Impaired SARS-CoV-2-Specific CD8+ T Cells After Infection or Vaccination but Robust Hybrid T Cell Immunity in Patients with Multiple Myeloma.

Background: Multiple myeloma (MM) patients are at high risk of severe infections including COVID-19 due to an immune dysregulation affecting both innate and adaptive immune responses. However, our understanding of the immune responses to infection and vaccination in MM patients is limited. To gain more detailed insights into infection- and vaccine-elicited T cell immunity in MM, we studied the CD8+ T cell response on the single-epitope level in SARS-CoV-2 convalescent and mRNA-vaccinated MM patients.

Outdoor recess is associated with more positive attitudes toward physical activity among pre-adolescent students and their parents.

Introduction: School day structure has the potential to increase students' physical activity (PA) levels and form positive attitudes about PA. Including various PA opportunities and free play possibilities in the school schedule, especially outdoor recess, can improve students' moderate-to-vigorous PA (MVPA) levels during school time. Therefore, the main aim of the study was to investigate students' and their parents' attitudes about outdoor recess and PA opportunities in schools with different recess opportunities.

The proteogenomic landscape of multiple myeloma reveals insights into disease biology and therapeutic opportunities.

Multiple myeloma (MM) is a plasma cell malignancy of the bone marrow. Despite therapeutic advances, MM remains incurable, and better risk stratification as well as new therapies are therefore highly needed. The proteome of MM has not been systematically assessed before and holds the potential to uncover insight into disease biology and improved prognostication in addition to genetic and transcriptomic studies.

Toward Adoption of Health Risk Assessment in Population-Based and Clinical Scenarios: Lessons From JADECARE.

Introduction: Health risk assessment (HRA) strategies are cornerstone for health systems transformation toward value-based patient-centred care. However, steps for HRA adoption are undefined. This article analyses the process of transference of the Adjusted Morbidity Groups (AMG) algorithm from the Catalan Good Practice to the Marche region (IT) and to Viljandi Hospital (EE), within the JADECARE initiative (2020-2023).

High dose vitamin D supplementation decreases the risk of deficiency in male conscripts, but has no effect on physical performance-A randomized study.

Purpose: Physical load during military training might increase the need for vitamin D; therefore, supplementation could be beneficial for 25(OH)D serum levels and physical performance.

Methods: One hundred and twelve male conscripts were randomized into two vitamin D oil capsule supplementation groups: 55 participants in the 600 IU group and 57 in the 4000 IU group with a follow-up period from July 2021 to May 2022. Physical fitness tests were performed in July, October and May.

Predicting the Activity of Unidentified Chemicals in Complementary Bioassays from the HRMS Data to Pinpoint Potential Endocrine Disruptors.

The majority of chemicals detected via nontarget liquid chromatography high-resolution mass spectrometry (HRMS) in environmental samples remain unidentified, challenging the capability of existing machine learning models to pinpoint potential endocrine disruptors (EDs). Here, we predict the activity of unidentified chemicals across 12 bioassays related to EDs within the Tox21 10K dataset. Single- and multi-output models, utilizing various machine learning algorithms and molecular fingerprint features as an input, were trained for this purpose.

CDK6 protein expression is associated with disease progression and treatment resistance in multiple myeloma.

Multiple myeloma (MM) is a heterogeneous malignancy of plasma cells. Despite improvement in the prognosis of MM patients after the introduction of many new drugs in the past decades, MM remains incurable since most patients become treatment-resistant. Cyclin-dependent kinase 6 (CDK6) is activated in many types of cancer and has been associated with drug resistance in MM.

Real-world analysis of teclistamab in 123 RRMM patients from Germany.

Teclistamab, a B-cell maturation antigen (BCMA) × CD3 directed bispecific antibody, has shown high response rates and durable remissions in the MAJESTEC-1 trial in patients with relapsed and refractory multiple myeloma (RRMM). We retrospectively assessed efficacy and tolerability in 123 patients treated at 18 different German centers to determine whether outcome is comparable in the real-world setting. Most patients had triple-class (93%) or penta-drug (60%) refractory disease, 37% of patients had received BCMA-directed pretreatment including idecabtagene vicleucel (ide-cel) CAR-T cell therapy (21/123, 17.

Results from Estonia's 2022 Report Card on Physical Activity for Children and Youth: Research Gaps and Five Key Messages and Actions to Follow.

The aim of this article is to summarize the results of the 2022 Estonian Physical Activity Report Card across 10 indicators based on available scientific data and national databases, and, additionally, to compare the current results with previous Report Card results. A national expert panel, consisting of research and policy experts, identified the available sources and synthesized as well as graded relevant data related to the physical activity (PA) of Estonian children and youth. Grade B was assigned to Organized Sports and Physical Activity (B-), Community and Environment (B+), and Government (B).

Magic shotgun approach to anti-inflammatory pharmacotherapy: Synthesis of novel thienopyrimidine monomers/heterodimer as dual COX-2 and 15-LOX inhibitors endowed with potent antioxidant activity.

Emerging evidence points to the intertwining framework of inflammation and oxidative stress in various ailments. We speculate on the potential impact of the magic shotgun approach in these ailments as an attempt to mitigate the drawbacks of current NSAIDs. Hence, we rationally designed and synthesized new tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine monomers/heterodimer as dual selective COX-2/15-LOX inhibitors with potent antioxidant activity.

Does Dietary Polyunsaturated Fatty Acid Intake Associate With Bone Mineral Density and Limb Structural Changes in Early Rheumatoid Arthritis?

Background: Rheumatoid arthritis (RA) is an inflammatory disease that can result in bone erosion, lean mass lowering, and increase of fat mass without changes in body weight. The dietary consumption of polyunsaturated fatty acids (PUFAs) has been assessed in many studies due to their potential anti-inflammatory effect.

Aim: The aim of this research was to identify if dietary intake of PUFAs associates with bone mineral density (BMD) and limb structural changes in early rheumatoid arthritis (ERA) compared to a population-based control group.

Hardness, Modulus, and Refractive Index of Plasma-Assisted Atomic-Layer-Deposited Hafnium Oxide Thin Films Doped with Aluminum Oxide.

Coatings with tunable refractive index and high mechanical resilience are useful in optical systems. In this work, thin films of HfO doped with AlO were deposited on silicon at 300 °C by using plasma-enhanced atomic layer deposition (PE-ALD). The mainly amorphous 60-80 nm thick films consisted Al in the range of 2 to 26 at.

School Children's Physical Activity and Preferred Activities during Outdoor Recess in Estonia: Using Accelerometers, Recess Observation, and Schoolyard Mapping.

Studies about recess have found that children have higher physical activity (PA) during outdoor recess compared to indoor recess, and well-constructed schoolyards play an important role in stimulating PA in children. This study aimed at investigating the affordances of schoolyards and outdoor recess PA in two urban and two rural primary schools in Estonia. Schoolyards were described with the geographical mapping method, children's activities during outdoor recess were registered by using observations, and PA levels were measured with accelerometers.

A multi-sensor dataset with annotated activities of daily living recorded in a residential setting.

SPHERE is a large multidisciplinary project to research and develop a sensor network to facilitate home healthcare by activity monitoring, specifically towards activities of daily living. It aims to use the latest technologies in low powered sensors, internet of things, machine learning and automated decision making to provide benefits to patients and clinicians. This dataset comprises data collected from a SPHERE sensor network deployment during a set of experiments conducted in the 'SPHERE House' in Bristol, UK, during 2016, including video tracking, accelerometer and environmental sensor data obtained by volunteers undertaking both scripted and non-scripted activities of daily living in a domestic residence.

Immunophenotypical profiling of myeloid neoplasms with erythroid predominance using mass cytometry (CyTOF).

Acute erythroid leukemia (AEL) is a disease continuum between Myelodysplastic syndrome (MDS) and Acute myeloid leukemia (AML) with the cellular hallmark of uncontrolled proliferation and impaired differentiation of erythroid progenitor cells. First described by Giovanni di Guglielmo in 1917 AEL accounts for less than 5% of all de novo AML cases. There have been efforts to characterize AEL at a molecular level, describing recurrent alterations in TP53, NPM1 and FLT3 genes.

Towards a One Health Food Safety Strategy for Palestine: A Mixed-Method Study.

Foodborne diseases, together with increasing antimicrobial resistance (AMR), pose a threat to public health in an era of huge challenges with climate change and the risks of zoonotic epidemics. A One Health approach to foster food safety is a key for improvement, particularly in complex socio-ecological systems such as in Palestine, to examine human-animal-environment interfaces and promote intersectoral action. This study aimed to assess food safety from farm to public health toward an operational One Health strategy for Palestine.

Severe deficiency of vitamin D has no negative effect on physical performance during military training.

Background: Decreased physical fitness and inferior physical performance are potentially life-threatening risk factors in a combat situation. To examine the effect of vitamin D on physical performance, a prospective study of young men conscripts in the Estonian Army was designed. The hypothesis of the study was that severe deficiency of vitamin D has a negative effect on physical performance.

Seven-month wintertime supplementation of 1200 IU vitamin D has no effect on hand grip strength in young, physically active males: A randomized, controlled study.

Background: There has been a growing interest in the role of vitamin D for the well-being and physical performance of humans under heavy training such as conscripts in military service; however, there is a lack of long-term supplementation studies performed on members of this type of young, physically active, male population. The hypothesis of the study was that vitamin D supplementation during wintertime will decrease the prevalence of critically low vitamin D blood serum levels and increase hand grip strength during the winter season among young male conscripts.

Study Design: Longitudinal, triple-blinded, randomized, placebo-controlled trial.

Factors associated with hand bone changes in early rheumatoid arthritis.

Background: The aim of this research was to assess if hand bone mineral density (HBMD) changes associated with the appearance of erosions in early rheumatoid arthritis (ERA), compared with the population-based control group. Additionally, we tried to identify if there are novel factors that associate with HBMD and erosive changes (EC), and if they are dissimilar. The study was conducted as the data are limited.

Hybrid -Acylcysteines as Dual-Acting Matrix Disruptive and Anti-Quorum Sensing Agents Fighting Biofilms: Design, Synthesis, Molecular Docking Studies, and Assays.

Biofilms facilitate the pathogenesis of life-threatening infections by coating mucosal surfaces or invasive devices and offer protection from antimicrobial therapy and the host immune response, thus increasing mortality rates and financial burden. Herein, new hybrid -acylcysteines (NAC) incorporating selected acyl groups from organic acids and their derivatives, which are capable of quenching pathogen quorum sensing (QS) systems, were designed and their antibiofilm activity and anti-QS were evaluated. -acylcysteines () were synthesized and characterized by H NMR and C NMR, and their purity was confirmed by elemental analyses.

Sodium adduct formation with graph-based machine learning can aid structural elucidation in non-targeted LC/ESI/HRMS.

Non-targeted screening with LC/ESI/HRMS aims to identify the structure of the detected compounds using their retention time, exact mass, and fragmentation pattern. Challenges remain in differentiating between isomeric compounds. One untapped possibility to facilitate identification of isomers relies on different ionic species formed in electrospray.

Proteomic profiling reveals CDK6 upregulation as a targetable resistance mechanism for lenalidomide in multiple myeloma.

The immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide are highly effective treatments for multiple myeloma. However, virtually all patients eventually relapse due to acquired drug resistance with resistance-causing genetic alterations being found only in a small subset of cases. To identify non-genetic mechanisms of drug resistance, we here perform integrated global quantitative tandem mass tag (TMT)-based proteomic and phosphoproteomic analyses and RNA sequencing in five paired pre-treatment and relapse samples from multiple myeloma patients.

Autoimmune Hemolytic Anemia: A Case Study Presentation.

Autoimmune hemolytic anemia (AIHA) is a rare and potentially life-threatening condition. This article presents a case study of AIHA in a patient with a history of acute myelogenous leukemia in remission. Differentiating the cause and type of HA (extrinsic versus intrinsic) will be discussed, along with information on follow-up and refractory AIHA.

Cereblon enhancer methylation and IMiD resistance in multiple myeloma.

Cereblon is the direct binding target of the immunomodulatory drugs (IMiDs) that are commonly used to treat multiple myeloma (MM), the second most frequent hematologic malignancy. Patients respond well to initial treatment with IMiDs, but virtually all patients develop drug resistance over time, and the underlying mechanisms are poorly understood. We identified an as yet undescribed DNA hypermethylation in an active intronic CRBN enhancer.