Mobility Group Research Articles

The need for and prospects of developing a modern mobile laboratory complex for equipping sanitary and preventive organizations of the Russian Ministry of Defense

Presently, an increasing volume of laboratory tests performed by sanitary and preventive organizations of the Russian Ministry of Defense (centers of state sanitary and epidemiological supervision) are carried out directly in the field during various combat training activities and special tasks and the localization and elimination of epidemic foci of infectious diseases in organized military collectives. Thus, non-staff mobile sanitary-epidemiological groups are formed. However, the regular special military equipment—medical field laboratory—used to equip such groups, is outdated and does not provide the basic principles of their autonomous functioning (mobility, autonomy, multidisciplinarity, high manufacturability, zoning of workplaces, compliance with biological safety requirements). Hence, the need for and prospects of developing a new automotive laboratory complex for equipping sanitary and prophylactic organizations of the Russian Ministry of Defense are investigated. This study analyzes the experience of military sanitary-preventive organizations for the period 2011–2021. The tactical and technical characteristics of the staff laboratory of the medical field laboratory of the state sanitary and epidemiological supervision centers of the Russian Ministry of Defense are compared with available analogues, including those in the institutions of other ministries and departments. As the number of long visits of military sanitary specialists and preventive organizations significantly increases to the extent of providing temporary accommodation for military units to ensure the sanitary and epidemiological well-being of the personnel, the need for laboratory research in isolation from the network of stationary laboratories to objectify the activities of the state sanitary and epidemiological supervision and ensure the anti-epidemic protection of troops also significantly increases. Moreover, the drawbacks of the standard medical field laboratory and its analogues and hence their limited use in the interests of the Russian Ministry of Defense in existing configurations were identified. The obtained results enabled reasoning for the need for a new automotive laboratory complex for equipping sanitary and preventive organizations of the Russian Ministry of Defense considering the successful solutions in laboratory complexes of other ministries and departments.

Abstract A024: SOX11: An Achilles heel of mantle cell lymphoma enhancing sensitivity to DNA damaging agents by impairing DNA repair

Abstract Mantle cell lymphoma (MCL) is an aggressive malignancy with mature B-cell differentiation and a median overall survival of 5 years. A characteristic hallmark of MCL is the aberrant expression of the transcription factor sex determining region on Y chromosome (SRY)-related and high mobility group (HMG) domain containing protein 11 (SOX11) in approximately 90% of the cases. The role of SOX11 in MCL pathogenesis has been attributed to transcriptional dysregulation, ultimately driving malignant gene expression profile of MCL. However, little is known about the potential transcription factor-independent modes of action of SOX11. Our co-immunprecipitation and proteomic analysis showed that SOX11 binds to factors of DNA damage response (DDR), nucleosome remodeling and chromatin regulation, among others. Sterile Alpha motif and HD domain containing protein 1 (SAMHD1) is top-listed among the SOX11 binding partners in MCL. We recently showed that SOX11 binds via its HMG domain to SAMHD1, disturbing its homo-tetramerization. A growing body of evidence unveiled the implication of SAMHD1 in DDR, particularly in promoting homologous recombination. Immunofluorescent imaging showed that SOX11 impairs homologous recombination in MCL, evidenced by reduced accumulation of RAD51 foci upon chromatin in response to treatment with the topoisomerase1 inhibitor camptothecin (CPT). This was further consistent with abrogated phosphorylation of DNA-break binding protein RPA32 (S4/8), but not total RPA32, in response to CPT treatment in SOX11-positive conditions. Inducing SOX11 expression in SOX11-negative MCL cell line (JVM-2) resulted in increased accumulation of cytosolic single-stranded DNA upon CPT treatment. This was translated in an enhanced sensitivity to CPT in SOX11-expressing MCL cell lines as compared to SOX11-negative conditions. Moreover, this enhanced sensitivity was reflected in increased levels of cleaved PARP1, cleaved caspase 3 and persistent γ-H2A.X in SOX11-positive cells. Simian Immunodeficiency Virus protein (Vpx)-mediated depletion of SAMHD1 yielded a similar, yet attenuated, sensitive phenotype to CPT compared to SOX11 induction in JVM-2. SAMHD1 depletion in addition to SOX11 induction showed no significant additional impact on the response to CPT in JVM-2 under the conditions tested. Intriguingly, T592 phosphorylation of SAMHD1 was reduced upon inducing SOX11 expression in JVM-2, suggesting a mode of action by which SOX11 inhibits SAMHD1. However, the mechanism behind increased levels of SAMHD1 post-translational modification upon SOX11 induction requires further investigation. Altogether, our findings suggest that SOX11 may impair homologous recombination, at least in part, through inhibiting SAMHD1. These results highlight SOX11 as an Achilles heel that renders MCL vulnerable to DNA damaging and suggest that incorporating DNA damaging agents including topoisomerase inhibitors or anthracyclines into currently used treatment modalities for MCL might be clinically beneficial. Citation Format: HA Morsy, Virginia Amador, Birger Christensson, Nikolas Herold, Birgitta Sander. SOX11: An Achilles heel of mantle cell lymphoma enhancing sensitivity to DNA damaging agents by impairing DNA repair [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr A024.

Returners and explorers dichotomy in the face of natural hazards

Understanding human mobility patterns amid natural hazards is crucial for enhancing urban emergency responses and rescue operations. Existing research on human mobility has delineated two primary types of individuals: returners, who exhibit a tendency to frequent a limited number of locations, and explorers, characterized by a more diverse range of movement across various places. Yet, whether this mobility dichotomy endures in the context of natural hazards remains underexplored. This study addresses this gap by examining anonymized high-resolution mobile phone location data from Lee County, Florida residents, aiming to unravel the dynamics of these distinct mobility groups throughout different phases of Hurricane Ian. The results indicate that returners and explorers maintained their distinct mobility characteristics even during the hurricane, showing increased separability. Before the hurricane, returners favored shorter trips, while explorers embarked on longer journeys, a trend that continued during the hurricane. However, the hurricane heightened people’s inclination to explore, leading to a notable increase in longer-distance travel for both groups, likely influenced by evacuation considerations. Spatially, both groups exhibited an uptick in trips towards the southern regions, away from the hurricane’s path, particularly converging on major destinations such as Miami, Fort Lauderdale, Naples, and West Palm Beach during the hurricane.

MAIN MEANS OF CREATING AND DEVELOPING INCLUSIVE ROUTES

The article considers the problem of creating and developing inclusive routes. It analyses current trends in this field, including the impact of technology and sociocultural changes, classifies the requirements for the design of inclusive routes, and defines the main groups of elements and means of arranging inclusive routes. The study of barrier-free environments is an essential component of the work of many academics and researchers in inclusion and accessibility. Developing a barrier-free environment is a necessary need of modern times and a powerful catalyst for the progress of any country. Barrier-free access opens up new opportunities for the active participation of many people in public life who couldn’t fully use their potential before, which is especially true for less mobile population groups and persons with disabilities, particularly. The authors have studied and classified the requirements for the arrangement of inclusive routes, addressing the needs of population groups with reduced mobility, and determined the main criteria and priorities: accessibility, informativeness, safety, and convenience. The defined advantages of inclusive routes are: inclusion and integration – inclusive routes contribute to a more inclusive society where all people have the opportunity to move freely and participate in different aspects of life; improving the quality of life – access to inclusive routes facilitates the daily movements of people with disabilities and improves their quality of life; economic advantages – the creation of inclusive routes contributes to the development of local economies and increases the attractiveness of the region for tourists and investors; social interaction – inclusive routes unite different population groups and support social interaction and mutual understanding. Considering and analysing the main groups of elements and means of developing inclusive routes will allow for determining the main calculation parameters in further studies of inclusive routes. Keywords: inclusiveness, route, accessibility, safety, comfortable movement, barrier-free.

GEOINFORMATION SUPPORT FOR DEMINING THE TERRITORIES OF THE KHARKIV REGION

Modern conflicts and military actions result in massive landmine laying, making them dangerous for civilians. After the completion of hostilities, there is an urgent need to clear these areas to restore human life and infrastructure. The article presents the application of geographic information systems (GIS) and databases for the inventory and management of explosive ordnance data in post-conflict areas using the example of the Kharkiv region. The paper explains the structure and functioning of the explosive ordnance database, designed to optimise the demining process and increase its efficiency and safety. The explosive object database receives information from various sources, including mobile groups of the State Emergency Service of Ukraine, the National Police, and other units. The primary tool for fixing the coordinates of explosive objects is GPS devices. The database contains information about the coordinates of unexploded ordnance, their type, condition, date of discovery, the group that discovered it, and other information. The database allows searching and filtering of explosive objects by various criteria, generating reports on the number and types of explosives found in different areas of the region. Also, it is possible to visualise the data from the database on maps to enhance understanding of the distribution of explosive objects. Using the database can significantly improve the planning and coordination of demining work, track the progress of demining, assess the resources required for demining, warn the civilian population about the danger, analyse risks, conduct statistical analysis, report to the authorities, and train sappers. Implementing such a database will allow optimising demining planning, increasing the safety of sappers, and accelerating the restoration of a safe life for the population. The technology’s adaptability also means it can be utilised in other post-conflict regions, highlighting its potential for broader application. This system underscores the importance of integrating modern technological solutions in addressing the challenges of post-conflict reconstruction and safety. Keywords: geographic information systems, database, explosive ordnance, demining, security, recovery.

Association between circulatory microRNA-218 expression, serum PCSK9 levels, inflammatory markers, and monocyte subsets in coronary artery disease patients: impact of statin therapy

BackgroundProprotein convertase subtilisin/kexin type-9 (PCSK9), an enzyme produced mainly by hepatocytes and breaks low-density lipoprotein receptor (LDL-R), inflammatory markers [toll like receptor 4 (TLR4), high mobility group box 1 (HMGB1), tumor necrosis factor alpha (TNFα), c-reactive protein (CRP)], and monocyte subtypes are associated with coronary artery disease (CAD) pathogenesis. The circulating microRNA-218 (miR-218) can relieve CAD through the suppression of HMGB1 in monocyte-derived inflammatory cytokines. Herein, we explored the association between circulatory miR-218 expression and serum levels of PCSK9, inflammatory markers, and monocyte subtypes in statin and non-statin CAD patients. This study involved 91 healthy (control) and 91 stable CAD participants which were subdivided into no-statin (NS, n = 25), low-statin (LS, n = 25), and high-statin (HS, n = 41) groups. low-density lipoprotein cholesterol (LDL-C) and CRP serum levels were calorimetrically determined. Serum levels of PCSK9, TLR4, HMGB1, and TNFα were detected by ELISA, while monocyte subsets [classical (CM), intermediate (IM), non-classical (NC)] were calculated by flow cytometry. Circulatory miR-218 expression was detected by real-time PCR.ResultsThe CAD group had significantly lower miR-218 expression and significantly higher levels of PCSK9, inflammatory markers (HMGB1, CRP, TLR4, and TNFα), and IM% than the control group. Among CAD patients, LS and HS groups had significantly lower miR-218 expression, LDL-C levels, and inflammatory markers and significantly higher levels of PCSK9 than the NS group. The HS group exhibited the lowest miR-218 expression and inflammatory markers and the highest PCSK9 levels. However, there were no significant changes in IM% among statin and non-statin groups. In the three CAD groups, miR-218 showed a significantly negative correlation with PCSK9 and inflammatory markers (HMGB1, CRP, TLR4, and TNFα), while this expression exhibited a significantly negative correlation with CM%, IM%, and NCM% only in the NS group. Results of multivariable linear regression indicated a correlation between miR-218 and five independent variables (PCSK9, HMGB1, CRP, TLR4, and TNFα) in the total statin (LS + HS) group, and eight independent variables (PCSK9, HMGB1, CRP, TLR4, and TNFα, CM%, IM%, NCM%) in the NS group. Provided that all other independent variables are constant, miR-218 expression was significantly correlated to CRP (Beta = 0.234) and PCSK9 (Beta = − 0.875) in the total statin group; TLR4 (Beta = − 0.554) in the LS group; HMGB1 (Beta = − 0.507) in the HS group; and CRP (Beta = − 0.745) in the NS group.ConclusionsStatin-treated CAD patients have a unique negative correlation between miR-218 and PCSK9, HMGB1, and TLR4, and subsequently with CAD progress. Therefore, it could be recommended to combine activators of miR-218 and inhibitors of PCSK9, HMGB1, and TLR4 with statin to efficiently treat CAD.

HMBG-1: A Biomarker in the Management of Diabetic Retinopathy

Introduction: High mobility group box (HMGB)-1 protein is a promising prognostic marker for predicting the course of retinopathy and the prognosis in patients with diabetic retinopathy (DR). The aim of this study is to investigate whether serum HMGB-1 protein levels can be used as a biomarker about the severity of the disease in patients with diabetic retinopathy. Material and methods: This study was carried out in the internal medicine and ophthalmology departments of the Gaziantep Medicalpark Hospital. The records of 50 patients diagnosed with type 2 diabetes mellitus with diabetic retinopathy and 47 healthy subjects who applied to our clinic between January 2016 and December 2018 were retrospectively scanned. Five cc of venous blood was taken from the patients, and control groups were included in the study for routine laboratory tests and serum HMGB-1 levels to be studied under appropriate conditions. Human HMGB-1 levels were measured using the ELISA method. Results: There was a significant difference among the groups in terms of HMGB-1 levels (p<0.001) (Table-1). There was a positive correlation between blood glucose and HMGB-1 in the diabetic retinopathy group (Spearman's rho (ρ)=0.07). Similarly, there was a positive correlation between HbA1c and HMGB-1 levels in the diabetic retinopathy group. (Spearman's rho (ρ)=0.06). Conclusions: Our study suggests that HMGB-1 may be a useful biomarker in managing DR, aiding in the prediction and treatment of microvascular complications.

Effect of Gong's Mobilization Versus Conventional Physiotherapy Among Type II Diabetic Patients With Adhesive Capsulitis.

Adhesive capsulitis (AC) causes a spontaneous onset of discomfort and a progressive loss of shoulder mobility among type II diabetic patients. These patients experience severe loss of shoulder function, which impairs their day-to-day tasks and requires immediate care. According to scientific evidence, Gong's mobilization has an immediate effect on improving shoulder mobility. Therefore, the objective of this study is to determine the effectiveness of Gong's mobilization along with conventional physiotherapy in order to reduce pain and enhance the range of motion (ROM). This study aims to compare the effectiveness of Gong's mobilization and conventional physiotherapy for type II diabetic patients with AC. This experimental study included 32 participants between the ages of 40 and 60 years who were diagnosed with shoulder AC which followed type II diabetes. The participants were randomly allocated into two groups: the Gong's mobilization group and the conventional physiotherapy group. The participants in both groups received the intervention for four weeks. Outcome measures used for assessment before and after treatment were the Shoulder Pain and Disability Index (SPADI) and ROM.Data was analyzed using paired and unpaired t-tests. This study's results suggested that there was a better improvement in the pre- and post-test mean values of SPADI and shoulder ROM (p < 0.001) in both groups following a four-week intervention. There was a statistically significant difference in the post-intervention results between the two groups (P<0.05), indicating that Gong's mobilization technique is more effective than conventional treatment. The study findings showed reduced discomfort, and improved ROMand SPADI scores after the intervention. Both the treatments (Gong's mobilization and conventional approach) applied to AC for type II diabetes patients were beneficial. However, Gong's mobilization technique is more effective in treating AC in fewer treatment appointments compared with conventional therapy.

Effectiveness of Two Types of Distraction Techniques in the Management of Pain and Anxiety during Dental Treatment in 6-9-year-old Children.

To determine the effectiveness of distraction with virtual reality (VR) distraction devices in comparison with mobile phone video games in the management of pain and anxiety during dental treatment in 6-9-year-old children. It was a comparative observational study. A total of 33 children aged 6-9 years who reported to the department for their first dental visit were selected and the subjects were divided into three groups. Group I patients were in a normal clinical environment without any distractions. Group II patients were given mobile phone video games. Group III patients were given a VR distraction device as a means of distraction.The anxiety levels of patients before treatment, after using a distraction device preoperatively, during local anesthesia injection, and after dental treatment were assessed. Pain after local anesthesia injection in each group was assessed. The easability of handling the patient and carrying out the procedure was assessed using a questionnaire. All data were collected and analyzed. The results showed when compared to the children in groups I and II, children in group III obtained significantly lower anxiety scores after treatment, and they also reported significantly decreased pain perception during dental treatment (p < 0.001). The pain while administering local anesthesia was greater for the control group and lowest for the VR group. It was observed that VR group patients were easier to handle and easier to carry out procedures than those in the mobile phone group. Virtual reality distraction is an effective distraction technique for reducing pain and anxiety in children during various treatment procedures. Virtual reality distraction can be used effectively in clinics.It is a patient-friendly technique and is more comfortable for both patients and dentists during treatment.It does not require any previous education and training and has a positive impact on memories of the treatment, leading to behavior modification. Chandran LS, Issac JS, Girija P, et al. Effectiveness of Two Types of Distraction Techniques in the Management of Pain and Anxiety during Dental Treatment in 6-9-year-old Children. Int J Clin Pediatr Dent 2024;17(3):291-296.

Tumor cell-released autophagosomes (TRAPs) induce PD-L1-decorated NETs that suppress T-cell function to promote breast cancer pulmonary metastasis

BackgroundLung metastasis is the primary cause of breast cancer-related mortality. Neutrophil extracellular traps (NETs) are involved in the progression of breast cancer. However, the mechanism of NET formation is not...

Involvement of RAGE in radiation-induced acquisition of malignant phenotypes in human glioblastoma cells

Glioblastoma (GBM), a highly aggressive malignant tumor of the central nervous system, is mainly treated with radiotherapy. However, since irradiation may lead to the acquisition of migration ability by cancer cells, thereby promoting tumor metastasis and invasion, it is important to understand the mechanism of cell migration enhancement in order to prevent recurrence of GBM. The receptor for advanced glycation end products (RAGE) is a pattern recognition receptor activated by high mobility group box 1 (HMGB1). In this study, we found that RAGE plays a role in the enhancement of cell migration by γ-irradiation in human GBM A172 cells. γ-Irradiation induced actin remodeling, a marker of motility acquisition, and enhancement of cell migration in A172 cells. Both phenotypes were suppressed by specific inhibitors of RAGE (FPS-ZM1 and TTP488) or by knockdown of RAGE. The HMGB1 inhibitor ethyl pyruvate similarly suppressed γ-irradiation-induced enhancement of cell migration. In addition, γ-irradiation-induced phosphorylation of STAT3 was suppressed by RAGE inhibitors, and a STAT3 inhibitor suppressed γ-irradiation-induced enhancement of cell migration, indicating that STAT3 is involved in the migration enhancement downstream of RAGE. Our results suggest that HMGB1-RAGE-STAT3 signaling is involved in radiation-induced enhancement of GBM cell migration, and may contribute to GBM recurrence by promoting metastasis and invasion.

Influence of Frequent Corticosteroid Local Injections on the Expression of Genes and Proteins Related to Fatty Infiltration, Muscle Atrophy, Inflammation, and Fibrosis in Patients With Chronic Rotator Cuff Tears: A Pilot Study.

The effect of local corticosteroid (CS) injections on rotator cuff muscles remains poorly defined, despite the significance of muscle quality as a crucial prognostic factor for patients with rotator cuff tears (RCTs). To compare alterations in gene and protein expression patterns in the rotator cuff muscles of patients with RCTs who received frequent joint CS injections with alterations in those without a history of CS injections. Controlled laboratory study. A total of 24 rotator cuff muscle samples with medium-sized tears from 12 patients with a frequent joint CS injection history (steroid group; 7 men and 5 women who had received ≥5 injections with at least 1 within the previous 3 months; mean age, 63.0 ± 7.2 years) and 12 age- and sex-matched control patients without a history of CS injections (no-steroid group) were acquired. Alterations in the expression of genes and proteins associated with adipogenesis, myogenesis, inflammation, and muscle fibrosis were compared between the groups using quantitative reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemistry. Statistical analysis included comparison of group means using the Mann-Whitney U test, chi-square test, or Fisher exact test and logistic regression for multivariate analysis. In the steroid group, the mRNA expression levels of adipogenic CCAAT/enhancer-binding protein alpha (C/EBPα; P = .008) and muscle atrophy-related genes (atrogin; P = .019) were significantly higher, and those of myogenic differentiation 1 (MyoD; P = .035), inflammatory interleukin 6 (IL-6; P = .035), and high mobility group box 1 (P = .003) were significantly lower compared with the no-steroid group. In addition, MyoD (P = .041) and IL-6 (P = .026) expression were decreased in the steroid versus no-steroid group. Immunohistochemistry revealed increased expression of C/EBPα and atrogin and decreased expression of MyoD and IL-6 in the steroid versus no-steroid group. Patients with RCTs and a history of frequent CS injections exhibited an upregulation of adipogenic and muscle atrophy-related genes and proteins within the rotator cuff muscles and a downregulation in the expression of myogenic and inflammatory genes and proteins in the same muscles. These altered gene and protein expressions by frequent local CS injections may cause poor outcomes in patients with RCTs.

High Mobility Group Box 1 Protein: A Plausible Therapeutic Molecular Target in Parkinson's Disease.

Parkinson's disease (PD) is a widespread neurodegenerative disorder that exerts a broad variety of detrimental effects on people's health. Accumulating evidence suggests that mitochondrial dysfunction, neuroinflammation, α-synuclein aggregation and autophagy dysfunction may all play a role in the development of PD. However, the molecular mechanisms behind these pathophysiological processes remain unknown. Currently, research in PD has focussed on high mobility group box 1 (HMGB1), and different laboratory approaches have shown promising outcomes to some level for blocking HMGB1. Given that HMGB1 regulates mitochondrial dysfunction, participates in neuroinflammation, and modulates autophagy and apoptosis, it is hypothesised that HMGB1 has significance in the onset of PD. In the current review, research targeting multiple roles of HMGB1 in PD pathology was integrated, and the issues that need future attention for targeted therapeutic approaches are mentioned.

Chromatin modifier Hmga2 promotes adult hematopoietic stem cell function and blood regeneration in stress conditions

The molecular mechanisms governing the response of hematopoietic stem cells (HSCs) to stress insults remain poorly defined. Here, we investigated effects of conditional knock-out or overexpression of Hmga2 (High mobility group AT-hook 2), a transcriptional activator of stem cell genes in fetal HSCs. While Hmga2 overexpression did not affect adult hematopoiesis under homeostasis, it accelerated HSC expansion in response to injection with 5-fluorouracil (5-FU) or in vitro treatment with TNF-α. In contrast, HSC and megakaryocyte progenitor cell numbers were decreased in Hmga2 KO animals. Transcription of inflammatory genes was repressed in Hmga2-overexpressing mice injected with 5-FU, and Hmga2 bound to distinct regions and chromatin accessibility was decreased in HSCs upon stress. Mechanistically, we found that casein kinase 2 (CK2) phosphorylates the Hmga2 acidic domain, promoting its access and binding to chromatin, transcription of anti-inflammatory target genes, and the expansion of HSCs under stress conditions. Notably, the identified stress-regulated Hmga2 gene signature is activated in hematopoietic stem progenitor cells of human myelodysplastic syndrome patients. In sum, these results reveal a TNF-α/CK2/phospho-Hmga2 axis controlling adult stress hematopoiesis.

Anti-HMGB1 mAb Therapy Reduces Epidural Hematoma Injury.

Epidural and subdural hematomas are commonly associated with traumatic brain injury. While surgical removal is the primary intervention for these hematomas, it is also critical to prevent and reduce complications such as post-traumatic epilepsy, which may result from inflammatory responses in the injured brain areas. In the present study, we observed that high mobility group box-1 (HMGB1) decreased in the injured brain area beneath the epidural hematoma (EDH) in rats, concurrent with elevated plasma levels of HMGB1. Anti-HMGB1 monoclonal antibody therapy strongly inhibited both HMGB1 release and the subsequent increase in plasma levels. Moreover, this treatment suppressed the up-regulation of inflammatory cytokines and related molecules such as interleukin-1-beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and inducible nitric oxide synthase (iNOS) in the injured areas. Our in vitro experiments using SH-SY5Y demonstrated that hematoma components-thrombin, heme, and ferrous ion- prompted HMGB1 translocation from the nuclei to the cytoplasm, a process inhibited by the addition of the anti-HMGB1 mAb. These findings suggest that anti-HMGB1 mAb treatment not only inhibits HMGB1 translocation but also curtails inflammation in injured areas, thereby protecting the neural tissue. Thus, anti-HMGB1 mAb therapy could serve as a complementary therapy for an EDH before/after surgery.

Association of deletion polymorphism rs10573247 in the HMGA2 gene with the risk of breast cancer: bioinformatic and experimental analyses

BackgroundThe high mobility group A2 (HMGA2) gene is expressed extensively during early embryonic development but is inactivated in adulthood, and it is also reactivated in various benign and malignant tumors, including breast cancer. We first assessed the potential functional significance of the unstudied deletion polymorphism rs10573247 at the 3′UTR of HMGA2 on miRNA binding using bioinformatic tools, and subsequently, the association between this polymorphism and breast cancer susceptibility was investigated.Materials and methodsWe applied the RNAhybrid tool to predict the functional effects of polymorphism rs10573247 located within the 3’ UTR of the HMGA2 gene on miRNA binding. Then, following DNA extraction, 141 breast cancer patients and 123 healthy controls were genotyped for polymorphism rs10573247 using RFLP-PCR with the restriction enzyme Eam1104I.ResultsOur bioinformatic data have shown that polymorphism rs10573247 is located in the region that serves as a potential target site for eight miRNAs binding. Among them, miR-3125 exhibited decreased binding affinity for the allele delTT (MFE = -21.8) when compared to the allele TT (MFE = -23.9), but miR-4476 increased binding affinity for the allele delTT (MFE = -22.4) compared to the allele TT (MFE = -22.2). In addition, our results showed that the genotype TT/delTT (p = 0.005) and the genotype delTT/delTT (p = 0.029) were significantly associated with an increased risk of developing breast cancer compared to the genotype TT/TT using RFLP-PCR.Discussion and ConclusionOur findings suggest that polymorphism rs10573247 may contribute to the risk of breast cancer through the functional effect of this polymorphism on miRNA binding.

Is an earlier strategy for harvesting peripheral blood stem cells in healthy allogeneic donors feasible?

IntroductionPeripheral blood stem cells (PBSC) mobilization with granulocyte colony stimulating factor (G-CSF) for healthy donors is generally performed at 5th day. However, earlier collection is sometimes feasible, raising the question of whether to initiate apheresis early to limit further G-CSF exposure, while considering the risk of mobilization failure. In the current study, we examined the factors predicting successful 4th day collection and developed a model that can be used practically. Patients and methodsThe study was carried out by obtaining the data of PBSC mobilizations performed between January 2009 and September 2022 in our transplantation center. ResultsA total of 141 healthy donors with a median donor age of 32 (18–64) were included. Adequate mobilization was achieved in 115 (81.6 %) patients. Median peripheral CD34 + cell count was 69.4/μL in the adequate mobilization group and 46/μL in the mobilization failure group (p < 0001). Multivariate analysis revealed that donor/recipient weight ratio and the 4th day peripheral CD34 + cell count≥ 50/μL were independent markers for 4th day collection success. A predictive model of our center including these parameters was available with 0.765 sensitivity and 0.968 specificity [(AUC):0.948 (95 % CI, 0.90–0.99), p < 0.001]. ConclusionThe result of the current study shows that peripheral 4th day collection can be performed in selected donors, taking into account peripheral CD34+ cell count and donor/recipient weight ratio. In addition, using these indicators, new predictive models can be created that may assist clinicians in daily practice.

Mobility-aware proactive video caching based on asynchronous federated learning in mobile edge computing systems

With the rapid advance of the Internet of Things (IoT) and the surging user-centric smart devices, video services such as short videos, real-time video streaming, and Virtual Reality (VR) gaming are emerging. Traditional cloud-centric caching is no longer able to satisfy the low-latency needs of mobile user groups. Predicting the most popular content in advance and caching it on edge devices such as small base stations (SBS) is a promising solution to alleviate network congestion and supply better Quality of Service (QoS) for mobile users. However, frequently changing popular content, limited edge caching resources, privacy of user data, and user mobility pose significant challenges to edge video caching. To tackle these challenges, we propose an efficient asynchronous federated learning (AFL)-based mobility-aware proactive video caching scheme (AF-MPVC), which significantly improves the overall network performance while preventing the risk of user data leakage. First, we model the proactive video caching problem in mobile edge computing systems and consider the impact of user mobility on AFL, representing the problem as an autoencoder (AE) model loss minimization problem. Then, a proactive video caching algorithm is proposed based on a filtering model, which uses the hidden features obtained from the trained AE model to compute the user similarity to find the popular videos that are most likely to be accessed by users and combine them with the most frequently requested videos. Meanwhile, we take into account the short duration of high mobility users staying on the current SBS and cache some videos to neighboring edge servers to have more redundant space to store more less popular videos. Finally, experiments on three real-world datasets demonstrate that the presented caching scheme outperforms other baseline caching schemes with respect to cache hit rate and latency reduction.

Soundscapes of infant care and infant-directed communication in two hunter-gatherer societies

This study contributes an ethnographic perspective to the study of infant-directed (ID) communicative activities. We compare soundscapes of infant care and ID vocal communication in two egalitarian, forest-dwelling, mobile hunter-gatherer groups: Mbendjele BaYaka/Aka in Northern Congo-Brazzaville and the Maniq of Southern Thailand. Across the unique patterns of speech and song specific to these different cultures, common threads emerged in infants’ soundscapes that suggest the centrality of musically enriched ID-speech for communication with infants. A conspicuous under-elaboration of music among Maniq people suggests that while musical activity in a culture may vary greatly, ID-speech does not. The ID-speech register thus emerges as more central to childhood socialisation and development in these hunter-gatherer societies than does the ID-song register. Although the use of lullabies (ID-song) by mothers has been claimed to be a human universal ( Trehub 2001 ; Mehr et al 2019 ) the ethnography from these hunter-gatherer societies supports Takada’s (2020:139–142) conclusion that ID-speech and song demonstrate important cultural diversity. This paper contributes to ethnographic accounts of the diversity of ways that cultures organise communicative exchanges with children.

Geometric growth of the normal human craniocervical junction from 0 to 18 years old.

The craniocervical junction (CCJ) forms the bridge between the skull and the spine, a highly mobile group of joints that allows the mobility of the head in every direction. The CCJ plays a major role in protecting the inferior brainstem (bulb) and spinal cord, therefore also requiring some stability. Children are subjected to multiple constitutive or acquired diseases involving the CCJ: primary bone diseases such as in FGFR-related craniosynostoses or acquired conditions such as congenital torticollis, cervical spine luxation, and neurological disorders. To design efficient treatment plans, it is crucial to understand the relationship between abnormalities of the craniofacial region and abnormalities of the CCJ. This can be approached by the study of control and abnormal growth patterns. Here we report a model of normal skull base growth by compiling a collection of geometric models in control children. Focused analyses highlighted specific developmental patterns for each CCJ bone, emphasizing rapid growth during infancy, followed by varying rates of growth and maturation during childhood and adolescence until reaching stability by 18 years of age. The focus was on the closure patterns of synchondroses and sutures in the occipital bone, revealing distinct closure trajectories for the anterior intra-occipital synchondroses and the occipitomastoid suture. The findings, although based on a limited dataset, showcased specific age-related changes in width and closure percentages, providing valuable insights into growth dynamics within the first 2 years of life. Integration analyses revealed intricate relationships between skull and neck structures, emphasizing coordinated growth at different stages. Specific bone covariation patterns, as found between the first and second cervical vertebrae (C1 and C2), indicated synchronized morphological changes. Our results provide initial data for designing inclusive CCJ geometric models to predict normal and abnormal growth dynamics.