bluuebunny/crossref_metadata_2025 huggingface dataset:
Uso de corticoides no tratamento da Alopecia Areata
Authors: Lima Caroline Oliveira , Costa Eduarda Silva , Franco Jéssyka Viana Valadares , Braz Dayanna Cristina , Campos Lanusse Samira , Cal Giselle Gharder Varela , Cavalcante Amanda Chistina Nunes
Published: April 2023

A Alopecia Areata (AA) é uma patologia que afeta a unidade folicular e as alterações ungueais concomitantemente ao quadro, de causa indefinida e multifatorial e evidentes manifestações autoimunes e genéticas. Portanto, objetiva-se avaliar o uso dos corticoides no tratamento da Alopecia Arreata. Trata-se de uma revisão metódica de literatura, teve como proposta realizar uma pesquisa de artigos científicos através de pesquisa eletrônica, baseados nos dados listado: SCIELO (Biblioteca Eletrônica Científica Online) Lilacs (Literatura Latino-americana e do Caribe em Ciências da Saúde), Bireme (Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde), Pubmed (Plataforma de busca da National Library of Medicine), entre os anos de 2010 a 2022. Nos resultados, a segurança e eficácia dos corticoides para pacientes afetados por AA se mostrou responsiva e segura. Nos estudos selecionados, entendeu-se que esse medicamento tem como mecanismo de ação há o estímulo do fólico piloso, aumentando assim a duração da sua fase anágena.
En route to better treatment of rhabdomyosarcoma
Authors:   , Meister Michael Torsten
Published: April 2023

Rhabdomyosarcomas (RMS) are the most common tumors of the soft tissues (sarcomas) in children and adolescents. RMS grow aggressively and show a propensity to spread in the body (metastasize). Treatment is harsh and consists of chemotherapy and local therapy which can be radiotherapy and/or surgical removal. Depending on the localization in the body, children with localized disease can be cured in 50-70% of cases, often at the cost of severe long-term effects. Children with metastases, however, face poor survival with 40% survival at best. Thus, new therapies are needed for patients with RMS.
The development of such new therapies has been hampered by several factors of which a number are addressed in this thesis. First, we explore the relationship between aberrant so-called Hedgehog signaling pathway activity and programmed cell death (PCD) in RMS cell lines. We propose mechanisms by which RMS cells evade PCD induction and thereby acquire a growth advantage. Furthermore, we study how to overcome this mechanism by using combination treatments.
Cell lines are in vitro models derived from primary tumor material which have been altered to allow for indefinite growth. However, due to these alterations, cell lines reflect patient tumors to a lesser degree, thereby limiting their applicability. Thus, we sought to generate novel preclinical models of RMS which more closely resemble patient tumors. To this end, we established so-called tumor organoid models of RMS. Extensive characterization experiments indicate that RMS tumor organoid models indeed reflect patient tumors to a high degree. We could establish such models from most RMS subtypes, thereby expanding the arsenal of preclinical RMS models.
A key characteristic of tumors is their cellular heterogeneity, i.e., the variation between tumor cells within one or between tumors. Furthermore, it is important to understand what other cell types are present in a tumor as their presence and activation state (such as it is the case for immune cells) can be crucial for the survival of tumor cells. To address these two aspects, we performed single-cell RNA-sequencing of primary RMS tumors. With this novel technique, the gene expression of individual cells within a tumor sample can be measured. Using this information, we show that the relative contribution of tumor cells within a tumor exhibiting certain so-called transcriptional meta-programs is predictive for the survival of a patient. Furthermore, we propose a direct cell-cell interaction between tumor and immune cells by which the tumor cells inactivate the immune cells, thereby facilitating their own survival.
In conclusion, this thesis provides novel insights into the biology of RMS and proposes avenues for development of new treatment options.
VPLYV JUDIKATÚRY EURÓPSKEHO SÚDU PRE ĽUDSKÉ PRÁVA NA VÝVOJ ÚSTAVY SLOVENSKEJ REPUBLIKY – VYBRANÉ OTÁZKY
Authors: Šikuta Ján
Published: April 2023

Autor sa v príspevku venuje vplyvu judikatúry Európskeho súdu pre ľudské práva na zmeny Ústavy Slovenskej republiky predovšetkým v podobe zavedenia ústavnej sťažnosti podľa článku 127 Ústavy Slovenskej republiky a zavedenia inštitútu obnovy konania o sťažnosti. V ďalšej časti príspevku analyzuje vybrané otázky výkladu princípu zákazu diskriminácie podľa článku 12 ods. 2 Ústavy Slovenskej republiky vo svetle judikatúry Európskeho súdu pre ľudské práva k článku 14 Dohovoru o ochrane ľudských práv a základných slobôd a ochrany súkromia podľa článku 16 ods. 1 a 19 ods. 2 Ústavy Slovenskej republiky vo svetle judikatúry Európskeho súdu pre ľudské práva k článku 8 Dohovoru o ochrane ľudských práv a základných slobôd.
Mathematical analysis of the impact of community ignorance on the population dynamics of dengue
Authors: Aldila Dipo , Aulia Puspadani Chita , Rusin Rahmi
Published: April 2023

This study proposes a dengue spread model that considers the nonlinear transmission rate to address the level of human ignorance of dengue in their environment. The SIR − UV model has been proposed, where SIR denotes the classification of the human population and UV denotes the classification of the mosquito population. Assuming that the total human population is constant, and the mosquito population is already in its steady-state condition, using the Quasi-Steady State Approximation (QSSA) method, we reduce our SIR − UV model into a more simple IR-model. Our analytical result shows that a stable disease-free equilibrium exists when the basic reproduction number is <1. Furthermore, our model also shows the possibility of a backward bifurcation. The more ignorant the society is about dengue, the higher the possibility that backward bifurcation phenomena may appear. As a result, the condition of the basic reproduction number being <1 is insufficient to guarantee the extinction of dengue in a population. Furthermore, we found that increasing the recovery rate, reducing the waning immunity rate, and mosquito life expectancy can reduce the possibility of backward bifurcation phenomena. We use dengue incidence data from Jakarta to calibrate the parameters in our model. Through the fast Fourier transform analysis, it was found that dengue incidence in Jakarta has a periodicity of 52.4, 73.4, and 146.8 weeks. This result indicates that dengue will periodically appear at least every year in Jakarta. Parameter estimation for our model parameters was carried out by assuming the infection rate of humans as a sinusoidal function by determining the three most dominant frequencies. Numerical and sensitivity analyses were conducted to observe the impact of community ignorance on dengue endemicity. From the sensitivity analysis, we found that, although a larger community ignorance can trigger a backward bifurcation, this threshold can be minimized by increasing the recovery rate, prolonging the temporal immunity, or reducing the mosquito population. Therefore, to control dengue transmission more effectively, media campaigns undertaken by the government to reduce community ignorance should be accompanied by other interventions, such as a good treatment in the hospital or vector control programs. With this combination of interventions, it will be easier to achieve a condition of dengue-free population when the basic reproduction number is less than one.
Analysis of the correlation between biomechanical properties and corneal densitometry in myopic eyes
Authors: Zheng Yuwei , Xue Chao , Wang Jing , Chen Xuan , Wang Xiaohui , Wang Yan
Published: April 2023

Background: To investigate the correlation between corneal biomechanical characteristics (in vitro and in vivo) and corneal densitometry in myopia.

Methods: The Pentacam (Oculus, Wetzlar, Germany) corneal densitometry (CD) and Corvis ST (Oculus, Wetzlar, Germany) exams were conducted prior to surgery for myopic patients who were intended to undergo small-incision lenticule extraction (SMILE). CD values (grayscale units, GSUs), and in vivo biomechanical parameters were obtained. The stromal lenticule was subjected to a uniaxial tensile test to obtain the elastic modulus E in vitro. We exam the correlations among in vivo, in vitro biomechanical characteristics and CD values.

Results: In this study, 37 myopic patients (63 eyes) were included. The mean age of participants was 25.14 ± 6.74 years (range:16–39 years). The mean CD values of the total cornea, anterior layer, intermediate layer, posterior layer, 0–2 mm region and 2–6 mm region were 15.03 ± 1.23 GSU, 20.35 ± 1.98 GSU, 11.76 ± 1.01 GSU, 10.95 ± 0.83 GSU, 15.57 ± 1.12 GSU and 11.94 ± 1.77 GSU, respectively. Elastic modulus E (in vitro biomechanical indicator) was negatively correlated with intermediate layer CD (r = −0.35, p = 0.01) and 2–6 mm region CD (r = −0.39, p = 0.00). A negative correlation was also found between 0-2 mm central region CD and in vivo biomechanical indicator SP-HC (r = −0.29, p = 0.02).

Conclusion: In myopic patients, densitometry is negatively correlated with biomechanical properties both in vivo and in vitro. With an increase in CD, the cornea deformed more easily.
Designed NiMoC@C and NiFeMo2C@C core-shell nanoparticles for oxygen evolution in alkaline media
Authors: Li Xiang , Giordano Cristina
Published: April 2023

Electrochemical water splitting is one of the most promising and clean ways to produce hydrogen as a fuel. Herein, we present a facile and versatile strategy for synthesizing non-precious transition binary and ternary metal-based catalysts encapsulated in a graphitic carbon shell. NiMoC@C and NiFeMo2C@C were prepared via a simple sol-gel based method for application in the Oxygen Evolution Reaction (OER). The conductive carbon layer surrounding the metals was introduced to improve electron transport throughout the catalyst structure. This multifunctional structure showed synergistic effects, possess a larger number of active sites and enhanced electrochemical durability. Structural analysis indicated that the metallic phases were encapsulated in the graphitic shell. Experimental results demonstrated that the optimal core-shell material NiFeMo2C@C exhibited the best catalytic performance for the OER in 0.5 M KOH, reaching a current density of 10 mA cm-2 at low overpotential of 292 mV for the OER, superior to the benchmark IrO2 nanoparticles. The good performances and stability of these OER electrocatalysts, alongside an easily scalable procedure makes these systems ideal for industrial purposes.
Microinvasive mitral valve surgery: Current status and status quo
Authors: Tomšič Anton , Klautz Robert J. M. , Borger Michael A. , Palmen Meindert
Published: April 2023

Surgical mitral valve repair, performed either through median sternotomy or minimal invasive approach, presents the gold standard treatment for degenerative mitral valve disease. In dedicated centres, high repair and low complication rates have been established with excellent valve repair durability. Recently, new techniques have been introduced, that allow mitral valve repair to be performed through small surgical incisions and while avoiding cardio-pulmonary bypass. These new techniques, however, conceptually differ significantly when compared to surgical repair and it remains questionable whether they are capable of reproducing the results of surgical treatment.
Associated factors of cardiac valve calcification and its prognostic effects among patients with chronic kidney disease: a systematic review and meta-analysis
Authors: Zhang Jialing , Pang Qi , Wang Shiyuan , Wu Leiyun , Zhang Aihua
Published: April 2023

Background

Cardiac valve calcification (CVC) is highly prevalent and a risk factor for adverse outcomes in patients with chronic kidney disease (CKD). This meta-analysis aimed to investigate the risk factors for CVC and association between CVC and mortality in CKD patients.

Method

Three electronic databases including PubMed, Embase, and Web of Science were searched for relevant studies up to November 2022. Hazard ratios (HR), odds ratios (OR), and 95% confidence intervals (CI) were pooled using random-effect meta-analyses.

Results

22 studies were included in the meta-analysis. Pooled analyses showed that CKD patients with CVC were relatively older, had a higher body mass index, left atrial dimension, C-reaction protein level, and a declined ejection fraction. Calcium and phosphate metabolism dysfunction, diabetes, coronary heart disease, and duration of dialysis were all predictors for CVC in CKD patients. The presence of CVC (both aortic valve and mitral valve) increased the risk of all-cause and cardiovascular mortality in CKD patients. However, the prognostic value of CVC for mortality was not significant anymore in patients with peritoneal dialysis.

Conclusion

CKD patients with CVC had a greater risk of all-cause and cardiovascular mortality. Multiple associated factors for development of CVC in CKD patients should be taken into consideration by healthcare professionals to improve prognosis.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/, identifier [CRD42022364970].
Economic evaluation in cardiac electrophysiology: Determining the value of emerging technologies
Authors: Hijazi Waseem , Vandenberk Bert , Rennert-May Elissa , Quinn Amity , Sumner Glen , Chew Derek S.
Published: April 2023

Cardiac electrophysiology is a constantly evolving speciality that has benefited from technological innovation and refinements over the past several decades. Despite the potential of these technologies to reshape patient care, their upfront costs pose a challenge to health policymakers who are responsible for the assessment of the novel technology in the context of increasingly limited resources. In this context, it is critical for new therapies or technologies to demonstrate that the measured improvement in patients' outcomes for the cost of achieving that improvement is within conventional benchmarks for acceptable health care value. The field of Health Economics, specifically economic evaluation methods, facilitates this assessment of value in health care. In this review, we provide an overview of the basic principles of economic evaluation and provide historical applications within the field of cardiac electrophysiology. Specifically, the cost-effectiveness of catheter ablation for both atrial fibrillation (AF) and ventricular tachycardia, novel oral anticoagulants for stroke prevention in AF, left atrial appendage occlusion devices, implantable cardioverter defibrillators, and cardiac resynchronization therapy will be reviewed.
Left atrial appendage occlusion combined with cryoballoon or radiofrequency ablation: One-year follow-up comparison
Authors: Ma Yibo , Guo Lanyan , Hu Miaoyang , Yan Qun , Liu Haitao , Yi Fu
Published: April 2023

Background

A one-stop procedure involving catheter ablation and left atrial appendage occlusion (LAAO) is an option for high-risk atrial fibrillation patients. Few studies have reported the efficacy and safety of cryoballoon ablation (CBA) combined with LAAO, and no studies have compared the combination of LAAO with CBA or radiofrequency ablation (RFA).

Methods

A total of 112 patients were enrolled in the present study; 45 patients received CBA combined with LAAO (group 1), and 67 patients received RFA combined with LAAO (group 2). Patient follow-up was performed for 1 year to detect peri-device leaks (PDLs) and safety outcomes (defined as a composite of peri-procedural and follow-up adverse events).

Results

The number of PDLs at the median 59 days follow-up was comparable between the two groups (33.3% in group 1 vs. 37.3% in group 2, p = 0.693). Safety outcomes were also comparable between the two groups (6.7% in group 1 vs. 7.5% in group 2, p = 1.000). Multivariable regression showed that PDLs risk and safety outcomes were all similar between the two groups. Subgroup analysis of PDLs indicated no significant differences. Follow-up safety outcomes were related to anticoagulant medication, and patients without PDLs were more likely to discontinue antithrombotic therapy. The total procedure and ablation times were all significantly shorter for group 1.

Conclusion

When compared with left atrial appendage occlusion combined with radiofrequency, left atrial appendage occlusion combined with cryoballoon ablation has the same risk of peri-device leaks and safety outcomes, but the procedure time was significantly reduced.
Modified dipeptide based nanospheres as a potent adjuvating delivery system for recombinant vaccines
Authors: Biswas Saikat , Yadav Nitin , Somanathan Anjali , Mukherjee Paushali , Chauhan Virander Singh
Published: April 2023

Recombinant protein vaccines offer an advantage without a safety risk in eliciting desired humoral and cell-mediated immune responses against infectious diseases. But one of their disadvantages is their low immunogenicity, thus requiring adjuvants that augment their immunogenicity. It is necessary to explore new technology that could provide a non-toxic, biodegradable, and biocompatible delivery system with adjuvant characteristics and nanotechnology provides an excellent platform for nanomaterial-based vaccine adjuvants. Here, we have synthesized a modified dipeptide, Arg-α, β-dehydrophenyalanine (RΔF) containing ΔF at its C-terminal, and characterized it using reversed-phase high-performance liquid chromatography (RP-HPLC) and mass spectrometry techniques. RΔF upon its self-assembly to spherical nanoparticles (NPs) efficiently condensed a recombinant Plasmodium falciparum surface protein, histidine-tagged MSPFu24 (Fu24H). The morphological characteristics of the nanoparticle formulation was characterized using TEM. RΔF NPs and RΔF-Fu24H complex showed excellent in vitro biocompatibility toward two mammalian cell lines and human red blood cells (RBCs). Furthermore, mice treated with R∆F NPs showed histological and haematological properties similar to the untreated control group which indicated their very high in vivo biocompatibility. Mice treated with RΔF-Fu24H nanoformulation induced a high titers of anti-Fu24H specific antibodies and showed a mixed Th1 and Th2 profile, comparable to the FDA-approved adjuvant Alhydrogel®. The sera from immunized mice inhibited the erythrocyte invasion activity of P. falciparum’s laboratory line 3D7 in vitro which was comparable to that of Alhydrogel®. The present study suggests that the highly biocompatible dipeptide-based nanoparticle formulation can further be developed and used in clinic as a promising antigen delivery platform to elicit immune responses.
Climate change and pulse migration: intermittent Chugach Inuit occupation of glacial fiords on the Kenai Coast, Alaska
Authors: Crowell Aron L. , Arimitsu Mayumi
Published: April 2023

For millennia, Inuit peoples of the Arctic and Subarctic have been challenged by the impacts of climate change on the abundance of key subsistence species. Responses to climate-induced declines in animal populations included switching to alternative food sources and/or migrating to regions of greater availability. We examine these dynamics for the Chugach Inuit (Sugpiat) people of southern coastal Alaska by synthesizing a large body of evidence from archeological sites, including radiocarbon dates and archaeofaunal assemblages, and by applying contemporary knowledge of glaciomarine ecosystems, spatial patterns of resource richness, and ocean-climate induced regime shifts in the Gulf of Alaska. We hypothesize that Chugach groups migrated from Cook Inlet and Prince William Sound to the Kenai Peninsula during periods of low sea surface temperatures (SSTs) to harvest harbor seals, which were seasonally aggregated near tidewater glaciers during pupping season, as well as piscivorous seabirds, Pacific cod, and other species that thrive under cool ocean conditions. During warming phases, the Chugach returned to Cook Inlet and Prince William Sound to fish for salmon and other species that abound during higher SSTs. Drivers of this coupled human-natural system of repeated (pulse) migration include the Pacific Decadal Oscillation (PDO), the dominant pattern of sea surface temperatures in the North Pacific that has been shown to generate step-like regime shifts in the marine food web; and coastal glaciers that structure the functioning of fiord ecosystems and support high levels of biological productivity. The culturally-constructed Chugach niche in the glaciomarine habitat of the Gulf of Alaska was based on intergenerationally transmitted ecological knowledge that enabled a resilient, mobile response to climate and resource variation.
Gamma irradiation-induced genetic variability and its effects on the phenotypic and agronomic traits of groundnut (Arachis hypogaeaL.)
Authors: Saibari Imane , Barrijal Saïd , Mouhib Mohammed , Belkadi Najlae , Hamim Ahlam
Published: April 2023

In order to increase genetic variability for the improvement of groundnut, two varieties, namely Kp29 and Fleur11, were treated with six different gamma irradiation doses. A significant effect of mutagenesis was distinctly observed in the stem lengths, roots, and survival percentage in both varieties. The radio-sensitivity test showed a mean lethal dose of 436.51Gy for Kp29 and 501.18 Gy for Fleur11. Furthermore, this study revealed putative mutants with variable agro-morphological traits. Seven chlorophyll mutants and various seed shape and color mutants were obtained. This study demonstrates the potency of gamma irradiation to induce high genetic variability that led to the emergence of certain mutations of economic importance.
Conversion therapy for advanced hepatocellular carcinoma with vascular invasion: a comprehensive review
Authors: Zhang Zunyi , Zhang Erlei
Published: April 2023

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and has a high mortality rate worldwide. The percentage of HCC patients with vascular invasion at the time of initial HCC diagnosis is 10%–40%. According to most guidelines, HCC with vascular invasion is classified as advanced stage, and resection is only suggested for a minority of such patients. Recently, advances in systemic and locoregional treatments for such patients have resulted in amazing response rates. Therefore, a “conversion therapy” strategy including systemic and locoregional treatments is proposed to select patients from an initially unresectable state to eventually undergo R0 resection. Recently, many studies have proven that conversion therapy followed by subsequent surgery is achievable in well-selected advanced HCC patients and can provide prolonged long-term outcomes. Based on published research, this review has summarized the clinical experience and evidence of conversion treatment in HCC patients with vascular invasion.
The necroptosis related gene LGALS3 can be used as a biomarker for the adverse progression from chronic HBV infection to HCC
Authors: Dong Jianming , Zhang Rongzheng , Xia Yan , Jiang Xu , Zhou Kun , Li Jiaqi , Guo Mengrui , Cao Xinyang , Zhang Shuyun
Published: April 2023

The number of patients with hepatocellular carcinoma (HCC) caused by hepatitis B virus (HBV) infection remains large, despite the remarkable effectiveness of antiviral drugs and vaccines for HBV in preventing and treating HBV infection. Necroptosis is closely related to the occurrence of inflammation, clearance of viral infection, and tumor progression. Presently, little is known about the changes in necroptosis-related genes in the progression from chronic HBV infection (CHI) to HBV-related hepatic fibrosis (HBV-HF) and HBV-related hepatocellular carcinoma (HBV-HCC). In this study, Cox regression analysis was performed using GSE14520 chip data and a necroptosis-related genes survival prognosis score (NRGPS) was established for HBV-HCC patients. NRGPS was constructed using three model genes (G6PD, PINK1 and LGALS3), and verified by data sequencing in the TCGA database. The HBV-HCC cell model was established by transfection of pAAV/HBV1.2C2, constructed by homologous recombination, into HUH7 and HEPG2 cells. The expression levels of G6PD, PINK1, and LGALS3 were detected using RT-qPCR. We further analyzed the expression of the model genes in GSE83148, GSE84044, and GSE14520 and found that LGALS3 was consistently highly expressed in CHI, high fibrosis score and high NRGPS. In addition, immune microenvironment analysis showed that LGALS3 was not only associated with the infiltration of regulatory T cells in the immune microenvironment but also with expression of CCL20 and CCR6. The expression levels of model genes, FOXP3 and CCR6, were analyzed using RT-qPCR in peripheral blood mononuclear cells of 31 hepatitis B surface antibody positive patients, 30 CHI, 21 HBV-HF, and 20 HBV-HCC. In further cell-model experiments, we analyzed the expression of CCL20 by RT-qPCR and the changes in cell proliferation and migration by CCK8 and transwell assays, respectively, in HBV-HCC cell models after LGALS3 knockdown. The findings of this study suggest that LGALS3 could be a biomarker for adverse progression following chronic HBV infection and may also be involved in the regulation of the immune microenvironment, making it a potential therapeutic target.
IL-3 produced by T cells is crucial for basophil extravasation in hapten-induced allergic contact dermatitis
Authors: Hachem Carole El , Marschall Pierre , Hener Pierre , Karnam Anupama , Bonam Srinivasa Reddy , Meyer Pierre , Flatter Eric , Birling Marie-Christine , Bayry Jagadeesh , Li Mei
Published: April 2023

Basophils have been recognized as a characterized cellular player for Th2 immune responses implicated in allergic diseases, but the mechanisms responsible for basophil recruitment to allergic skin remain not well understood. Using a hapten fluorescein isothiocyanate (FITC)-induced allergic contact dermatitis (ACD) mouse model, we show that basophils in FITC-treated IL-3-knockout mice are defective in crossing the vascular endothelium to enter the inflamed skin. By generating mice in which IL-3 is selectively ablated in T cells, we further demonstrate that IL-3 produced by T cells mediates basophil extravasation. Moreover, basophils sorted from FITC-treated IL-3-knockout mice exhibit a decreased expression of integrins Itgam, Itgb2, Itga2b and Itgb7, which are potentially implicated in extravasation process. Interestingly, we observed that these basophils had a reduced expression of retinaldehyde dehydrogenase 1 family member A2 (Aldh1a2), an enzyme responsible for the production of retinoic acid (RA), and administration of all-trans RA restored partially the extravasation of basophils in IL-3-knockout mice. Finally, we validate that IL-3 induces the expression of ALDH1A2 in primary human basophils, and provide further evidence that IL-3 stimulation induces the expression of integrins particularly ITGB7 in an RA-dependent manner. Together, our data propose a model that IL-3 produced by T cells activates ALDH1A2 expression by basophils, leading to the production of RA, which subsequently induces the expression of integrins crucially implicated in basophil extravasation to inflamed ACD skin.
Galanin ameliorates liver inflammation and fibrosis in mice by activating AMPK/ACC signaling and modifying macrophage inflammatory phenotype
Authors: He Lingnan , Huang Chao , Wang Hui , Yang Naibin , Zhang Jianbin , Xu Leiming , Gu Ting , Li Zhenghong , Chen Yuanwen
Published: April 2023

Background and aims

Galanin is a naturally occurring peptide that plays a critical role in regulating inflammation and energy metabolism, with expression in the liver. The exact involvement of galanin in non-alcoholic fatty liver disease and related fibrosis remains controversial.

Methods

The effects of subcutaneously administered galanin were studied in mice with non-alcoholic steatohepatitis (NASH) induced by a high-fat and high-cholesterol diet for 8 weeks, and in mice with liver fibrosis induced by CCl4 for 7 weeks. The underlying mechanism was also studied in vitro on murine macrophage cells (J774A.1 and RAW264.7).

Results

Galanin reduced inflammation, CD68-positive cell count, MCP-1 level, and mRNA levels of inflammation-related genes in the liver of NASH mice. It also mitigated liver injury and fibrosis caused by CCl4. In vitro, galanin had anti-inflammatory effects on murine macrophages, including reduced phagocytosis and intracellular reactive oxygen species (ROS). Galanin also activated AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling.

Conclusion

Galanin ameliorates liver inflammation and fibrosis in mice, potentially by modifying macrophage inflammatory phenotype and activating AMPK/ACC signaling.
Intrinsic features of the cancer cell as drivers of immune checkpoint blockade response and refractoriness
Authors: Ursino Chiara , Mouric Cécile , Gros Laurent , Bonnefoy Nathalie , Faget Julien
Published: April 2023

Immune checkpoint blockade represents the latest revolution in cancer treatment by substantially increasing patients’ lifetime and quality of life in multiple neoplastic pathologies. However, this new avenue of cancer management appeared extremely beneficial in a minority of cancer types and the sub-population of patients that would benefit from such therapies remain difficult to predict. In this review of the literature, we have summarized important knowledge linking cancer cell characteristics with the response to immunotherapy. Mostly focused on lung cancer, our objective was to illustrate how cancer cell diversity inside a well-defined pathology might explain sensitivity and refractoriness to immunotherapies. We first discuss how genomic instability, epigenetics and innate immune signaling could explain differences in the response to immune checkpoint blockers. Then, in a second part we detailed important notions suggesting that altered cancer cell metabolism, specific oncogenic signaling, tumor suppressor loss as well as tight control of the cGAS/STING pathway in the cancer cells can be associated with resistance to immune checkpoint blockade. At the end, we discussed recent evidences that could suggest that immune checkpoint blockade as first line therapy might shape the cancer cell clones diversity and give rise to the appearance of novel resistance mechanisms.
Neutrophil diversity in inflammation and cancer
Authors: Carnevale Silvia , Di Ceglie Irene , Grieco Giovanna , Rigatelli Anna , Bonavita Eduardo , Jaillon Sebastien
Published: April 2023

Neutrophils are the most abundant circulating leukocytes in humans and the first immune cells recruited at the site of inflammation. Classically perceived as short-lived effector cells with limited plasticity and diversity, neutrophils are now recognized as highly heterogenous immune cells, which can adapt to various environmental cues. In addition to playing a central role in the host defence, neutrophils are involved in pathological contexts such as inflammatory diseases and cancer. The prevalence of neutrophils in these conditions is usually associated with detrimental inflammatory responses and poor clinical outcomes. However, a beneficial role for neutrophils is emerging in several pathological contexts, including in cancer. Here we will review the current knowledge of neutrophil biology and heterogeneity in steady state and during inflammation, with a focus on the opposing roles of neutrophils in different pathological contexts.
Public participation in marine spatial planning in Iceland
Authors: Wilke Maria
Published: April 2023

Introduction

Marine Spatial Planning (MSP) aims at ecosystem-based management of ocean resources that brings different stakeholders and the public together to discuss their conflicts of interest and forge a sustainable path forward. Public participation is a crucial element of MSP to make it democratically legitimate and sustainable in the long-term. MSP was formally introduced by law in Iceland in 2018 and two projects were initiated in the Westfjords and Eastfjords in 2019, with one further planned in Skjálfandi Bay.

Methods

To assess the scope and depth of public participation in those MSP projects, data was collected through semi-structured interviews (n=80), conversations, observations and document analysis during the data gathering and proposal stages of the planning processes.

Results

The results show that a limited group of people including institutional actors and formal stakeholders had been engaged in the information gathering stages of the process, but in the later phases of decision-making, local community members were notably absent.

Discussion/Conclusion

This lack of public participation highlights the need for more in-depth communication about the MSP process and marine issues in the adjacent communities as well as an urgent need for inclusion of the public into marine decision-making and MSP.
Interconnections between urolithiasis and oral health: a cross-sectional and bidirectional Mendelian randomization study
Authors: Xu Jin-Zhou , Sun Jian-Xuan , Miao Lin-Tao , Zhang Si-Han , Wang Wen-Jie , Liu Chen-Qian , Xia Qi-Dong , Lu Jun-Lin , Zhou Peng , Lv Yong-Man , Xun Yang , Guan Wei , Cui Lei
Published: April 2023

Introduction

Urolithiasis is one of the most common diseases for urologists and it is a heavy burden for stone formers and society. The theory of the oral–genitourinary axis casts novel light on the pathological process of genitourinary system diseases. Hence, we performed this study to characterize the crosstalk between oral health conditions and urolithiasis to provide evidence for prevention measures and mechanisms of stone formation.

Materials and methods

This population-based cross-sectional study included 86,548 Chinese individuals who had undergone a comprehensive examination in 2017. Urolithiasis was diagnosed depending on the results of ultrasonographic imaging. Logistic models were utilized to characterize the association between oral health conditions and urolithiasis. We further applied bidirectional Mendelian randomization to explore the causality between oral health conditions and urolithiasis.

Results

We observed that presenting caries indicated a negative correlation with the risk for urolithiasis while presenting gingivitis [OR (95% CI), 2.021 (1.866–2.187)] and impacted tooth [OR (95% CI), 1.312 (1.219–1.411)] shown to be positively associated with urolithiasis. Furthermore, we discovered that genetically predicted gingivitis was associated with a higher risk of urolithiasis [OR (95% CI), 1.174 (1.009–1.366)] and causality from urolithiasis to impacted teeth [OR(95% CI), 1.207 (1.027–1.418)] through bidirectional Mendelian randomization.

Conclusion

The results cast new light on the risk factor and pathogenesis of kidney stone formation and could provide novel evidence for the oral–genitourinary axis and the systematic inflammatory network. Our findings could also offer suggestions for tailored clinical prevention strategies against stone diseases.
Monkeypox: a global health emergency
Authors: Stilpeanu Ruxandra Ilinca , Stercu Ana Maria , Stancu Andreea Lucia , Tanca Antoanela , Bucur Octavian
Published: April 2023

Over the past 2 years, the world has faced the impactful Coronavirus Disease-2019 (COVID-19) pandemic, with a visible shift in economy, medicine, and beyond. As of recent times, the emergence of the monkeypox (mpox) virus infections and the growing number of infected cases have raised panic and fear among people, not only due to its resemblance to the now eradicated smallpox virus, but also because another potential pandemic could have catastrophic consequences, globally. However, studies of the smallpox virus performed in the past and wisdom gained from the COVID-19 pandemic are the two most helpful tools for humanity that can prevent major outbreaks of the mpox virus, thus warding off another pandemic. Because smallpox and mpox are part of the same virus genus, the Orthopoxvirus genus, the structure and pathogenesis, as well as the transmission of both these two viruses are highly similar. Because of these similarities, antivirals and vaccines approved and licensed in the past for the smallpox virus are effective and could successfully treat and prevent an mpox virus infection. This review discusses the main components that outline this current global health issue raised by the mpox virus, by presenting it as a whole, and integrating aspects such as its structure, pathogenesis, clinical aspects, prevention, and treatment options, and how this ongoing phenomenon is being globally approached.
Antibacterial and anti-biofilm activity of radezolid against Staphylococcus aureus clinical isolates from China
Authors: Wang Cong , Xiong Yanpeng , Bao Chai , Wei Ying , Wen Zewen , Cao Xinyi , Yu Zhijian , Deng Xiangbing , Li Guiqiu , Deng Qiwen
Published: April 2023

Although the potent antibacterial ability of radezolid against Staphylococcus aureus has been widely reported worldwide, its antibacterial and anti-biofilm activity against the S. aureus clinical isolates from China remains elusive. In this study, the minimum inhibitory concentration (MIC) of radezolid was determined in S. aureus clinical isolates from China using the agar dilution method, and the relationship between radezolid susceptibility and ST distribution was also investigated. The anti-biofilm activity of radezolid against S. aureus was determined by a crystal violet assay and compared with that of linezolid and contezolid. The quantitative proteomics of S. aureus treated with radezolid was analyzed, and the genetic mutations in radezolid-induced resistant S. aureus were determined by whole-genome sequencing. The dynamic changes in transcriptional expression levels of several biofilm-related genes were analyzed by quantitative RT-PCR. Our data showed that radezolid MIC ranged from ≤0.125 to 0.5 mg/L, which was almost 1/4 × MIC of linezolid against S. aureus, indicating the greater antibacterial activity of radezolid than linezolid. The S. aureus clinical isolates with radezolid MICs of 0.5 mg/L were most widely distributed in ST239 of MRSA and ST7 of MSSA. Moreover, the more robust anti-biofilm activity of radezolid with subinhibitory concentrations (1/8 × MIC and 1/16 × MIC) was demonstrated against S. aureus when compared with that of contezolid and linezolid. Genetic mutations were found in glmS, 23S rRNA, and DUF1542 domain-containing protein in radezolid-induced resistant S. aureus selected by in vitro induction of drug exposure. Quantitative proteomic analysis of S. aureus indicated that the global expression of some biofilm-related and virulence-related proteins was downregulated. Quantitative RT-PCR further confirmed that the expressions of some downregulated biofilm-related proteins, including sdrD, carA, sraP, hlgC, sasG, spa, sspP, fnbA, and oatA, were decreased after 12 h and 24 h of exposure to radezolid. Conclusively, radezolid shows robust antibacterial and anti-biofilm activity against S. aureus clinical isolates from China when compared with contezolid and linezolid.
Identification of associations between lncRNA and drug resistance based on deep learning and attention mechanism
Authors: Gao Meihong , Shang Xuequn
Published: April 2023

Introduction

Abnormal lncRNA expression can lead to the resistance of tumor cells to anticancer drugs, which is a crucial factor leading to high cancer mortality. Studying the relationship between lncRNA and drug resistance becomes necessary. Recently, deep learning has achieved promising results in predicting biomolecular associations. However, to our knowledge, deep learning-based lncRNA-drug resistance associations prediction has yet to be studied.

Methods

Here, we proposed a new computational model, DeepLDA, which used deep neural networks and graph attention mechanisms to learn lncRNA and drug embeddings for predicting potential relationships between lncRNAs and drug resistance. DeepLDA first constructed similarity networks for lncRNAs and drugs using known association information. Subsequently, deep graph neural networks were utilized to automatically extract features from multiple attributes of lncRNAs and drugs. These features were fed into graph attention networks to learn lncRNA and drug embeddings. Finally, the embeddings were used to predict potential associations between lncRNAs and drug resistance.

Results

Experimental results on the given datasets show that DeepLDA outperforms other machine learning-related prediction methods, and the deep neural network and attention mechanism can improve model performance.

Dicsussion

In summary, this study proposes a powerful deep-learning model that can effectively predict lncRNA-drug resistance associations and facilitate the development of lncRNA-targeted drugs. DeepLDA is available at https://github.com/meihonggao/DeepLDA.
Mirror-terminated Mach-Zehnder interferometer based on SiNOI slot and strip waveguides for sensing applications using visible light
Authors: Sultan Alaa , Sabry Yasser M. , Samir Ahmed , El-Aasser Mostafa A.
Published: April 2023

In this work, a highly sensitive sensor based on silicon nitride (SiN) waveguide is proposed that can be used for gas sensing using visible light. The whole sensor waveguide uses a silicon dioxide (SiO2) cladding while the sensing arm uses a fluidic cladding such as water. The proposed device is based on loop-mirror terminated (LMT) Mach-Zehnder interferometer (MZI), where the reference arm is exposed to the reference SiO2 medium, while the sensing arm is exposed to the sensing medium leading to a change in the refractive index of the waveguide cladding. The sensor performance is overall optimized by optimizing the design performance of all the components of the structure one by one. The waveguide sensitivity of both strip and slot types is analyzed for gaseous medium in order to compare their sensitivities and select the dimensions of the waveguide that results in the highest device sensitivity. Transverse-electric (TE) polarization is considered in this study for strip waveguide, where a higher sensitivity is founded with respect to the transverse-magnetic (TM) polarization. The field confinement in the slot waveguide in the sensing region is investigated and verified with a mode solver, where the optimum dimensions are obtained using finite difference eigenmode and finite difference time domain solvers. With a sensing arm length of 150 μm only, the proposed sensor achieves a device sensitivity of about 1,320 nm/RIU and a figure-of-merit (FOM) as high as 641 RIU−1 at the wavelength of 650 nm, which is the highest reported FOM up to the author’s knowledge. Higher values of the FOM are possible by employing a longer sensing arm.
Neural correlates of cocaine-induced conditioned place preference in the posterior cerebellar cortex
Authors: Rodríguez-Borillo Olga , Roselló-Jiménez Lorena , Guarque-Chabrera Julian , Palau-Batet María , Gil-Miravet Isis , Pastor Raúl , Miquel Marta , Font Laura
Published: April 2023

Introduction

Addictive drugs are potent neuropharmacological agents capable of inducing long-lasting changes in learning and memory neurocircuitry. With repeated use, contexts and cues associated with consumption can acquire motivational and reinforcing properties of abused drugs, triggering drug craving and relapse. Neuroplasticity underlying drug-induced memories takes place in prefrontal-limbic-striatal networks. Recent evidence suggests that the cerebellum is also involved in the circuitry responsible for drug-induced conditioning. In rodents, preference for cocaine-associated olfactory cues has been shown to correlate with increased activity at the apical part of the granular cell layer in the posterior vermis (lobules VIII and IX). It is important to determine if the cerebellum’s role in drug conditioning is a general phenomenon or is limited to a particular sensory modality.

Methods

The present study evaluated the role of the posterior cerebellum (lobules VIII and IX), together with the medial prefrontal cortex (mPFC), ventral tegmental area (VTA), and nucleus accumbens (NAc) using a cocaine-induced conditioned place preference procedure with tactile cues. Cocaine CPP was tested using ascending (3, 6, 12, and 24 mg/kg) doses of cocaine in mice.

Results

Compared to control groups (Unpaired and Saline animals), Paired mice were able to show a preference for the cues associated with cocaine. Increased activation (cFos expression) of the posterior cerebellum was found in cocaine CPP groups and showed a positive correlation with CPP levels. Such increases in cFos activity in the posterior cerebellum significantly correlated with cFos expression in the mPFC.

Discussion

Our data suggest that the dorsal region of the cerebellum could be an important part of the network that mediates cocaine-conditioned behavior.
Lactoferrin/sialic acid prevents adverse effects of intrauterine growth restriction on neurite length: investigations in an in vitro rabbit neurosphere model
Authors: Kühne Britta Anna , Gutierrez-Vázquez Lara , Sánchez Lamelas Estela , Guardia-Escote Laia , Pla Laura , Loreiro Carla , Gratacós Eduard , Barenys Marta , Illa Miriam
Published: April 2023

Introduction

Intrauterine growth restriction (IUGR) is a well-known cause of impaired neurodevelopment during life. In this study, we aimed to characterize alterations in neuronal development underlying IUGR and discover strategies to ameliorate adverse neurodevelopment effects by using a recently established rabbit in vitro neurosphere culture.

Methods

IUGR was surgically induced in pregnant rabbits by ligation of placental vessels in one uterine horn, while the contralateral horn remained unaffected for normal growth (control). At this time point, rabbits were randomly assigned to receive either no treatment, docosahexaenoic acid (DHA), melatonin (MEL), or lactoferrin (LF) until c-section. Neurospheres consisting of neural progenitor cells were obtained from control and IUGR pup’s whole brain and comparatively analyzed for the ability to differentiate into neurons, extend neurite length, and form dendritic branching or pre-synapses. We established for the very first time a protocol to cultivate control and IUGR rabbit neurospheres not only for 5 days but under long-term conditions up to 14 days under differentiation conditions. Additionally, an in vitro evaluation of these therapies was evaluated by exposing neurospheres from non-treated rabbits to DHA, MEL, and SA (sialic acid, which is the major lactoferrin compound) and by assessing the ability to differentiate neurons, extend neurite length, and form dendritic branching or pre-synapses.

Results

We revealed that IUGR significantly increased the neurite length after 5 days of cultivation in vitro, a result in good agreement with previous in vivo findings in IUGR rabbits presenting more complex dendritic arborization of neurons in the frontal cortex. MEL, DHA, and SA decreased the IUGR-induced length of primary dendrites in vitro, however, only SA was able to reduce the total neurite length to control level in IUGR neurospheres. After prenatal in vivo administration of SAs parent compound LF with subsequent evaluation in vitro, LF was able to prevent abnormal neurite extension.

Discussion

We established for the first time the maintenance of the rabbit neurosphere culture for 14 days under differentiation conditions with increasing complexity of neuronal length and branching up to pre-synaptic formation. From the therapies tested, LF or its major compound, SA, prevents abnormal neurite extension and was therefore identified as the most promising therapy against IUGR-induced changes in neuronal development.