The Role of Crystalline Intermediates in Mechanochemical Cyclorhodation Reactions Elucidated by in-Situ X-ray Powder Diffraction and Computation.

The occurrence of crystalline intermediates in mechanochemical reactions might be more widespread than previously assumed. For example, a recent study involving the acetate-assisted C-H activation of N-Heterocycles with [Cp*RhCl ] by ball milling revealed the formation of transient cocrystals between the reagents prior to the C-H activation step. However, such crystalline intermediates were only observed through stepwise intervallic ex-situ analysis, and their exact role in the C-H activation process remained unclear.

Carbon Dioxide Cycloaddition to Epoxides Promoted by Nicotinamidium Halide Catalysts: A DFT Investigation.

The utilization of CO as building block for the production of cyclic carbonate is a promising route to simultaneously mitigate the global warming issue and obtain valuable commercial chemicals. In this work, the activity of nicotinamidium halide catalysts towards the CO conversion into cyclic carbonate has been explored by means of density functional theory (DFT) calculations. DFT calculations support the ability, suggested experimentally, of the pyridium α-C-H proton of the catalysts to activate the epoxide ring via a hydrogen bond.

Leucopterin, the white pigment in butterfly wings: structural analysis by PDF fit, FIDEL fit, Rietveld refinement, solid-state NMR and DFT-D.

Leucopterin (CHNO) is the white pigment in the wings of Pieris brassicae butterflies, and other butterflies; it can also be found in wasps and other insects. Its crystal structure and its tautomeric form in the solid state were hitherto unknown. Leucopterin turned out to be a variable hydrate, with 0.

Language Delay in Patients with CLN2 Disease: Could It Support Earlier Diagnosis?

Neuronal ceroid lipofuscinosis type 2 (CLN2 disease) is a rare pediatric disorder associated with rapid neurodegeneration, and premature death in adolescence. An effective enzyme replacement therapy (cerliponase alfa) has been approved that can reduce this predictable neurological decline. The nonspecific early symptoms of CLN2 disease frequently delay diagnosis and appropriate management.

Effect of Hemodiafiltration or Hemodialysis on Mortality in Kidney Failure.

Background: Several studies have suggested that patients with kidney failure may benefit from high-dose hemodiafiltration as compared with standard hemodialysis. However, given the limitations of the various published studies, additional data are needed.

Methods: We conducted a pragmatic, multinational, randomized, controlled trial involving patients with kidney failure who had received high-flux hemodialysis for at least 3 months.

Five-year follow-up of KEYNOTE-087: pembrolizumab monotherapy for relapsed/refractory classical Hodgkin lymphoma.

Previous analyses of the phase 2 KEYNOTE-087 (NCT02453594) trial of pembrolizumab monotherapy demonstrated effective antitumor activity with acceptable safety in patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL). However, long-term response durability and outcome of patients who receive a second course after treatment discontinuation after complete response (CR) remain of clinical interest. We present KEYNOTE-087 data after >5 years of median follow-up.

Long-term survival with IDH wildtype glioblastoma: first results from the ETERNITY Brain Tumor Funders' Collaborative Consortium (EORTC 1419).

Background: Median survival with glioblastoma remains in the range of 12 months on population levels. Only few patients survive for more than 5 years. Patient and disease features associated with long-term survival remain poorly defined.

A New Generation of IMiDs as Treatments for Neuroinflammatory and Neurodegenerative Disorders.

The immunomodulatory imide drug (IMiD) class, which includes the founding drug member thalidomide and later generation drugs, lenalidomide and pomalidomide, has dramatically improved the clinical treatment of specific cancers, such as multiple myeloma, and it combines potent anticancer and anti-inflammatory actions. These actions, in large part, are mediated by IMiD binding to the human protein cereblon that forms a critical component of the E3 ubiquitin ligase complex. This complex ubiquitinates and thereby regulates the levels of multiple endogenous proteins.

Near-Infrared Spectroscopy and Machine Learning for Accurate Dating of Historical Books.

Non-destructive, fast, and accurate methods of dating are highly desirable for many heritage objects. Here, we present and critically evaluate the use of near-infrared (NIR) spectroscopic data combined with three supervised machine learning methods to predict the publication year of paper books dated between 1851 and 2000. These methods provide different accuracies; however, we demonstrate that the underlying processes refer to common spectral features.

Reverse Engineering of Digital Measures: Inviting Patients to the Conversation.

Background: Digital measures offer an unparalleled opportunity to create a more holistic picture of how people who are patients behave in their real-world environments, thereby establishing a better connection between patients, caregivers, and the clinical evidence used to drive drug development and disease management. Reaching this vision will require achieving a new level of co-creation between the stakeholders who design, develop, use, and make decisions using evidence from digital measures.

Summary: In September 2022, the second in a series of meetings hosted by the Swiss Federal Institute of Technology in Zürich, the Foundation for the National Institutes of Health Biomarkers Consortium, and sponsored by Wellcome Trust, entitled "Reverse Engineering of Digital Measures," was held in Zurich, Switzerland, with a broad range of stakeholders sharing their experience across four case studies to examine how patient centricity is essential in shaping development and validation of digital evidence generation tools.

Protein Biomarkers of New-Onset Heart Failure: Insights From the Heart Omics and Ageing Cohort, the Atherosclerosis Risk in Communities Study, and the Framingham Heart Study.

Background: We sought to identify protein biomarkers of new-onset heart failure (HF) in 3 independent cohorts (HOMAGE cohort [Heart Omics and Ageing], ARIC study [Atherosclerosis Risk in Communities], and FHS [Framingham Heart Study]) and assess if and to what extent they improve HF risk prediction compared to clinical risk factors alone.

Methods: A nested case-control design was used with cases (incident HF) and controls (without HF) matched on age and sex within each cohort. Plasma concentrations of 276 proteins were measured at baseline in ARIC (250 cases/250 controls), FHS (191/191), and HOMAGE cohort (562/871).

Site-selective methylene C-H oxidation of an alkyl diamine enabled by supramolecular recognition using a bioinspired manganese catalyst.

Site-selective oxidation of aliphatic C-H bonds is a powerful synthetic tool because it enables rapid build-up of product complexity and diversity from simple precursors. Besides the poor reactivity of alkyl C-H bonds, the main challenge in this reaction consists in differentiating between the multiple similar sites present in most organic molecules. Herein, a manganese oxidation catalyst equipped with two 18-benzo-6-crown ether receptors has been employed in the oxidation of the long chain tetradecane-1,14-diamine.

Goods and Bads of the Endocannabinoid System as a Therapeutic Target: Lessons Learned after 30 Years.

The cannabis derivative marijuana is the most widely used recreational drug in the Western world and is consumed by an estimated 83 million individuals (∼3% of the world population). In recent years, there has been a marked transformation in society regarding the risk perception of cannabis, driven by its legalization and medical use in many states in the United States and worldwide. Compelling research evidence and the Food and Drug Administration cannabis-derived cannabidiol approval for severe childhood epilepsy have confirmed the large therapeutic potential of cannabidiol itself, Δ-tetrahydrocannabinol and other plant-derived cannabinoids (phytocannabinoids).

Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma.

Background: The efficacy and safety of treatment with cabozantinib in combination with nivolumab and ipilimumab in patients with previously untreated advanced renal-cell carcinoma are unknown.

Methods: In this phase 3, double-blind trial, we enrolled patients with advanced clear-cell renal-cell carcinoma who had not previously received treatment and had intermediate or poor prognostic risk according to the International Metastatic Renal-Cell Carcinoma Database Consortium categories. Patients were randomly assigned to receive 40 mg of cabozantinib daily in addition to nivolumab and ipilimumab (experimental group) or matched placebo in addition to nivolumab and ipilimumab (control group).

Raman Evidence of Multiple Adsorption Sites and Structural Transformation in ZIF-4.

The zeolitic imidazolate framework, ZIF-4, exhibits soft porosity and is known to show pore volume changes with temperatures, pressures, and guest adsorption. However, the mechanism and adsorption behavior of ZIF-4 are not completely understood. In this work, we report an open to narrow pore transition in ZIF-4 around ∼ 253 K upon lowering the temperature under vacuum (10 Torr) conditions, facilitated by C-H···π interactions.

2023 Update on European Atherosclerosis Society Consensus Statement on Homozygous Familial Hypercholesterolaemia: new treatments and clinical guidance.

This 2023 statement updates clinical guidance for homozygous familial hypercholesterolaemia (HoFH), explains the genetic complexity, and provides pragmatic recommendations to address inequities in HoFH care worldwide. Key strengths include updated criteria for the clinical diagnosis of HoFH and the recommendation to prioritize phenotypic features over genotype. Thus, a low-density lipoprotein cholesterol (LDL-C) >10 mmol/L (>400 mg/dL) is suggestive of HoFH and warrants further evaluation.

Efficacy and safety of damoctocog alfa pegol prophylaxis in patients ⩾40 years with severe haemophilia A and comorbidities: analysis from the PROTECT VIII study.

Background: Advances in treatment have enabled patients with haemophilia A to live longer and therefore may be subjected to comorbidities associated with ageing, in addition to disease-associated morbidities. There have been few reports to date on efficacy and safety of treatment specifically in patients with severe haemophilia A and comorbidities.

Objective: To explore the efficacy and safety of damoctocog alfa pegol prophylaxis in patients with severe haemophilia A aged ⩾40 years with comorbidities of interest.

Cu-loaded zeolites enable the selective activation of ethane to ethylene at low temperatures and pressure.

Cu-zeolites are found to activate the C-H bond of ethane already at 150 °C in a cyclic protocol and form ethylene with a high selectivity. Both the zeolite topology and Cu content are found to impact the ethylene yield. Ethylene adsorption studies with FT-IR, demonstrate that oligomerization of ethylene occurs over protonic zeolites, while this reaction does not occur over Cu-zeolites.

Cerebral Oximetry Monitoring in Extremely Preterm Infants.

Background: The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking.

Methods: In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we assigned extremely preterm infants (gestational age, <28 weeks), within 6 hours after birth, to receive treatment guided by cerebral oximetry monitoring for the first 72 hours after birth or to receive usual care.

Olfactory Nomenclature: An Orchestrated Effort to Clarify Terms and Definitions of Dysosmia, Anosmia, Hyposmia, Normosmia, Hyperosmia, Olfactory Intolerance, Parosmia, and Phantosmia/Olfactory Hallucination.

Background: Definitions are essential for effective communication and discourse, particularly in science. They allow the shared understanding of a thought or idea, generalization of knowledge, and comparison across scientific investigation. The current terms describing olfactory dysfunction are vague and overlapping.