-Functionalization of Pillar[4]arene[1]benzoquinone Monoxime via Selective 1,4-Addition of Grignard Reagents.

-functionalization of pillar[]arenes has been a formidable challenge, partially due to the fragility of their macrocyclic skeletons. In this concise report, we describe a facile synthetic method for monoarylation/alkylation at the position to the oxime functionality in pillar[4]arene[1]benzoquinone monoxime () via addition of Grignard reagents. The described method enables the creation of various mono--alkyl/aryl-substituted pillar[5]arene derivatives that were previously inaccessible.

Using Classifiers To Predict Catalyst Design for Polyketone Microstructure.

We applied a classifier method to predict palladium catalysts for the formation of nonalternating polyketones via the copolymerization of CO and ethylene; current examples are limited to using phosphine sulfonate and diphosphazane monoxide supporting ligands. With the reported workflow, we discovered two new classes of palladium complexes capable of achieving the synthesis of nonalternating polyketones with a lower CO content than those made by known palladium catalysts. Our results show that we doubled the number of classes of palladium compounds that can catalyze the formation of this type of polymer.

Destabilization of Soil Carbon After Saltwater Intrusion in Coastal Agricultural Soils.

Saltwater intrusion (SWI) is a concerning issue impacting agricultural production and soil C cycling, which can have a wider effect on the climate. Complex soil processes driving soil C cycling following saltwater intrusion have not yet been fully quantified. Agricultural fields with varying degrees of saltwater intrusion, unaffected control, and native tidal marsh were studied to understand the impacts of saltwater intrusion on soil properties and soil carbon dynamics.

Palliative Care Spiritual Assessment and Goals-of-Care Discussions in the Neurocritical Care Unit: Collaborating with Chaplains.

Introduction: Neuropalliative care is an emerging subspecialty of palliative care designed to address the unique supportive care needs of patients with serious neurological illness, including those receiving neurocritical care in intensive care units. Spiritual care is a vital component in the provision of holistic and humanized care to these patients. A chaplain who is specially trained and credentialed in care for those with serious illness is the health care professional responsible for making spiritual assessments and contributes to the plan of care, facilitating decision making, and guiding other clinicians in the provision of generalist spiritual care.

Comparisons of neurodegenerative disease biomarkers across different biological fluids from patients with Huntington's disease.

Fluid biomarkers play important roles in many aspects of neurodegenerative diseases, such as Huntington's disease (HD). However, a main question relates to how well levels of biomarkers measured in CSF are correlated with those measured in peripheral fluids, such as blood or saliva. In this study, we quantified levels of four neurodegenerative disease-related proteins, neurofilament light (NfL), total tau (t-tau), glial fibrillary acidic protein (GFAP) and YKL-40 in matched CSF, plasma and saliva samples from Huntingtin (HTT) gene-positive individuals (n = 21) using electrochemiluminescence assays.

Distinct pro-inflammatory/pro-angiogenetic signatures distinguish children with Long COVID from controls.

Background: Recent proteomic studies have documented that Long COVID in adults is characterized by a pro-inflammatory signature with thromboinflammation. However, if similar events happen also in children with Long COVID has never been investigated.

Methods: We performed an extensive protein analysis of blood plasma from pediatric patients younger than 19 years of age Long COVID and a control group of children with acute COVID-19, MIS-C, and healthy controls resulted similar for sex distribution and age.

Computational design of highly signalling-active membrane receptors through solvent-mediated allosteric networks.

Protein catalysis and allostery require the atomic-level orchestration and motion of residues and ligand, solvent and protein effector molecules. However, the ability to design protein activity through precise protein-solvent cooperative interactions has not yet been demonstrated. Here we report the design of 14 membrane receptors that catalyse G protein nucleotide exchange through diverse engineered allosteric pathways mediated by cooperative networks of intraprotein, protein-ligand and -solvent molecule interactions.

Relationships between structural stigma, societal stigma, and minority stress among gender minority people.

Structural stigma towards gender minority (GM; people whose current gender does not align with sex assigned at birth) people is an important contributor to minority stress (i.e., stress experienced due to one's marginalized GM identity), although existing variables are unclear in their inclusion of social norms, or societal stigma, as a key component of the construct.

Characterizing safety, toxicity, and breast cancer risk reduction using a long-term fulvestrant eluting implant.

For individuals at high risk of developing breast cancer, interventions to mitigate this risk include surgical removal of their breasts and ovaries or five years treatment with the anti-estrogen tamoxifen or aromatase inhibitors. We hypothesized that a silicone based anti-estrogen-eluting implant placed within the breast would provide the risk reduction benefit of hormonal therapy, but without the adverse effects that limit compliance. To this end, we demonstrate that when placed adjacent to mammary tissue in the 7,12-dimethylbenz[a]anthracene-induced rat breast cancer model a fulvestrant-eluting implant delays breast cancer with minimal systemic exposure.

Pharmacokinetics of remimazolam, midazolam and diazepam in sheep.

Objective: To model pharmacokinetics of three benzodiazepines and their metabolites in sheep.

Study Design: A nonblinded, prospective, experimental study.

Animals: A group of six adult Hampshire-Suffolk cross-bred sheep (three females, three castrated males), 73 ± 3 kg (mean ± standard deviation).

Contraceptive use and pregnancy in cystic fibrosis: Survey findings from 10 cystic fibrosis centers.

Background: Reproductive life planning is key, now that people with cystic fibrosis (pwCF) may live into their 60s. This study explores contraceptive use, pregnancy trends, and whether concomitant cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy reduces contraceptive effectiveness.

Methods: Females with CF aged 18-45 years from 10 U.

Differential effects of volanesorsen on apoC-III, triglycerides and pancreatitis in familial chylomicronemia syndrome diagnosed by genetic or non-genetic criteria.

Background: Familial chylomicronemia syndrome (FCS) is diagnosed by genetic or non-genetic criteria.

Objective: To assess responses to treatment of apolipoprotein (apo)C-III, triglycerides, and pancreatitis events in patients with FCS-based diagnostic methods.

Methods: APPROACH enrolled 66 patients with FCS randomized to volanesorsen or placebo for 12 months.

Azygos Vein Stenosis in Frontotemporal Dementia Sagging Brain Syndrome.

Background And Purpose: Symptoms indistinguishable from behavioral-variant frontotemporal dementia (bvFTD) can develop in patients with spontaneous intracranial hypotension associated with severe brain sagging. An underlying spinal CSF leak can be identified in only a minority of these patients and the success rate of nondirected treatments, such as epidural blood patching and dural reduction surgery, is low. The disability associated with bvFTD sagging brain syndrome is high and, because of the importance of the venous system in the pathophysiology of CSF leaks in general, we have investigated the systemic venous circulation in those patients with recalcitrant symptoms.

Assessment of Attenuation in Pericarotid Fat among Patients with Carotid Plaque and Spontaneous Carotid Dissection.

Background And Purpose: Changes in perivascular fat density (PFD) and its association with inflammation have been topics of interest in both atherosclerotic and nonatherosclerotic vasculopathies. The objective of this study was to assess the PFD in patients with spontaneous internal carotid artery dissection (SICAD) or carotid atherosclerotic plaque, with and without intraplaque hemorrhage (IPH).

Materials And Methods: A cross-sectional retrospective bicentric analysis of 130 patients (30 with SICAD and 100 with carotid atherosclerotic plaque) who underwent CT angiography was performed.

Computational Nuclear Oncology Toward Precision Radiopharmaceutical Therapies: Ethical, Regulatory, and Socioeconomic Dimensions of Theranostic Digital Twins.

Computational nuclear oncology for precision radiopharmaceutical therapy (RPT) is a new frontier for theranostic treatment personalization. A key strategy relies on the possibility to incorporate clinical, biomarker, image-based, and dosimetric information in theranostic digital twins (TDTs) of patients to move beyond a one-size-fits-all approach. The TDT framework enables treatment optimization by real-time monitoring of the real-world system, simulation of different treatment scenarios, and prediction of resulting treatment outcomes, as well as facilitating collaboration and knowledge sharing among health care professionals adopting a harmonized TDT.

KDIGO 2025 clinical practice guideline for the evaluation, management, and treatment of autosomal dominant polycystic kidney disease (ADPKD): executive summary.

The Kidney Disease: Improving Global Outcomes (KDIGO) 2025 Clinical Practice Guideline for the Evaluation, Management, and Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) represents the first KDIGO guideline on this subject. Its scope includes nomenclature, diagnosis, prognosis, and prevalence; kidney manifestations; chronic kidney disease (CKD) management and progression, kidney failure, and kidney replacement therapy; therapies to delay progression of kidney disease; polycystic liver disease; intracranial aneurysms and other extrarenal manifestations; lifestyle and psychosocial aspects; pregnancy and reproductive issues; pediatric issues; and approaches to the management of people with ADPKD. The guideline has been developed with patient partners, clinicians, and researchers around the world, with the goal to generate a useful resource for healthcare providers and patients by providing actionable recommendations.

B7-H3 CAR-T cell therapy combined with irradiation is effective in targeting bulk and radiation-resistant chordoma cancer cells.

Background: Chordoma is a slow-growing, primary malignant bone tumor that arises from notochordal tissue in the midline of the axial skeleton. Surgical excision with negative margins is the mainstay of treatment, but high local recurrence rates are reported even with negative margins. High-dose radiation therapy (RT), such as with proton or carbon ions, has been used as an alternative to surgery, but late local failure remains a problem.

Metabolic dysfunction-associated steatotic liver disease in children.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, is the most common cause of chronic liver disease in children. MASLD encompasses a spectrum of liver disease and can be severe, with 10% of affected children presenting with advanced fibrosis. While biopsy remains the most accurate method for diagnosing and staging the disease, MRI proton density fat fraction and magnetic resonance elastography are the most reliable non-invasive measures for assessing steatosis and fibrosis, respectively.

Applying implementation science frameworks to understand why fisherfolk continue or discontinue pre-exposure prophylaxis for HIV prevention in Uganda: a qualitative analysis.

Introduction: In Uganda, fisherfolk have an HIV prevalence between 15% and 40%, significantly higher than the national average of 5.5%. Pre-exposure prophylaxis (PrEP) is effective in preventing HIV but faces challenges in uptake and continuation among fisherfolk.