Biocatalytic Synthesis of α-Amino Esters via Nitrene C-H Insertion.

α-Amino esters are precursors to noncanonical amino acids used in developing small-molecule therapeutics, biologics, and tools in chemical biology. α-C-H amination of abundant and inexpensive carboxylic acid esters through nitrene transfer presents a direct approach to α-amino esters. Methods for nitrene-mediated amination of the protic α-C-H bonds in carboxylic acid esters, however, are underdeveloped.

Oncologic outcomes after Total Mesometrial Resection (TMMR) or treatment according to current international guidelines in FIGO (2009) stages IB1-IIB cervical cancer: an observational cohort study.

Background: According to international guidelines, standard treatment (ST) with curative intent in cervical cancer (CC) comprises radical hysterectomy and pelvic lymphadenectomy in early stages (International Federation of Gynecology and Obstetrics (FIGO) 2009 IB1, IIA1), adjuvant chemoradiation is recommended based on risk factors upon final pathology. Definitive chemoradiation is recommended in locally advanced stages (FIGO 2009 IB2, IIA2, IIB). Total mesometrial resection (TMMR) with therapeutic lymph node dissection (tLND) without adjuvant radiation has emerged as a promising treatment.

Stereospecific Enzymatic Conversion of Boronic Acids to Amines.

Boronic acids and esters are highly regarded for their safety, unique reactivity, and versatility in synthesizing a wide range of small molecules, bioconjugates, and materials. They are not exploited in biocatalytic synthesis, however, because enzymes that can make, break, or modify carbon-boron bonds are rare. We wish to combine the advantages of boronic acids and esters for molecular assembly with biocatalysis, which offers the potential for unsurpassed selectivity and efficiency.

Directed evolution of P411 enzymes for amination of inert C-H bonds.

Functionalizing inert C-H bonds selectively is a formidable task due to their strong bond energy and the difficulty of distinguishing chemically similar C-H bonds. While enzymatic oxygenation of C-H bonds is ubiquitous and well established, there is currently no known natural enzymatic process for direct nitrogen insertion. Instead, nature typically relies on pre-oxidized compounds for nitrogen incorporation.

Enzymatic Nitrogen Incorporation Using Hydroxylamine.

Hydroxylamine-derived reagents have enabled versatile nitrene transfer reactions for introducing nitrogen-containing functionalities in small-molecule catalysis, as well as biocatalysis. These reagents, however, result in a poor atom economy and stoichiometric organic waste. Activating hydroxylamine (NHOH) for nitrene transfer offers a low-cost and sustainable route to amine synthesis, since water is the sole byproduct.

A federated approach to identify women with early-stage cervical cancer at low risk of lymph node metastases.

Objective: Lymph node metastases (pN+) in presumed early-stage cervical cancer negatively impact prognosis. Using federated learning, we aimed to develop a tool to identify a group of women at low risk of pN+, to guide the shared decision-making process concerning the extent of lymph node dissection.

Methods: Women with cervical cancer between 2005 and 2020 were identified retrospectively from population-based registries: the Danish Gynaecological Cancer Database, Swedish Quality Registry for Gynaecologic Cancer and Netherlands Cancer Registry.

Accuracy of colposcopy in the Swedish screening program.

Introduction: Sensitivity and specificity of colposcopy vary greatly between studies and efficacy in clinical studies seldom corresponds with effectiveness in a real-life setting. It is unclear whether colposcopists' experience affects assessment; studies show divergent results. The study's objective was to investigate the accuracy of colposcopies in the Swedish screening program, the variability in colposcopists' assessments and whether degree of experience affects accuracy in a routine setting.

Chemodivergent C(sp)-H and C(sp)-H Cyanomethylation Using Engineered Carbene Transferases.

The ubiquity of C-H bonds presents an attractive opportunity to elaborate and build complexity in organic molecules. Methods for selective functionalization, however, often must differentiate among multiple chemically similar and, in some cases indistinguishable, C-H bonds. An advantage of enzymes is that they can be finely tuned using directed evolution to achieve control over divergent C-H functionalization pathways.

New Additions to the Arsenal of Biocatalysts for Noncanonical Amino Acid Synthesis.

Noncanonical amino acids (ncAAs) merge the conformational behavior and native interactions of proteinogenic amino acids with nonnative chemical motifs and have proven invaluable in developing modern therapeutics. This blending of native and nonnative characteristics has resulted in essential drugs like nirmatrelvir, which comprises three ncAAs and is used to treat COVID-19. Enzymes are appearing prominently in recent syntheses of ncAAs, where they demonstrate impressive control over the stereocenters and functional groups found therein.

Enzymatic Nitrogen Insertion into Unactivated C-H Bonds.

Selective functionalization of aliphatic C-H bonds, ubiquitous in molecular structures, could allow ready access to diverse chemical products. While enzymatic oxygenation of C-H bonds is well established, the analogous enzymatic nitrogen functionalization is still unknown; nature is reliant on preoxidized compounds for nitrogen incorporation. Likewise, synthetic methods for selective nitrogen derivatization of unbiased C-H bonds remain elusive.

Colposcopic assessment by Swedescore, evaluation of effectiveness in the Swedish screening programme: a cross-sectional study.

Objective: To evaluate the effectiveness and performance of Swedescore in the Swedish screening programme.

Design: Cross-sectional register study.

Setting And Population: All Swedish women aged over 18 years with a colposcopic assessment linked to a biopsy in the Swedish National Cervical Screening Registry, 2015-20.

α-Heteroarylation of Thioethers via Photoredox and Weak Brønsted Base Catalysis.

We report the C-H activation of thioethers to α-thio alkyl radicals and their addition to -methoxyheteroarenium salts for the redox-neutral synthesis of α-heteroaromatic thioethers. Studies are consistent with a two-step activation mechanism, where oxidation of thioethers to sulfide radical cations by a photoredox catalyst is followed by α-C-H deprotonation by a weak Brønsted base catalyst to afford α-thio alkyl radicals. Further, -methoxyheteroarenium salts play additional roles as a source of methoxyl radical that contributes to α-thio alkyl radical generation and a sacrificial oxidant that regenerates the photoredox catalytic cycle.

Spatialization of breeding values of Brangus animals associated with climatic, physical, and socio-economic factors.

This study was realized to analyze the combinations of climatic, physical, and socio-economic variables on distribution of breeding values for performance characteristics and scrotal circumference of Brangus cattle. Records of 84,703 Brangus animals, born from 2000 to 2010 distributed in 65 farms in Brazil were used. The characteristics analyzed were average daily gain from birth to weaning and from weaning to yearling (WW and YW), visual scores of conformations (WC and YC), muscle score (WM and YM), precocity score (WP and YS), and size score (WS and YS) at weaning and yearling and scrotal circumference (SC) at yearling.

Different methods of assessing udder temperature through thermography and their relation with rectal temperature.

Infrared thermography of the lateral side portion of the udder was taken from 38 lactating cows in a 6-day experiment. Thermograms were analyzed using specific software with the use of eight different methods. The experiment was aimed at correlating the different methods with each other and with rectal temperature (RT), in order to suggest a method to assess udder side temperature, and also at creating regression equations to enable RT calculation through the use of thermographic data.

Increased Institutional Surgical Experience in Robot-Assisted Radical Hysterectomy for Early Stage Cervical Cancer Reduces Recurrence Rate: Results from a Nationwide Study.

The aim of this study was to evaluate the impact of institutional surgical experience on recurrence following robotic radical hysterectomy (RRH) for early stage cervical cancer. All women in Sweden who underwent an RRH for stage IA2-IB1 cervical cancer at tertiary referral centers from its implementation in December 2005 until June 2017 were identified using a Swedish nationwide register and local hospital registers. Registry data were controlled by a chart review of all women.

Photoredox Generated Carbonyl Ylides Enable a Modular Approach to Aryltetralin, Dihydronaphthalene, and Arylnaphthalene Lignans.

A one-pot synthesis of dihydronaphthalenes and arylnaphthalenes from epoxides and common dipolarophiles is described. The reaction proceeds through photoredox activation of epoxides to carbonyl ylides, which undergo concerted [3 + 2] dipolar cycloaddition with dipolarophiles to provide tetrahydrofurans or 2,5-dihydrofurans. In the same flask, acid promoted rearrangement affords densely functionalized dihydronaphthalenes and arylnaphthalenes, respectively, in an overall redox-neutral sequence of transformations.

Mammary gland cell's tight junction permeability from dairy cows producing stable or unstable milk in the ethanol test.

Tight junctions are almost impermeable structures located near the apical border of epithelial cells; increase in the permeability of mammary gland cells' tight junctions may alter milk composition and its suitability for industrialization. Sixteen Holstein dairy cows were studied to evaluate mammary gland cells' tight junction permeability (indicated by plasma lactose levels) from cows producing stable or unstable milk to ethanol at 72 °GL concentration. Rectal temperature, respiratory rate and milk parameters were also compared and weather conditions (temperature-humidity index) monitored.

Risk of vaginal cancer among hysterectomised women with cervical intraepithelial neoplasia: a population-based national cohort study.

Objective: To study the risk of vaginal cancer among hysterectomised women with and without cervical intraepithelial neoplasia (CIN).

Design: Population-based national cohort study.

Setting And Population: All Swedish women, 5 million in total, aged 20 and up, 1987-2011 using national registries.

A sterically encumbered photoredox catalyst enables the unified synthesis of the classical lignan family of natural products.

Herein, we detail a unified synthetic approach to the classical lignan family of natural products that hinges on divergence from a common intermediate that was strategically identified from nature's biosynthetic blueprints. Efforts toward accessing the common intermediate through a convergent and modular approach resulted in the discovery of a sterically encumbered photoredox catalyst that can selectively generate carbonyl ylides from electron-rich epoxides. These can undergo concerted [3 + 2] dipolar cycloadditions to afford tetrahydrofurans, which were advanced (2-4 steps) to at least one representative natural product or natural product scaffold within all six subtypes in classical lignans.

No survival difference between robotic and open radical hysterectomy for women with early-stage cervical cancer: results from a nationwide population-based cohort study.

Purpose: The aim of the study was to compare overall survival (OS) and disease-free survival (DFS) after open and robotic radical hysterectomy for early-stage cervical cancer.

Patients And Methods: This was a nationwide population-based cohort study on all women with cervical cancer stage IA1-IB of squamous, adenocarcinoma or adenosquamous histological subtypes, from January 2011 to December 2017, for whom radical hysterectomy was performed. The Swedish Quality Register of Gynaecologic Cancer was used for identification.

One-pot synthesis of epoxides from benzyl alcohols and aldehydes.

A one-pot synthesis of epoxides from commercially available benzyl alcohols and aldehydes is described. The reaction proceeds through in situ generation of sulfonium salts from benzyl alcohols and their subsequent deprotonation for use in Corey-Chaykovsky epoxidation of aldehydes. The generality of the method is exemplified by the synthesis of 34 epoxides that were made from an array of electronically and sterically varied alcohols and aldehydes.

Redesign of a Pyrylium Photoredox Catalyst and Its Application to the Generation of Carbonyl Ylides.

We report the exploration into photoredox generation of carbonyl ylides from benzylic epoxides using newly designed 4-mesityl-2,6-diphenylpyrylium tetrafluoroborate (MDPT) and 4-mesityl-2,6-di-p-tolylpyrylium tetrafluoroborate (MD(p-tolyl)PT) catalysts. These catalysts are excited at visible wavelengths, are highly robust, and exhibit some of the highest oxidation potentials reported. Their utility was demonstrated in the mild and efficient generation of carbonyl ylides from benzylic epoxides that otherwise could not be carried out by current common photoredox catalysts.

Effect of Fee on Cervical Cancer Screening Attendance--ScreenFee, a Swedish Population-Based Randomised Trial.

Background: Attendance in the cervical cancer screening programme is one of the most important factors to lower the risk of contracting the disease. Attendance rates are often low in areas with low socioeconomic status. Charging a fee for screening might possibly decrease attendance in this population.

Relationship between physical attributes and heat stress in dairy cattle from different genetic groups.

Dairy cattle raised under harsh conditions have to adapt and prevent heat stress. The aim of this study was to evaluate physical characteristics and their association with heat tolerance in different genetic groups of dairy cattle. Thickness of the skin and coat, length and number of hairs, body measurements, as well as physiological parameters and body temperatures by infrared thermography were determined in 19 Holstein and 19 Girolando (½ and ¾ Holstein) cows.

A 6-month regimen for EPTB with intermittent treatment in the continuation phase: a study of 679 cases.

Background: No large studies have demonstrated the effectiveness of a 6-month regimen for all forms of extra-pulmonary tuberculosis (EPTB).

Methods: Retrospective, observational analysis to evaluate the effectiveness of a 6-month treatment regimen (2HRZE/4H3R3) for all patients diagnosed with EPTB in Caracas, Venezuela, from 1 January 1998 to 31 December 2000, using direct observation.

Results: Of 679 patients enrolled, 101 (14.