening autoimmune skin disease characterized by blistering on skin and/or mucous membranes. The physiological process of blister formation involves IgG antibodies against the desmogleins (Dsgs) and desmocollins (Dscs). Additional autoAbs have also been suggested to mediate the disease heterogeneity, such as anti-thyroid peroxidase (anti-TPO) and antithyroglobulin (anti-Tg) antibodies, the essential culprits of the immune system in autoimmune thyroid diseases.

Purpose

To investigate the levels and antibody positivity of anti-TPO and anti-Tg antibodies in pemphigus patients.

Methods

Antibody positivity and levels of anti-TPO and anti-Tg antibodies in pemphigus patients as compared to healthy controls were examined. A meta-analysis was conducted by reviewing six similar studies.

Results

98 Chinese pemphigus patients and 65 healthy controls were enrolled in the study. Our meta-analysis revealed a significant correlation between increased presence of positive anti-TPO and anti-Tg antibodies and pemphigus, particularly for pemphigus vulgaris (PV). Such correlation was also observed in our own hospitalized PV patients, but not in pemphigus foliaceus (PF) patients. In addition, the status of anti-TPO and anti-Tg antibodies were also compared between females and males within PV patients, PF patients or controls, as well as compared for females or males between pemphigus patients and controls. In the analysis of T cell counts, we found abnormal low CD3 + T cell counts (< 690 n/µl) were only detected in patients whose thyroid antibody levels were less than 20 IU/ml.

Conclusion

Pemphigus patients showed higher levels and antibody positivity of anti-TPO and anti-Tg antibodies than healthy controls. Further investigations are needed to identify the pathogenic functions of these antibodies in pemphigus, as well as to identify the potential shared susceptibility genes.
ANCA Testing in Clinical Practice: From Implementation to Quality Control and Harmonization
Authors: Damoiseaux Jan
Published: March 2021

Analyses for the presence of anti-neutrophil cytoplasmic antibodies (ANCA) are important in the diagnostic work-up of patients with small vessel vasculitis. Since current immuno-assays are predominantly designed for diagnosis of patients with ANCA-associated vasculitis (AAV), implementation in routine clinical practice, internal and external quality control, and harmonization are focused on this particular use. However, ANCA testing may also be relevant for monitoring therapy efficacy and for predicting a clinical relapse in AAV patients, and even for diagnostic purposes in other clinical situations. In the current review, the topics of implementation, quality control, and standardization vs. harmonization are discussed while taking into account the different applications of the ANCA assays in the context of AAV.
Non-neutralizing Antibodies May Contribute to Suppression of SIVmac239 Viremia in Indian Rhesus Macaques
Authors: Pedreño-Lopez Nuria , Rosen Brandon C. , Flores Walter J. , Gorman Matthew J. , Voigt Thomas B. , Ricciardi Michael J. , Crosno Kristin , Weisgrau Kim L. , Parks Christopher L. , Lifson Jeffrey D. , Alter Galit , Rakasz Eva G. , Magnani Diogo M. , Martins Mauricio A. , Watkins David I.
Published: March 2021

The antiviral properties of broadly neutralizing antibodies against HIV are well-documented but no vaccine is currently able to elicit protective titers of these responses in primates. While current vaccine modalities can readily induce non-neutralizing antibodies against simian immunodeficiency virus (SIV) and HIV, the ability of these responses to restrict lentivirus transmission and replication remains controversial. Here, we investigated the antiviral properties of non-neutralizing antibodies in a group of Indian rhesus macaques (RMs) that were vaccinated with vif, rev, tat, nef, and env, as part of a previous study conducted by our group. These animals manifested rapid and durable control of viral replication to below detection limits shortly after SIVmac239 infection. Although these animals had no serological neutralizing activity against SIVmac239 prior to infection, their pre-challenge titers of Env-binding antibodies correlated with control of viral replication. To assess the contribution of anti-Env humoral immune responses to virologic control in two of these animals, we transiently depleted their circulating antibodies via extracorporeal plasma immunoadsorption and inhibition of IgG recycling through antibody-mediated blockade of the neonatal Fc receptor. These procedures reduced Ig serum concentrations by up to 80% and temporarily induced SIVmac239 replication in these animals. Next, we transferred purified total Ig from the rapid controllers into six vaccinated RMs one day before intrarectal challenge with SIVmac239. Although recipients of the hyperimmune anti-SIV Ig fraction were not protected from infection, their peak and chronic phase viral loads were significantly lower than those in concurrent unvaccinated control animals. Together, our results suggest that non-neutralizing Abs may play a role in the suppression of SIVmac239 viremia.
Utility of a Simplified Iliac Artery Calcium Scoring System to Guide Perioperative Management for Renal Transplantation
Authors: Werlin Evan C. , Braun Hillary J. , Walker Joy P. , Freise Jonathan E. , Amara Dominic , Liu Iris H. , Mello Anna , Tavakol Mehdi , Stock Peter G. , Hiramoto Jade S.
Published: March 2021

Non-contrast computed tomography scans of the abdomen and pelvis (CTAP) are often obtained prior to renal transplant to evaluate the iliac arteries and help guide surgical implantation. The purpose of this study was to describe the association of iliac calcification scores with operative and clinical outcomes using a simplified scoring system. A retrospective review of 204 patients who underwent renal transplant from 1/2013 to 11/2014 and who had a CTAP within 3 years prior to transplant was performed. Data were collected from the electronic medical record. Common iliac artery (CIA) and external iliac artery (EIA) calcification on CTAP were assessed using a simple scoring system. Descriptive statistics, logistic regression, and survival analyses were performed. A total of 204 patients were included in the analysis. The mean age was 57.4 ± 11.2 years and 134/204 (66%) were men. Nineteen patients (9%) had a history of peripheral artery disease (PAD), 78 (38%) had coronary artery disease, and 22 (11%) had a previous cerebrovascular accident (CVA). Patients with severe right EIA plaque morphology were significantly more likely to require arterial reconstruction compared to those without severe plaque (3/14[21%] 4/153 [3%], p = 0.03). Eleven patients (5%) had one or more amputations (toe, foot, or transtibial) following transplant. In UV logistic regression, severe EIA plaque morphology (OR 8.1, CI 2.2–29.6, p = 0.002) and PAD (OR 10.7, CI 2.8–39.9, p = 0.0004) were associated with increased odds of amputation. In the MV model containing both variables, EIA plaque morphology (OR 4.4, CI 0.99–18.3, p = 0.04) and PAD (OR 6.3, CI 1.4–26.4, p = 0.01) remained independently associated with increased odds of amputation. Over a median follow up of 3.3 years (IQR 2.9–3.6), 21 patients (10%) had post-operative major adverse cardiac events (MACE, defined as myocardial infarction, coronary intervention, or CVA), and 23 patients died (11%). In unadjusted Kaplan Meier analysis, CIA plaque (p = 0.00081) and >75% CIA length calcification (p = 0.0015) were significantly associated with MACE. Plaque burden in the EIA is associated with increased need for intra-operative arterial reconstruction and post-operative lower extremity amputations, while CIA plaque is associated with post-operative MACE. Assessment of CIA and EIA calcification scores on pre-transplant CT scans in high risk patients may guide operative strategy and perioperative management to improve clinical outcomes.
Innovations Developed by Patients and Informal Caregivers for Needs Associated to Rheumatic Diseases
Authors: Jacinto Maria João , Oliveira Pedro , Canhão Helena
Published: March 2021

Until recently, innovation in healthcare was mainly achieved through the development of new drugs, therapies, and medical devices by big pharma and medtech companies; however, the innovative potential for this field is much broader. The patients and caregivers' role in healthcare is often associated with disease management, demand for their own illness data, and its exchange with other patients. However, the patients and caregivers' capacity to innovate to cope with limitations associated with their health condition is a growing phenomenon and starting to be supported by healthcare stakeholders to achieve a truly patient-centric system. Our previous research has shown that these uncommon innovators can develop a wide range of solutions, from simple adaptations and products to highly technological biomedical devices. In this paper, we present novel solutions developed by rheumatic patients, their caregivers, and collaborators, published on the “Patient Innovation” platform (https://patient-innovation.com/), with a focus on the innovator profile, the need that triggers the innovative process, the type of motivation behind the product, and the products developed. The most significant needs that motivate innovation are the will to increase the level of independence (71%) and to be able to perform daily routine activities (65%). In over 80% of cases, the fact that the market does not fully fulfill the needs felt during daily activities is the main motivation to innovate. It is thus concluded that there is room for innovation in rheumatic diseases with solutions developed by patients and informal caregivers that intend to solve needs that the healthcare market is not covering.
Could Azithromycin Be Part of Pseudomonas aeruginosa Acute Pneumonia Treatment?
Authors: Leroy Anne-Gaëlle , Caillon Jocelyne , Caroff Nathalie , Broquet Alexis , Corvec Stéphane , Asehnoune Karim , Roquilly Antoine , Crémet Lise
Published: March 2021

Azithromycin (AZM) is a 15-membered-ring macrolide that presents a broad-spectrum antimicrobial activity against Gram-positive bacteria and atypical microorganisms but suffers from a poor diffusion across the outer-membrane of Gram-negative bacilli, includingPseudomonas aeruginosa(PA). However, AZM has demonstrated clinical benefits in patients suffering from chronic PA respiratory infections, especially cystic fibrosis patients. Since the rise of multidrug-resistant PA has led to a growing need for new therapeutic options, this macrolide has been proposed as an adjunctive therapy. Clinical trials assessing AZM in PA acute pneumonia are scarce. However, a careful examination of the available literature provides good rationales for its use in that context. In fact, 14- and 15-membered-ring macrolides have demonstrated immunomodulatory and immunosuppressive effects that could be of major interest in the management of acute illness. Furthermore, growing evidence supports a downregulation of PA virulence dependent on direct interaction with the ribosomes, and based on the modulation of several key regulators from the Quorum Sensing network. First highlightedin vitro, these interesting properties of AZM have subsequently been confirmed in the animal models. In this review, we systematically analyzed the literature regarding AZM immunomodulatory and anti-PA effects.In vitroandin vivostudies, as well as clinical trials were reviewed, looking for rationales for AZM use in PA acute pneumonia.
NMR Characterization of the Interactions Between Glycosaminoglycans and Proteins
Authors: Bu Changkai , Jin Lan
Published: March 2021

Glycosaminoglycans (GAGs) constitute a considerable fraction of the glycoconjugates found on cellular membranes and in the extracellular matrix of virtually all mammalian tissues. The essential role of GAG-protein interactions in the regulation of physiological processes has been recognized for decades. However, the underlying molecular basis of these interactions has only emerged since 1990s. The binding specificity of GAGs is encoded in their primary structures, but ultimately depends on how their functional groups are presented to a protein in the three-dimensional space. This review focuses on the application of NMR spectroscopy on the characterization of the GAG-protein interactions. Examples of interpretation of the complex mechanism and characterization of structural motifs involved in the GAG-protein interactions are given. Selected families of GAG-binding proteins investigated using NMR are also described.
Absence of Pannexin 1 Stabilizes Hippocampal Excitability After Intracerebral Treatment With Aβ (1-42) and Prevents LTP Deficits in Middle-Aged Mice
Authors: Südkamp Nicolina , Shchyglo Olena , Manahan-Vaughan Denise
Published: March 2021

Beta-amyloid protein [Aβ(1-42)] plays an important role in the disease progress and pathophysiology of Alzheimer's disease (AD). Membrane properties and neuronal excitability are altered in the hippocampus of transgenic AD mouse models that overexpress amyloid precursor protein. Although gap junction hemichannels have been implicated in the early pathogenesis of AD, to what extent Pannexin channels contribute to Aβ(1-42)-mediated brain changes is not yet known. In this study we, therefore, investigated the involvement of Pannexin1 (Panx1) channels in Aβ-mediated changes of neuronal membrane properties and long-term potentiation (LTP) in an animal model of AD. We conducted whole-cell patch-clamp recordings in CA1 pyramidal neurons 1 week after intracerebroventricular treatments of adult wildtype (wt) and Panx1 knockout (Panx1-ko) mice with either oligomeric Aβ(1-42), or control peptide. Panx1-ko hippocampi treated with control peptide exhibited increased neuronal excitability compared to wt. In addition, action potential (AP) firing frequency was higher in control Panx1-ko slices compared to wt. Aβ-treatment reduced AP firing frequency in both cohorts. But in Aβ-treated wt mice, spike frequency adaptation was significantly enhanced, when compared to control wt and to Aβ-treated Panx1-ko mice. Assessment of hippocampal LTP revealed deficits in Aβ-treated wt compared to control wt. By contrast, Panx1-ko exhibited LTP that was equivalent to LTP in control ko hippocampi. Taken together, our data show that in the absence of Pannexin1, hippocampi are more resistant to the debilitating effects of oligomeric Aβ. Both Aβ-mediated impairments in spike frequency adaptation and in LTP that occur in wt animals, are ameliorated in Panx1-ko mice. These results suggest that Panx1 contributes to early changes in hippocampal neuronal and synaptic function that are triggered by oligomeric Aβ.