A cellulose synthase-like protein governs the biosynthesis of alkaloids.

Decades of research on the infamous antinutritional steroidal glycoalkaloids (SGAs) in Solanaceae plants have provided deep insights into their metabolism and roles. However, engineering SGAs in heterologous hosts has remained a challenge. We discovered that a protein evolved from the machinery involved in building plant cell walls is the crucial link in the biosynthesis of SGAs.

Covered Stent Correction for Sinus Venosus Atrial Septal Defects, an Emerging Alternative to Surgical Repair: Results of an International Registry.

Background: Covered stent correction for a sinus venosus atrial septal defect (SVASD) was first performed in 2009. This innovative approach was initially viewed as experimental and was reserved for highly selected patients with unusual anatomic variants. In 2016, increasing numbers of procedures began to be performed, and in several centers, it is now offered as a standard of care option alongside surgical repair.

Medical chart-reported alcohol consumption, substance use, and mental health issues in association with HIV pre-exposure prophylaxis (PrEP) nonadherence among gay, bisexual, and other men-who-have-sex-with-men.

Background: Although some evidence suggests that alcohol, substance use, and mental health issues diminish adherence to HIV Pre-Exposure Prophylaxis (PrEP) among gay, bisexual, and other men-who-have-sex-with-men (gbMSM), findings are somewhat inconsistent and have primarily derived from studies involving non-random samples. Medical chart extraction can provide unique insight by in part surmounting sampling-related limitations, as data for entire PrEP clinic populations can be examined. Our investigation entailed comprehensive chart extraction to assess the extent to which chart-reported alcohol, substance use, and mental health issues were associated with chart-reported PrEP nonadherence.

Protein purification with light via a genetically encoded azobenzene side chain.

Affinity chromatography is the method of choice for the rapid purification of proteins from cell extracts or culture supernatants. Here, we present the light-responsive Azo-tag, a short peptide comprising p-(phenylazo)-L-phenylalanine (Pap), whose side chain can be switched from its trans-ground state to the metastable cis-configuration by irradiation with mild UV light. Since only trans-Pap shows strong affinity to α-cyclodextrin (α-CD), a protein exhibiting the Azo-tag selectively binds to an α-CD chromatography matrix under daylight or in the dark but elutes quickly under physiological buffer flow when illuminating the column at 355 nm.

Rivastigmine interferes with the pharmacological activity of hydromethylthionine on presynaptic proteins in the line 66 model of frontotemporal dementia.

The negative interference of treatments between the acetylcholinesterase inhibitor rivastigmine and the tau aggregation inhibitor hydromethylthionine mesylate (HMTM) has been reported in Line 1 tau-transgenic mice, which overexpress a truncated species of tau protein that is found in the core of paired helical filaments in Alzheimer´s disease (AD). However, little is known about whether such interactions could affect synapses in mice overexpressing tau carrying pathogenic mutations. Here, we have used Line 66 (L66) mice which overexpress full-length human tau carrying the P301S mutation as a model in which tau accumulates in synapses.

Plastic input and dynamics in industrial composting.

Green and biowaste, processed within large facilities into compost, is a key fertilizer for agricultural and horticultural soils. However, due to improper waste disposal of plastic, its residues often remain or even lead to the formation ofmicroplastics (1 µm - 5 mm, MiPs) in the final compost product. To better understand the processes, we first quantified 'macroplastics' (> 20 mm, MaPs) input via biowaste collection into an industrial composting plant, and, then determined MiP concentrations at five stages during the composting process (before and after shredding and screening processes), and in the water used for irrigation.

Long-term follow-up of patients with a first clinical demyelinating event (clinically isolated syndrome) who received cladribine tablets in CLASSIC-MS: Findings for the ORACLE-MS cohort.

Background: CLASSIC-MS explored long-term outcomes of patients treated with cladribine tablets.

Objective: Assess long-term efficacy in patients previously enrolled in ORACLE-MS, a Phase III parent trial.

Methods: ORACLE-MS included patients with a first clinical demyelinating event (FCDE or clinically isolated syndrome) who received ⩾1 course of cladribine tablets or placebo.

Moderate-to-vigorous physical activity modulates the association between serum 25-hydroxyvitamin D and bone stiffness in European children and adolescents.

It remains unclear how serum 25-hydroxyvitamin D (25(OH)D) concentrations relate to childhood bone health. We hypothesized that 25(OH)D was inversely associated with bone turnover biomarkers and positively associated with bone stiffness. Cross-sectional analyses were performed using data from participants (2-15-year-old, 51% boys) from the Identification and Prevention of Dietary- and Lifestyle-induced Health Effects in Children and Infants Study (IDEFICS)/I.

Abatacept Induces Long-Term Reconstitution of the B-Cell Niche in a Patient With CTLA-4 Haploinsufficiency: A Case Report.

Objectives: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) haploinsufficiency is a rare genetic condition characterized by development of immune cytopenia, hypogammaglobulinemia, and/or lymphoproliferative disorder, as well as multiple autoimmunity. Treatment with abatacept was shown to alleviate autoimmune conditions, yet its long-lasting impact on bone marrow function remains undetermined.

Methods: We here present the case of a now 39-year-old woman with CTLA-4 haploinsufficiency with predominant CNS affection, yet multiorgan autoimmunity and lymphopenia.

Large Language Model Ability to Translate CT and MRI Free-Text Radiology Reports Into Multiple Languages.

Background High-quality translations of radiology reports are essential for optimal patient care. Because of limited availability of human translators with medical expertise, large language models (LLMs) are a promising solution, but their ability to translate radiology reports remains largely unexplored. Purpose To evaluate the accuracy and quality of various LLMs in translating radiology reports across high-resource languages (English, Italian, French, German, and Chinese) and low-resource languages (Swedish, Turkish, Russian, Greek, and Thai).

Exploring the Effects of Prefrontal Transcranial Direct Current Stimulation on Brain Metabolites: A Concurrent tDCS-MRS Study.

Transcranial Direct Current Stimulation (tDCS) is a non-invasive brain stimulation technique used to modulates cortical brain activity. However, its effects on brain metabolites within the dorsolateral prefrontal cortex (DLPFC), a crucial area targeted for brain stimulation in mental disorders, remain unclear. This study aimed to investigate whether prefrontal tDCS over the left and right DLPFC modulates levels of key metabolites, including gamma-aminobutyric acid (GABA), glutamate (Glu), glutamine/glutamate (Glx), N-acetylaspartate (NAA), near to the target region and to explore potential sex-specific effects on these metabolite concentrations.

Intravenous immunoglobulin therapy: usage patterns and response to treatment in Qatar over ten years.

Background: IVIg is a blood-derived antibody product initially designed as a replacement therapy in inborn errors of immunity (IEIs). However, over the last 50 years, IVIg has been used to treat a growing range of autoimmune, autoinflammatory, and secondary immunodeficiency disorders. The US FDA has licensed IVIg for use in the treatment of nine clinical indications; although, IVIg global usage extends to off-label indications with variable treatment responses.

Prevalence and Associated Risk Factors for Hypovitaminosis D in Patients Scheduled for Primary Total Knee Arthroplasty in Germany.

Objective: Several studies have reported a high prevalence of hypovitaminosis D in orthopedic patients. The purpose of this prospective observational study was to report on the prevalence of hypovitaminosis D in patients scheduled for elective primary total knee arthroplasty (TKA) and its associated risk factors.

Methods: In this monocentric cohort study, 25(OH) vitamin D serum levels were measured in 687 consecutive patients undergoing primary total knee arthroplasty (TKA) over a period of twelve months.

Anemia in Myelofibrosis: A Focus on Proactive Management and the Role of Momelotinib.

Anemia is a common and progressive clinical manifestation of myelofibrosis that may occur as part of the disease pathogenesis as well as due to the myelosuppressive effects of some treatments, with a substantial impact on quality of life, prognosis, and healthcare resource utilization. Despite these burdens, anemia management has traditionally been a secondary priority to spleen and symptom control, due in part to the limitations of available therapeutic approaches. With the initial regulatory approvals of momelotinib, a Janus kinase 1 (JAK1), JAK2, and activin A receptor type 1 inhibitor that provides anemia-related benefits in addition to addressing splenomegaly and symptoms, re-evaluation of anemia as an early and prominent treatment consideration is warranted.

Association between magnesium and vitamin D status in adults with high prevalence of vitamin D deficiency and insufficiency.

Purpose: It has been assumed that magnesium (Mg) status may interact with vitamin D status. We therefore aimed at investigating the association between Mg and vitamin D status in a large cohort of adult individuals with a high prevalence of deficient/insufficient vitamin D and Mg status.

Methods: We used data from the Ludwigshafen Risk and Cardiovascular Health Study (n = 2,286) to analyze differences according to serum Mg status in circulating 25-hydroxyvitamin D [25(OH)D] (primary endpoint), 24,25-dihydroxyvitamin D [24,25(OH)D], vitamin D metabolite ratio and calcitriol, and odds ratios for deficient or insufficient 25(OH)D (secondary endpoints).

Multi-clustering study on the association between human leukocyte antigen and hepatitis B virus-related hepatocellular carcinoma and cirrhosis in Viet Nam.

Background: Human leukocyte antigen (HLA) class II molecules are cell surface receptor proteins found on antigen-presenting cells. Polymorphisms and mutations in the gene can affect the immune system and the progression of hepatitis B.

Aim: To study the relation between rs2856718 of , rs3077, and rs9277535 of , hepatitis B virus (HBV)-related cirrhosis, and hepatocellular carcinoma (HCC).

CT-Defined Pectoralis Muscle Density Predicts 30-Day Mortality in Hospitalized Patients with COVID-19: A Nationwide Multicenter Study.

Rationale And Objectives: The prognostic role of computed tomography (CT)-defined skeletal muscle features in COVID-19 is still under investigation. The aim of the present study was to evaluate the prognostic role of CT-defined skeletal muscle area and density in patients with COVID-19 in a multicenter setting.

Materials And Methods: This retrospective study is a part of the German multicenter project RACOON (Radiological Cooperative Network of the COVID-19 pandemic).

Novel risk predictor of arrhythmias for patients with potassium channel-related congenital long QT syndrome.

Background: Congenital long QT syndrome (LQTS) is characterized by delayed ventricular repolarization, predisposing to potentially lethal ventricular arrhythmias. The variability in disease severity among patients remains largely unexplored, underscoring the limitations of current risk stratification methods.

Objective: We aimed to evaluate the potential utility of electrocardiographic markers from the exercise stress test (EST) in identifying patients with high-risk LQTS.

Mixture of neonicotinoid and fungicide affects foraging activity of honeybees.

The use of plant protection products (PPPs) is a major factor contributing to global insect decline. We here use the honeybee (Apis mellifera) as a model to study combined effects of the last neonicotinoid in the EU (acetamiprid) and different fungicides on live-long foraging flights using radio frequency identification. The mixture of the sterol-biosynthesis-inhibiting fungicide difenoconazole and the insecticide acetamiprid significantly reduced the number of foraging trips per day compared to the control and each PPP alone, while a mixture of the insecticide with the non-sterol-biosynthesis inhibiting fungicide boscalid/dimoxystrobin did not affect behaviour.

Dipeptides in CSF and plasma: diagnostic and therapeutic potential in neurological diseases.

Dipeptides (DPs), composed of two amino acids (AAs), hold significant therapeutic potential but remain underexplored. Given the crucial role of AAs in central nervous system (CNS) function, this study investigated the presence of DPs in cerebrospinal fluid (CSF) and their correlation with corresponding AAs, potentially indicating their role as AA donors. Plasma and CSF samples were collected from 43 children with neurological or metabolic conditions of unknown origin, including 23 with epilepsy.

Versatile MRI acquisition and processing protocol for population-based neuroimaging.

Neuroimaging has an essential role in studies of brain health and of cerebrovascular and neurodegenerative diseases, requiring the availability of versatile magnetic resonance imaging (MRI) acquisition and processing protocols. We designed and developed a multipurpose high-resolution MRI protocol for large-scale and long-term population neuroimaging studies that includes structural, diffusion-weighted and functional MRI modalities. This modular protocol takes almost 1 h of scan time and is, apart from a concluding abdominal scan, entirely dedicated to the brain.

The conserved noncoding RNA ModT coordinates growth and virulence in Clostridioides difficile.

Bacterial noncoding RNAs fulfill a variety of cellular functions as catalysts, as scaffolds in protein complexes or as regulators of gene expression. They often exhibit complex tertiary structures that are a key determinant of their biochemical function. Here, we characterize the structured "raiA motif" RNA from Clostridioides difficile, which is conserved in more than 2,500 bacterial species from the phyla Bacillota and Actinomycetota.