Green Oxidation of Aromatic Hydrazide Derivatives Using an Oxoammonium Salt.

Aromatic diazenes are often prepared by oxidation of the corresponding hydrazides using stoichiometric quantities of nonrecyclable oxidants. We developed a convenient alternative protocol for the oxidation of aromatic hydrazides using Bobbitt's salt (), a metal-free, recyclable, and commercially available oxoammonium reagent. A variety of aryl hydrazides were oxidized within 75 min at room temperature using the developed protocol.

3-Chloropropylbis(catecholato)silicate as a Bifunctional Reagent for the One-Pot Synthesis of Tetrahydroquinolines from -Bromosulfonamides.

Bis(catecholato)silicate salts are easily accessible reagents that can be used to install alkyl fragments through photoredox-enabled cross-coupling. These reagents can incorporate various functional groups including pendant alkyl halides. A halogenated organosilicate reagent was leveraged to develop a one-pot synthesis of tetrahydroquinolines from -bromosulfonamides, where the bifunctional reagent participates in a nickel/photoredox cross-coupling followed by intramolecular nucleophilic substitution.

Multisite Verification of a Targeted CFTR Polymerase Chain Reaction/Capillary Electrophoresis Assay That Evaluates Pathogenic Variants Across Diverse Ethnic and Ancestral Groups.

Context.—: Existing targeted cystic fibrosis screening assays miss important pathogenic CFTR variants in the ethnically diverse US population.

Objective.

Bicyclobutanes: from curiosities to versatile reagents and covalent warheads.

The unique chemistry of small, strained carbocyclic systems has long captivated organic chemists from a theoretical and fundamental standpoint. A resurgence of interest in strained carbocyclic species has been prompted by their potential as bioisosteres, high fraction of sp carbons, and limited appearance in the patent literature. Among strained ring systems, bicyclo[1.

Recommendations for Interpreting and Reporting Silent Carrier and Disease-Modifying Variants in SMA Testing Workflows.

Genetic testing for SMA diagnosis, newborn screening, and carrier screening has become a significant public health interest worldwide, driven largely by the development of novel and effective molecular therapies for the treatment of spinal muscular atrophy (SMA) and the corresponding updates to testing guidelines. Concurrently, understanding of the underlying genetics of SMA and their correlation with a broad range of phenotypes and risk factors has also advanced, particularly with respect to variants that modulate disease severity or impact residual carrier risks. While testing guidelines are beginning to emphasize the importance of these variants, there are no clear guidelines on how to utilize them in a real-world setting.

Postoperative Oral Antibiotics and Sinonasal Outcomes Following Endoscopic Transsphenoidal Surgery for Pituitary Tumors Study: A Multicenter, Prospective, Randomized, Double-Blinded, Placebo-Controlled Study.

Background: Postoperative prophylactic antibiotics are commonly used in pituitary surgery, but evidence supporting their use is lacking, which has implications for antibiotic stewardship.

Objective: To evaluate whether receipt of postoperative oral antibiotics results in superior sinonasal quality of life (QOL) compared with placebo among patients who undergo endoscopic endonasal transsphenoidal pituitary surgery.

Methods: Patients were randomized to receive either oral placebo or cefdinir (trimethoprim-sulfamethoxazole in patients intolerant to cefdinir) for 7 d after surgery.

Assessment of the Validity of the Sinonasal Outcomes Test-22 in Pituitary Surgery: A Multicenter Prospective Trial.

Objectives/hypothesis: Sinonasal Outcomes Test-22 (SNOT-22) is used widely as a patient-reported sinonasal quality-of-life (QOL) instrument for endoscopic endonasal pituitary surgery. However, it has never been validated in this population. This study explores the psychometric validity of SNOT-22 to determine if it is a valid scale in patients undergoing endoscopic pituitary surgery.

Multisite Evaluation and Validation of a Sensitive Diagnostic and Screening System for Spinal Muscular Atrophy that Reports SMN1 and SMN2 Copy Number, along with Disease Modifier and Gene Duplication Variants.

Spinal muscular atrophy is a severe autosomal recessive disease caused by disruptions in the SMN1 gene. The nearly identical SMN2 gene copy number is associated with disease severity. SMN1 duplication markers, such as c.

Radical-Polar Crossover Annulation: A Platform for Accessing Polycyclic Cyclopropanes.

Photoredox-mediated radical/polar crossover (RPC) processes provide unique solutions to challenging annulations. Herein, we describe an approach to the cyclopropanation of olefins that are embedded within bicyclic scaffolds. Whereas these systems are notoriously recalcitrant toward classical cyclopropanation approaches, RPC cyclopropanation can be executed with ease, leading to polycarbocyclic and polyheterocyclic cyclopropanes.

Photoredox Radical/Polar Crossover Enables Construction of Saturated Nitrogen Heterocycles.

Photoredox-mediated radical/polar crossover (RPC) processes offer new avenues for the synthesis of cyclic molecules. This process has been realized for the construction of medium-sized saturated nitrogen heterocycles. Photocatalytically generated alkyl radicals possessing pendant leaving groups engage imines in C-C bond formation, and subsequent reduction of the intermediate nitrogen-centered radical triggers anionic ring closure.

Radical/Polar Annulation Reactions (RPARs) Enable the Modular Construction of Cyclopropanes.

An annulation process for the construction of 1,1-disubstituted cyclopropanes via a radical/polar crossover process is described. The cyclopropanation proceeds by the addition of a photocatalytically generated radical to a homoallylic tosylate. Reduction of the intermediate radical alkylation adduct (via single electron transfer) furnishes an anion that undergoes an intramolecular substitution.

Alkyl Carbon-Carbon Bond Formation by Nickel/Photoredox Cross-Coupling.

The union of photoredox and nickel catalysis has resulted in a renaissance in radical chemistry as well as in the use of nickel-catalyzed transformations, specifically for carbon-carbon bond formation. Collectively, these advances address the longstanding challenge of late-stage cross-coupling of functionalized alkyl fragments. Empowered by the notion that photocatalytically generated alkyl radicals readily undergo capture by Ni complexes, wholly new feedstocks for cross-coupling have been realized.

Fumarate hydratase inactivation in hereditary leiomyomatosis and renal cell cancer is synthetic lethal with ferroptosis induction.

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a hereditary cancer syndrome characterized by inactivation of the Krebs cycle enzyme fumarate hydratase (FH). HLRCC patients are at high risk of developing kidney cancer of type 2 papillary morphology that is refractory to current radiotherapy, immunotherapy and chemotherapy. Hence, an effective therapy for this deadly form of cancer is urgently needed.

Evolution of a Thermophilic Strand-Displacing Polymerase Using High-Temperature Isothermal Compartmentalized Self-Replication.

Strand-displacing polymerases are a crucial component of isothermal amplification (IA) reactions, where the lack of thermal cycling reduces equipment needs and improves the time to answer, especially for point-of-care applications. In order to improve the function of strand-displacing polymerases, we have developed an emulsion-based directed evolution scheme, high-temperature isothermal compartmentalized self-replication (HTI-CSR) that does not rely on thermal cycling. Starting from an algorithm-optimized shuffled library of exonuclease-deficient Family A polymerases from Geobacillus stearothermophilus (Bst LF) and Thermus aquaticus (Klentaq), we have applied HTI-CSR to generate a more thermostable strand-displacing polymerase variant that performs well in loop-mediated isothermal amplification and rolling circle amplification, even after thermal challenges of up to 95 °C that lead to better primer annealing.

The Minimal Clinically Important Difference of the Anterior Skull Base Nasal Inventory-12.

Background: The minimal clinically important difference (MCID) is defined as the smallest change in health-related quality of life (QOL) that patients consider meaningful. The MCID is essential for determining clinically significant changes, rather than simply statistically significant changes, in QOL scores. The Anterior Skull Base Nasal Inventory-12 (ASK Nasal-12), a site-specific sinonasal QOL instrument, has emerged as a standard instrument for assessing QOL in patients who have undergone endonasal transsphenoidal surgery.

Shuffle Optimizer: A Program to Optimize DNA Shuffling for Protein Engineering.

DNA shuffling is a powerful tool to develop libraries of variants for protein engineering. Here, we present a protocol to use our freely available and easy-to-use computer program, Shuffle Optimizer. Shuffle Optimizer is written in the Python computer language and increases the nucleotide homology between two pieces of DNA desired to be shuffled together without changing the amino acid sequence.

Hydrophosphination of Bicyclo[1.1.0]butane-1-carbonitriles.

Hydrophosphination of bicyclo[1.1.0]butyl nitriles with phosphine boranes and phosphites provided novel cyclobutyl-P derivatives.

In Vitro Selection for Small-Molecule-Triggered Strand Displacement and Riboswitch Activity.

An in vitro selection method for ligand-responsive RNA sensors was developed that exploited strand displacement reactions. The RNA library was based on the thiamine pyrophosphate (TPP) riboswitch, and RNA sequences capable of hybridizing to a target duplex DNA in a TPP regulated manner were identified. After three rounds of selection, RNA molecules that mediated a strand exchange reaction upon TPP binding were enriched.

Comparison of sinonasal quality of life and health status in patients undergoing microscopic and endoscopic transsphenoidal surgery for pituitary lesions: a prospective cohort study.

Object: Despite the widespread adoption of endoscopic transsphenoidal surgery for pituitary adenomas, the sinonasal quality of life (QOL) and health status in patients who have undergone this technique have not been compared with these findings in patients who have undergone the traditional direct uninostril microsurgical technique. In this study, the authors compared the sinonasal QOL and patient-reported health status after use of these 2 surgical techniques.

Methods: The study design was a nonblinded prospective cohort study.

Predictors of sinonasal quality of life and nasal morbidity after fully endoscopic transsphenoidal surgery.

Object: Despite the increasing application of endoscopic transsphenoidal surgery for pituitary lesions, the prognostic factors that are associated with sinonasal quality of life (QOL) and nasal morbidity are not well understood. The authors examine the predictors of sinonasal QOL and nasal morbidity in patients undergoing fully endoscopic transsphenoidal surgery.

Methods: An exploratory post hoc analysis was conducted of patients who underwent endoscopic pituitary surgery and were enrolled in a prospective multicenter QOL study.

Robust strand exchange reactions for the sequence-specific, real-time detection of nucleic acid amplicons.

Loop-mediated isothermal amplification (LAMP) of DNA is a powerful isothermal nucleic acid amplification method that can generate upward of 10(9) copies from less than 100 copies of template DNA within an hour. Unfortunately, although the amplification reactions are extremely powerful, real-time and specific detection of LAMP products remains analytically challenging. In order to both improve the specificity of LAMP detection and to make readout simpler and more reliable, we have replaced the intercalating dye typically used for monitoring in real-time fluorescence with a toehold-mediated strand exchange reaction termed one-step strand displacement (OSD).

Synthesis of phosphaguanidines by hydrophosphination of carbodiimides with phosphine boranes.

The direct addition of anionic secondary phosphine boranes to carbodiimides yields both chiral and achiral phosphaguanidine boranes under ambient temperature conditions. An analogous preparation of menthol-derived phosphinite boranes is also described. These products can be deborinated to give the corresponding phosphines, and subsequently oxidized to give phosphine oxides.

Prospective validation of a patient-reported nasal quality-of-life tool for endonasal skull base surgery: The Anterior Skull Base Nasal Inventory-12.

Object: Patient-reported quality-of-life (QOL) end points are becoming increasingly important health care metrics. To date, no nasal morbidity instrument specifically designed for patients undergoing endonasal skull base surgery has been developed. In this study, the authors describe the development and validation of a site-specific nasal morbidity instrument to assess patient-reported rhinological outcomes following endonasal skull base surgery.