Exploring potential working mechanisms of accelerated HF-rTMS in refractory major depression with a focus on locus coeruleus connectivity.

Background: This study investigates the effects of accelerated high-frequency repetitive transcranial magnetic stimulation (aHF-rTMS), applied to the left dorsolateral prefrontal cortex (DLPFC), on locus coeruleus (LC) functional connectivity in the treatment of refractory medication-resistant major depression (MRD).

Methods: We studied 12 antidepressant-free refractory MRD patients, focusing on how aHF-rTMS affects the LC, a central component of the brain's noradrenergic system and key to mood regulation and stress response.

Results: A stronger decrease in LC functional connectivity following aHF-rTMS treatment resulted in better clinical improvement.

Policy for transitioning childhood-onset growth hormone deficiency from pediatric to adult endocrine care in Belgium.

Growth hormone (GH) deficiency (GHD) in children and adolescents can vary in severity and origin, with GH replacement therapy proving effective in achieving genetic target height. Optimal outcomes are seen in those treated early and with higher doses. As patients approach adult height, priorities shift towards optimizing metabolic effects, maintaining body composition, and enhancing bone mass and muscle strength.

Mixed methods process evaluation of an advance care planning intervention among nursing home staff.

Background: We developed the ACP+ intervention to support nursing home staff with implementation of advance care planning. While ACP+ was found to improve staff's self-efficacy, it did not change their knowledge about advance care planning.

Aim: To describe the level of implementation, mechanisms of impact, and contextual factors.

Role of rheumatoid arthritis registries worldwide: What have they taught us?

Rheumatoid arthritis (RA) is one of the most common rheumatic conditions, impacting quality of life on several domains. Major breakthroughs have been achieved over the past three decades in the management benefitting the patients' lives. With increasing as well as novel treatment options, clinical registries have been established and continuously evolve to portray patient characteristics, monitor disease activity of RA, effectiveness and safety of the novel compounds.

Intracranial administration of anti-PD-1 and anti-CTLA-4 immune checkpoint-blocking monoclonal antibodies in patients with recurrent high-grade glioma.

Background: Recurrent high-grade glioma (rHGG) lacks effective life-prolonging treatments and the efficacy of systemic PD-1 and CTLA-4 immune checkpoint inhibitors is limited. The multi-cohort Glitipni phase I trial investigates the safety and feasibility of intraoperative intracerebral (iCer) and postoperative intracavitary (iCav) nivolumab (NIVO) ± ipilimumab (IPI) treatment following maximal safe resection (MSR) in rHGG.

Materials And Methods: Patients received 10 mg IV NIVO within 24 h before surgery, followed by MSR, iCer 5 mg IPI and 10 mg NIVO, and Ommaya catheter placement in the resection cavity.

Crucial role of a takeout protein in white-backed planthopper Sogatella furcifera (Horváth) orientation towards its host rice plants.

The takeout (TO) gene family impacts diverse physiological and behavioral functions in insects, yet specific olfactory-associated roles for the family have yet to be fully elucidated. To provide insights into TO function in rice planthoppers, the genomes of three rice planthoppers (white-backed planthopper, brown planthopper and small brown planthopper) were searched for TO homologs and their degree of conservation assessed via chromosomal localization, exon-intron boundaries, phylogenetic relationships and protein domains/motifs. We performed a tissue-specific expression analysis of the 20 TO genes in the white-backed planthopper (WBPH, Sogatella furcifera) and found that SfTO17 is enriched in adult antennae.

Structural basis of μ-opioid receptor targeting by a nanobody antagonist.

The μ-opioid receptor (μOR), a prototypical G protein-coupled receptor (GPCR), is the target of opioid analgesics such as morphine and fentanyl. Due to the severe side effects of current opioid drugs, there is considerable interest in developing novel modulators of μOR function. Most GPCR ligands today are small molecules, however biologics, including antibodies and nanobodies, represent alternative therapeutics with clear advantages such as affinity and target selectivity.

Effects of per- and polyfluoroalkyl substances on the liver: Human-relevant mechanisms of toxicity.

Per- and polyfluoroalkyl substances (PFAS) are abundantly used in a plethora of products with applications in daily life. As a result, PFAS are widely distributed in the environment, thus providing a source of exposure to humans. The majority of human exposure to PFAS is attributed to the human diet, which encompasses drinking water.

Case report: A case of severe capecitabine toxicity due to confirmed in trans compound heterozygosity of a common and rare DPYD variant.

Variations in the activity of the enzyme dihydropyrimidine dehydrogenase (DPD) are associated with toxicity to fluoropyrimidine-containing chemotherapy. Testing of DPD deficiency either by targeted genotyping of the corresponding gene or by quantification of plasma concentration of uracil and dihydrouracil (phenotyping approach) are the two main methods capable of predicting reduced enzymatic activity in order to reduce adverse reactions after fluoropyrimidine treatment. In this paper, we describe a patient with locally advanced colon carcinoma with severe toxicity following capecitabine therapy.

Single time-point analysis of product and substrate inhibition.

When enzyme inhibition by either the product or excess substrate occurs, it is possible to determine the characteristic kinetic parameters based on [P]/t measurements, even when a large proportion of the substrate is converted. The advantages of various approaches are discussed. Most of them allow a good estimation of the V and K values.

Unveiling the Complexity of cis-Regulation Mechanisms in Kinases: A Comprehensive Analysis.

Protein cis-regulatory elements (CREs) are regions that modulate the activity of a protein through intramolecular interactions. Kinases, pivotal enzymes in numerous biological processes, often undergo regulatory control via inhibitory interactions in cis. This study delves into the mechanisms of cis regulation in kinases mediated by CREs, employing a combined structural and sequence analysis.

AXL as immune regulator and therapeutic target in Acute Myeloid Leukemia: from current progress to novel strategies.

Until recently, treatment options for patients diagnosed with Acute Myeloid Leukemia (AML) were limited and predominantly relied on various combinations, dosages, or schedules of traditional chemotherapeutic agents. Patients with advanced age, relapsed/refractory disease or comorbidities were often left without effective treatment options. Novel advances in the understanding of leukemogenesis at the molecular and genetic levels, alongside recent progress in drug development, have resulted in the emergence of novel therapeutic agents and strategies for AML patients.

Vertical root fracture detection with cone-beam computed tomography in Biodentine™ filled teeth.

Purpose: This study aimed to evaluate the accuracy of detecting vertical root fractures in Biodentine™-filled teeth using the Promax 3Dmax cone-beam computed tomography (CBCT) unit compared to periapical radiographs. It tested hypotheses regarding CBCT's diagnostic superiority in non-root-filled and Biodentine™-root-filled maxillary central incisors and assessed the impact of smaller field of view and lower intensity settings on detection accuracy.

Materials And Methods: Extracted maxillary incisors were divided into groups based on fracture status and root filling material, then placed in a Thiel-embalmed skull to simulate clinical conditions.

Structural basis of thiamine transport and drug recognition by SLC19A3.

Thiamine (vitamin B) functions as an essential coenzyme in cells. Humans and other mammals cannot synthesise this vitamin de novo and thus have to take it up from their diet. Eventually, every cell needs to import thiamine across its plasma membrane, which is mainly mediated by the two specific thiamine transporters SLC19A2 and SLC19A3.

The ecological and evolutionary dynamics of inselbergs.

Islands are fundamental model systems in ecology, biogeography, and evolutionary biology. However, terrestrial islands, unlike their aquatic counterparts, have received comparatively less attention. Among these land islands, inselbergs (i.