General Profile Research Articles

Foundational Competencies and Responsibilities of a Research Software Engineer

The term Research Software Engineer, or RSE, emerged a little over 10 years ago as a way to represent individuals working in the research community but focusing on software development. The term has been widely adopted and there are a number of high-level definitions of what an RSE is. However, the roles of RSEs vary depending on the institutional context they work in. At one end of the spectrum, RSE roles may look similar to a traditional research role. At the other extreme, they resemble that of a software engineer in industry. Most RSE roles inhabit the space between these two extremes. Therefore, providing a straightforward, comprehensive definition of what an RSE does and what experience, skills and competencies are required to become one is challenging. In this community paper we define the broad notion of what an RSE is, explore the different types of work they undertake, and define a list of foundational competencies as well as values that outline the general profile of an RSE. Further research and training can build upon this foundation of skills and focus on various aspects in greater detail. We expect that graduates and practitioners will have a larger and more diverse set of skills than outlined here. On this basis, we elaborate on the progression of these skills along different dimensions. We look at specific types of RSE roles, propose recommendations for organisations, give examples of future specialisations, and detail how existing curricula fit into this framework.

Opioid antagonists: clinical utility, pharmacology, safety, and tolerability.

Opioid antagonists block opioid receptors, a mechanism associated with utility in several therapeutic indications. Here, we review the sites of action, clinical uses, pharmacology, and general safety profiles of US Food and Drug Administration (FDA)-approved opioid antagonists. A review of the literature and product labels of opioid antagonists was conducted. The unique clinical uses of approved opioid antagonists are related to their ability to block opioid receptors centrally and/or peripherally. Centrally acting opioid antagonists treat opioid and alcohol use disorders (AUDs) and reverse opioid overdose. Because the opioid system influences weight and metabolism, one opioid antagonist combination product is approved for chronic weight management; another, approved for adults with schizophrenia or bipolar I disorder, mitigates olanzapine-associated weight gain. Peripherally acting opioid antagonists are approved for opioid-induced constipation; another accelerates gastrointestinal recovery after bowel surgery. Opioid antagonists are generally well tolerated; they are not associated with physiologic dependence or abuse. However, opioid antagonists can precipitate acute opioid withdrawal in patients using or undergoing withdrawal from opioid agonists. Likewise, their use can confer a risk for opioid overdose if attempts are made to overcome opioid antagonist blockade of opioid receptors via the intake of additional opioids. Opioid receptor antagonists have diverse therapeutic benefits based on their respective pharmacology and sites of action; understanding their respective nuances facilitates the safe and effective use of these agents.

Anorexia Nervosa in Comorbidity With Borderline Personality Disorder in Adolescence: A Specific Clinical Endophenotype?

Anorexia nervosa and borderline personality disorder are often associated and share some core elements, including emotional dysregulation and affective instability. Nevertheless, the association of these two conditions in adolescence is still little studied. The present study aims at investigating, through a multidimensional assessment, the psychopathological characteristics of adolescents affected by anorexia nervosa in comorbidity with borderline personality disorder on a sample of 127 female adolescents, through the comparison with adolescents with borderline personality disorders and adolescents with anorexia nervosa. All participants completed a validated psychometric battery assessing alexithymia (Toronto Alexithymia Scale-20), depression (Children's Depression Inventory), psychological symptoms (Symptom Checklist-90-Revised) and psychological symptoms relevant in eating disorders (Eating Disorders Inventory-3). Adolescents with anorexia nervosa in comorbidity with borderline personality disorder show intermediate features between the two disorders individually in the general psychopathological profile, but a peculiar psychological profile regarding the eating symptomatology, with worse features compared to adolescents with the sole anorexia nervosa. Results suggest a peculiar clinical and psychopatological endophenotype in adolescents with anorexia nervosa in comorbidity with borderline personality disorders, indicating the need to define specific and tailored treatment for this population.

CORRELATION OF OXIDATIVE STRESS MARKERS IN MULTIPLE BIOFLUIDS OF END-STAGE RENAL DISEASE PATIENTS

A study established that patients with ESRD have high oxidative stress levels that spike the progression of the disease and its complications. Knowledge about the levels of the Oxidative stress biomarkers in various biofluids including Urine, serum, and saliva can explain the oxidative condition and probable diagnostic accuracy of these markers in ESRD patients. A descriptive cross-sectional exploratory research design was used to perform a comparison of 50 ESRD patients with 50 healthy subjects. On demographic, clinical, and hematological parameters data were obtained. Blood MDA, 8-OHdG, and saliva TAC were determined as the indicators of oxidative stress. Multivariate analysis was conducted to compare the levels of these markers in the biofluids and probable neurological disorders, and the participants’ demographic and clinical data were evaluated. Demographic profiling revealed that ESRD patients’ mean BMI was 26.3 ± 3.9 kg/m², compared to controls 24.8 ± 3.4 km/m², p = 0.032; more of them being smokers’ p = 0.045. ESRD patient’s general hematologic profile showed that their mean hemoglobin level was 10.2 ± 1.5 g/dL and the mean hematocrit was 32.5 ± 4.3 % and the difference was significant when compared with the control group (p<0.05). ESRD was associated with an increase in WMBC, percentage of neutrophils, and CRP level compared with the control group (p<0.05). Acute phase marker study indicates that the MDA level was significantly higher in serum (5.6 ± 1.1 nmol/L) than in urine (3.2 ± 0.8 nmol/L) and saliva (2.8 ± 0.7 nmol/L, p=0.016). The levels of 8-OHdG were significantly higher in serum (10.3 ± 2.1 ng/mL) than in urine and saliva (p=0.027). Salivary TAC was the least suggesting reduced antioxidant defense (p<0.05). The study revealed that ESRD patients have increased levels in the markers of oxidative stress in urine and serum samples, as well as saliva compared to healthy individuals. The studies have identified serum as the most representative biofluid for evaluating oxidative stress in ESRD and therefore assured the practical application of the results for the identification of the best candidates for early interventions.

Long-Term Risk of Autoimmune and Autoinflammatory Connective Tissue Disorders Following COVID-19

Few studies have investigated the association between COVID-19 and autoimmune and autoinflammatory connective tissue disorders; however, research with long-term observation remains insufficient. To investigate the long-term risk of autoimmune and autoinflammatory diseases after COVID-19 over an extended observation period. This retrospective nationwide population-based study investigated the Korea Disease Control and Prevention Agency-COVID-19-National Health Insurance Service (K-COV-N) cohort. Individuals with confirmed COVID-19 from October 8, 2020, to December 31, 2022, and controls identified among individuals who participated in the general health examination in 2018 were included in the analysis. Confirmed COVID-19. Incidence and risk of autoimmune and autoinflammatory connective tissue disorders in patients after COVID-19. Various covariates, such as demographic characteristics, general health data, socioeconomic status, and comorbidity profiles, were balanced using inverse probability weighting. A total of 6 912 427 participants (53.6% male; mean [SD] age, 53.39 [20.13] years) consisting of 3 145 388 with COVID-19 and 3 767 039 controls with an observational period of more than 180 days were included. Alopecia areata (adjusted hazard ratio [AHR], 1.11 [95% CI, 1.07-1.15]), alopecia totalis (AHR, 1.24 [95% CI, 1.09-1.42]), vitiligo (AHR, 1.11 [95% CI, 1.04-1.19]), Behçet disease (AHR, 1.45 [95% CI, 1.20-1.74]), Crohn disease (AHR, 1.35 [95% CI, 1.14-1.60]), ulcerative colitis (AHR, 1.15 [95% CI, 1.04-1.28]), rheumatoid arthritis (AHR, 1.09 [95% CI, 1.06-1.12]), systemic lupus erythematosus (AHR, 1.14 [95% CI, 1.01-1.28]), Sjögren syndrome (AHR, 1.13 [95% CI, 1.03-1.25]), ankylosing spondylitis (AHR, 1.11 [95% CI, 1.02-1.20]), and bullous pemphigoid (AHR, 1.62 [95% CI, 1.07-2.45]) were associated with higher risk in the COVID-19 group. Subgroup analyses revealed that demographic factors, including male and female sex, age younger than 40 years, and age 40 years and older, exhibited diverse associations with the risk of autoimmune and autoinflammatory outcomes. In addition, severe COVID-19 infection requiring intensive care unit admission, the Delta period, and not being vaccinated were associated with higher risk. This retrospective cohort study with an extended follow-up period found associations between COVID-19 and the long-term risk of various autoimmune and autoinflammatory connective tissue disorders. Long-term monitoring and care of patients is crucial after COVID-19, considering demographic factors, disease severity, and vaccination status, to mitigate these risks.

Smartphone addiction, depression, distress, eustress, loneliness, and sleep deprivation in adolescents: a latent profile and network analysis approach

BackgroundPrevious research on adolescent smartphone addiction has tended to focus on general populations that are assumed to be homogeneous, overlooking latent profiles. Furthermore, previous research has not focused on potentially important differences in the latent profiles of adolescent smartphone addiction in networks. The present study aimed to reveal the latent profiles of smartphone addiction, depression, stress, eustress, loneliness, and sleep deprivation in adolescents, and general and latent profiles were examined in the network.MethodsThe study group consisted of 436 (222 boys and 214 girls) adolescents, aged between 13 and 18 years. The findings of the present study were provided using Pearson correlation, ANOVA, latent profile analysis and network analysis. The data were analyzed using SPSS, JASP, and Mplus.ResultsThe results of the study showed solutions with three latent profiles. The non-addicted group constituted 20.87%, the addicted group covered 29.82% and the risky group included 49.31% of the study group. Although the general profile and the addicted latent group had similar characteristics, the differences in the risky and non-addicted groups contributed to the current literature by providing a further and remarkable perspective on smartphone addiction, depression, distress, eustress, loneliness, and sleep deprivation in adolescents.ConclusionsThe theoretical and practical implications of the present results will provide contributions to researchers and practitioners in understanding smartphone addiction.

Terminology of medicines used to control seizure disorders: 2024 ILAE Recommendations and profile of real-world term use

Background. The International League Against Epilepsy (ILAE) has provided recommendations on the terminology of medicines for control of seizure disorders, which should be adapted into different languages.Objective: to evaluate the usage profile of terms describing the effects of medicines used in patients with epilepsy.Material and methods. The search query analysis systems Google Trends and Yandex Wordstat as well as PubMed/MEDLINE, Google Scholar and eLibrary databases were used to evaluate the general public and professional usage profile, respectively.The following terms in Russian and English were studied: “antiepileptic”, “antiepileptic drug”, “antiseizure”, “antiseizure drug”. In order to ascertain a prevailing opinion within professional and patient communities, a questionnaire survey was conducted on the public online resources of the non-profit partnership “The Association of Epileptologists and Patients” carried out via the cloud-based cross-platform social media as well as instant messaging service Telegram and the social media platform VK.Results. In the English-speaking internet segment, the term “antiepileptic” is used more than 5 times frequently than “antiseizure” by the general public. Conversely, in the Russian-language segment, the term “antiseizure” is almost 2.5 times more common. The term “antiepileptic” is more prevalent in scientific community in both segments. This finding aligns with the profile of terminology usage observed among epileptologists and epilepsy patients. The questionnaire survey results revealed that 56.42% of 179 respondents were in favor of the terms “antiepileptic drug”, “AED” and “antiepileptic therapy”, whereas as few as 17.32% of those endorsed the ILAE-proposed terminology.Conclusion. In light of the established practice of terminology use in both professional scientific community and among practicing epileptologists and epileptic patients, as well as the differences in the semantics of English- and Russian-language terms and the identified lack of precision in the ILAE definition of epilepsy, it can be concluded that for the Russian-speaking population, the terms “antiepileptic drug”, “AED” are more preferable rather than the terms “antiseizure medication”, “ASM”. Additionally, it is preferable to use the terms “convulsive ictus” and “epileptic ictus” due to negative connotation with term “seizure” in Russian. The terms “antiseizure” and “antiepileptic” should not be regarded as mutually exclusive in the context of treatment that has a direct impact on epilepsy course. Finally, it is necessary to further refine epilepsy definition and classification.

The last-success stopping problem with random observation times

AbstractSuppose N independent Bernoulli trials with success probabilities $$p_1, p_2,\ldots $$ p 1 , p 2 , … are observed sequentially at times of a mixed binomial process. The task is to maximise, by using a nonanticipating stopping strategy, the probability of stopping at the last success. The case $$p_k=1/k$$ p k = 1 / k has been studied by many authors as a version of the familiar best choice problem, where both N and the observation times are random. We consider a more general profile $$p_k=\theta /(\theta +k-1)$$ p k = θ / ( θ + k - 1 ) and assume that the prior distribution of N is negative binomial with shape parameter $$\nu $$ ν , so the arrivals occur at times of a mixed Poisson process. The setting with two parameters offers a high flexibility in understanding the nature of the optimal strategy, which we show is intrinsically related to monotonicity properties of the Gaussian hypergeometric function. Using this connection, we find that the myopic stopping strategy is optimal if and only if $$\nu \ge \theta $$ ν ≥ θ . Furthermore, we derive formulas to assess the winning probability and discuss limit forms of the problem for large N.

Complex therapy of mineral metabolism in service dogs

The high physical and functional load of service dogs causes changes not only in body systems, but also in metabolism as a whole. An integrated approach to the study of this problem and the search for a pharmacotherapeutic solution will allow us to correct biochemical changes in the body of dogs and improve the performance and quality of life of animals. The purpose of the study was to study the therapeutic effectiveness of a complex of metabolic stimulants for the correction of mineral metabolism. For the study, 16 service dogs were selected in the area of application of the general search profile, belonging to the Ministry of Internal Affairs of Russia in the Altai Territory. Blood was drawn at the beginning and end of the study to analyze red blood cell counts, hemoglobin, hematocrit, glucose, cholesterol, triglycerides, iron, magnesium, zinc, calcium, phosphorus, and chloride. According to the results of the study, it was established that a violation of homeostasis in service dogs was accompanied by changes in some indicators of red blood, as well as pathology of mineral metabolism. After a course of pharmacotherapy, an increase in red blood cells (up to 7.9±0.22*×1012 cells/l) and hemoglobin (up to 141.66±7.32 g/l) was observed in dogs. Carbohydrate metabolism in both groups was characterized by hypoglycemia (3.34±0.21–3.43±0.28 mmol/l). By the end of the study, the glucose level in the experimental group significantly increased by 31.4% relative to the animals in the control group. By the end of the study, cholesterol levels in dogs in the experimental group decreased more rapidly compared to the control group. The study of the dynamics of mineral metabolism indicators revealed a significant increase in iron levels in the experimental group of animals (up to 25.3±1.9 µmol/l), which was 22.8% higher than the control value. Changes in other indicators of mineral metabolism did not differ significantly between the groups, although dogs receiving stimulating therapy showed positive dynamics of changes in mineral metabolism indicators. The use of a complex of metabolic stimulants “Suiferrovita”, “Strolitin”, “Amber Acid” stabilized red blood counts and contributed to the development of a tendency towards the restoration of mineral metabolism.

Role of chirping in pulsed single-photon spectroscopy

We investigate the precision of estimating the interaction strength between a two-level system (TLS) and a single-photon pulse when the latter is subject to chirping. We consider linear, quadratic, and sinusoidal temporal phases applied to Gaussian and exponential temporal profiles. At the asymptotic time, when the TLS has fully decayed to its ground state, the fundamental precision depends solely on the magnitude of its spectral amplitude. For quadratically phase-modulated Gaussian pulses, this is entirely determined by the spectral bandwidth. We provide expressions for evaluating the fundamental precision for general temporal profiles and phase modulations. Finally, we show that experimentally feasible mode-resolved measurements are optimal, or close to it, for chirped, pulsed single-photon spectroscopy. Published by the American Physical Society 2024

The general glycan profiling of Dendrobium officinale and their protective effects on MIN6 cells via ERK signaling pathway

Based on structural elucidation of natural and hydrolyzed glycans, the general glycans profiling of D. officinale were unequivocally established for the first time as follows: [Display omitted] The results indicated that the structure of D. officinale glycans with low degree of polymerization (DP ≤ 22) was linear α-D-1,4-glucan, whereas the structure of glycans with high degree of polymerization (DP > 24) was linear acetylated 1,4-glucomannan. The content of acetyl groups and mannose to glucose (M/G) ratio increased with the degree of polymerization of D. officinale glycans. In addition, this study showed that natural D. officinale glycans protected pancreatic β-cell damage induced by glucotoxicity through the extracellular signal–regulated kinase (ERK)1/2 pathway.

Identifying Culturally Relevant School Support Profiles and Links to Academic Functioning in Adolescents.

There is limited knowledge about patterns of adolescents' experiences of general teacher support and support for critical consciousness and cultural competence development in school settings, which are key experiences proposed to promote academic functioning. Furthermore, less is known about potential developmental and ethnic-racial differences in these patterns. Using a person-centered approach, this study examined culturally relevant school support profiles in a sample of sixth and ninth grade students (N = 717; 49.9% girls) from the U.S. Southwest. Participants were aged 10 to 18 years (M = 13.73; SD = 1.54) and were ethnoracially diverse (31.8% Hispanic/Latinx, 31.5% Multiethnic, 25.7% White, 7.3% Black or African American, 1.4% Asian American or Pacific Islander, 1.4% American Indian or Alaska Native, and 1% Arab, Middle Eastern, or North African). Four culturally relevant school support profiles were identified: (1) low general, devoid cultural & critical support; (2) moderate general, moderate cultural, & devoid critical support; (3) high general, moderate cultural & critical support; and (4) high general, cultural, & critical support. Youth in the high general, cultural, & critical support profile had higher concurrent emotional and behavioral engagement. No significant differences were found between early (6th grade) and middle adolescent (9th grade) youth, pointing to the relevance and associations of the identified profiles across development. One significant difference emerged when comparing White and ethnoracially minoritized youth; among White youth, those in the high general, cultural, & critical support and high general, moderate cultural & critical support profiles had higher academic expectations than those in the low general, devoid cultural & critical support profile. The discussion focuses on characterizing heterogeneous and culturally relevant school support profiles, the associations between these profiles and indicators of academic functioning for ethnoracially diverse youth to advance developmental theory and the importance of promoting culturally relevant school support practices to foster developmental competencies among youth.

The operationally ready full 3D magnetohydrodynamic model from the Sun to Earth: COCONUT+Icarus

Context. Solar wind modelling has become a crucial area of study due to the increased dependence of modern society on technology, navigation, and power systems. Accurate space weather forecasts can predict upcoming threats to Earth’s geospace and allow for harmful socioeconomic impacts to be mitigated. Coronal and heliospheric models must be as realistic as possible to achieve successful predictions. In this study, we examine a novel full magnetohydrodynamic (MHD) chain from the Sun to Earth. Aims. The goal of this study is to demonstrate the capabilities of the full MHD modelling chain from the Sun to Earth by finalising the implementation of the full MHD coronal model into the COolfluid COroNa UnsTructured (COCONUT) model and coupling it to the MHD heliospheric model Icarus. The resulting coronal model has significant advantages compared to the pre-existing polytropic alternative, as it includes more physics and allows for a more realistic modelling of bi-modal wind, which is crucial for heliospheric studies. In particular, we examine different empirical formulations for the heating terms in the MHD equations to determine an optimal one that would be able to mimic a realistic solar wind configuration most accurately. Methods. New heating source terms were implemented into the MHD equations of the pre-existing polytropic COCONUT model. A realistic specific heat ratio was applied. In this study, only thermal conduction, radiative losses, and approximated coronal heating function were considered in the energy equation. Multiple approximated heating profiles were examined to see the effect on the solar wind. The output of the coronal model was used to onset the 3D MHD heliospheric model Icarus. A minimum solar activity case was chosen as the first test case for the full MHD model. The numerically simulated data in the corona and the heliosphere were compared to observational products. First, we compared the density data to the available tomography data near the Sun and then the modelled solar wind time series in Icarus was compared to OMNI 1-min data at 1 AU. Results. A range of approximated heating profiles were used in the full MHD coronal model to obtain a realistic solar wind configuration. The bi-modal solar wind was obtained for the corona when introducing heating that is dependent upon the magnetic field. The modelled density profiles are in agreement with the tomography data. The modelled wind in the heliosphere is in reasonable agreement with observations. Overall, the density is overestimated, whereas the speed at 1 AU is more similar to OMNI 1-min data. The general profile of the magnetic field components is modelled well, but its magnitude is underestimated. Conclusions. We present a first attempt to obtain the full MHD chain from the Sun to Earth with COCONUT and Icarus. The coronal model has been upgraded to a full MHD model for a realistic bi-modal solar wind configuration. The approximated heating functions have modelled the wind reasonably well, but simple approximations are not enough to obtain a realistic density-speed balance or realistic features in the low corona and farther, near the outer boundary. The full MHD model was computed in 1.06 h on 180 cores of the Genius cluster of the Vlaams Supercomputing Center, which is only 1.8 times longer than the polytropic simulation. The extended model gives the opportunity to experiment with different heating formulations and improves the approximated function to model the real solar wind more accurately.

Monitoring of plant diseases caused by Fusarium commune and Rhizoctonia solani in bok choy using hyperspectral remote sensing and machine learning.

Local vegetable production is susceptible to various fungal pathogens, the most common and lethal of which are Fusarium commune and Rhizoctonia solani. Early detection of these pathogens is challenging, and by the time visual symptoms appear, the pathogens may have already spread extensively, causing massive damage to the production. In this study, we explored the use of hyperspectral data for early detection of diseases caused by F. commune or R. solani in bok choy Brassica rapa subsp. chinensis by collecting hyperspectral data from healthy plants and plants inoculated with either fungal pathogen in a controlled experimental set-up. Based on the collected data, we employed various tree-based, distribution-based, geometric, neural networks and ensemble learning algorithms to train detection models. Among the trained models, Multi-Layer Perceptron (MLP) models performed the best with overall accuracy reaching 95.9 ± 0.26%. MLP models could differentiate between healthy and infected plants with 99% precision after 1 day of infection, and distinguish between different fungal pathogens with 99% precision after 2 days. During this period, no visible symptoms of fungal infection could be observed. Further analysis into trained MLP models and general reflectance profiles of plants also revealed a high correlation of the spectral regions 445-460, 560-595, 606-620 and 719-728 nm with fungal infection in bok choy plants. Our findings highlight the potential of hyperspectral imaging as a highly precise early detection tool for fungal diseases in plants. © 2024 Society of Chemical Industry.

Study of Dependence of the Energy of the Field in Weakly Conductive Fiberlight-Guide with Gradient Refractive Index Profile Without Regard to Polarization

A round-in-cross-section weakly guiding fiber optic light guide is considered. The system of Maxwellian equations for electrically conductive transparent media without due regard to polarization with an index of refraction in the case under consideration is reduced to the homogeneous Helmholtz equation, a particular solution of which is found using the Green's function. For a unimodalmode a common decision was obtained for the field and energy inside the fiber in the general case of a gradient refractive index profile depending on the radial coordinate. The concept of normalized energy is introduced as the ratio of the energy inside a fiber with gradient refractive index profile to the energy inside a fiber with a step-index profile. Since in a single-mode regime the zero-order Bessel function, which describes the field inside a step-index profile fiber, can be replaced by a Gaussoid, then, when extending this replacement to the case of a single-mode gradient fiber, as a first approximation we shall obtain a finite expression for the normalized energy for a general gradient profile. The dependences of the normalized energy on the waveguide number were obtained for each of the degrees from the first to the fourth inclusive. It is shown that in the considered approximation, the energy increases up to a certain parameter values (for the first degree – a triangle profile) or slowly decreases (other profiles), after this value the energy increases for all profiles. The results obtained will help to select a suitable single-mode fiber for practical application.

Akademik Liyakat: VOSviewer ile Bibliyometrik Bir Haritalama Analizi ve İçerik Analizi (WOS Örneği)

This study was conducted to create a general profile of academic studies on academic merit. For this purpose, bibliometric data of different types of studies published between the years 1983 and 2024 scanned in the Web of Science (WOS) database were used. The data set was created by searching with the keyword “academic merit”, which is the English translation of the concept of “academic merit”, in the “full record” by determining the search criteria “topic”. In the findings obtained,, 112 scientific studies that met this criterion were analyzed according to the year of publication, index, number of citations, WOS categories, publication language, and most influential author collaborations and keywords. According to the findings, it is seen that most of the studies were written in 2016-2018, most of the studies are journals indexed in the Social Sciences Citation Index (SSCI), and the highest number of citations belongs to Krefting (2003) with 117 citations, according to the WOS category, most of the studies were conducted in the field of educational research. Most of the publications were made in the English language. However, in VOSviewer software, it was found that “academic merit”, “university”, and “research” were the most frequently used common keywords, the authors with the highest number of collaborations were five authors with a link strength of 8 with 17 citations for 2 studies, and the most influential countries were “USA”, “Canada” and “Austria”. Keywords: Merit, Academic Merit, Bibliometric Analysis JEL Codes: M10, M12, M14

Molecular Susceptibility and Treatment Challenges in Melanoma.

Melanoma is the most aggressive subtype of cancer, with a higher propensity to spread compared to most solid tumors. The application of OMICS approaches has revolutionized the field of melanoma research by providing comprehensive insights into the molecular alterations and biological processes underlying melanoma development and progression. This review aims to offer an overview of melanoma biology, covering its transition from primary to malignant melanoma, as well as the key genes and pathways involved in the initiation and progression of this disease. Utilizing online databases, we extensively explored the general expression profile of genes, identified the most frequently altered genes and gene mutations, and examined genetic alterations responsible for drug resistance. Additionally, we studied the mechanisms responsible for immune checkpoint inhibitor resistance in melanoma.

Discovery of a Potent and Orally Bioavailable Xanthine Oxidase/Urate Transporter 1 Dual Inhibitor as a Potential Treatment for Hyperuricemia and Gout.

The main uric acid-lowering agents in clinical use for hyperuricemia and gout are xanthine oxidase (XO) inhibitors or urate transporter 1 (URAT1) inhibitors. While these therapies can partially control the disease, they have various limitations. The development of XO/URAT1 dual inhibitors offers the potential to enhance therapeutic potency and reduce toxicity compared with single-target inhibitors. Through scaffold hopping from the XO inhibitor febuxostat (2) and the URAT1 inhibitor probenecid (3), followed by structure-activity relationship (SAR) studies, we identified compound 27 as a potent dual inhibitor of XO and URAT1. Compound 27 demonstrated significant dual inhibition in vitro (XO IC50 = 35 nM; URAT1 IC50 = 31 nM) and exhibited favorable pharmacology and pharmacokinetic (PK) profiles in multiple species including monkeys. Furthermore, toxicity studies in rats and monkeys revealed general safety profiles, supporting that compound 27 emerges as a promising novel drug candidate with potent XO/URAT1 dual inhibition for the treatment of gout.

Differences in HDL Remodeling during Healthy Pregnancy and Pregnancy with Cardiometabolic Complications.

This study investigated the longitudinal trajectory of changes in antioxidative and anti-inflammatory high-density lipoprotein (HDL) components during healthy pregnancy and pregnancy with cardiometabolic complications. We recruited and longitudinally followed 84 women with healthy pregnancies and 46 pregnant women who developed cardiometabolic pregnancy complications (gestational diabetes mellitus and hypertensive disorders of pregnancy). Their general lipid profiles, oxidative stress status, inflammatory status, and antioxidative and anti-inflammatory HDL components were analyzed. The results of our study confirmed the expected trajectory for the routine lipid parameters. Our study results indicate more intensive oxidative stress and a higher level of inflammation in the group with complications compared with the control group. Sphingosine-1-phosphate (S1P) was significantly lower in the first trimester in the group with complications compared with the control group (p < 0.05). We did not find significant differences in the apolipoprotein A1 (Apo A1) concentrations in the first trimester between the control group and the group with complications, but in the second and third trimesters, the group with complications had significantly higher concentrations (p < 0.001, p < 0.05, respectively). The S1P, paraoxonase 1 (PON1), and serum amyloid A (SAA) concentrations were significantly lower in the group with complications in the first trimester. During the second trimester, only the SAA concentrations were identified as significantly lower in the group with complications compared with the control group, while in the third trimester, the PON1, apolipoprotein M (Apo M), and SAA concentrations were all significantly lower in the group with complications. Through a multivariate binary logistic regression analysis, the S1P concentration in the first trimester was distinguished as an HDL-associated marker independently associated with cardiometabolic pregnancy complications. In conclusion, our study results showed that HDL remodeling differs between healthy pregnancies and pregnancies with maternal cardiometabolic complications, with changed HDL composition and functionality consequently impacting its biological functionality in the latter case.

Predictors of cognitive aging profiles over 15 years: A longitudinal population-based study.

The present study aimed to characterize profiles of cognitive aging and how these can be predicted from interindividual differences in demographic, lifestyle, health, and genetic factors. The participants were 1,966 older adults (mean baseline age = 71.6 years; 62.9% female), free from dementia at baseline and with at least two cognitive assessments over the 15-year follow-up, from the population-based Swedish National Study on Aging and Care in Kungsholmen. The cognitive assessment comprised tests of semantic and episodic memory, letter and category fluency, perceptual speed, and executive function. First, we estimated the level and change within each of the cognitive domains with linear mixed effect models, based on which we grouped our sample into participants with "maintained high cognition," "moderate cognitive decline," or "accelerated cognitive decline." Second, we analyzed determinants of group membership within each cognitive domain with multinomial logistic regression. Third, group memberships within each cognitive domain were used to derive general cognitive aging profiles with latent class analysis. Fourth, the determinants of these profile memberships were analyzed with multinomial logistic regression. Follow-up analyses targeted profiles and predictors specifically related to the rate of cognitive change. We identified three latent profiles of overall cognitive performance during the follow-up period with 31.6% of the sample having maintained high cognition, 50.6% having moderate cognitive decline, and 17.8% having accelerated cognitive decline. In multiadjusted analyses, maintained high cognition was predicted by female sex, higher education, and faster walking speed. Smoking, loneliness, and being an ε4 carrier were associated with a lower likelihood of maintained high cognition. Higher age, diagnosis of diabetes, depression, and carrying the apolipoprotein E ε4 allele increased the likelihood of accelerated cognitive decline. Factors at baseline that could significantly predict profile membership within the specific cognitive domains included age, sex, years of education, walking speed, diabetes, and the ε4 allele. Of note, these factors differed across cognitive domains. In sum, we identified demographic, lifestyle, health, and genetic factors of interindividual differences in domain-specific and general cognitive aging profiles, some of which are modifiable. (PsycInfo Database Record (c) 2024 APA, all rights reserved).