Broad Groups Research Articles

TBAB-catalyzed assisted C-C/C-N bond formations: An efficient approach to dihydrobenzo[b][1,8]naphthyridin derivatives via metal free Cascade annulation

An eco-friendly, metal-free approach for synthesizing dihydrobenzo[b][1,8]naphthyridine derivatives has been established. This method employs ortho-chloroquinolin-α,β-unsaturated ketones as dipolarophiles and acyclic enaminones as amphiphilic nucleophiles, enabling a formal [3 + 3] annulation reaction under phase-transfer catalysis to offed the targeted products. It boasts transition-metal-free conditions, broad functional group compatibility, and straightforward operational procedures.

Clinical and Imaging Follow-Up for High-Risk Cutaneous Melanoma: Current Evidence and Guidelines.

The most recent (eighth) edition of the American Joint Committee on Cancer (AJCC) staging system divides invasive cutaneous melanoma into two broad groups: "low-risk" (stage IA-IIA) and "high-risk" (stage IIB-IV). While surveillance imaging for high-risk melanoma patients makes intuitive sense, supporting data are limited in that they are mostly respective and used varying methods, schedules, and endpoints. As a result, there is a lack of uniformity across different dermatologic and oncologic organizations regarding recommendations for follow-up, especially regarding imaging. That said, the bulk of retrospective and prospective data support imaging follow-up for high-risk patients. Currently, it seems that either positron emission tomography (PET) or whole-body computerized tomography (CT) are reasonable options for follow-up, with brain magnetic resonance imaging (MRI) preferred for the detection of brain metastases in patients who can undergo it. The current era of effective systemic therapies (ESTs), which can improve disease-free survival (DFS) and overall survival (OS) beyond lead-time bias, has emphasized the role of imaging in detecting various patterns of EST response and treatment relapse, as well as the importance of radiologic tumor burden.

Regioselective hydroamination of unactivated olefins with diazirines as a diversifiable nitrogen source

Nitrogen-containing compounds, such as amines, hydrazines, and heterocycles, play an indispensable role in medicine, agriculture, and materials. Alkylated derivatives of these compounds, especially in sterically congested environments, remain a challenge to prepare. Here we report a versatile method for the regioselective hydroamination of readily available unactivated olefins with diazirines. Over fifty examples are reported, including the protecting group-free amination of fourteen different natural products. A broad functional group tolerance includes alcohols, ketones, aldehydes, and epoxides. The proximate products of these reactions are diaziridines, which, under mild conditions, are converted to primary amines, hydrazines, and heterocycles. Five target- and diversity-oriented syntheses of pharmaceutical compounds are shown, along with the preparation of a bis-15N diazirine validated in the late-stage isotopic labeling of an RNA splicing modulator candidate. In this work, we report using diazirine (1) as an electrophilic nitrogen source in a regioselective hydroamination reaction, and the diversification of the resulting diaziridines.

Photoinduced Vicinal Sulfamoyloximation of Alkenes: Harnessing Bifunctional Nitrosamines via a Rapid Radical Trapping Strategy.

We developed a photoinduced method for vicinal sulfamoyloximation of alkenes using N-nitrosamines as bifunctional reagents, with DABSO serving as both a sulfonyl source and a rapid aminyl radical trap. This strategy prevents radical recombination, enabling bifunctional activation under neutral conditions to generate key sulfamoyl radicals. It accommodates broad substrate scope and functional group compatibility, enabling late-stage modifications of bioactive molecules and expanding sulfonamide diversity in organic synthesis.

Suicidal ideation among non-physician hospital system staff: Prevalence and workplace correlates

BackgroundResearch suggests that healthcare workers are at greater risk for suicide than other occupations, but most published studies focus on physicians. This study examines the prevalence of suicidal ideation (SI) and associated occupational factors among a broad group of non-physician healthcare staff. MethodsAn anonymous online survey was sent to a random sample of 30 % of non-physician healthcare staff at a large urban healthcare system between September and November 2022. Weighted multivariable binary logistic regressions were conducted to determine the workplace and mental health factors associated with SI. ResultsThe 1084 respondents included nurses, administrative staff, research staff, medical assistants, nurse practitioners, physician assistants, and other roles. Of the sample, 8.8 % endorsed having SI over the prior two weeks. Results of the regression indicated that, after adjusting for demographic factors, greater odds of SI were associated with physical violence experienced from a patient or visitor (odds ratio [OR] = 2.15, 95 % confidence interval [CI] = 1.06–4.37), lower perceived leadership support (OR = 0.95, 95 % CI = 0.92–0.98), and positive screening for depression (OR = 4.66, 95 % CI = 2.45–8.86). Exploratory analysis suggests that depression may be a mediating factor between workplace stressors and SI. LimitationsLimitations include the response rate, the use of a single item to assess SI, and the cross-sectional design. ConclusionFindings suggest that workplace violence and leadership support are important occupational factors associated with SI among healthcare workers. Reducing and mitigating workplace violence, enhancing leadership support, and improving access to mental health care should be considered targets for interventions to decrease suicide risk in this population.

Selective Synthesis of Amides and α-Ketoamides via Electrochemical Decarboxylation and Dehydration.

An electrochemical and selective decarboxylation and dehydration using α-keto acids with amines is accomplished, which leads to the easy accessibility of amides and α-ketoamides, which are not only ubiquitous and valuable structure motifs found in pharmaceuticals, but also versatile building blocks in synthetic chemistry. Notably, for this efficient and green protocol, neither metal catalysts nor external oxidants are required. The process exhibits a broad scope and functional group tolerance to deliver various amides and α-ketoamides. Moreover, these two reactions have also been applied to late-stage derivatization and can be safely conducted on gram scale.

Chromium Catalyzed Asymmetric Reformatsky Reaction

AbstractThis study describes an unprecedented chromium‐catalyzed asymmetric Reformatsky reaction, enabling the synthesis of chiral β‐hydroxy carbonyl compounds from α‐chlorinated or α‐brominated esters and amides. By employing a chiral chromium/diarylamine bis(oxazoline) catalyst, we achieved relatively broad functional group tolerance. Distinct from known reports, the protocol operates under both classical and photoredox conditions, facilitated by the in situ formation of a nucleophilic chiral chromium intermediate through a radical‐polar crossover mechanism. Preliminary mechanistic insights, supported by DFT calculations, identify the nucleophilic aldehyde addition as the key stereo‐determining step. This approach not only overcomes the limitations of existing Reformatsky reactions but also provides a versatile strategy for accessing complex chiral molecules.

Chromium Catalyzed Asymmetric Reformatsky Reaction.

This study describes an unprecedented chromium-catalyzed asymmetric Reformatsky reaction, enabling the synthesis of chiral β-hydroxy carbonyl compounds from α-chlorinated or α-brominated esters and amides. By employing a chiral chromium/diarylamine bis(oxazoline) catalyst, we achieved relatively broad functional group tolerance. Distinct from known reports, the protocol operates under both classical and photoredox conditions, facilitated by the in situ formation of a nucleophilic chiral chromium intermediate through a radical-polar crossover mechanism. Preliminary mechanistic insights, supported by DFT calculations, identify the nucleophilic aldehyde addition as the key stereo-determining step. This approach not only overcomes the limitations of existing Reformatsky reactions but also provides a versatile strategy for accessing complex chiral molecules.

Digital Educational Tools for Undergraduate Nursing Education: A Review of Serious Games, Gamified Applications and Non-Gamified Virtual Reality Simulations/Tools for Nursing Students

Educational technology has advanced tremendously in recent years, with several major developments becoming available in healthcare professionals’ education, including nursing. Furthermore, the COVID-19 pandemic resulted in obligatory physical distancing, which forced an accelerated digital transformation of teaching tools. This review aimed to summarize all the available digital tools for nursing undergraduate education developed from 2019 to 2023. A robust search algorithm was implemented in the Scopus database, resulting in 1592 publications. Overall, 266 relevant studies were identified enrolling more than 22,500 undergraduate nursing students. Upon excluding multiple publications on the same digital tool, studies were categorized into three broad groups: serious games (28.0%), gamified applications (34.5%), and VR simulations and other non-gamified digital interventions (37.5%). Digital tools’ learning activity type (categories = 8), geographical distribution (countries = 34), educational subjects (themes = 12), and inclusion within a curriculum course (n = 108), were also explored. Findings indicate that digital educational tools are an emerging field identified as a potential pedagogical strategy aiming to transform nursing education. This review highlights the latest advances in the field, providing useful insights that could inspire countries and universities which have not yet incorporated digital educational tools in their nursing curriculum, to invest in their implementation.

Calcium(II)-Mediated Three-Component Selenylation of gem-Difluoroalkenes: Access to α,α-Difluoroalkyl-β-selenides.

A calcium-mediated three-component selenylation of gem-difluoroalkenes using alcohols as nucleophiles and N-(phenylseleno)phthalimide as the selenylation agent has been developed for the efficient synthesis of various α,α-difluoroalkyl-β-selenides. This selenylation reaction exhibits broad substrate and functional group tolerance, along with high levels of chemo- and regioselectivity. Additionally, the synthetic utility of the developed transformation in the late-stage functionalization of drug molecules was demonstrated.

Palladium-Catalyzed Addition of Aryl Halides to N-Sulfinylamines for the Synthesis of Sulfinamides.

Sulfinamides are versatile, synthetically useful intermediates, and final motifs. Traditional methods to synthesize sulfinamides generally require substrates with preinstalled sulfur centers. However, these precursors have limited commercial availability, and the associated synthetic routes often require harsh reaction conditions and highly reactive reagents, thus severely limiting their application. Herein, we report the synthesis of sulfinamides from aryl and alkenyl (pseudo)halides and N-sulfinylamines, enabled by palladium catalysis. The reactions use mild conditions and are achieved without the use of highly reactive preformed organometallic reagents, resulting in transformations of broad generality and high functional group tolerance. In particular, substrates featuring protic and electrophilic functional groups can be used successfully. The modification of complex aryl cores and natural product derivatives demonstrates the utility of this method.

Asymmetric Synthesis of β,β-Disubstituted Alanines via a Sequential C(sp2)-C(sp3) Cross-Coupling-Hydrogenation Strategy.

We report the development of a sequential C(sp2)-C(sp3) Suzuki cross-coupling-asymmetric hydrogenation strategy which allows access to a diverse array of valuable β,β-disubstituted alanine derivatives. This synthesis exhibits broad functional group tolerance, and permits efficient access to β-aryl-β-alkyl, and the more rarely reported β,β-dialkyl Ala derivatives with high yield and excellent enantioselectivity. This transformation has been exhibited on decagram quantity, and can be used to generate Fmoc amino acid derivatives which are useful for SPPS.

Muscular Dystrophies: An Update Review

A broad group of illnesses known as muscular dystrophies are defined by pathologic alterations found in muscle tissue following biopsy. A progressive weakening of the skeletal muscles characterises the clinical appearance of these disorders. The most common type of muscular dystrophy is Duchenne Muscular Dystrophy, an X-linked recessive disease. Distal muscular dystrophy is most common in people between the ages of 40 and 60 and primarily affects the lower limbs, such as the hands, feet, arms, and legs. The development of muscle weakness during infancy or early childhood, usually before the age of two, is a common symptom of congenital muscular dystrophy. The majority of MD types frequently result in respiratory issues that affect the diaphragm and other breathing muscles. Several MD subtypes are linked to cardiac arrhythmias or cardiomyopathy. This class of disorders is the main target of gene transfer and gene repair therapies.

Youth as Death

Since the end of apartheid, life in South Africa has been marked by an epidemic of death among the youth—people between the ages of fifteen and thirty-five. First as a result of HIV/AIDS and political violence, and more recently as a result of “these diseases,” a broad group of illnesses that affect the youth, homicide and suicide, this epidemic is in part a consequence of ongoing processes of settler colonialism and racial capitalism in South Africa. This epidemic of death can also be understood as an example of necropolitics—the failure of the postapartheid state. At the same time, as the stories in this article reveal, no one or two analytical approach(es) can fully make sense of what it means to live in a place where the youth are dying at such a high rate. Drawing inspiration from work in Black studies, and Black feminisms more specifically, and driven by the stories of those living through loss in South Africa, this article sketches what it means to live in a place where youth is defined by death.

Consistency, completeness and external validity of ethnicity recording in NHS primary care records: a cohort study in 25 million patients’ records at source using OpenSAFELY

BackgroundEthnicity is known to be an important correlate of health outcomes, particularly during the COVID-19 pandemic, where some ethnic groups were shown to be at higher risk of infection and adverse outcomes. The recording of patients’ ethnic groups in primary care can support research and efforts to achieve equity in service provision and outcomes; however, the coding of ethnicity is known to present complex challenges. We therefore set out to describe ethnicity coding in detail with a view to supporting the use of this data in a wide range of settings, as part of wider efforts to robustly describe and define methods of using administrative data.MethodsWe describe the completeness and consistency of primary care ethnicity recording in the OpenSAFELY-TPP database, containing linked primary care and hospital records in > 25 million patients in England. We also compared the ethnic breakdown in OpenSAFELY-TPP with that of the 2021 UK census.Results78.2% of patients registered in OpenSAFELY-TPP on 1 January 2022 had their ethnicity recorded in primary care records, rising to 92.5% when supplemented with hospital data. The completeness of ethnicity recording was higher for women than for men. The rate of primary care ethnicity recording ranged from 77% in the South East of England to 82.2% in the West Midlands. Ethnicity recording rates were higher in patients with chronic or other serious health conditions. For each of the five broad ethnicity groups, primary care recorded ethnicity was within 2.9 percentage points of the population rate as recorded in the 2021 Census for England as a whole. For patients with multiple ethnicity records, 98.7% of the latest recorded ethnicities matched the most frequently coded ethnicity. Patients whose latest recorded ethnicity was categorised as Other were most likely to have a discordant ethnicity recording (32.2%).ConclusionsPrimary care ethnicity data in OpenSAFELY is present for over three quarters of all patients, and combined with data from other sources can achieve a high level of completeness. The overall distribution of ethnicities across all English OpenSAFELY-TPP practices was similar to the 2021 Census, with some regional variation. This report identifies the best available codelist for use in OpenSAFELY and similar electronic health record data.

Implementing a free lending of sports and leisure equipment service: a cross-sectional survey exploring user characteristics, utilization patterns, and significance among children and youth

BackgroundThe escalating costs of sports equipment, coupled with socioeconomic disparities, hinder children’s participation in physical activities. The Leisure Equipment Library (LEL), a unique service in Sweden, addresses this challenge by providing free equipment lending. This study investigated the significance of providing free lending of sports and recreational equipment for children’s and youth’s opportunities to engage in physical activities during leisure time.MethodUtilizing a cross-sectional survey during the summer-2022 period, the study is based on data from 427 LEL users aged 7 to 25 years. User characteristics (demography, socioeconomic status, physical activity profiles), equipment usage patterns and perceived significance are also analyzed. The findings are discussed using the concept of consumer-brand identification.ResultsThe results showed that LEL reaches a broad and diverse group of children and young people in terms of gender, age, socioeconomic status, and physical activity profile. The borrowed equipment, primarily used for play and recreation, serves as an essential resource for children and youths and, in particular, for those with low socioeconomic status. LEL is considered highly important by all user groups, with a majority emphasizing its significance in facilitating leisure activities.ConclusionsThe study suggests LEL’s success lies in its accessibility and that users identify with the brand of LEL. Users perceive LEL as a service catering to various recreational needs rather than sports, fostering inclusivity. The localization of stores in various types of areas, combined with high-quality products, enable children and young people from different socioeconomic areas to use the service. LEL’s success hinges on maintaining a positive brand image and promoting a recreation-oriented identity. Opportunities exist to strengthen emotional bonds with users, enhance branding strategies, and position LEL as a valuable resource for inclusive recreational activities. In conclusion, this study highlights the potential of free lending services, such as LEL, to bridge socioeconomic gaps in the promotion of physical activity among children and young people.

Nickel‐Catalyzed Highly Selective Radical C−C Coupling from Carboxylic Acids with Photoredox Catalysis

AbstractControlling the cross‐coupling reaction between two different radicals is a long‐standing challenge due to the process occurring statistically, which would lead to three products, including two homocoupling products and one cross‐coupling product. Generally, the cross‐coupling selectivity is achieved by the persistent radical effect (PRE) that requires the presence of a persistent radical and a transient radical, thus resulting in limited radical precursors. In this paper, a highly selective cross‐coupling of alkyl radicals with acyl radicals to construct C(sp2)−C(sp3) bonds, or with alkyl radicals to construct C(sp3)−C(sp3) bonds have been achieved with the readily available carboxylic acids and their derivatives (NHPI ester) as coupling partners. The success originates from the use of tridentate ligand (2,2′ : 6′,2′′‐terpyridine) to enable radical cross‐coupling process to Ni‐mediated organometallic mechanism. This protocol offers a facile and flexible access to structurally diverse ketones (up to 90 % yield), and also a new solution for the challenging double decarboxylative C(sp3)−C(sp3) coupling. The broad utility and functional group tolerance are further illustrated by the late‐stage functionalization of natural‐occurring carboxylic acids and drugs.

Nickel-Catalyzed Highly Selective Radical C-C Coupling from Carboxylic Acids with Photoredox Catalysis.

Controlling the cross-coupling reaction between two different radicals is a long-standing challenge due to the process occurring statistically, which would lead to three products, including two homocoupling products and one cross-coupling product. Generally, the cross-coupling selectivity is achieved by the persistent radical effect (PRE) that requires the presence of a persistent radical and a transient radical, thus resulting in limited radical precursors. In this paper, a highly selective cross-coupling of alkyl radicals with acyl radicals to construct C(sp2)-C(sp3) bonds, or with alkyl radicals to construct C(sp3)-C(sp3) bonds have been achieved with the readily available carboxylic acids and their derivatives (NHPI ester) as coupling partners. The success originates from the use of tridentate ligand (2,2' : 6',2''-terpyridine) to enable radical cross-coupling process to Ni-mediated organometallic mechanism. This protocol offers a facile and flexible access to structurally diverse ketones (up to 90 % yield), and also a new solution for the challenging double decarboxylative C(sp3)-C(sp3) coupling. The broad utility and functional group tolerance are further illustrated by the late-stage functionalization of natural-occurring carboxylic acids and drugs.

Therapeutic effect of Momordica charantia on cardiomyopathy in a diabetic maternal rat model.

Myocardial structural and functional abnormalities are hallmarks of diabetic cardiomyopathy (DCM), a chronic consequence of diabetes mellitus (DM). Maternal DM affects and increases the risk of heart defects in diabetic mothers compared with nondiabetic mothers. Momordica charantia exhibits antidiabetic effects due to various bioactive compounds that are phytochemicals, a broad group that includes phenolic compounds, alkaloids, proteins, steroids, inorganic compounds, and lipids. Pregnant maternal rats were split into four groups: control (C), M. charantia-treated (MC), type 2 diabetes mellitus (T2DM) (DM), and diabetic (MC + DM) groups. Diabetes mothers had increased serum glucose, insulin, total cholesterol, triglyceride, and low-density lipoprotein cholesterollevels and reduced high-density lipoprotein cholesterollevels. Cardiac biomarkers such as cardiac troponin T (cTnT), creatine kinase-myocardial band (CK-MB), and lactate dehydrogenasewere increased. Hormone levels of follicle-stimulating hormone, luteinizing hormone, progesterone, and estrogen decreased significantly. Inflammatory markers such as interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and vascular adhesion molecule-1 (VCAM-1) were elevated in diabetic mothers. Oxidative stress markers indicated increased malondialdehydeand nitric oxidelevels, while antioxidants such as glutathione, superoxide dismutase, and catalasewere decreased in maternal heart tissue. The levels of apoptotic markers such as tumor suppressor 53 (P53) and cysteine aspartic protease-3 (caspase-3) were significantly greater in diabetic maternal heart tissue. Histopathological analysis revealed heart tissue abnormalities in diabetic maternal rats. M. charantia extract improved maternal diabetes-induced changes in inflammation, antioxidant levels, and heart tissue structure.

Clinicopathological Study of Fibroepithelial Lesions of the Breast in a Tertiary Care Hospital in South India.

Introduction Fibroepithelial lesions of the breast mainly include fibroadenoma and phyllodes tumors with overlapping morphological features and varied clinical behavior. This study aims to determine the histopathological spectrum of fibroepithelial lesions of the breast in a tertiary care hospital. Methods This is a cross-sectional study that was carried out in the pathology department from 1stJanuary 2015 to 31stDecember 2023. Relevant data of all fibroepithelial lesions reported during the study period were retrieved from the medical records, tabulated, and analyzed. The Pearson chi-square test was used to determine the significant association between the various clinicopathological parameters of fibroepithelial lesions. A p-value of less than 0.05 was taken as statistically significant. Results Out of a total of 195 fibroepithelial lesions, 185 (95%) were fibroadenoma, 07 (3.5%) were phyllodes tumors, and three (1.5%) were fibroadenoma with tubular adenoma. The most common age group was 21 to 40 years, with the majority of phyllodes tumors being more than 5 cm in size compared to fibroadenomas. The association between the clinicopathological characteristics such as age of patients, tumor size, and histological grade was statistically insignificant in this study. Conclusions The implementation and usage of morphological diagnostic criteria will help in diagnosing and categorizing this broad group of fibroepithelial lesions, thereby facilitating appropriate treatment forpatients.