bluuebunny/crossref_metadata_2025 huggingface dataset:
Forms of termination of legal acts at the will of the subjects of law: theoretical and legal aspect
Authors: Okunev I. S.
Published: December 2023

The article at the general theoretical level examines the concept and types of forms of termination of transactions at the will of legal subjects under the legislation of Ukraine.

The practice of applying legal norms shows that in certain cases the need to suspend legal acts arises in order to restore the state of legality, protect the rights and interests of individuals and legal entities, state and public interests, which, as a rule, occurs as expressed in the established form by the will of the subjects of law, the scope of which is defined by law.

The author singles out the following forms of termination of legal acts: «cancellation of a legal act», «recognition of a legal act as illegal», «recognition of a legal act as unconstitutional», «recognition of a legal act as invalid», «annulment of a legal act», «revocation of a legal act» and other.

The article defines the concept of «forms of termination of legal acts» and their classification according to the described criteria.

Forms of termination of legal acts as provided for by the legislation of the system of actions, measures defined by law, aimed at terminating the effect (validity) of certain legal acts (parts thereof), occurring within the framework of a certain legal regime and carried out by entities authorized to do so, are diverse in current legislation of Ukraine.

On the basis of the conducted analysis, it was concluded that the termination of any legal acts at the will of the subjects of the law is carried out in a certain order and by legal measures in various forms, which may differ among themselves: by spheres of implementation; by entities that have the right to initiate the termination of the legal act in a certain way; by entities that have the right to make a decision to terminate the legal act in a certain way; upon termination of the legal act; according to the legal consequences that occur in the event of the termination of the legal act in a certain way and for other reasons.

The classification of the forms of termination of legal acts allows to find out more deeply the essence, determine the grounds, the procedure for the implementation of the relevant forms with the aim of their correct selection by law enforcement subjects taking into account specific circumstances, increasing the effectiveness of the termination of legal acts, avoiding errors in the application of the law.

Key words: legal act; termination of the legal act; forms of termination of the legal act.
Hoping against the Odds: Understanding Refugee Youths' Aspirations for Gaining Overseas Scholarships
Authors: Aden Hassan
Published: December 2023

Why do young refugees in the Dadaab camps in Kenya aspire to gain resettlement-based scholarships for tertiary education when the odds of getting them are minimal? The existing literature sheds light on the strong educational aspirations of refugee youth. However, our understanding is obscure of why they persistently pursue lofty educational goals when the chances of achieving them is not optimistic, especially through emergency education programs. This study contributes to our understanding of this puzzle, theoretically and empirically. In the study, I draw from ethnographic research, including semistructured interviews and future aspiration mapping exercises with Form One students, as well as interviews with their teachers. I then present several interconnected explanations that address the research question. First, students believe that success in education is a way for them to get out of the camps. Second, they imagine that getting an overseas scholarship will resolve their difficult economic conditions and academic restrictions. Third, they believe that, by working hard to succeed and being motivated by the dream of getting an education abroad, their chances for other tertiary education will increase. In this study, I argue that the cultural logic of hoping to achieve a better future through education sustains young people's motivation to pursue overseas scholarships, which outweighs the low odds of attaining them.
My profession is geodesist
Authors:   Production Association ", Shitikov P. K. ,   Engineering Geodesy"
Published: December 2023

The author of this paper – Peter Konstantinovich Shitikov, was born in the village of Bochkarevo, Kyshtovsky district, NSO on 29 November 1950. After graduating from Kyshtovsky secondary school, in 1967 he entered NIIGAiK and graduated in 1972 with a specialisation in astronomy and geodesy. As a result of distribution he was sent to the Aerogeodesic Enterprise No. 8, now JSC "PO Engineering Geodesy", Novosibirsk. There he worked, except for 2 years (1975-1976) in Novosibirskenergo, all the following years, passing many steps of the career ladder up to the position of Chief Engineer of his Enterprise in 2003. All these years were occupied with topographic-geodetic provision of the country's territory, first of all its northern and eastern regions, in the last decades with the application of technologies not inferior to the best world samples, which ensured the creation of one of the best in the world national coordinate systems and spatial data infrastructure as a whole. All these years, there have been a constant contact with NIIGAiK, which became the Siberian University of Geosystems and Technologies in 2015, its specialized departments and specialists. This is what the author of this essay recalls.
Methodological and technological support for assessing the reliability of forensic examinations to determine the boundaries of water bodies
Authors:   Siberian State University of Geosystems and Technologies, Dubrovsky A. V. , Skopinskaya E. A. ,   Department of Property and Land Relations of the Novosibirsk region
Published: December 2023

The article examines the problems of ecological, environmental, regulatory and technological nature that arise due to the absence of boundaries of zones with special conditions for the use of the territory (ZSCUT) of water bodies. Such zones include water protection zones (WPZ), shoreline protected belts (SPB), flood zones (FZ), underflood zones (UFZ). Shoreline territories are actively involved in eco-nomic use. In order to prevent violations of their legal regime, it is necessary to carry out work to establish the boundaries of ZSCUT. The main problem in this process is the definition of the upper room of the water body, from which the boundaries of all other zones (WPZ, SPB, FZ, UFZ) are constructed. The boundaries of a water body are set depending on its type. To determine the boundary of a water body, information collected by hydrometeorological observation points is used. This information is based on average long-term water levels. The water level value is determined for each water body. According to the relief mark, the boundary of the water body is determined. Therefore, the article discusses the work on entering information about the boundaries of water bodies into the Unified State Register of Real Estate, the features of the legal status of the lands of shoreline territories and the regime of use of special zones, technological features of determining the boundaries of a water body, examples of forensic examinations to check the boundaries of water bodies. Based on the accumulated practical experience in verifying compliance with the requirements of water and land legislation when performing work on the establishment of special zones of water bodies, a number of criteria are recommended. These criteria can be applied in assessing the reliability of forensic examinations to determine the boundaries of water bodies.
Ecosystem services assessment and mapping in Altai Krai
Authors:   Institute for Water and Environmental Problems SB RAS, Krasnoyarova B. A. , Nazarenko A. E. ,   Institute for Water and Environmental Problems SB RAS, Plutalova T. G. ,   Institute for Water and Environmental Problems SB RAS, Sharabarina S. N. ,   Institute for Water and Environmental Problems SB RAS
Published: December 2023

In Russia, ecosystem service assessments at the regional level (as opposed to national and local) are currently underdeveloped. The article presents a regional assessment of the main groups of ecosystem services and the results of their approbation for the territory of the Altai Kraj; their spatial differentiation was revealed depending on natural and socio-economic conditions. The main units of analysis are the regions of the Altai Kraj. The assessment was carried out taking into account the structure of the economy and the nature of land use in the study region, as well as the importance of individual ecosystem services for its economy. Based on the results of the assessment, the territory was zoned and compared with its landscape structure; schematic maps were drawn up. The zone of high value of reg-ulating and cultural ecosystem services is spread in the Altai and Salairo-Kuznetsk-Alataus mountain-ous landscape areas of the region, as well as in the northern part of the Kulunda province of the steppe zonal area. It is characterized by the high value of carbon sequestration by forests, game animals and the attractiveness of landscapes. The second zone is formed by areas with valuable arable land and hayfields providing ecosystem services. In natural terms, these are steppe (South-Prialeiskaya prov-ince) and forest-steppe (Upper-Obskaya province) regions. They produce the most valuable crop products in the region. The zone of medium and low value of regulating and insufficiently developed supporting ecosystem services is represented by the areas of western and southern parts of the steppe zonal area, northern and central parts of the forest-steppe zonal area. These territories do not have a high value of any ecosystem services. The results of the study contribute to improving the structure of land use in municipal organisations of Altai Krai and the development of strategies for their development, aimed at an optimal combination of the goals of socio-economic development and preservation of the quality of life-supporting functions of its ecosystems.
PACT Tropical Moist Forest Accreditation Methodology
Authors: Balmford Andrew , Coomes David , Hartup James , Jaffer Sadiq , Keshav Srinivasan , Lam Miranda , Madhavapeddy Anil , Message Robin , Rau E-Ping , Swinfield Thomas , Wheeler Charlotte
Published: December 2023

This draft document describes the methodology developed by the Cambridge Center for Carbon Credits (4C) for estimating the number of credits to be issued to a project in the tropical moist forest (TMF) biome. It expands on the methodology outlined in (Swinfield and Balmford, 2023). We welcome comments and suggestions in the associated online document at https://tinyurl.com/cowgreport.
Spheroid size influences cellular senescence and angiogenic potential of mesenchymal stromal cell-derived soluble factors and extracellular vesicles
Authors: Rovere Matteo , Reverberi Daniele , Arnaldi Pietro , Palamà Maria Elisabetta Federica , Gentili Chiara
Published: December 2023

Introduction: The secretome of mesenchymal stromal cells (MSCs) serves as an innovative tool employed in the regenerative medicine approach. In this particular context, three-dimensional (3D) culture systems are widely utilized to better replicate in vivo conditions and facilitate prolonged cell maintenance during culture. The use of spheroids enables the preservation of the classical phenotypical characteristics of MSCs. However, the distinct microenvironment within the spheroid may impact the secretome, thereby enhancing the angiogenic properties of adult MSCs that typically possess a reduced angiogenic potential compared to MSCs derived from perinatal tissues due to the hypoxia created in the internal region of the spheroid.

Methods: In this study, large spheroids (2,600 cells, ∼300 μm diameter) and small spheroids (1,000 cells, ∼200 μm diameter) were used to examine the role of spheroid diameter in the generation of nutrients and oxygen gradients, cellular senescence, and the angiogenic potential of secreted factors and extracellular vesicles (EVs).

Results: In this study, we demonstrate that large spheroids showed increased senescence and a secretome enriched in pro-angiogenic factors, as well as pro-inflammatory and anti-angiogenic cytokines, while small spheroids exhibited decreased senescence and a secretome enriched in pro-angiogenic molecules. We also demonstrated that 3D culture led to a higher secretion of EVs with classical phenotypic characteristics. Soluble factors and EVs from small spheroids exhibited higher angiogenic potential in a human umbilical vein endothelial cell (HUVEC) angiogenic assay.

Discussion: These findings highlighted the necessity of choosing the appropriate culture system for obtaining soluble factors and EVs for specific therapeutic applications.
ROS-scavenging materials for skin wound healing: advancements and applications
Authors: Dong Yongkang , Wang Zheng
Published: December 2023

The intricate healing process of skin wounds includes a variety of cellular and molecular events. Wound healing heavily relies on reactive oxygen species (ROS), which are essential for controlling various processes, including inflammation, cell growth, angiogenesis, granulation, and the formation of extracellular matrix. Nevertheless, an overabundance of reactive oxygen species (ROS) caused by extended oxidative pressure may result in the postponement or failure of wound healing. It is crucial to comprehend the function of reactive oxygen species (ROS) and create biomaterials that efficiently eliminate ROS to enhance the healing process of skin wounds. In this study, a thorough examination is presented on the role of reactive oxygen species (ROS) in the process of wound healing, along with an exploration of the existing knowledge regarding biomaterials employed for ROS elimination. In addition, the article covers different techniques and substances used in the management of skin wound. The future prospects and clinical applications of enhanced biomaterials are also emphasized, highlighting the potential of biomaterials that scavenge active oxygen to promote skin repair. This article seeks to enhance the understanding of the complex processes of ROS in the healing of wounds and the application of ROS-scavenging materials. Its objective is to create novel strategies for effective treatment skin wounds.
Outcome of antithrombotic therapy in cancer patients with catheter-related thrombosis: a systematic review
Authors: Yin Qinan , Zheng Xingyue , Han Lizhu , Huang Xuefei , Wang Yueyuan , Song Yujie , Zhang Yuan , Bian Yuan
Published: December 2023

Introduction

The guidelines' recommendations for anticoagulation in cancer patients with catheter-related thrombosis are unclear. The aim of this systematic review was to assess anticoagulation management in cancer patients with catheter-related thrombosis (CRT) based on previously published studies.

Methods

As of June 10, 2023,we searched databases including PubMed, Embase, and Cochrane and included 11 observational studies that met the criteria. We evaluated 770 adults with active cancer and objectively confirmed patients with CRT who were using drugs including warfarin, LMWH, and new oral anticoagulants as antithrombotic therapy.

Results

We extracted outcome data, including thrombosis recurrence, catheter dysfunction, major bleeding, and death, and performed a meta-analysis.

Discussion

In this study we found that the risk of VTE recurrence was higher with rivaroxaban, the risk of bleeding and death appeared to be greater with warfarin, and although the risk of catheter dysfunction due to LMWH is a concern, it is still a more reasonable option for cancer patients with catheter-related thrombosis.

Systematic Review Registration

http://www.clinicaltrials.gov, identifier (CRD42022367979).
Chronological age enhances aging phenomena and protein nitration in oocyte
Authors: Goud Pravin T. , Goud Anuradha P. , Camp Olivia G. , Bai David , Gonik Bernard , Diamond Michael P. , Abu-Soud Husam M.
Published: December 2023

Background

The average age of childbearing has increased over the years contributing to infertility, miscarriages, and chromosomal abnormalities largely invoked by an age-related decline in oocyte quality. In this study, we investigate the role of nitric oxide (NO) insufficiency and protein nitration in oocyte chronological aging.

Methods

Mouse oocytes were retrieved from young breeders (YB, 8-14 weeks [w]), retired breeders (RB, 48-52w) and old animals (OA, 80-84w) at 13.5 and 17 hours after ovulation trigger. They were assessed for zona pellucida dissolution time (ZPDT); ooplasmic microtubule dynamics (OMD); cortical granule (CG) status and spindle morphology (SM), as markers of oocyte quality. Sibling oocytes from RB were exposed to NO supplementation and assessed for aging phenomena (AP). All oocyte cumulus complexes were subjected to fluorescence nitrotyrosine (NT) immunocytochemistry and confocal microscopy to assess morphology and protein nitration.

Results

At 13.5 h from hCG trigger, oocytes from RB compared to YB had significantly increased ZPDT (37.8 ± 11.9 vs 22.1 ± 4.1 seconds [s]), OMD (46.9 vs 0%), CG loss (39.4 vs 0%), and decreased normal SM (30.3 vs 81.3%), indicating premature AP that worsened among oocytes from RB at 17 hours post-hCG trigger. When exposed to SNAP, RB AP significantly decreased (ZPDT: 35.1 ± 5.5 vs 46.3 ± 8.9s, OMD: 13.3 vs 75.0% and CG loss: 50.0 vs 93.3%) and SM improved (80.0 vs 14.3%). The incidence of NT positivity was significantly higher in cumulus cells (13.5 h, 46.7 ± 4.5 vs 3.4 ± 0.7%; 17 h, 82.2 ± 2.9 vs 23.3 ± 3.6%) and oocytes (13.5 h, 57.1 vs 0%; 17 h, 100.0 vs 55.5%) from RB compared to YB. Oocytes retrieved decreased with advancing age (29.8 ± 4.1 per animal in the YB group compared to 10.2 ± 2.1 in RB and 4.0 ± 1.6 in OA). Oocytes from OA displayed increased ZPDT, major CG loss, increased OMD and spindle abnormalities, as well as pronuclear formation, confirming spontaneous meiosis to interphase transition.

Conclusion(s)

Oocytes undergo zona pellucida hardening, altered spindle and ooplasmic microtubules, and premature cortical granule release, indicative of spontaneous meiosis-interphase transition, as a function of chronological aging. These changes are also associated with NO insufficiency and protein nitration and may be alleviated through supplementation with an NO-donor.
Nanocrystalline cellulose reinforced poly(ethylene oxide) electrolytes for lithium-metal batteries with excellent cycling stability
Authors: Kim Guk-Tae , Antonelli Claire , Iojoiu Cristina , Löffler Marlou , Bresser Dominic , Molméret Yannick , Sanchez Jean-Yves , Passerini Stefano
Published: December 2023

Polyethylene oxide (PEO) based polymer electrolytes are still the state of the art for commercial lithium-metal batteries (LMBs) despite their remaining challenges such as the limited ionic conductivity at ambient temperature. Accordingly, the realization of thin electrolyte membranes and, thus, higher conductance is even more important, but this requires a sufficiently high mechanical strength. Herein, the incorporation of nanocrystalline cellulose into PEO-based electrolyte membranes is investigated with a specific focus on the electrochemical properties and the compatibility with lithium-metal and LiFePO4-based electrodes. The excellent cycling stability of symmetric Li||Li cells, including the complete stripping of lithium from one electrode to the other, and Li||LiFePO4 cells renders this approach very promising for eventually yielding thin high-performance electrolyte membranes for LMBs.
Cellular RNA and DNA sensing pathways are essential for the dose-dependent response of human monocytes to ionizing radiation
Authors: Mikhalkevich Natallia , Russ Eric , Iordanskiy Sergey
Published: December 2023

Circulating monocytes are important players of the inflammatory response to ionizing radiation (IR). These IR-resistant immune cells migrate to radiation-damaged tissues and differentiate into macrophages that phagocytize dying cells, but also facilitate inflammation. Besides the effect of damage-associated molecular patterns, released from irradiated tissues, the inflammatory activation of monocytes and macrophages is largely dependent on IR-induced DNA damage and aberrant transcriptional activity, which may facilitate expression of type I interferons (IFN-I) and numerous inflammation-related genes. We analyzed the accumulation of dsRNA, dsDNA fragments, and RNA:DNA hybrids in the context of induction of RNA-triggered MAVS-mediated and DNA-triggered STING-mediated signaling pathways, in primary human monocytes and a monocytic cell line, THP1, in response to various doses of gamma IR. We found that exposure to lower doses (<7.5 Gy) led to the accumulation of dsRNA, along with dsDNA and RNA:DNA hybrids and activated both MAVS and STING pathway-induced gene expression and signaling activity of IFN-I. Higher doses of IR resulted in the reduced dsRNA level, degradation of RNA-sensing mediators involved in MAVS signaling and coincided with an increased accumulation of dsDNA and RNA:DNA hybrids that correlated with elevated STING signaling and NF-κB-dependent gene expression. While both pathways activate IFN-I expression, using MAVS- and STING-knockout THP1 cells, we identified differences in the spectra of interferon-stimulated genes (ISGs) that are associated with each specific signaling pathway and outlined a large group of STING signaling-associated genes. Using the RNAi technique, we found that increasing the dose of IR activates STING signaling through the DNA sensor cGAS, along with suppression of the DDX41 helicase, which is known to reduce the accumulation of RNA:DNA hybrids and thereby limit cGAS/STING signaling activity. Together, these results indicate that depending on the applied dose, IR leads to the activation of either dsRNA-induced MAVS signaling, which predominantly leads to the expression of both pro- and anti-inflammatory markers, or dsDNA-induced STING signaling that contributes to pro-inflammatory activation of the cells. While RNA:DNA hybrids boost both MAVS- and STING-mediated signaling pathways, these structures being accumulated upon high IR doses promote type I interferon expression and appear to be potent enhancers of radiation dose-dependent pro-inflammatory activation of monocytes.
Single-cell RNA-seq analyses inform necroptosis-associated myeloid lineages influence the immune landscape of pancreas cancer
Authors: Dong Weiwei , Zhao Huixia , Xiao Shanshan , Zheng Liuqing , Fan Tongqiang , Wang Li , Zhang He , Hu Yanyan , Yang Jingwen , Wang Tao , Xiao Wenhua
Published: December 2023

Introduction

Tumor-infiltrating myeloid cells (TIMs) are key regulators in tumor progression, but the similarity and distinction of their fundamental properties in pancreatic ductal adenocarcinoma (PDAC) remain elusive.

Method

In this study, we conducted scRNA-seq data analysis of cells from 12 primary tumor (PT) tissues, 4 metastatic (Met) tumor tissues, 3 adjacent normal pancreas tissues (Para), and PBMC samples across 16 PDAC patients, and revealed a heterogeneous TIMs environment in PDAC.

Result

Systematic comparisons between tumor and non-tumor samples of myeloid lineages identified 10 necroptosis-associated genes upregulated in PDAC tumors compared to 5 upregulated in paratumor or healthy peripheral blood. A novel RTM (resident tissue macrophages), GLUL-SQSTM1- RTM, was found to act as a positive regulator of immunity. Additionally, HSP90AA1+HSP90AB1+ mast cells exhibited pro-immune characteristics, and JAK3+TLR4+ CD16 monocytes were found to be anti-immune. The findings were validated through clinical outcomes and cytokines analyses. Lastly, intercellular network reconstruction supported the associations between the identified novel clusters, cancer cells, and immune cell populations.

Conclusion

Our analysis comprehensively characterized major myeloid cell lineages and identified three subsets of myeloid-derived cells associated with necroptosis. These findings not only provide a valuable resource for understanding the multi-dimensional characterization of the tumor microenvironment in PDAC but also offer valuable mechanistic insights that can guide the design of effective immuno-oncology treatment strategies.
Utilizing predictive machine-learning modelling unveils feature-based risk assessment system for hyperinflammatory patterns and infectious outcomes in polytrauma
Authors: Fachet Melanie , Mushunuri Raghava Vinaykanth , Bergmann Christian B. , Marzi Ingo , Hoeschen Christoph , Relja Borna
Published: December 2023

Purpose

Earlier research has identified several potentially predictive features including biomarkers associated with trauma, which can be used to assess the risk for harmful outcomes of polytraumatized patients. These features encompass various aspects such as the nature and severity of the injury, accompanying health conditions, immune and inflammatory markers, and blood parameters linked to organ functioning, however their applicability is limited. Numerous indicators relevant to the patients` outcome are routinely gathered in the intensive care unit (ICU) and recorded in electronic medical records, rendering them suitable predictors for risk assessment of polytraumatized patients.

Methods

317 polytraumatized patients were included, and the influence of 29 clinical and biological features on the complication patterns for systemic inflammatory response syndrome (SIRS), pneumonia and sepsis were analyzed with a machine learning workflow including clustering, classification and explainability using SHapley Additive exPlanations (SHAP) values. The predictive ability of the analyzed features within three days after admission to the hospital were compared based on patient-specific outcomes using receiver-operating characteristics.

Results

A correlation and clustering analysis revealed that distinct patterns of injury and biomarker patterns were observed for the major complication classes. A k-means clustering suggested four different clusters based on the major complications SIRS, pneumonia and sepsis as well as a patient subgroup that developed no complications. For classification of the outcome groups with no complications, pneumonia and sepsis based on boosting ensemble classification, 90% were correctly classified as low-risk group (no complications). For the high-risk groups associated with development of pneumonia and sepsis, 80% of the patients were correctly identified. The explainability analysis with SHAP values identified the top-ranking features that had the largest impact on the development of adverse outcome patterns. For both investigated risk scenarios (infectious complications and long ICU stay) the most important features are SOFA score, Glasgow Coma Scale, lactate, GGT and hemoglobin blood concentration.

Conclusion

The machine learning-based identification of prognostic feature patterns in patients with traumatic injuries may improve tailoring personalized treatment modalities to mitigate the adverse outcomes in high-risk patient clusters.
Serum proteomics reveals a tolerant immune phenotype across multiple pathogen taxa in wild vampire bats
Authors: Vicente-Santos Amanda , Lock Lauren R. , Allira Meagan , Dyer Kristin E. , Dunsmore Annalise , Tu Weihong , Volokhov Dmitriy V. , Herrera Claudia , Lei Guang-Sheng , Relich Ryan F. , Janech Michael G. , Bland Alison M. , Simmons Nancy B. , Becker Daniel J.
Published: December 2023

Bats carry many zoonotic pathogens without showing pronounced pathology, with a few exceptions. The underlying immune tolerance mechanisms in bats remain poorly understood, although information-rich omics tools hold promise for identifying a wide range of immune markers and their relationship with infection. To evaluate the generality of immune responses to infection, we assessed the differences and similarities in serum proteomes of wild vampire bats (Desmodus rotundus) across infection status with five taxonomically distinct pathogens: bacteria (Bartonella spp., hemoplasmas), protozoa (Trypanosoma cruzi), and DNA (herpesviruses) and RNA (alphacoronaviruses) viruses. From 19 bats sampled in 2019 in Belize, we evaluated the up- and downregulated immune responses of infected versus uninfected individuals for each pathogen. Using a high-quality genome annotation for vampire bats, we identified 586 serum proteins but found no evidence for differential abundance nor differences in composition between infected and uninfected bats. However, using receiver operating characteristic curves, we identified four to 48 candidate biomarkers of infection depending on the pathogen, including seven overlapping biomarkers (DSG2, PCBP1, MGAM, APOA4, DPEP1, GOT1, and IGFALS). Enrichment analysis of these proteins revealed that our viral pathogens, but not the bacteria or protozoa studied, were associated with upregulation of extracellular and cytoplasmatic secretory vesicles (indicative of viral replication) and downregulation of complement activation and coagulation cascades. Additionally, herpesvirus infection elicited a downregulation of leukocyte-mediated immunity and defense response but an upregulation of an inflammatory and humoral immune response. In contrast to our two viral infections, we found downregulation of lipid and cholesterol homeostasis and metabolism with Bartonella spp. infection, of platelet-dense and secretory granules with hemoplasma infection, and of blood coagulation pathways with T. cruzi infection. Despite the small sample size, our results suggest that vampire bats have a similar suite of immune mechanisms for viruses distinct from responses to the other pathogen taxa, and we identify potential biomarkers that can expand our understanding of pathogenesis of these infections in bats. By applying a proteomic approach to a multi-pathogen system in wild animals, our study provides a distinct framework that could be expanded across bat species to increase our understanding of how bats tolerate pathogens.
Mitochondrial-regulated Tregs: potential therapeutic targets for autoimmune diseases of the central nervous system
Authors: Han Aoya , Peng Tingting , Xie Yinyin , Zhang Wanwan , Sun Wenlin , Xie Yi , Ma Yunqing , Wang Cui , Xie Nanchang
Published: December 2023

Regulatory T cells (Tregs) can eliminate autoreactive lymphocytes, induce self-tolerance, and suppress the inflammatory response. Mitochondria, as the energy factories of cells, are essential for regulating the survival, differentiation, and function of Tregs. Studies have shown that patients with autoimmune diseases of the central nervous system, such as multiple sclerosis, neuromyelitis optica spectrum disorder, and autoimmune encephalitis, have aberrant Tregs and mitochondrial damage. However, the role of mitochondrial-regulated Tregs in autoimmune diseases of the central nervous system remains inconclusive. Therefore, this study reviews the mitochondrial regulation of Tregs in autoimmune diseases of the central nervous system and investigates the possible mitochondrial therapeutic targets.
Diagnostic efficacy of serum presepsin for postoperative infectious complications: a meta-analysis
Authors: Lu Chun-Ying , Kao Chia-Li , Hung Kuo-Chuan , Wu Jheng-Yan , Hsu Hui-Chen , Yu Chia-Hung , Chang Wei-Ting , Feng Ping-Hsun , Chen I-Wen
Published: December 2023

Background

Postoperative infectious complications (PICs) are major concerns. Early and accurate diagnosis is critical for timely treatment and improved outcomes. Presepsin is an emerging biomarker for bacterial infections. However, its diagnostic efficacy for PICs across surgical specialties remains unclear.

Methods

In this study, a systematic search on MEDLINE, Embase, Google Scholar, and Cochrane Library was performed on September 30, 2023, to identify studies that evaluated presepsin for diagnosing PICs. PIC is defined as the development of surgical site infection or remote infection. Pooled sensitivity, specificity, and hierarchical summary receiver operating characteristic (HSROC) curves were calculated. The primary outcome was the assessment of the efficacy of presepsin for PIC diagnosis, and the secondary outcome was the investigation of the reliability of procalcitonin or C-reactive protein (CRP) in the diagnosis of PICs.

Results

This meta-analysis included eight studies (n = 984) and revealed that the pooled sensitivity and specificity of presepsin for PIC diagnosis were 76% (95% confidence interval [CI] 68%–82%) and 83% (95% CI 75%–89%), respectively. The HSROC curve yielded an area under the curve (AUC) of 0.77 (95% CI 0.73–0.81). Analysis of six studies on procalcitonin showed a combined sensitivity of 78% and specificity of 77%, with an AUC of 0.83 derived from the HSROC. Meanwhile, data from five studies on CRP indicated pooled sensitivity of 84% and specificity of 79%, with the HSROC curve yielding an AUC of 0.89.

Conclusion

Presepsin exhibits moderate diagnostic accuracy for PIC across surgical disciplines. Based on the HSROC-derived AUC, CRP has the highest diagnostic efficacy for PICs, followed by procalcitonin and presepsin. Nonetheless, presepsin demonstrated greater specificity than the other biomarkers. Further study is warranted to validate the utility of and optimize the cutoff values for presepsin.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42023468358.
Investigating the endocrine disruption effects of four disinfection byproducts on zebrafish estrogen receptor-α
Authors: Lee Sang-Ah , Ryu Chang Seon , Park Chang Gyun , Cho Hyunki , Jun Indong , Park Chang-Beom , Esterhuizen Maranda , Kim Young Jun
Published: December 2023

Reports have shown an increase in the use of disinfectants in wastewater treatment plants, prompted by the detection of residual viruses in sewage. However, the release of disinfection byproducts (DBPs) in final effluents has raised concerns about their potential adverse effects, such as endocrine disruption, on aquatic environments. Despite these concerns, few studies have examined the endocrine-disrupting effects of DBPs on fish, which may be vulnerable to DBPs. The aim of this case study was to investigate the endocrine-disrupting properties of four commonly formed DBPs: chloroiodomethane (CIM), dibromochloromethane (DBCM), bromodichloromethane (BDCM), and trichloroacetic acid (TCA) on the estrogen receptor-α in zebrafish (zERα). The results indicated that all four DBPs have high anti-estrogenic activity against zERα; with CIM, BDCM, DBCM, and TCA yielding 80.8%, 78.4%, 49.0%, and 64.1% anti-estrogenic effects on zERα, respectively. Moreover, all DBPs demonstrated negligible estrogenic effects on zERα. Our study sheds new light on the adverse effects of DBPs, particularly the endocrine-disrupting activity of CIM, which, as part of the dihalomethanes group, has received limited research attention in the past. This study shows the molecular interactions in terms of the endocrine disruption of DBP on zERα, warranting further studies to understand the overall impact of fish in affected aquatic ecosystems.
Efficacy of canakinumab in patients with Still’s disease across different lines of biologic therapy: real-life data from the International AIDA Network Registry for Still’s Disease
Authors: Vitale Antonio , Caggiano Valeria , Sfikakis Petros P. , Dagna Lorenzo , Lopalco Giuseppe , Ragab Gaafar , La Torre Francesco , Almaghlouth Ibrahim A. , Maggio Maria Cristina , Sota Jurgen , Tufan Abdurrahman , Hinojosa-Azaola Andrea , Iannone Florenzo , Loconte Roberta , Laskari Katerina , Direskeneli Haner , Ruscitti Piero , Morrone Maria , Mayrink Giardini Henrique A. , Panagiotopoulos Alexandros , Di Cola Ilenia , Martín-Nares Eduardo , Monti Sara , De Stefano Ludovico , Kardas Rıza Can , Duran Rahime , Campochiaro Corrado , Tomelleri Alessandro , Alabdulkareem Abdulaziz Mohammed , Gaggiano Carla , Tarsia Maria , Bartoloni Elena , Romeo Mery , Hussein Mohamed A. , Laymouna Ahmed Hatem , Parente de Brito Antonelli Isabele , Dagostin Marilia Ambiel , Fotis Lampros , Bindoli Sara , Navarini Luca , Alibaz-Oner Fatma , Sevik Gizem , Frassi Micol , Ciccia Francesco , Iacono Daniela , Crisafulli Francesca , Portincasa Piero , Jaber Nour , Kawakami-Campos Perla Ayumi , Wiesik-Szewczyk Ewa , Iagnocco Annamaria , Simonini Gabriele , Sfriso Paolo , Balistreri Alberto , Giacomelli Roberto , Conti Giovanni , Frediani Bruno , Fabiani Claudia , Cantarini Luca
Published: December 2023

Introduction

The effectiveness of canakinumab may change according to the different times it is used after Still’s disease onset. This study aimed to investigate whether canakinumab (CAN) shows differences in short- and long-term therapeutic outcomes, according to its use as different lines of biologic treatment.

Methods

Patients included in this study were retrospectively enrolled from the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to Still’s disease. Seventy-seven (51 females and 26 males) patients with Still’s disease were included in the present study. In total, 39 (50.6%) patients underwent CAN as a first-line biologic agent, and the remaining 38 (49.4%) patients were treated with CAN as a second-line biologic agent or subsequent biologic agent.

Results

No statistically significant differences were found between patients treated with CAN as a first-line biologic agent and those previously treated with other biologic agents in terms of the frequency of complete response (p =0.62), partial response (p =0.61), treatment failure (p >0.99), and frequency of patients discontinuing CAN due to lack or loss of efficacy (p =0.2). Of all the patients, 18 (23.4%) patients experienced disease relapse during canakinumab treatment, 9 patients were treated with canakinumab as a first-line biologic agent, and nine patients were treated with a second-line or subsequent biologic agent. No differences were found in the frequency of glucocorticoid use (p =0.34), daily glucocorticoid dosage (p =0.47), or concomitant methotrexate dosage (p =0.43) at the last assessment during CAN treatment.

Conclusion

Canakinumab has proved to be effective in patients with Still’s disease, regardless of its line of biologic treatment.
Evidence of tick-borne encephalitis virus neutralizing antibodies in Serbian individuals exposed to tick bites
Authors: Banović Pavle , Mijatović Dragana , Bogdan Ivana , Simin Verica , Meletis Eleftherios , Kostoulas Polychronis , Resman Rus Katarina , Knap Nataša , Korva Miša , Avšič-Županc Tatjana , Cabezas-Cruz Alejandro
Published: December 2023

Introduction

Tick-borne encephalitis (TBE) is an emerging vector-borne and food-borne disease caused by the tick-borne encephalitis virus (TBEV; Orthoflavivirus encephalitidis), with a distribution spanning the Eurasian continent. Despite its significant public health impact in various European regions, TBE remains largely underdiagnosed in Serbia due to limited awareness and diagnostic challenges. In response to this, our study aimed to comprehensively assess TBEV exposure in individuals infested with ticks and to identify potential TBEV foci within Serbia.

Materials and methods

From 2019 to 2021, we conducted an observational study involving 450 patients who reported tick infestations.

Results

Our demographic analysis revealed a median age of 38 years, with a slight male predominance among the participants. We documented tick infestations in 38 municipalities across 14 districts of Serbia, with a notable concentration in proximity to Fruška Gora Mountain. The ticks most frequently removed were Ixodes ricinus, with nymphs and adult females being the predominant stages. On average, nymphs were removed after about 27.1 hours of feeding, while adult females remained attached for approximately 44.4 hours. Notably, we found age as a significant predictor of infestation time for both nymphs and adult females. Furthermore, we detected TBEV-neutralizing antibodies in 0.66% of the serum samples, shedding light on potential TBEV foci, particularly in Fruška Gora Mountain and other regions of Serbia.

Conclusion

Our study emphasizes the urgent need for active TBE surveillance programs, especially in areas suspected of hosting TBEV foci, in order to assess the true TBE burden, identify at-risk populations, and implement effective preventive measures.
Calcium signaling mediates proliferation of the precursor cells that give rise to the ciliated left-right organizer in the zebrafish embryo
Authors: Abdel-Razek Osama , Marzouk Amanda , MacKinnon Madison , Guy Edward T. , Pohar Sonny A. , Zhushma Emily , Liu Junjie , Sia Isabel , Gokey Jason J. , Tay Hwee Goon , Amack Jeffrey D.
Published: December 2023

Several of our internal organs, including heart, lungs, stomach, and spleen, develop asymmetrically along the left-right (LR) body axis. Errors in establishing LR asymmetry, or laterality, of internal organs during early embryonic development can result in birth defects. In several vertebrates—including humans, mice, frogs, and fish—cilia play a central role in establishing organ laterality. Motile cilia in a transient embryonic structure called the “left-right organizer” (LRO) generate a directional fluid flow that has been proposed to be detected by mechanosensory cilia to trigger asymmetric signaling pathways that orient the LR axis. However, the mechanisms that control the form and function of the ciliated LRO remain poorly understood. In the zebrafish embryo, precursor cells called dorsal forerunner cells (DFCs) develop into a transient ciliated structure called Kupffer’s vesicle (KV) that functions as the LRO. DFCs can be visualized and tracked in the embryo, thereby providing an opportunity to investigate mechanisms that control LRO development. Previous work revealed that proliferation of DFCs via mitosis is a critical step for developing a functional KV. Here, we conducted a targeted pharmacological screen to identify mechanisms that control DFC proliferation. Small molecule inhibitors of the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) were found to reduce DFC mitosis. The SERCA pump is involved in regulating intracellular calcium ion (Ca2+) concentration. To visualize Ca2+ in living embryos, we generated transgenic zebrafish using the fluorescent Ca2+ biosensor GCaMP6f. Live imaging identified dynamic cytoplasmic Ca2+ transients (“flux”) that occur unambiguously in DFCs. In addition, we report Ca2+ flux events that occur in the nucleus of DFCs. Nuclear Ca2+ flux occurred in DFCs that were about to undergo mitosis. We find that SERCA inhibitor treatments during DFC proliferation stages alters Ca2+ dynamics, reduces the number of ciliated cells in KV, and alters embryo laterality. Mechanistically, SERCA inhibitor treatments eliminated both cytoplasmic and nuclear Ca2+ flux events, and reduced progression of DFCs through the S/G2 phases of the cell cycle. These results identify SERCA-mediated Ca2+ signaling as a mitotic regulator of the precursor cells that give rise to the ciliated LRO.
Network analysis and relationship of symptom factors to functional outcomes and quality of life following mild traumatic brain injury: a TRACK-TBI study
Authors: Eagle Shawn R. , Jain Sonia , Sun Xiaoying , Preszler Jonathan , McCrea Michael A. , Giacino Joseph T. , Manley Geoffrey T. , Okonkwo David O. , Nelson Lindsay D. ,   The TRACK-TBI Investigators
Published: December 2023

Introduction

Mild traumatic brain injury (mTBI) is a heterogenous injury which can be difficult to characterize and manage. Using cross-sectional network analysis (NA) to conceptualize mTBI symptoms offers an innovative solution to identify how mTBI symptoms relate to each other. The centrality hypothesis of network theory posits that certain symptoms in a network are more relevant (central) or have above average influence over the rest of the network. However, no studies have used NA to characterize the interrelationships between symptoms in a cohort of patients who presented with mTBI to a U.S. Level 1 trauma center emergency department and how subacute central symptoms relate to long-term outcomes.

Methods

Patients with mTBI (Glasgow Coma Scale = 13–15) evaluated across 18 U.S. Level 1 trauma centers from 2013 to 2019 completed the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) at 2 weeks (W2) post-injury (n = 1,593) and at 3 months (M3), 6 months (M6), and 12 months (M12) post-injury. Network maps were developed from RPQ subscale scores at each timepoint. RPQ scores at W2 were associated with M6 and M12 functional and quality of life outcomes.

Results

Network structure did not differ across timepoints, indicating no difference in symptoms/factors influence on the overall symptom network across time. The cognitive factor had the highest expected influence at W2 (1.761), M3 (1.245), and M6 (1.349). Fatigue had the highest expected influence at M12 (1.275). The emotional factor was the only other node with expected influence >1 at any timepoint, indicating disproportionate influence of emotional symptoms on overall symptom burden (M3 = 1.011; M6 = 1.076).

Discussion

Several symptom factors at 2-weeks post-injury were more strongly associated with incomplete recovery and/or poorer injury-related quality of life at 6 and 12 months post-injury than previously validated demographic and clinical covariates. The network analysis suggests that emotional, cognitive, and fatigue symptoms may be useful treatment targets in this population due to high centrality and activating potential of the overall symptom network.
2022 revised European recommendations for the coding of the basis of diagnosis of cancer cases in population-based cancer registries
Authors: Visser Otto , Kościańska Beata , Caetano dos Santos Florentino Luciano , Cuccaro Francesco , Forjaz Gonçalo , Michalek Irmina Maria , Mousavi Mohsen , Sulkowska Urszula , Martos Carmen , Giusti Francesco
Published: December 2023

The basis of diagnosis recommendations for population-based cancer registries aim to provide a standardized coding tool that reflects the certainty of cancer diagnosis, especially when pathological confirmation is lacking. The proportion of clinical diagnoses serves as an indicator of data quality. Given the evolving nature of diagnostic techniques, regular revision of the basis of diagnosis rules is crucial. To address this, a working group comprising representatives from the steering committee and member registries of the European Network of Cancer Registries was established. The original 1999 recommendations were comprehensively reviewed, resulting in the publication of an updated version. These new recommendations came into effect for incident cancer cases starting from January 1, 2023. The updated recommendations comprise an adapted code list for the basis of diagnosis, optional codes for histology cases, revisions related to flow cytometry, liquid biopsy, and cytogenetic/molecular testing, consolidation of histology codes 6 and 7, introduction of a new code 8 for cytogenetic/molecular confirmation, and establishment of new criteria for registering specific morphology codes in cancers lacking pathological confirmation.