Rare variants in the melanocortin 4 receptor gene (MC4R) are associated with abdominal fat and insulin resistance in youth with obesity.

Background: Rare variants in melanocortin 4 receptor gene (MC4R) result in a severe form of early-onset obesity; however, it is unclear how these variants may affect abdominal fat distribution, intrahepatic fat accumulation, and related metabolic sequelae.

Methods: Eight hundred seventy-seven youth (6-21 years) with overweight/obesity, recruited from the Yale Pediatric Obesity Clinic in New Haven, CT, underwent genetic analysis to screen for functionally damaging, rare variants (MAF < 0.01) in MC4R.

Daily glucose variability is associated with intrahepatic fat content, β cell sensitivity, and biomarkers of glycolysis in youth with obesity.

Objective: Pediatric obesity is associated with insulin resistance, which, in turn, impacts glucose and lipid metabolism. This study sought to assess how glucose variability relates to intrahepatic fat content, β cell insulin sensitivity, and glycolysis in youth with obesity.

Methods: A total of 27 youth with obesity (11 girls, BMI percentile, median [25th-75th percentiles]: 99.

Continuous Glucose Monitoring among Infants Born Very Preterm: Evidence for Accuracy in Neonatal Intensive Care.

Objective: To evaluate the accuracy of a device for continuous glucose monitoring (CGM) among infants born preterm admitted to the neonatal intensive care unit.

Study Design: We analyzed paired CGM sensor glucose (SG) and point-of-care blood glucose (BG) measurements collected in infants born at ≤32 weeks of gestation or with a birth weight ≤1500 g. CGM was initiated within 48 hours from birth and maintained for 5 days.

Adipose tissue insulin resistance in children and adolescents: linking glucose and free fatty acid metabolism to hepatic injury markers.

Obesity is one of the leading causes of the development of insulin resistance, diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD) in children. With the progression of insulin resistance, both glucose and free fatty acid (FFA) plasma levels are elevated, leading to cardiometabolic complications such as impaired glucose tolerance (IGT), type 2 diabetes, and liver fat accumulation. In this study, oral minimal models were used to estimate insulin sensitivity indexes (SI and SI) in 375 adolescents with obesity.

Morbidity burden of imported chronic schistosomiasis among West African migrants.

Background: Past exposure to schistosomiasis is frequent among migrants from endemic countries, and chronic untreated infection may lead to long-term morbidities.

Methods: We carried out a prospective population-based cross-sectional study among migrants from endemic Sub-Saharan countries living in Barcelona, Spain. Participants had not been previously diagnosed or treated for schistosomiasis.

Modeling Glucose, Insulin, C-Peptide, and Lactate Interplay in Adolescents During an Oral Glucose Tolerance Test.

Background: Lactate is not considered just a "waste product" of anaerobic glycolysis anymore. It has been proved to play a key role in several metabolic diseases, such as in the metabolic dysfunction-associated steatotic liver disease, obesity, and diabetes. The capability of simulating glucose-insulin-lactate interaction would be useful to design and test drugs targeting lactate metabolism in such pathological conditions.

Modelling and assessment of glucose-lactate kinetics in youth with overweight, obesity and metabolic dysfunction-associated steatotic liver disease: A pilot study.

Aim: In this study, we investigated glucose and lactate kinetics during a 75 g oral glucose tolerance test (OGTT) in 23 overweight and obese adolescents and assessed putative differences among participants with and without metabolic dysfunction-associated steatotic liver disease (MASLD).

Methods: We enrolled 23 young people (six girls) with obesity [body mass index 33 (29-37)]. Glucose-lactate kinetics parameters (disposal glucose insulin sensitivity, SI; fraction of glucose converted into lactate, fr; fractional lactate clearance rate, k) and lactate production rate (LPR) were estimated using the oral glucose-lactate minimal model.

Smart Algorithms for Efficient Insulin Therapy Initiation in Individuals With Type 2 Diabetes: An in Silico Study.

Background: Insulin-naive subjects with type 2 diabetes (T2D) start basal insulin titration from a low initial insulin dose (IID), which is adjusted weekly or twice per week based on fasting plasma glucose (FPG) measurement as recommended by the American Diabetes Association (ADA). The procedure to reach the optimal insulin dose (OID) is time-consuming, especially in subjects with high insulin needs (HIN). The aim of this study is to provide a fast and effective, but still safe, insulin titration algorithm in insulin-naive T2D subjects with HIN.

Habitat is more important than climate for structuring soil fungal communities associated in truffle sites.

The ectomycorrhizal fungi Tuber melanosporum Vittad. and Tuber aestivum Vittad. produce highly valuable truffles, but little is known about the soil fungal communities associated with these truffle species in places where they co-occur.

Tailoring the Padova Type 2 Diabetes Simulator for Treatment Guidance in Target Populations.

Objective: The Padova type 2 diabetes (T2D) simulator (T2DS) has been recently proposed to optimize T2D treatments including novel long-acting insulins. It consists of a physiological model and an in silico population describing glucose dynamics, derived from early-stage T2D subjects studied with sophisticated tracer-based experimental techniques. This limits T2DS domain of validity to this specific sub-population.

Use of a mini balloon microcatheter to facilitate penetration of fine vascular networks and curative embolization in vein of Galen malformations.

Patients with vein of Galen malformations (VOGMs) can develop fine angiogenic networks with fistulous connections to the precursor of the vein of Galen. In these cases, transarterial embolization (TAE) with liquid embolic agents (LEAs) is challenging due to reflux in the pedicle leading to the network, causing poor penetration. Transvenous approaches carry a risk of hemorrhage from pathologic vasculature.

[Test for abnormal niacin response syndrome in schizophrenia: reclaiming the oral route].

Introduction: Although there is an abnormal presentation of Niacin Response Syndrome (ANRS) in schizophrenic patients (SZ) compared to subjects with other psychiatric illnesses and with healthy individuals. However, most of the literature is based on studies that have used tests of niacin topical administration, observing, on the other hand, less scientific production of its oral administration. The objective was to determine the sensitivity of the oral niacin test as a method of detecting ASRN in EZ.

SBILib: a handle for protein modeling and engineering.

Summary: The SBILib Python library provides an integrated platform for the analysis of macromolecular structures and interactions. It combines simple 3D file parsing and workup methods with more advanced analytical tools. SBILib includes modules for macromolecular interactions, loops, super-secondary structures, and biological sequences, as well as wrappers for external tools with which to integrate their results and facilitate the comparative analysis of protein structures and their complexes.

The coexistence of diabetic retinopathy and diabetic nephropathy is associated with worse kidney outcomes.

Background: Up to 50-60% of patients with diabetes have non-diabetic kidney disease (NDKD) on kidney biopsy. Diabetic retinopathy (DR) is a microvascular complication of diabetes frequently associated with diabetic nephropathy (DN). The objective of the current study was to investigate the kidney outcomes and survival in patients with biopsy diagnoses of DN and NDKD according to the presence of DR.

A new oral model of free fatty acid kinetics to assess lipolysis in subjects with and without type 2 diabetes.

Assessing free fatty acids (FFAs) kinetics and the role of insulin and glucose on FFA lipolysis and disposal may improve our understanding of the pathogenesis of type 2 diabetes (T2D). Some models have been proposed to describe FFA kinetics during an intravenous glucose tolerance test and only one during an oral glucose tolerance test. Here, we propose a model of FFA kinetics during a meal tolerance test and use it to assess possible differences in postprandial lipolysis in individuals with type 2 diabetes (T2D) and individuals with obesity without type 2 diabetes (ND).

A PD-L1/EGFR bispecific antibody combines immune checkpoint blockade and direct anti-cancer action for an enhanced anti-tumor response.

Immune checkpoint blockade (ICB) with antibodies has shown durable clinical responses in a wide range of cancer types, but the overall response rate is still limited. Other effective therapeutic modalities to increase the ICB response rates are urgently needed. New bispecific antibody (bsAb) formats combining the ICB effect and a direct action on cancer cells could improve the efficacy of current immunotherapies.

Schistosomiasis screening in non-endemic countries from a cost perspective: Knowledge gaps and research priorities. The case of African long-term residents in a Metropolitan Area, Spain.

Background: Imported schistosomiasis is an emerging issue in European countries as a result of growing global migration from schistosomiasis-endemic countries, mainly in sub-Saharan Africa. Undetected infection may lead to serious long-term complications with an associated high cost for public healthcare systems especially among long-term migrants.

Objective: To evaluate from a health economics perspective the introduction of schistosomiasis screening programs in non-endemic countries with high prevalence of long-term migrants.

[Functional capacity and cognitive performance of adults from Argentina in cardiopulmonary rehabilitation].

Unlabelled: Introduction: Functional capacity is decreased in people with Cardiovascular Diseases and Chronic Respiratory Diseases. These diseases have also been associated with cognitive dysfunction. The study examines the efficacy of a cardiopulmonary rehabilitation program in the recovery of functional capacity and analyzes whether subjects with cardiopulmonary diseases suffer from cognitive dysfunction.

Silvicultural management and altitude prevail on soil properties and fungal community in shaping understorey plant communities in a Mediterranean pine forest.

Understorey vegetation plays a key role in Mediterranean forest ecosystem functioning. However, we still lack a thorough understanding of the patterns and drivers of understorey composition and diversity. As a result, understoreys are often ignored during assessments of forest functioning under climate change.

A generic framework for hierarchical de novo protein design.

De novo protein design enables the exploration of novel sequences and structures absent from the natural protein universe. De novo design also stands as a stringent test for our understanding of the underlying physical principles of protein folding and may lead to the development of proteins with unmatched functional characteristics. The first fundamental challenge of de novo design is to devise "designable" structural templates leading to sequences that will adopt the predicted fold.

The fall of the summer truffle: Recurring hot, dry summers result in declining fruitbody production of Tuber aestivum in Central Europe.

Global warming is pushing populations outside their range of physiological tolerance. According to the environmental envelope framework, the most vulnerable populations occur near the climatic edge of their species' distributions. In contrast, populations from the climatic center of the species range should be relatively buffered against climate warming.