Design, Synthesis, and Unprecedented Interactions of Covalent Dipeptide-Based Inhibitors of SARS-CoV-2 Main Protease and Its Variants Displaying Potent Antiviral Activity.

The main protease (M) of SARS-CoV-2 is a key drug target for the development of antiviral therapeutics. Here, we designed and synthesized a series of small-molecule peptidomimetics with various cysteine-reactive electrophiles. Several compounds were identified as potent SARS-CoV-2 M inhibitors, including compounds (IC = 0.

sp. nov., a novel endophytic bacterium with plant growth-promoting potential, isolated from root nodules of in Northwestern Algeria.

A thorough polyphasic taxonomic study, integrating genome-based taxonomic approaches, was carried out to characterize the RB5 strain isolated from root nodules of growing on the coastal dunes of Bousfer Beach (Oran, Algeria). The 16S rRNA gene sequence analysis revealed that strain RB5 had the highest similarity to LMG27940 (98.94%) and IzPS32d (98.

imaging of subacute myocardial infarction with ultra-short echo time 3D quantitative T- and T -mapping magnetic resonance imaging in mice.

Aims: The aim of this study was to develop an ultra-short echo time 3D magnetic resonance imaging (MRI) method for imaging subacute myocardial infarction (MI) quantitatively and in an accelerated way. Here, we present novel 3D T- and T -weighted Multi-Band SWeep Imaging with Fourier Transform and Compressed Sensing (MB-SWIFT-CS) imaging of subacute MI in mice hearts .

Methods And Results: Relaxation time-weighted and under-sampled 3D MB-SWIFT-CS MRI were tested with manganese chloride (MnCl) phantom and mice MI model.

Synthesis of zeolite from rice husk ash and kaolinite clay for the removal of methylene blue from aqueous solution.

Zeolite was successfully synthesized using a mixture of kaolinite clay (which served as the alumina source) and rice husk ash (silica source). The aim of this work was to synthesize highly efficient zelolite to remove methyle blue dye from aqueous solution. The synthesized adsorbent was characterised using Fourier Transform Infrared (FTIR) spectroscopy, powder x-ray diffraction (PXRD) analysis, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and pH at the point of zero charge (pHpzc).

Occupational noise exposure and maternal pregnancy complications: register-based cohort from urban areas in four Nordic countries.

Objective: To assess the role of occupational noise exposure on pregnancy complications in urban Nordic populations.

Methods: A study population covering five metropolitan areas in Denmark, Finland, Norway and Sweden was generated using national birth registries linked with occupational and residential environmental exposures and sociodemographic variables. The data covered all pregnancies during 5-11 year periods in 2004‒2016, resulting in 373 184 pregnancies.

Molecular Determinants of Protein Pathogenicity at the Single-Aggregate Level.

Determining the structure-function relationships of protein aggregates is a fundamental challenge in biology. These aggregates, whether formed in vitro, within cells, or in living organisms, present significant heterogeneity in their molecular features such as size, structure, and composition, making it difficult to determine how their structure influences their functions. Interpreting how these molecular features translate into functional roles is crucial for understanding cellular homeostasis and the pathogenesis of various debilitating diseases like Alzheimer's and Parkinson's.

Self-Reported Performance and Hormonal-Cycle-Related Symptoms in Competitive Female Athletes.

Introduction: The present scientific consensus is that the menstrual cycle (MC) and hormonal contraceptive (HC) cycle only influence performance trivially. Nevertheless, athletes perceive changes in performance that they associate with different phases of their hormonal cycle.

Methods: A total of 959 female athletes completed a questionnaire, of which 750 were included in the present analysis.

Point of view: Challenges in implementation of new immunotherapies for Alzheimer's disease.

The advancement of disease-modifying treatments (DMTs) for Alzheimer's disease (AD), along with the approval of three amyloid-targeting therapies in the US and several other countries, represents a significant development in the treatment landscape, offering new hope for addressing this once untreatable chronic progressive disease. However, significant challenges persist that could impede the successful integration of this class of drugs into clinical practice. These challenges include determining patient eligibility, appropriate use of diagnostic tools and genetic testing in patient care pathways, effective detection and monitoring of side effects, and improving the healthcare system's readiness by engaging both primary care and dementia specialists.

Key considerations for combination therapy in Alzheimer's clinical trials: Perspectives from an expert advisory board convened by the Alzheimer's drug discovery foundation.

There is growing consensus in the Alzheimer's community that combination therapy will be needed to maximize therapeutic benefits through the course of the disease. However, combination therapy raises complex questions and decisions for study sponsors, from preclinical research through clinical trial design to regulatory, statistical, and operational considerations. In January 2024, the Alzheimer's Drug Discovery Foundation convened an expert advisory board to discuss the key considerations in each of these areas.

Changes in employment status and income and workplace organizational support among cancer survivors: A descriptive study in Iran.

Purpose: Cancer is the second leading cause of mortality in Iran, significantly impacting patients' lives and the public health system. This study aims to investigate changes in employment status and income and workplace organizational support among Iranian cancer survivors following their diagnosis.

Methods: This study was conducted at the Cancer Institute of Imam Khomeini Hospital complex in Tehran, Iran, in 2019.

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Effects of Betaine and Polydextrose on Intestinal Microbiota and Liver Ergothioneine in a High-Fat Diet-Fed Mouse Model and a Human Colonic Simulation Model.

Background/objectives: Ergothioneine (EGT) is an effective antioxidant that animals cannot produce and has an important anti-inflammatory role in cell protection, which can help lower the risk of various diseases. In this study, we investigated the potential role of gut microbiota in the production of EGT, which was found to increase in the mouse liver after dietary supplementation with betaine (BET) or polydextrose (PDX).

Methods: The effects of BET and PDX on the gut microbiota and tissue EGT content were investigated using a diet-induced obese mouse model and simulated fermentation in the human colon.

Epilepsy Diagnosis from EEG Signals Using Continuous Wavelet Transform-Based Depthwise Convolutional Neural Network Model.

Epilepsy is a prevalent neurological disorder characterized by seizures that significantly impact individuals and their social environments. Given the unpredictable nature of epileptic seizures, developing automated epilepsy diagnosis systems is increasingly important. Epilepsy diagnosis traditionally relies on analyzing EEG signals, with recent deep learning methods gaining prominence due to their ability to bypass manual feature extraction.

Epigenetic drug screening identifies enzyme inhibitors A-196 and TMP-269 as novel regulators of sprouting angiogenesis.

Epigenetic therapy has gained interest in treating cardiovascular diseases, but preclinical studies often encounter challenges with cell-type-specific effects or batch-to-batch variation, which have limited identification of novel drug candidates targeting angiogenesis. To address these limitations and improve the reproducibility of epigenetic drug screening, we redesigned a 3D in vitro fibrin bead assay to utilize immortalized human aortic endothelial cells (TeloHAECs) and screened a focused compound library with 105 agents. Compared to the established model using primary human umbilical vein endothelial cells, TeloHAECs needed a higher-density fibrin gel for optimal sprouting, successfully forming sprouts under both normoxic and hypoxic cell culture conditions.

Favourable Outcome of Relapsed PCNSL Among Transplant Eligble Patients.

Purpose: The prognosis of relapsed primary central nervous system lymphoma remains a concern. This study aimed to compare the effects of various patient- and disease-related factors on the prognosis of relapsed primary central nervous system lymphoma (PCNSL).

Methods: We retrospectively collected real-world data from eight Finnish hospitals on 198 patients diagnosed with PCNSL between 2003 and 2020.

Sense of Coherence and Past and/or Present Mental Health Problems Among Conscripts at Military Call-up in Northern Finland.

Introduction: Sense of coherence (SOC) refers to the psychosocial aspects and origins of health. Sense of coherence is related to physical and psychological health and quality of life. Military studies on SOC are commonly related to military deployment or operations, military training, and military fitness.

Patient-Related Factors Associated With the Initiation of Potentially Inappropriate Medication in Home Care: An Observational Study Based on Resident Assessment Instrument Data.

Background: The harmful outcomes of potentially inappropriate medications (PIMs) are highlighted among multimorbid older home care clients using several medicines. The aim of this study was to identify patient-related factors associated with the initiation of PIMs.

Methods: This register-based study used Resident Assessment Instrument-Home Care (RAI-HC) assessments (n = 6176) from year 2014 to 2015.

Melanin-Binding-Based Discovery of Topically Instilled Carbonic Anhydrase Inhibitors for Targeted Delivery and Prolonged Action in the Eye.

Glaucoma is a vision-threatening disease that is currently treated with intraocular-pressure-reducing eyedrops that are instilled once or multiple times daily. Unfortunately, the treatment is associated with low patient adherence and suboptimal treatment outcomes. We developed carbonic anhydrase II inhibitors (CAI-II) for a prolonged reduction of intraocular pressure (IOP).

Egg consumption, sleep, and mental health status among women with type II diabetes.

To evaluate if egg consumption is associated with sleep quality and psychological health (depression, anxiety, and stress) in women with type 2 diabetes. A cross-sectional study was conducted on women with type 2 diabetes (n = 230). Weight, height, waist circumference (WC), and blood pressure were measured.

The Significance of Information Quality for the Secondary Use of the Information in the National Healthcare Quality Registers in Finland.

Background The aim of the national healthcare quality registers is to monitor, assess, and improve the quality of care. The information utilized in quality registers must be of high quality to ensure that the information produced by the registers is reliable and useful. In Finland, one of the key sources of information for the quality registers is the national Kanta services.

Static Magnetic Field Exposure Causes Small Cell Cycle Disruptions and Changes in Reactive Oxygen Species Levels in Ionizing Radiation Exposed Human Neuroblastoma Cells.

Although static magnetic fields (SMFs) have been reported to induce only minimal biological effects, it has been proposed that they may alter the effects of other agents, such as ionizing radiation. We sham-exposed or exposed human SH-SY5Y neuroblastoma cells to 0.5-, 1.

Lifetime Treatment Trajectories of Mantle Cell Lymphoma: Simulation Based Analysis of 20 Years of Real-World Data.

Mantle cell lymphoma is a rare type of B-cell lymphoma, which is considered incurable yet treatable. In recent years, the treatment options of mantle cell lymphoma have multiplied, and the focus of treatment is expected to shift from traditional chemoimmunotherapy toward precision medicine. However, this development is hindered by the high costs of targeted therapies.

Outreach acute care for nursing homes: an observational study on the quality and cost-effectiveness of the Mobile Hospital.

Background: The global trend of emergency department (ED) crowding can be mitigated with outreach care. The Mobile Hospital is an outreach acute care service in Espoo, Finland. This study describes the results of the Mobile Hospital intervention to nursing homes in a pre-post study setting with benchmarking validation data.

Effect of pipe material and disinfectant on active bacterial communities in drinking water and biofilms.

Aims: We investigated the combined effects of pipe materials and disinfection chemicals on bacterial community and its active RNA fraction in water and biofilms in a pilot-scale premise plumbing system.

Methods And Results: The changes in bacterial communities were studied within four pipelines using copper and cross-linked polyethylene (PEX) pipe with chlorine or chloramine disinfection. The total and active bacterial communities and the presence of opportunistic pathogens (Legionella spp.