Initial Sample Research Articles

Myeloid-derived suppressor cells and T cell populations in children with Multisystem Inflammatory Syndrome.

Multisystem inflammatory syndrome in children (MIS-C) represents a hyperinflammatory state that can result in multi-organ dysfunction and death. Myeloid-derived suppressor cells (MDSC) are an immunosuppressive cell population that expands under inflammatory conditions and suppresses T cell function. We hypothesized that MDSC would be increased in children with MIS-C and that MDSC expansion would be associated with T cell lymphopenia. We conducted a prospective, observational study. Initial blood samples were collected within 48 h of admission. Age-matched healthy controls underwent sampling once. MDSC and T cell populations were identified by flow cytometric methods. We enrolled 22 children with MIS-C (12 ICU, 10 ward) and 21 healthy controls (HC). Children with MIS-C demonstrated significantly higher MDSC compared to HC, and MDSC expansion persisted for >3 weeks in the ICU group. Children with MIS-C admitted to the ICU demonstrated significantly lower absolute numbers of T cells and natural killer cells. There were no significant associations between MDSC and cardiac dysfunction, duration of hospitalization, or vasoactive inotrope score. Our study suggests that children critically ill with MIS-C have expansion of MDSC and associated decreased T cell and NK cell populations. Our results did not demonstrate associations between MDSC and clinical outcomes. Multisystem inflammatory syndrome in children (MIS-C) is a dysregulated immune response occurring several weeks after SARS-CoV-2 infection that can result in multi-organ dysfunction and death. Children severely ill with MIS-C demonstrated increased myeloid-derived suppressor cells and decreased absolute numbers of CD4+ and CD8 + T cells and NK cells compared to healthy controls. There was no significant association between MDSC numbers and clinical outcomes; including cardiac dysfunction, length of stay, or requirement of vasoactive support, in children with MIS-C.

Analysis of the different roles of teen dating violence in peer victimization and aggression

Different studies show the relationship between peer violence and teen dating violence. However, more knowledge is needed about this relationship. The aim of this study was to explore possible differences in peer violence (perpetrated and suffered) in adolescents with different role in teen dating violence (aggressor, victim, aggressor-victim, and not involved). The initial sample was composed of 1078 adolescents, but for the purposes of this study, only those students who had a partner in the last year were considered, 672 students (51.6% girls) aged 12-18 years (M= 14.45, SD= 1.62). These adolescents completed the CADRI scale, the VE-I peer victimization scale, and the violent behavior scale by Little et al. (2003). The results indicated that peer violence victimization and perpetration were closely related to dating abuse (victimization and perpetration) in adolescents. Students with frequent aggressor-victim role in partner relationships showed more peer violence behaviors. Girls victims of teen dating violence were more victimized by their classmates. These results show a strong relationship between these two problems, which seriously affect the well-being of adolescents.

Practical Approach to Care Kit: Innovation for nurses' clinical practice in HIV management.

to analyze the use of the Practical Approach to Care Kit as a technology adopted in nurses' clinical practice for HIV management in Primary Health Care. an exploratory and descriptive research study anchored in the methodological framework of the Constructivist Grounded Theory. The participants were defined through initial sampling, with 12 nurses, and theoretical sampling, with five managers, totaling 17 participants. The data were collected by means of intensive interviews and documentary analysis, and they were analyzed in two stages: 1) Initial coding; and 2) Focused coding. the professionals identified the Practical Approach to Care Kit as a technological innovation that contributed to expanding the clinical practice and to empowering nurses in the clinical management of HIV infection. They also highlighted its importance as a tool for guiding the different responsibilities and duties while sharing care, contributing to the provision of evidence-based practices. The Practical Approach to Care Kit is a technological innovation that has transformed nurses' clinical practice in HIV management, expanding their scope of activities in carrying out the diagnosis, assessing the health condition and counseling, evaluating adherence to the treatment, adverse effects and prescription of exams, medications, and immunobiological.

Abstract A125: Clinical evaluation of a functional combinatorial precision medicine platform to predict combination immunotherapy responses in hematological malignancies

Abstract Purpose: Proliferation of immune checkpoint inhibitors and lineage-specific antigen-based therapy have made identifying the most appropriate immunotherapy for specific patients or subgroups of patients increasingly difficult. Furthermore, combination of these therapeutic antibodies with other targeted agents or chemotherapy is often required to achieve durable response. To address the large search space of possible combinations of these immunotherapies with available targeted and cytotoxic drug partners, we applied a hybrid experimental-analytical platform, Flow Cytometry Immunophenotyping–Quadratic Phenotypic Optimization Platform (FCI-QPOP), on primary patient samples from acute myeloid leukemia (AML) and multiple myeloma (MM) cases to predict patient and subtype-specific combination immunotherapy responses. Successful development of this functional combinatorial precision medicine platform could help guide combination therapy treatment while also providing a tool for improving combination therapy design for emerging immunotherapies. Experimental Detail: Single drug dosage response analysis of a set of immunotherapies, targeted small molecules and cytotoxic agents were performed from initial patient samples and used to inform subsequent dosing levels for 8-drug, 3-level FCI-QPOP. In FCI-QPOP, primary AML or MM patient samples composed of both cancer cells and normal cells were treated with an array of test combinations and analyzed by flow cytometry to provide a quantitative phenotypic output for each test combination. This OACD dataset was then analyzed by QPOP to rank all possible drug combinations towards a predicted treatment outcome. Concordance analysis was then performed comparing patient sample results with parallel treatment initiated at time of sample collection. Results: Drug-dose response analysis by flow cytometry could accurately identify samples-specific response, including IC50 determination, to both therapeutic antibodies and small molecule drugs. Following this, 8-drug, 3-level FCI-QPOP was successfully performed on 14 of 17 primary patient samples. Concordance analysis could be performed on 9 cases, with 5 cases still pending clinical follow-up. Concordance to both antibody therapies as well as small molecule treatments were analyzed following FCI-QPOP. FCI-QPOP had a sensitivity of 80% and specificity of 75% and a total predictive value (TPV) of 77.78%. Additionally, FCI-QPOP provided potentially effective combination rankings for a diverse range of therapeutic antibodies, including gemtuzumab-based combination therapies. Conclusion: The results show the potential for FCI-QPOP to predict clinical response to immunotherapy-based treatments. Furthermore, FCI-QPOP can improve drug development pipelines through patient samples-based design of effective immunotherapy-based combinations that may benefit larger populations of patients or specific subgroups of patients. Citation Format: Noor Rashidha Bte Meera Sahib, Masturah Rashid, Sanjay de Mel, Wei Ying Jen, Melissa Ooi, Edward K Chow. Clinical evaluation of a functional combinatorial precision medicine platform to predict combination immunotherapy responses in hematological malignancies [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A125.

The ability of Psychosocial Care Centers specialized in Alcohol and Drugs to handle crises.

(1) To our knowledge, this is the first study to evaluate CAPSAD's ability to handle crises. (2) The ability to handle crises of the CAPSAD from downtown São Paulo was86.6%. (3) Of the nine users referred to other services, only one evolved to hospitalization. to assess the ability of 24-hour Psychosocial Care Centers specialized in Alcohol and Other Drugs to handle the users' crises in comprehensive care. a quantitative, evaluative, and longitudinal study was conducted from February to November2019. The initial sample consisted of 121users, who were part of the comprehensibly care in crises by two 24-hour Psychosocial Care Centers specialized in Alcohol and other Drugs in downtown São Paulo. These users were re-evaluated 14days after admission. The ability to handle the crisis was assessed using a validated indicator. The data were analyzed using descriptive statistics and regression of mixed-effects models. 67users(54.9%) finished the follow-up period. During crises, nine users (13.4%; p=0.470) were referred to other services from the health network: seven due to clinical complications, one due to a suicide attempt, and another for psychiatric hospitalization. The ability to handle the crisis in the services was 86.6%, which was evaluated as positive. both of the services analyzed were able to handle crises in their territory, avoiding hospitalizations and enjoying network support when necessary, thus achieving the de-institutionalization objectives.

Capacidade de manejo de situações de crise por Centros de Atenção Psicossocial Álcool e Drogas

Objective: to assess the ability of 24-hour Psychosocial Care Centers specialized in Alcohol and Other Drugs to handle the users’ crises in comprehensive care. Method: a quantitative, evaluative, and longitudinal study was conducted from February to November 2019. The initial sample consisted of 121 users, who were part of the comprehensibly care in crises by two 24-hour Psychosocial Care Centers specialized in Alcohol and other Drugs in downtown São Paulo. These users were re-evaluated 14 days after admission. The ability to handle the crisis was assessed using a validated indicator. The data were analyzed using descriptive statistics and regression of mixed-effects models. Results: 67 users (54.9%) finished the follow-up period. During crises, nine users (13.4%; p=0.470) were referred to other services from the health network: seven due to clinical complications, one due to a suicide attempt, and another for psychiatric hospitalization. The ability to handle the crisis in the services was 86.6%, which was evaluated as positive. Conclusion: both of the services analyzed were able to handle crises in their territory, avoiding hospitalizations and enjoying network support when necessary, thus achieving the de-institutionalization objectives.

A novel hybrid adaptive framework for support vector machine-based reliability analysis: A comparative study

This study presents an innovative hybrid Adaptive Support Vector Machine - Monte Carlo Simulation (ASVM-MCS) framework for reliability analysis in complex engineering structures. These structures often involve highly nonlinear implicit functions, making traditional gradient-based first or second order reliability algorithms and Monte Carlo Simulation (MCS) time-consuming. The application of surrogate models has proven effective in addressing computational challenges associated with a large number of simulations. Support Vector Machine (SVM), as an emerging machine learning method suitable for small-sample scenarios, offers a well-established theoretical foundation and presents an effective model substitution approach for reliability analysis in engineering structures. However, the existing literature lacks a comprehensive and thorough comparative analysis of SVM's hybrid adaptive modeling approach, encompassing initial sampling methods and learning functions, with regards to both computational efficiency and accuracy. Additionally, there is a gap in adaptive modeling methods capable of accommodating diverse types of input uncertainty, the nonlinearity of limit state functions, and various application scenarios. In response to these gaps, this article introduces the ASVM-MCS framework, which addresses these challenges by considering different types of input variables and various failure modes. Moreover, this study provides a comprehensive evaluation of the ASVM-MCS framework's performance, including its initial sampling methods and learning functions, across a range of application scenarios, such as scenarios involving only random variables, mixed variables, and the reliability of series-parallel systems.

Sequential Explanatory Approach: Digital Marketing Implementation Acceleration Programme that Supports the Marketing Performance of Msme Actors

Abstract Subject and purpose of work Because there was a reduced market for their products as a result of the COVID-19 pandemic, several micro, small & medium-sized enterprise (MSME) actors went out of business. One way to boost marketing performance is through digital marketing. The goal of this study is to create a strategy that will hasten the adoption of digital marketing for MSMEs. This study was focused on the Association of Retired Workers and Families (Pertakina), an SME of Blitar Regency, which has various kinds of businesses producing very varied and creative products, including food, drinks, services, and handicrafts. Materials and methods This study used mixed methods with a sequential explanatory design, which combined quantitative research methods in the first stage, followed by sequential qualitative research. Using a straightforward random sampling technique, 72 MSME actors who have used digital marketing were chosen as samples. Quantitative data samples are MSME actors who have used digital marketing to market their products. An initial sample of qualitative data sources was selected purposively, using the chairman of Pertakina Blitar and Pertakina MSMEs as the key informant. Subsequent informants were then selected by snowball sampling based on the information given by the key informant; they were Pertakina MSME actors who have not done digital marketing. The researchers consider the sample to be saturated (data saturation) with as many as 18 respondents. The information was gathered through literature reviews, surveys, interviews, observations, and documentation. Results The results show that digital marketing has a significant effect on marketing performance. The barriers to implementing digital marketing are lack of qualified human resources, infrastructure needs, internet networks, and the ability to produce content. Additionally, the acceleration programme was created based on the barriers in implementing digital marketing identified in this study to enhance the marketing effectiveness of MSME players. Conclusions It is suggested that Pertakina conduct training by a competent trainer in the field of digital marketing technology to improve the MSMEs actors’ abilities. Furthermore, this can be done in collaboration with the government and universities.

Дюрометричний аналіз зміцнення приповерхневого шару ADI при терті під впливом TRIP-ефекту

Features of strengthening of the near-surface layer of ADI during friction due to strain-induced martensitic transformation were analyzed by duromeric methods. Indentation under continuous loading (Meyer hardness, HM) and Vickers microhardness Hμ were used. Pop–ins are observed on the ADI continuous load curves, which indicate martensitic transformations during indentation. The effect usually exists at a load of ~0,1 H and an depth of ~1,5 μk. The average microhardness of the initial sample is Hμ ≈ 4,89 GPa. After wear, the average value increases to Hμ ≈ 6,92 GPa. Statistical analysis of the microhardness distribution of the sample after wear revealed that a third of the indentations have abnormally high hardness, which is characteristic of deformation-induced martensite. Probably, these indents are obtained from regions of the structure where deformation-induced martensitic transformation took place. Increasing the indentation load practically does not affect the determination of the microhardness of the initial sample, but reduces the hardness of the sample after wear. This indicates the gradient nature of deformation and phase-structural rearrangements in the near-surface layer during wear. As the friction temperature increases, there is a decrease in microhardness in the wear zone. This is explained by the departure from the temperature range of the martensitic transformation, due to which the TRIP effect is weakened. The maximum degradation of microhardness is observed between room temperature and 50 oC. Keywords: ADI materials, durometric studies, TRIP-effect, wear.

Influence of psychosocial characteristics of patients and opinions of their relatives on indication for surgical treatment of pectus excavatum.

To assess the subjective experience of patients and their parents or relatives about the existing pectus excavatum deformity and to contribute to the definition of indications for surgical treatment of this deformity. The initial sample of psychosocial characteristics consisted of self-assessments and observations of patients (and parents) regarding their health, self-image, health care, possible environmental response to their physical appearance, expectations regarding treatment. A modified version of the original Nuss questionnaire on quality of life was used in the psychological part of the examination. The study included a sample of 58 patients aged 10 to 30 years, and a sample of 58 family members of the patient (parents, relatives). The experience of poor emotional status, withdrawals, and bad self-image in patients older than 15 years than younger were significant. The tendency for female patients to have a worse experience is pronounced and significant. The largest percentage of parents have an 'indecisive' or 'weakly expressed' attitude towards surgery. Parents at a significantly higher rate show greater concern for female children. A systematic evaluation of the psychosocial perception of patients and their relatives (who will consent for the operation) may be a useful diagnostic assessment before correcting an anterior chest wall malformation.

Improvement of water quality with probiotics inclusion during simulated transport of Yellowfin Seabream Acanthopagrus latus larvae.

The expansion of marine aquaculture requires the shipment of early life stages from hatcheries to breeding centers. Thus, maintaining water quality parameters during transportation is crucial. This experiment investigated the effects of a commercial probiotic mixture (PM) (consisting of Bacillus licheniformis, Bacillus subtilis, Pediococcus acidilactici, and Lactobacillus acidophilus with a total count of 107 CFU/g) on water quality, bacterial population, and the survival of larvae of Yellowfin Seabream Acanthopagrus latus during a 24-h simulated transportation experiment. To simulate transportation, purified seawater was used as a control and purified seawater supplemented with 3 g of PM was used as the PM48 treatment. For the PM48 treatment, 3 g of PM was added to 1 L of purified seawater and mixed with 200 L of purified seawater 48 h prior to the main experiment. The use of probiotics resulted in an increase in larval survival up to 93.3% compared with 89.85% in the control group. Initial sampling showed a statistically significant difference in levels between the control and PM48 treatments. After transportation, the pH of the control treatment showed a significant decrease. The total number of bacteria and the total number of Vibrio spp. in water and fish larvae showed that within 48 h, the probiotics became the dominant population in the PM48 treatment. After 24 h, water samples and larvae from the control treatment showed a significant increase in bacterial load. The results showed that probiotics can play a significant role in maintaining biotic and abiotic water quality parameters, leading to a better survival rate of larvae during transportation. These findings represent an important step in improving long-distance transport protocols.

Prediction Model with Validation for Polioseronegativity in Malnourished Children from Poliomyelitis Transmission High-Risk Area of the Democratic Republic of the Congo (DRC).

Malnutrition is identified as a risk factor for insufficient polio seroconversion in the context of a vaccine-derived poliovirus (VDPV) outbreak-prone region. In the Democratic Republic of Congo (DRC), underweight decreased from 31% (in 2001) to 26% (in 2018). Since 2004, VDPV serotype 2 outbreaks (cVDPV2) have been documented and were geographically limited around the Haut-Lomami and Tanganyika Provinces. To develop and validate a predictive model for poliomyelitis vaccine response in malnourished infants, a cross-sectional household study was carried out in the Haut-Lomami and Tanganyika provinces. Healthy children aged 6 to 59 months (n=968) were enrolled from eight health zones (HZ) out of 27, in March 2018. We performed a bivariate and multivariate logistics analysis. Final models were selected using a stepwise Wald method, and variables were selected based on the criterion p < 0.05. The association between nutritional variables, explaining polio seronegativity for the three serotypes, was assessed using the receiver operating characteristic curve (ROC curve). Factors significantly associated with seronegativity to the three polio serotypes were underweight, non-administration of vitamin A, and the age group of 12 to 59 months. The sensitivity was 10.5%, and its specificity was 96.4% while the positive predictive values (PPV) and negative (PNV) were 62.7% and 65.3%, respectively. We found a convergence of the curves of the initial sample and two split samples. Based on the comparison of the overlapping confidence intervals of the ROC curve, we concluded that our prediction model is valid. This study proposed the first tool which variables are easy to collect by any health worker in charge of vaccination or in charge of nutrition. It will bring on top, the collaboration between the Immunization and the Nutritional programs in DRC integration policy, and its replicability in other low- and middle-income countries with endemic poliovirus.

The Smartphone Addiction Measure (SAM): Subscales, Validity, and Reliability.

Dependence on smartphones continues to grow, with young adults showing the highest usage. In fact, reliance on smartphones may indicate a behavioral addiction, a concept gaining interest in both research and clinical practice. However, valid and reliable assessments of smartphone addiction are needed. To this end, we developed the Smartphone Addiction Measure (SAM) with an initial sample (113 participants; 32 males, 81 females) and assessed the validity and reliability of this new measure. Principle components analysis with an additional sample (286 participants; 78 males, 207 females, 1 other) revealed four factors generally associated with addiction, including salience, mood modification, withdrawal, and conflict, thus providing support for the SAM as a valid measure of addictive behavior related to smartphone use. Analyses also revealed good validity and reliability (221 participants; 38 males, 179 females, 4 other) that sufficiently support the SAM as a psychometrically sound assessment for smartphone addiction.

Перспективы применения пространственного подхода к регулированию развития национального рынка FoodNet в контексте цифровизации

Studying the features of the formation and development of the national FoodNet market in the context of feder-al districts in the context of digital transformation is of particular interest in light of the high differentiation of the constituent entities of the Russian Federation and the growing digital divide between them. The aim of the arti-cle is to reveal conceptual-theoretical and applied aspects of the formation and development of the national FoodNet market in the context of digital transformation. In order to coordinate the spatial management of the national FoodNet market and clarify the understanding of agricultural integration and digital development, the authors of the article developed a model for constructing an interconnected model for coordinating the pro-cesses of digitalization of agriculture in the regions of the Russian Federation. The fundamental mechanisms of the digital economy and their spatial impact on the high-quality growth of the national FoodNet market are considered, and the indices of agricultural production and digital economy are evaluated. The empirical study was conducted using data from each federal district from 2010 to 2022 as the initial sample. The data obtained indicate that until 2015, in all federal districts, the degree of coordination of the development of agricultural sec-tors and the digital economy was less than 0.2. The digital adoption rate showed a moderate growth trend from 2016 to 2020, increasing by 583,33 % from 2010 to 2022, indicating that as the digital economy expands, the agricultural services sector is also developing in a qualitative manner. The authors proposed a number of measures to manage the processes of transformation of national agriculture to solve the problems of food se-curity in the constituent entities of the federal districts of the Russian Federation.

Proposed New Cutoff Value for Troponin in the Diagnosis of Acute Myocardial Infarction (AMI) in Patients with Congestive Heart Failure (CHF) and/or End Stage Renal Disease (ESRD)

Abstract Introduction/Objective In a recent publication, we assessed the efficacy of two serum biomarkers for AMI, cardiac Troponin I (cTnI) and creatine kinase-MB (CK-MB), for patients presenting to our emergency department (ED) with acute chest pain. We found that two conditions, CHF and ESRD in 85 patients, caused a significant number of false positive results that resulted in lowering the specificity and positive predictive value of both tests, which were already reduced by the low prevalence of AMI in our patient population. Removal of these patients resulted in significant increases in the two latter parameters. In this study, we focus on cTnI to determine if changing the cutoff value can increase the sensitivity and specificity of diagnosing acute MI in patients with CHF and ESRD. Methods/Case Report A cohort of 380 patients who presented with acute chest pain in the ED and worked up for acute MI were included, 85 of whom had CHF and/or ESRD. A total of 47 patients (15.4% prevalence) were definitively diagnosed with AMI. An initial serum cTnI sample was collected for each patient. Specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) were then compared using the routine cutoff cTnI value (0.05 ng/mL) and the higher cutoff of 0.2 ng/mL. Results (if a Case Study enter NA) Using the original cutoff of 0.05 ng/mL for cTnI in the patients with CHF or ESRD, the sensitivity and NPV were both 100%, while the specificity and PPV were low at 40.3% and 23%, respectively. Interestingly, when the cutoff was raised from 0.05 to 0.2 ng/mL, the sensitivity decreased by about 8% to 92.3 (12 out of 13 patients with AMI), and the specificity increased almost two-fold to 76.4%. The PPV increased to 40.4% and NPV was 98.2%. These values are comparable with the sensitivity, specificity, PPV and NPV of the total population at 85.3%, 82.4%, 38.7% and 97.7%, respectively. Conclusion The original cutoff value for cTnI in patients with ESRD and CHF produces a very low specificity and PPV. The results of this study suggest that an acceptable cutoff for cTnI to rule-out AMI patients who have CHF and or ESRD is 0.2 ng/mL which is four times higher than the original, but has comparable specificity, sensitivity, PPV and PPV to the total patient population. We note that this study must be regarded as a pilot study since the numbers of patients are small. We recommend a larger study to determine the validity of these conclusions.

Ab Initio Prediction of 3-D Conformations for Protein Long Loops with High Accuracy and Applications to Antibody CDRH3 Modeling.

Residue-level potentials of mean force were widely used for protein backbone refinements to avoid simultaneous sampling of side-chain conformations. The interaction energy between the reduced side chains and backbone atoms was not considered explicitly. In this study, we developed novel methods to calculate the residue-atom interaction energy in combination with atomic and residue-level terms. The parameters were optimized step by step to remove the overcounting or overlap problem between different energy terms. The mixing energy functions were then used to evaluate the generated backbone conformations at the initial sampling stage of protein loop modeling (OSCAR-loop), including the interaction energy between the reduced loop residues and full atoms of the protein framework. The accuracies of top-ranked decoys were 1.18 and 2.81 Å for 8-residue and 12-residue loops, respectively. We then selected diverse decoys for side-chain modeling, backbone refinement, and energy minimization. The procedure was repeated multiple times to select one prediction with the lowest energy. Consequently, we obtained an accuracy of 0.74 Å for a prevailing test set of 12-residue loops, compared with >1.4 Å reported by other researchers. The OSCAR-loop was also effective for modeling the H3 loops of antibody complementary determining regions (CDRs) in the crystal environment. The prediction accuracy of OSCAR-loop (1.74 Å) was better than the accuracy of the Rosetta NGK method (3.11 Å) or those achieved by deep learning methods (>2.2 Å) for the CDRH3 loops of 49 targets in the Rosetta antibody benchmark. The performance of OSCAR-loop in a model environment was also discussed.

Validation of genetic risk scores for obesity on a sample of the population of Russian regions

Aim. To validate and evaluate the accuracy of 15 genetic risk scores (GRSs) for obesity, created in populations of European origin in the sample of two European Russia regions. Material and methods. Genetic testing has been performed using next generation sequencing on a sample from the Russian population (n=1179). The study included 15 GRS associated with body mass index (BMI) or waist-to-hip ratio adjusted for BMI (WHRadjBMI).Results. The predictive power of 8 out of 9 GRSs for obesity based on BMI remains the same for the Russian population. The predictive power of 6 GRSs for obesity based on WHRadjBMI is lower in the Russian population than in the reference sample. GRS reproducibility increases with the size of initial samples and number of variants included in the GRS increase. The use of GRSs for obesity based on BMI in the Russian population created on European populations is justified.Conclusion. For the first time in Russia, 15 obesity GRSs developed in European populations have been validated. The data obtained on the effectiveness of the considered GRS can be used in the future to improve the obesity prediction and prevention in Russia.

Interleukin-18 and Soluble Interleukin-2 Receptor Are Useful Markers for Enhanced Diagnosis of Intravascular Lymphoma

Intravascular lymphoma (IVL) is an extremely rare and aggressive form of non-Hodgkin's lymphoma characterized by lymphoma cells localized within blood vessels. Due to its rapid progression and life-threatening nature, prompt diagnosis and swift treatment are essential. However, IVL often presents with nonspecific systemic symptoms such as fever, fatigue, weight loss, skin rash, and neurological impairment without noticeable lymph node enlargement. As a result, diagnosing IVL is highly challenging, and it is frequently misdiagnosed as other conditions. A definitive diagnosis of IVL requires tissue biopsy, like a random skin biopsy, although this may not always lead to the identification of IVL from the biopsy site. Consequently, when IVL is suspected, repeated random skin biopsies may be necessary, but the optimal number of biopsies remains unknown. To avoid repetitive invasive procedures, clinical indicators that raise suspicion of IVL more aggressively in patients with nonspecific symptoms are needed. IVL often presents with clinical features that resemble adult-onset Still disease (AOSD), particularly with systemic symptoms such as fever and hemophagocytic lymphohistiocytosis (HLH). Distinguishing between IVL and AOSD is crucial, but the lack of disease-specific markers for each condition makes differentiation challenging. While recent studies suggest the utility of genetic mutation analysis using cell-free DNA for diagnosing IVL, cost and technical limitations call for the development of simpler diagnostic adjunct markers. Therefore, our study aimed to explore potential useful indicators for differentiating IVL by comparing clinical parameters used for AOSD diagnosis in both IVL and AOSD patients. We conducted a comparative analysis using clinical data and initial samples from seven patients diagnosed histologically with IVL and five AOSD patients who were confirmed negative for IVL through long-term follow-up. Additionally, samples from six healthy donors were included for comparison. The median age of IVL patients was 64 years, while AOSD patients were 47 years old, with no significant difference between the groups (p=0.668). White blood cell count, hemoglobin concentration, platelet count,lactate dehydrogenase (LDH), triglycerides, fibrinogen, and C-reactive protein showed no significant differences between IVL and AOSD patients. On the other hand, ferritin levels were significantly lower in IVL patients compared to AOSD patients (539-9164 vs. 4690-91917 ng/mL, p=0.018), and soluble interleukin-2 receptor (sIL-2R) levels were significantly higher in IVL patients (4714-37572 vs. 935-4441 U/mL, p=0.003). Furthermore, the inflammatory cytokines IL-1β, IL-6, and IL-18 were measured, and while IL-1β and IL-6 showed no significant differences between IVL and AOSD patients, IL-18 was significantly higher in AOSD (0.77x10 3-8.04x10 3 vs. 1.07x10 5-2.05x10 5 pg/mL, p=0.003) (Figure). The presence of HLH did not impact ferritin, sIL-2R, or IL-18 levels in IVL patients. Additionally, the presence of bone marrow infiltration by IVL cells did not influence the clinical parameters, including ferritin, sIL-2R, and IL-18. Furthermore, ROC analysis was performed to assess the usefulness of ferritin, sIL-2R, and IL-18 in differentiating IVL and AOSD, revealing that less than 10000 pg/mL for IL-18 and above 5000 U/mL for sIL-2R ensured a reliable differentiation between IVL and AOSD. In conclusion, IL-18 and sIL-2R showed significant differences between IVL and AOSD, suggesting their potential as useful indicators for distinguishing the two conditions. Furthermore, when investigating cases of fever of unknown origin, it is crucial to diligently perform procedures such as random skin biopsies in patients strongly suspected of having IVL based on the values of IL-18 and sIL-2R.

Autoimmune Neutropenia of Infancy Is Almost Exclusively Caused By IgG Antibodies

Background The relevance of IgM antibodies in autoimmune mediated hemocytopenias remains a matter of debate. For autoimmune neutropenia, conflicting results were published. This study was performed as part of the Giessen Neutropenia Registry, which prospectively included children with suspected autoimmune neutropenia. Methods Children with suspected autoimmune neutropenia were prospectively enrolled and data central to their suspected diagnosis were collected over 3 years. Sera were tested for the presence of autoantibodies against neutrophils by granulocyte immunofluorescence test (GIFT) and granulocyte agglutination test (GAT). The presence of IgG and IgM antibodies was assessed in a subgroup of patients with positive initial GIFT in whom spontaneous remission of their neutropenia was documented. Results A total of 406 children were included in the study. A remission was reported for 114 patients during the study period. Of those, 96 children (84%) had an initial positive GIFT. Their median age at diagnosis was 11 months (7-17.5), and their mean neutrophil count was 293 (±267)/µL, ranging from 0 to 975. In total 75/96 (78%) of children had at least one documented infection at diagnosis. In 29/96 (30%), a bone marrow aspirate was available. At the documented time point of remission, children were 27 months (18-41) old. In the initial sample send for diagnosis, IgG antibodies against neutrophils were detected in 94/96 children (98%), and IgM antibodies were detected in 2/96 (2%). We did not observe children with autoantibodies of both Ig classes. Conclusion To our knowledge, this is the first study to demonstrate the contribution of IgG or IgM antibodies in a well-defined clinical cohort with a typical course including, spontaneous disease remission. IgG antibodies were present in 98%. Only very rarely, IgM antibodies can be detected. We conclude that in general, screening for IgG autoantibodies is appropriate as a first diagnostic step. In cases with strong clinical suspicion but negative GIFT with anti-IgG, anti-IgM testing may be considered.

Recent Patterns of Radiotherapy Use in Multiple Myeloma: Clinical Outcomes and Possible Radiologic, Biochemical, and Genomic Correlates of Response

Background/Objectives: Systemic therapies for multiple myeloma (MM) have advanced considerably, changing the landscape of MM treatment paradigms. Yet, the use of radiotherapy (RT) has remained heterogeneous, and even controversial, due to minimal data on outcomes. With the ultimate goal of guiding the design of prospective trials incorporating RT, we initiated a study of our institutional experience treating MM with RT since 1/1/2000. Here we report a preliminary feasibility analysis of an initial sample cohort, identifying patterns of RT use, outcomes, and the impact of RT on radiographic and biochemical markers, with genomic characterization for more recently treated patients. Materials/Methods: 506 pathologically confirmed MM patients who received RT to 1190 sites between 1/1/2000 and 6/1/2022 were identified. Patient, disease, and treatment characteristics were analyzed for 50 consecutive patients treated in 2019 (recent sampling but with reasonable follow for analysis) and tested for association with cumulative incidence of local and distant failure (LF, DF) using univariable and multivariable analysis. Genomic data was obtained via next generation sequencing using an institutional targeted sequencing panel (Memorial Sloan Kettering IMPACT). Results: Among the 50 patients analyzed (median 63 years), 90 lesions were treated with RT, 33% with concurrent systemic therapy, to a median dose of 20 Gy (8-46 Gy) over a median of 5 fractions (1-25). RT Indications were pain (56%), critical structure involvement (25%), peri-operative (9%), salvage/consolidation (8%), and bridging therapy (2%). Median size of RT-treated lesions was 4.2 cm (1.4-7.9) and included non-vertebral bones (62%), spine (24%), and extramedullary sites (14%). The median number of lines of pre-RT therapy was 7 (1-14) and 51% had &amp;gt;9 lesions on imaging, 47% involving both medullary and extramedullary sites. Pre-RT PET imaging was performed in a majority of patients (62%). With a median follow-up of 12.4 months (0.5-46), LF occurred in 5% of treated sites and 89% had DF, most commonly in both medullary + extramedullary (51.4%) sites. Of the patients with DF, 93% had sustained local control of the irradiated site. Absolute decreases 1-week to 1-month post-RT were observed in marrow plasma cell percentage, (median 4.0%), M spike (0.30 g/dL), total protein (0.3 g/dL), K:L ratio (0.01), lesion size (1.5cm), and lesion SUV (3.1) but in this limited sample, none were significantly associated with disease control. A cohort of 62 RT-treated MM patients from 2016-2022 had genomic data available; most common tumor mutations were in TP53 (35%), HIST1 (34%), NRAS (34%), and KRAS (23%). Conclusion: In this pilot analysis of a sampling cohort of RT-treated MM, we report on patterns of utilization, outcomes, and biochemical and radiographic correlates. Ultimately, we aim to characterize the role of RT in the modern era of systemic therapy to guide the design of future prospective trials and to inform novel approaches for incorporating RT into the treatment paradigm. At the meeting, we will present data from a larger cohort of MM patients, with further sub-analyses on the relevance of baseline imaging to subsequent irradiated lesions, as well as toxicity and outcomes data with the use of radiotherapy in conjunction with newer systemic agents (bi-specific antibodies and chimeric antigen receptor T-cell therapy).