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Nucleic acids, with their unique duplex structure, which is key for information replication, have sparked interest in self‐replication's role in life's origins. Early template‐based replicators, initially built on short oligonucleotides, expanded to include peptides and synthetic molecules. We explore here the potential of a class of synthetic duplex‐forming oligoanilines, as self‐replicators. We have recently developed oligoanilines equipped with 2‐trifluoromethylphenol–phosphine oxide H‐bond base pairs and we investigate whether the imine formed between aniline and aldehyde complementary monomers can self‐replicate. Despite lacking a clear sigmoidal kinetic profile, control experiments with a methylated donor and a competitive inhibitor support self‐replication. Further investigations with the reduced aniline dimer demonstrate templated synthesis, revealing a characteristic parabolic growth. After showing sequence selective duplex formation, templated synthesis and the emergence of catalytic function, the self‐replication behaviour further suggests that the unique properties of nucleic acids can be paralleled by synthetic recognition‐encoded molecules. [ABSTRACT FROM AUTHOR]

Background and purpose: Although there is extensive evidence about the safety of monoclonal antibodies against calcitonin gene‐related peptide (anti‐CGRP mAbs) in combination with traditional drugs, scarce data are available on the safety of their combination with other mAbs. This study aimed to evaluate the 6‐month effectiveness and tolerability of anti‐CGRP mAbs in combination with other mAbs for different diseases. Methods: Patients included in the Italian Headache Registry and treated concomitantly with an anti‐CGRP mAb and another mAb were included. Effectiveness outcomes for migraine included reduction from baseline of monthly headache days (MHDs), Migraine Disability Assessment (MIDAS) score, Headache Impact Test‐6 (HIT‐6) scores, and Patients' Global Impression of Change (PGIC) scale. Adverse events (AEs) were recorded. Results: Thirty‐eight patients were included. In 27 patients (71.1%), the anti‐CGRP mAb was added to a previously ongoing mAb. Nine patients (23.7%) discontinued one of the two mAbs before the end of treatment (seven discontinued the anti‐CGRP mAb and two the other mAb). One patient discontinued for AEs. Anti‐CGRP mAbs were discontinued due to ineffectiveness (n = 5, 55.5%) and one each (11.1%) for clinical remission and lost to follow‐up. MHDs significantly decreased from baseline to 3 months (p < 0.0001) and 6 months (p < 0.001), as did the MIDAS and the HIT‐6 scores at 3 and 6 months (p < 0.001). For anti‐CGRP mAbs, 27.4% of patients reported PGIC ≥ 5 at 3 months and 48.3% at 6 months. Mild AEs associated with introduction of a second mAb were detected in six patients (15.8%). Conclusions: In this real‐world study, anti‐CGRP mAbs showed safety and effectiveness when administered concomitantly with other mAbs. [ABSTRACT FROM AUTHOR]

In this work, we describe the synthesis of heterobimetallic Fe(II)/Pd(II) complexes bearing different halides and halide‐substituted butadienyl ligands. The synthetic approach involves the preparation of suitable Pd(II)‐butadienyl precursors containing a thioquinoline moiety, followed by the substitution of this relatively labile ligand with dppf (dppf=1,1′‐bis(diphenylphosphino)ferrocene). With the exception of complexes containing at least one iodine atom, all compounds were synthesized in high yields and purity, and thoroughly characterized using spectroscopic and diffractometric methods. The investigation of the antiproliferative activity of the synthesized organometallic complexes against ovarian and breast cancer cell lines revealed that all compounds exhibit noteworthy cytotoxicity, with IC50 values in the micromolar range and generally comparable to those of cisplatin. Interestingly, significant differences of cytotoxicity among the analysed compounds were observed in the case of MRC‐5 normal cells. Of particular interest is the dichloride derivative 3 a, which is essentially inactive towards non‐cancerous cells (IC50>100 μM), thus demonstrating promising in vitro selectivity that we believe warrants further investigation in the future. [ABSTRACT FROM AUTHOR]

Introduction: MGRS are new rare clinical entities, whose recognition and optimal management is evolving. Methods: To implement real‐life data, we retrospectively analysed a multicentre cohort of 60 patients with renal biopsy‐proven MGRS receiving mainly novel treatments (between 2006 and 2021) in eight Italian centres. Based on renal biopsy, patients were divided into two subgroups: AL amyloidosis (70%, n = 42) and other‐MGRS (30%, n = 18). Results: Baseline characteristics follow typical manifestations of MGRS disorders in terms of small clonal burden, laboratory and clinical features. More patients with AL amyloidosis had monotypic lambda light‐chain disease, estimated glomerular filtration rate (eGFR) ≥ 60 mL/min and nephrotic proteinuria than other‐MGRS group. The most widely used drug was bortezomib, and about one‐third of patients underwent ASCT. Overall response rate was 86% with no differences in the two subgroups. However, high‐quality hematologic responses ≥very good partial response (VGPR) were greater in AL amyloidosis than in other‐MGRS group (67% vs 28%, p = 0.015). The depth of haematological response influenced renal response, obtained in 32 (59%) of evaluable patients, similarly in the subgroups. Indeed, 75% patients with ≥ VGPR (p = 0.049) and none with stable disease (p ≤ 0.001) obtained a renal response. No association between renal response and histotypes (p = 0.9) or type of first‐line therapy (p = 0.3) was found. At a median follow‐up of 54.4 months (IQR 24.8–102.8), median progression‐free survival (PFS) was 100.1 months (95% CI 34.9–NR), and median overall survival not reached (95% CI 129.8–NR). No significant difference emerged between the two groups in terms of survival outcomes. Achieving ≥ VGPR was confirmed as the main independent predictor of prolonged PFS in the general population (HR = 0.29, p = 0.023) and AL amyloidosis group (HR 0.23; p = 0.023). Preserved renal function at diagnosis was predictive of improved PFS in the AL amyloidosis group (eGFR ≥ 60 mL/min: HR = 0.003; p = 0.018; eGFR 30–60 mL/min: HR = 0.04, p = 0.046). Conclusion: Further research is warranted to develop standardised response criteria and treatment strategies to improve MGRS management. [ABSTRACT FROM AUTHOR]

Background: A prediction model that estimates mortality at admission to the intensive care unit (ICU) is of potential benefit to both patients and society. Logistic regression models like Simplified Acute Physiology Score 3 (SAPS 3) and APACHE are the traditional ICU mortality prediction models. With the emergence of machine learning (machine learning) and artificial intelligence, new possibilities arise to create prediction models that have the potential to sharpen predictive accuracy and reduce the likelihood of misclassification in the prediction of 30‐day mortality. Methods: We used the Swedish Intensive Care Registry (SIR) to identify and include all patients ≥18 years of age admitted to general ICUs in Sweden from 2008 to 2022 with SAPS 3 score registered. Only data collected within 1 h of ICU admission was used. We had 153 candidate predictors including baseline characteristics, previous medical conditions, blood works, physiological parameters, cause of admission, and initial treatment. We stratified the data randomly on the outcome variable 30‐day mortality and created a training set (80% of data) and a test set (20% of data). We evaluated several hundred prediction models using multiple ML frameworks including random forest, gradient boosting, neural networks, and logistic regression models. Model performance was evaluated by comparing the receiver operator characteristic area under the curve (AUC‐ROC). The best performing model was fine‐tuned by optimizing hyperparameters. The model's calibration was evaluated by a calibration belt. Ultimately, we simplified the best performing model with the top 1–20 predictors. Results: We included 296,344 first‐time ICU admissions. We found age, Glasgow Coma Scale, creatinine, systolic blood pressure, and pH being the most important predictors. The AUC‐ROC was 0.884 in test data using all predictors, specificity 95.2%, sensitivity 47.0%, negative predictive value of 87.9% and positive predictive value of 70.7%. The final model showed excellent calibration. The ICU risk evaluation for 30‐day mortality (ICURE) prediction model performed equally well to the SAPS 3 score with only eight variables and improved further with the addition of more variables. Conclusion: The ICURE prediction model predicts 30‐day mortality rate at first‐time ICU admission superiorly compared to the established SAPS 3 score. [ABSTRACT FROM AUTHOR]

Cross‐sectional imaging is widely used to characterize adrenal gland tumors in humans. In small animal veterinary medicine, while some studies have attempted to distinguish between types of adrenal gland neoplasia using CT, peer‐reviewed studies investigating canine adrenal glands on MRI are scant. This prospective, pilot, single‐center, method comparison, cadaveric study aimed to assess the agreement between ex vivo MRI findings and analogous histopathological findings of the adrenal glands in dogs. The adrenal glands of randomly selected dogs presented for necropsy were examined by MRI (n = 31). Additionally, five adrenal masses in dogs who underwent invasive adrenalectomy (including three adrenocortical carcinomas, one pheochromocytoma, and one adenoma) were imaged. Subsequently, gross pathology and histopathology of all the specimens were performed and correlated with the imaging findings. Adrenal gland lesions were identified on MRI with a sensitivity of 24%, a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 31%, and an accuracy of 45%. The present study provides MRI features of multiple adrenal gland lesions that had never been described in dogs, including cortical hyperplasia, nodular fibrosis, hemorrhage, or multiple tumors, such as adenoma, carcinoma, and hemangiosarcoma. While MRI identified numerous adrenal gland lesions, a significant portion of those went undetected. Therefore, the absence of adrenal gland lesions on MRI does not exclude the possibility of histological lesions being present. [ABSTRACT FROM AUTHOR]

Isoëtes are iconic but understudied wetland plants, despite having suffered severe losses globally mainly because of alterations in their habitats. We therefore provide the first global ecological assessment of aquatic Isoëtes to identify their environmental requirements and to evaluate if taxonomically related species differ in their ecology.The assessment resulted in an extensive new database on aquatic Isoëtes, ecological niche analyses, and descriptive species accounts. We compiled a global database that includes all known environmental data collected from 1935 to 2023 regarding aquatic Isoëtes. We then evaluated the environmental drivers of 16 species using 2,179 global records. Additionally, we used hypervolume analysis to quantify the ecological niches of the two species with the greatest number of records, finding significant differences and evidence that Isoëtes echinospora occupies a wider ecological niche than Isoëtes lacustris.Fifty‐nine species (30% of the c. 200 Isoëtes species known today) were categorised as aquatic and were mainly reported in the Americas and northern Europe. About 38% of the aquatic species are threatened with extinction or are endemic to a small region, according to the International Union for Conservation of Nature's Red List in 2023. Many species were determined to be sensitive to certain water physical and chemical factors, generally preferring oligotrophic conditions such as low total phosphorus, moderate total nitrogen, moderate to low pH, and low conductivity.This analysis includes ecological data in the assessment of rare/threatened aquatic plants globally. This new database and the ecological analyses completed defined the ecological requirements of several species and identified knowledge gaps, which can aid management actions and future research.This paper highlights ecological significance and environmental sensitivities of aquatic Isoëtes. The current level of knowledge is inadequate for a large proportion of known taxa. We affirm the extreme need to support global, collaborative initiatives on which to build future conservation strategies. [ABSTRACT FROM AUTHOR]

Student academic representation is a staple feature in UK and international higher education. It provides a vital quality function whereby students, who are elected representatives of their programme, canvas the opinions of peers to inform quality assurance processes. In the UK, there is increasing regulatory pressure for universities and student unions to be dual owners of representation activity and much work has been done to enact this model. Nonetheless, little is known about the experiences of those serving as student representatives, despite this being a community of thousands of students across the UK, who hold an instrumental position in institutional quality assurance. We developed an instrument (SARA) to evaluate experiences of 773 active student representatives from 15 UK HE institutions. It explored key areas, including recruitment, training, working approaches and development outcomes. Data indicated low engagement in training in some key areas (e.g., representation of diverse groups and data gathering) and a narrow range of working approaches. These patterns may compromise the value of student representation both from the institutional perspective and that of individual representatives seeking to enhance their skills. Recommendations are suggested for enhancing future practice. [ABSTRACT FROM AUTHOR]

Aims: Roux‐en‐Y gastric bypass (RYGB) surgery alters postprandial glucose profiles, causing post‐bariatric hypoglycaemia (PBH) in some individuals. Due to the liver's central role in glucose homeostasis, hepatic glucose handling might differ in RYGB‐operated patients with PBH compared to non‐operated healthy controls (HC). Materials and Methods: We enrolled RYGB‐operated adults with PBH and HCs (n = 10 each). Participants ingested 60 g of [6,6′‐2H2]‐glucose (d‐glucose) after an overnight fast. Deuterium metabolic imaging (DMI) with interleaved 13C magnetic resonance spectroscopy was performed before and until 150 min post‐d‐glucose intake, with frequent blood sampling to quantify glucose enrichment and gluco‐regulatory hormones until 180 min. Glucose fluxes were assessed by mathematical modelling. Outcome trajectories were described using generalized additive models. Results: In RYGB subjects, the hepatic d‐glucose signal increased early, followed by a decrease, whereas HCs exhibited a gradual increase and consecutive stabilization. Postprandial hepatic glycogen accumulation and the suppression of endogenous glucose production were lower in RYGB patients than in HCs, despite higher insulin exposure, indicating lower hepatic insulin sensitivity. The systemic rate of ingested d‐glucose was faster in RYGB, leading to a higher, earlier plasma glucose peak and increased insulin secretion. Postprandial glucose disposal increased in RYGB patients, without between‐group differences in peripheral insulin sensitivity. Conclusions: Exploiting DMI with stable isotope flux analysis, we observed distinct postprandial hepatic glucose trajectories and parameters of glucose–insulin homeostasis in RYGB patients with PBH versus HCs. Despite altered postprandial glucose kinetics and higher insulin exposure, there was no evidence of impaired hepatic glucose uptake or output predisposing to PBH in RYGB patients. [ABSTRACT FROM AUTHOR]

Dermatomycoses are the most widespread fungal skin infections worldwide and directly affect patients' quality of life. They are challenging to manage because of the need for prolonged treatment and the development of resistance to antifungal agents. This article studies the antifungal activity of trifluoromethylthiolated cinnamate derivatives on Candida species and dermatophytes as well as possible mechanisms of action, irritability, and cytotoxicity tests. These molecules show activity against dermatophyte fungi with minimum inhibitory concentrations (MIC) as low as 0.39 μg mL−1. In particular, chloroaromatic derivatives demonstrated the best inhibition profile (1.56–6.25 μg mL−1). Importantly, our series of molecules were not active against Candida spp., being selective for dermatophytes. A study of the mechanism of action suggests that our SCF3 cinnamates do not bind directly to ergosterol or the cell wall. The physicochemical parameters and the absence of irritability resulting from the HET‐CAM test demonstrate that compound 8 can be considered a future candidate for the therapy of dermatophytosis. [ABSTRACT FROM AUTHOR]

A 4-month-old female entire Dalmatian was presented for persistently excessive ceruminous discharge, suspected left aural malformation and decreased hearing. Otoscopic examination of the left ear showed a normal external meatus with an abnormal ending of the ear canal in a cul-de-sac. Computed tomography (CT) study of the head showed a diffusely tortuous and convoluted external ear canal with saccular distension and a stenotic area with the presence of a septum. Based on the clinical presentation and imaging findings, total ear canal ablation and lateral bulla osteotomy were performed. Macroscopically, the ear canal appeared to be sigmoid, as in the CT study. Notably, in the stenotic area, there was a membrane separating the vertical and horizontal ear canals. The histopathology of the external ear canal was consistent with that of hyperplastic otitis externa. No growth was observed on bacterial culture. The dog recovered uneventfully and no abnormalities were detected on re-examination 2 weeks post-surgery. [ABSTRACT FROM AUTHOR]

We use a database composed of 2,545 Microfinance Institutions (MFIs) worldwide for the period 2008–18 to explore the effect of a larger share of women's workforce on both staff wages and overall monetary compensation within MFIs. MFIs are different from other industries, as they are traditionally women‐centered, i.e. they have a significant share of women employees at every level of the corporate hierarchy and mostly serve women clients. Applying both traditional estimation methodology and techniques aimed at accounting for possible endogeneity among the main variables, we find that a higher proportion of women on staff significantly increases the average expense per worker (which also includes the incentive components of remuneration) while the effects are considerably smoothed (or not significant) on the base salary. This leads us to conclude that, unlike what is seen in other sectors of the economy, MFIs do not pay women less. Yet, significant positive effects of women in the workforce, especially on average overall monetary compensation, suggest that women are likely to exploit their superior skills and/or gender affinity advantages with customers of the same gender to enhance MFIs' efficiency and profitability, thereby achieving higher incentive compensation, mostly in the form of bonuses and other benefits. [ABSTRACT FROM AUTHOR]

The liver plays a central role in metabolic homeostasis, as exemplified by a variety of clinical disorders with hepatic and systemic metabolic disarrays. Of particular interest are the complex interactions between lipid and carbohydrate metabolism in highly prevalent conditions such as obesity, diabetes, and fatty liver disease. Limited accessibility and the need for invasive procedures challenge direct investigations in humans. Hence, noninvasive dynamic evaluations of glycolytic flux and steady‐state assessments of lipid levels and composition are crucial for basic understanding and may open new avenues toward novel therapeutic targets. Here, three different MR spectroscopy (MRS) techniques that have been combined in a single interleaved examination in a 7T MR scanner are evaluated. 1H‐MRS and 13C‐MRS probe endogenous metabolites, while deuterium metabolic imaging (DMI) relies on administration of deuterated tracers, currently 2H‐labelled glucose, to map the spatial and temporal evolution of their metabolic fate. All three techniques have been optimized for a robust single‐session clinical investigation and applied in a preliminary study of healthy subjects. The use of a triple‐channel 1H/2H/13C RF coil enables interleaved examinations with no need for repositioning. Short‐echo‐time STEAM spectroscopy provides well resolved spectra to quantify lipid content and composition. The relative benefits of using water saturation versus metabolite cycling and types of respiratory synchronization were evaluated. 2H‐MR spectroscopic imaging allowed for registration of time‐ and space‐resolved glucose levels following oral ingestion of 2H‐glucose, while natural abundance 13C‐MRS of glycogen provides a dynamic measure of hepatic glucose storage. For DMI and 13C‐MRS, the measurement precision of the method was estimated to be about 0.2 and about 16 mM, respectively, for 5 min scanning periods. Excellent results were shown for the determination of dynamic uptake of glucose with DMI and lipid profiles with 1H‐MRS, while the determination of changes in glycogen levels by 13C‐MRS is also feasible but somewhat more limited by signal‐to‐noise ratio. [ABSTRACT FROM AUTHOR]

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, SID; fraction of glucose converted into lactate, fr; fractional lactate clearance rate, kL) and lactate production rate (LPR) were estimated using the oral glucose‐lactate minimal model. MASLD presence was assessed using the proton density fat fraction. We analysed glucose, lactate and LPR time to peak, peak values and area under the curve and evaluated differences using the Wilcoxon test. MASLD and no‐MASLD participants were compared using the Mann‐Whitney test. Correlations between parameters were assessed using the Spearman correlation coefficient (ρ). We also tested the performance of two (4 or 3 h OGTT) protocols in estimating oral glucose‐lactate minimal model and LPR parameters. Results: Glucose peaks 30 min earlier than lactate (p =.0019). This pattern was present in the no‐MASLD group (p <.001). LPR peaks 30 min later in the MASLD group (p =.02). LPR and kL were higher in MASLD, suggesting higher glycolysis and lactate utilization. SID and fr correlate significantly (ρ = −0.55, p =.008). SID and fr were also correlated with the body mass index, (ρ = −0.45, p =.04; and ρ = 0.45; p =.03). The protocol duration did not influence the estimates of the parameters. Discussion: Youth with MASLD showed a delayed glucose metabolism, possibly because of greater utilization of the underlying substrates. A 3‐h OGTT may be used to assess lactate metabolism effectively. [ABSTRACT FROM AUTHOR]

Cardiac glycosides are chemical defence toxins known to fatally inhibit the Na,K‐ATPase (NKA) throughout the animal kingdom. Several animals, however, have evolved target‐site insensitivity through substitutions in the otherwise highly conserved cardiac glycoside binding pocket of the NKA. The large milkweed bug, Oncopeltus fasciatus, shares a long evolutionary history with cardiac glycoside containing plants that led to intricate adaptations. Most strikingly, several duplications of the bugs' NKA1α gene provided the opportunity for differential resistance‐conferring substitutions and subsequent sub‐functionalization of the enzymes. Here, we analysed cardiac glycoside resistance and ion pumping activity of nine functional NKA α/β‐combinations of O. fasciatus expressed in cell culture. We tested the enzymes with two structurally distinct cardiac glycosides, calotropin, a host plant compound, and ouabain, a standard cardiac glycoside. The identity and number of known resistance‐conferring substitutions in the cardiac glycoside binding site significantly impacted activity and toxin resistance in the three α‐subunits. The β‐subunits also influenced the enzymes' characteristics, yet to a lesser extent. Enzymes containing the more ancient αC‐subunit were inhibited by both compounds but much more strongly by the host plant toxin calotropin than by ouabain. The sensitivity to calotropin was diminished in enzymes containing the more derived αB and αA, which were only marginally inhibited by both cardiac glycosides. This trend culminated in αAβ1 having higher resistance against calotropin than against ouabain. These results support the coevolutionary escalation of plant defences and herbivore tolerance mechanisms. The possession of multiple paralogs additionally mitigates pleiotropic effects by compromising between ion pumping activity and resistance. see also the Perspective by Franziska Beran and David G. Heckel [ABSTRACT FROM AUTHOR]

Although the epidermal growth factor receptor 2 (ErbB2) and Notch1 signaling pathways have both significant roles in regulating cardiac biology, their interplay in the heart remains poorly investigated. Here, we present evidence of a crosstalk between ErbB2 and Notch1 in cardiac cells, with effects on autophagy and proliferation. Overexpression of ErbB2 in H9c2 cardiomyoblasts induced Notch1 activation in a post‐transcriptional, p38‐dependent manner, while ErbB2 inhibition with the specific inhibitor, lapatinib, reduced Notch1 activation. Moreover, incubation of H9c2 cells with lapatinib resulted in stalled autophagic flux and decreased proliferation, consistent with the established cardiotoxicity of this and other ErbB2‐targeting drugs. Confirming the findings in H9c2 cells, exposure of primary neonatal mouse cardiomyocytes to exogenous neuregulin‐1, which engages ErbB2, stimulated proliferation, and this effect was abrogated by concomitant inhibition of the enzyme responsible for Notch1 activation. Furthermore, the hearts of transgenic mice specifically overexpressing ErbB2 in cardiomyocytes had increased levels of active Notch1 and of Notch‐related genes. These data expand the knowledge of ErbB2 and Notch1 functions in the heart and may allow better understanding the mechanisms of the cardiotoxicity of ErbB2‐targeting cancer treatments. [ABSTRACT FROM AUTHOR]

Aims: The potential harm associated with medication errors is widely reported, but data on actual harm are limited. When actual harm has been measured, assessment processes are often poorly described, limiting their ability to be reproduced by other studies. Our aim was to design and implement a new process to assess actual harm resulting from medication errors in paediatric inpatient care. Methods: Prescribing errors were identified through retrospective medical record reviews (n = 26 369 orders) and medication administration errors through direct observation (n = 5137 administrations) in a tertiary paediatric hospital. All errors were assigned potential harm severity ratings on a 5‐point scale. Multidisciplinary panels reviewed case studies for patients assigned the highest three potential severity ratings and determined the following: actual harm occurrence and severity level, plausibility of a link between the error(s) and identified harm(s) and a confidence rating if no harm had occurred. Results: Multidisciplinary harm panels (n = 28) reviewed 566 case studies (173 prescribing related and 393 administration related) and found evidence of actual harm in 89 (prescribing = 22, administration = 67). Eight cases of serious harm cases were found (prescribing = 1, administration = 7) and no cases of severe harm. The panels were very confident in 65% of cases (n = 302) where no harm was found. Potential and actual harm ratings varied. Conclusions: This harm assessment process provides a systematic method for determining actual harm from medication errors. The multidisciplinary nature of the panels was critical in evaluating specific clinical, therapeutic and contextual considerations including care delivery pathways, therapeutic dose ranges and drug–drug and drug–disease interactions. [ABSTRACT FROM AUTHOR]

Background: Ratio of arterial pressure of oxygen and fraction of inspired oxygen (P/F ratio) together with the fractional dead space (Vd/Vt) provides a global assessment of pulmonary gas exchange. The aim of this study was to assess the potential value of these variables to prognosticate 90‐day survival in patients with COVID‐19 associated ARDS admitted to the Intensive Care Unit (ICU) for invasive ventilatory support. Methods: In this single‐center observational, retrospective study, P/F ratios and Vd/Vt were assessed up to 4 weeks after ICU‐admission. Measurements from the first 2 weeks were used to evaluate the predictive value of P/F ratio and Vd/Vt for 90‐day mortality and reported by the adjusted hazard ratio (HR) and 95% confidence intervals [95%CI] by Cox proportional hazard regression. Results: Almost 20,000 blood gases in 130 patients were analyzed. The overall 90‐day mortality was 30% and using the data from the first ICU week, the HR was 0.85 [0.77–0.94] for every 10 mmHg increase in P/F ratio and 1.61 [1.20–2.16] for every 0.1 increase in Vd/Vt. In the second week, the HR for 90‐day mortality was 0.82 [0.75–0.89] for every 10 mmHg increase in P/F ratio and 1.97 [1.42–2.73] for every 0.1 increase in Vd/Vt. Conclusion: The progressive changes in P/F ratio and Vd/Vt in the first 2 weeks of invasive ventilatory support for COVID‐19 ARDS were significant predictors for 90‐day mortality. [ABSTRACT FROM AUTHOR]

In this article, we bring together a variety of studies, both old and new, to examine continuity and change in population dynamics in Italy during the medieval millennium (476–1492 AD). Though the available data are often sporadic and should be interpreted with great caution, it is possible to clarify certain dynamics, which can be useful for guiding future research. First, population fluctuations were not impacted by migration into or out of Italy. Second, medieval Italy was characterized by a high‐pressure demographic regime: e0 was around 20 years, with high adult mortality, and the birth rate was around 50 per mill. Third, despite high mortality, the Italian population grew (+50 percent) from the ninth century to 1347, mainly—but not exclusively—due to the absence of plague. Fourth, the stagnant population of the periods between the sixth and the eighth centuries and the 14th and 16th centuries was determined by the recurrent outbreaks of plague. Fifth, the population stagnation during the first and the last medieval centuries is also partly related to the increase in age at first marriage, while the demographic growth between the ninth and mid‐14th century is possibly connected to the decrease in age at first marriage among women. Sixth, the vitality of the medieval Italian population was partly ensured by a high rate of remarriage among widows. Seventh, data on statures show that mortality levels were determined by epidemic factors, rather than living standards. Finally, when the plague ceased in Europe in the middle of the Early Modern Age, adult survival was significantly higher than in the ancient and medieval centuries, despite the fact that neither hygienic‐sanitary nor epidemiological conditions, and certainly not nutrition, were better than in the centuries preceding the Black Death. [ABSTRACT FROM AUTHOR]

Considering the importance of promoting gender equality, Microfinance Institutions (MFIs) have emerged to reduce the gender gap by supplying credit opportunities to women. However, the microfinance literature has largely focused on the role of women in the client base while devoting less attention to their representation in the organizational structure of MFIs. This study aims to fill this gap. Using ANOVA and random effects models, our purpose is to investigate which types of MFIs more intensively promote gender equality within their workforce, at any of the organizational ladders. We analyze data from 1222 MFIs across 102 developing countries from 2010 to 2018. Empirical evidence reveals that the presence of females in both the workforce and the client base is significantly lower in commercially motivated MFIs (e.g., banks and other for‐profit institutions) compared to non‐government organizations (NGOs), and —to a lesser extent— credit unions, cooperatives and rural banks. Our results suggest that the microfinance sector would benefit from a stronger emphasis on NGO‐driven initiatives to promote female representation in terms of both employment opportunities and access to credit. [ABSTRACT FROM AUTHOR]

The renin‐angiotensin system (RAS) is an endocrine system composed of two main axes: the classical and the counterregulatory, very often displaying opposing effects. The classical axis, primarily mediated by angiotensin receptors type 1 (AT1R), is linked to obesity‐associated metabolic effects. On the other hand, the counterregulatory axis appears to exert antiobesity effects through the activation of two receptors, the G protein‐coupled receptor (MasR) and Mas‐related receptor type D (MrgD). The local RAS in adipose organ has prompted extensive research into white adipose tissue and brown adipose tissue (BAT), with a key role in regulating the cellular and metabolic plasticity of these tissues. The MasR activation favors the brown plasticity signature in the adipose organ by improve the thermogenesis, adipogenesis, and lipolysis, decrease the inflammatory state, and overall energy homeostasis. The MrgD metabolic effects are related to the maintenance of BAT functionality, but the signaling remains unexplored. This review provides a summary of RAS counterregulatory actions triggered by Mas and MrgD receptors on adipose tissue plasticity. Focus on the effects related to the morphology and function of adipose tissue, especially from animal studies, will be given targeting new avenues for treatment of obesity‐associated metabolic effects. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study is to evaluate and compare the impact of the bicaval technique versus the biatrial technique (by Lower and Shumway) in paediatric heart transplant patients. Only a few studies investigate this matter regarding the long‐term outcome after paediatric heart transplantation. We compared the two surgical methods regarding survival, the necessity of pacemaker implantation. Methods and results: All 134 patients (aged <18 years) – (group‐1) biatrial (n = 84), versus (group‐2) bicaval (n = 50), who underwent heart transplantation between October 1988 and December 2021, were analysed. Freedom from events were estimated using the Kaplan–Meier method. Potential differences were analysed using the log rank test and Cox proportional hazard models. Mean ± standard deviation: Bypass time (per minutes) was higher in the group 1 as compared with group 2 (P = 0.050). Survival was not significantly different (P = 0.604) in either groups. Eighteen patients required permanent pacemaker implantation in the group 1 and only one patient required it in the group 2 (P = 0.001). Conclusions: Paediatric heart transplantation using bicaval technique results similar long‐term survival compared with the biatrial technique. The incidence of atrial rhythm disorders was significantly higher in the biatrial group, requiring a higher frequency of pacemaker implantation in this group. As a results, the bicaval technique has replaced the biatrial technique in our centre. [ABSTRACT FROM AUTHOR]

Introduction: This study analysed whether the SAZAMED (Self‐assessment for dentistry studies) manual test conducted as an exercise or examination in the first year of dental studies, and the official aptitude test for medical studies (EMS), can predict future performance of dental students. Materials and Methods: Students enrolled in the dental curriculum at the University of Basel between 2009/10 and 2019/20 were categorized: Group A conducted the SAZAMED in the third bachelor year (BA) and second master year (MA), group B practiced in the first and third BA and second MA and group C had to pass the test in the first BA with repetition in the third BA and second MA. SAZAMED comprised (i) wire bending, (ii) modelling sphere and cube, (iii) drawing mirror‐inverted and (iv) indirect drawing over a mirror. Comparative variables were the EMS per cent rank and test scores in practical‐clinical examinations in the third BA and the second MA. Results: Data were available from 329 students over the 10‐year period. Repeaters and dropouts had poorer performance in the first BA SAZAMED than students who did not (p < 0.001). Among the four SAZAMED exercises, mirror‐inverted drawing was the strongest predictor of future student performance. The official aptitude test EMS correlated with the third BA certificate (p = 0.012), but failed to predict repeaters and dropouts. Conclusion: Since academic success was associated with significantly better scores on the first BA SAZAMED, it is considered a predictor and recommended in addition to the official EMS to identify students in need of intervention programmes or who should choose a different field of study. [ABSTRACT FROM AUTHOR]

Objective: In elderly people loneliness represents a risk factor for dementia and may negatively impact on mental and physical health. The specific contribute of loneliness to cognitive and behavioral functioning have not yet been determined in amyotrophic lateral sclerosis (ALS). Our hypothesis was that loneliness may be related to motor dysfunction with a negative impact on cognitive and behavioral decline, possibly related to specific cortical involvement. Methods: In 200 ALS patients (ALSpts) and 50 healthy controls (HCs) we measured loneliness, mood, and quality of life (QoL). ALSpts underwent comprehensive clinical, genetic, and neuropsychological assessment to define phenotypes. Seventy‐seven ALSpts performed 3T MRI scans to measure cortical thickness. Between‐group, partial correlation and regression analyses were used to examined clinical, neuropsychological, and cortical signatures of loneliness. Results: Feelings of loneliness were documented in 38% of ALSpts (ALS/L+pts) and in 47% of HCs. In both groups loneliness was associated with anxiety (P < 0.001), depression (P ≤ 0.005), and poor QoL (P < 0.001). ALS/L+pts had similar motor dysfunctions and cognitive abilities than non‐lonely ALSpts, but distinct behavioral profiles (P ≤ 0.005) and frontoparietal involvement (P < 0.05). Loneliness in ALS is related to behavioral changes, apathy, and emotional dysregulation (P < 0.001). Interpretation: Our cross‐sectional study indicates that, in ALS, the satisfaction of social environment is associated with a sense of life well‐being that is not limited to the motor status, proving instead that loneliness can impact on disease‐related neurobehavioral changes with a possible flashback on brain architecture. This suggests that sociality could promote personal resilience against behavioral and affective decline in ALS. [ABSTRACT FROM AUTHOR]

This work aimed to propose multivariate selection strategies reconciling the agronomic ideotype and vegetation indices to obtain genotypes with high tillering, early cycle, tolerant to lodging, and foliar diseases. The sowing of white oat lines was carried out on April 27, 2023, allocated in an experimental design of blocks augmented with interspersed controls. The regular treatments correspond to 593 lines of white oat and the common treatments were represented by the cultivars URS Olada, URS Altaneira, and IPR Artêmis arranged in four replications. The measurements of variables of agronomic interest took place in each experimental unit as follows: percentage of tillering, days to flowering, percentage of lodging, percentage of leaf rust, percentage of stem rust, and percentage of leaf spots. The phenomic analyses took place through flights carried out with a specialized drone, equipped with a 20 MP resolution camera and standard height (80 m). The best proposed indices were index for reducing the percentage of lodging with normalized green (NG), green–red ratio (IGR), soil color index (SCI), green leaf index (GLI), visible atmospheric resistant index (VARI), green leaf index 2 (GLI2), red–blue (RB), blue green pigment (BGI), normalized red–blue difference index (NRBDI), green–blue ratio, BIM, normalized green–blue difference index (NGBDI), and ExGR; index for reducing days to flowering with brightness index (BI), NRBDI, days to flowering (DF), gray (GRAY), IGR, average intensity (L), normalized red (NR), RGRI, SCI, BGI, BIM, GLI, NGBDI, and NG; and index for reducing the percentage of stem rust with NG, BI, Gray2, GLI2, RGRI, GLI, VARI, BGI, L, NR, RB, and coloration index. Only two lines were selected concomitantly with multivariate indices, line L167 (M5, SA) and L426 (M6, ETMS), that combine lodging tolerance and leaf rust genes. Core Ideas: New selection strategies for plant breeding with precision and speed.Genotype selection using remote sensing.Multivariate strategy using predicted data.Innovative protocol using phenomics in white oat trials.Agronomic Ideotype combined with indirect selection strategies by unmanned vehicles. [ABSTRACT FROM AUTHOR]

'PVL03' (Reg. no. CV‐159, PI 699656), a Provisia (BASF) long‐grain rice (Oryza sativa L.) cultivar, was developed by the Louisiana State University Agricultural Center at the H. Rouse Caffey Rice Research Station near Crowley, LA, and approved for release in 2020. PVL03 is the third rice cultivar released as part of the Provisia Rice System with resistance to Provisia herbicide, containing the active ingredient quizalofop‐p‐ethyl, an AACase (group 1) herbicide. PVL03 was derived from the cross 'PVL01'/'Catahoula'. Testing in the Provisia preliminary yield trial in 2018 and the multi‐location trial in 2019 indicated good yield potential and favorable agronomic characteristics. In 2020, PVL03 was evaluated in commercial advanced replicated trials across six locations in Louisiana. Four high‐yielding commercial cultivars were included as checks: 'PVL02', PVL01, 'CL153', and 'Cheniere'. The average grain yield of PVL03 was 9.6 t ha−1 compared with 8.0 t ha−1 for PVL02, 8.1 t ha−1 for PVL01, 9.8 t ha−1 for CL153, and 9.1 t ha−1 for Cheniere. PVL03 was shorter than the previous Provisia cultivar, PVL02. The milled grain length was longer than that of PVL02, with a length‐to‐width ratio of 3.0. It has a typical US long‐grain rice cooking quality with intermediate amylose and gelatinization temperature. PVL03 is moderately susceptible to sheath blight and moderately resistant to leaf blast and bacterial panicle blight. Core Ideas: PVL03 is the third cultivar released for the Provisia rice production system.PVL03 is higher yielding than the previous Provisia rice cultivars.PVL03 has better grain and milling quality than previous Provisia rice cultivars.PVL03 offers broad spectrum resistance to the fungal disease blast. [ABSTRACT FROM AUTHOR]

'CLL17' (Reg. no. CV‐160; PI 693941), a high‐yielding long‐grain rice (Oryza sativa L.) cultivar, was developed by the Louisiana State University Agricultural Center at the H. Rouse Caffey Rice Research Station near Crowley, LA, and approved for release in 2020. CLL17 contains the herbicide‐resistant gene for use in the Clearfield rice production system. The Clearfield rice production system is defined as the brand of rice cultivars that are tolerant to imidazolinone herbicides. CLL17 was derived from the cross 'CL131'/'Trenasse'. It showed good yield potential and favorable agronomic characteristics in the 2015 Clearfield Preliminary Yield Trial. In 2016, it was evaluated in the uniform regional rice nursery trial across four southern states. From 2017 to 2022, CLL17 was evaluated in 50 replicated trials across 10 locations in Louisiana. Three high‐yielding commercial cultivars were included as checks: 'Cheniere', 'CL153', and 'CL111'. The grain yield of CLL17 was 9.0 t ha−1 compared with 8.9 t ha−1 for CL153, 8.3 t ha−1 for CL111, and 8.2 t ha−1 for Cheniere across 25 commercial advanced trials from 2017 to 2020. CLL17 had a similar plant height to CL111, 2‐cm taller than CL153, and 5‐cm taller than Cheniere. It exhibits typical US long‐grain rice cooking quality with intermediate amylose and gel temperature. CLL17 is susceptible to sheath blight [caused by Rhizoctonia solani Kuhn ], resistant to Cercospora spp., leaf blast [caused by Magnaporthe grisea (T.T. Hebert)], and neck blast, and moderately susceptible to bacterial panicle blight (caused by Burkholderia glumae). Core Ideas: 'CLL17' is released for Clearfield rice production system.'CLL17' is a high‐yielding Clearfield long grain rice variety.'CLL17' is resistant to leaf blast. [ABSTRACT FROM AUTHOR]

Aims: Sodium glucose co-transporter-2 (SGLT2) inhibition lowers glucose levels independently of insulin, leading to reduced insulin secretion and increased lipolysis, resulting in elevated circulating free fatty acids (FFAs). While SGLT2 inhibition improves tissue insulin sensitivity, the increase in circulating FFAs could reduce insulin sensitivity in skeletal muscle and the liver. We aimed to investigate the effects of SGLT2 inhibition on substrate utilization in skeletal muscle and the liver and to measure beta-cell function and glucose tolerance. Methods: Thirteen metformin-treated individuals with type 2 diabetes were randomized to once-daily empagliflozin 25 mg or placebo for 4 weeks in a crossover design. Skeletal muscle glucose and FFA uptake together with hepatic tissue FFA uptake were measured using [18F]FDG positron emission tomography/computed tomography (PET/CT) and [11C]palmitate PET/CT. Insulin secretion and action were estimated using the oral minimal model. Results: Empagliflozin did not affect glucose (0.73 ± 0.30 vs. 1.16 ± 0.64, µmol/g/min p = 0.11) or FFA (0.60 ± 0.30 vs. 0.56 ± 0.3, µmol/g/min p = 0.54) uptake in skeletal muscle. FFA uptake in the liver (21.2 ± 10.1 vs. 19 ± 8.8, µmol/100 ml/min p = 0.32) was unaffected. Empagliflozin increased total beta-cell responsivity (20 ± 8 vs. 14±9, 10-9 min-1, p < 0.01) and glucose effectiveness (2.6 x 10-2 ± 0.3 x 10-2 vs. 2.4 x 10-2 ± 0.3 x 10-2, dL/kg/min, p = 0.02). Conclusions: Despite improved beta-cell function and glucose tolerance, empagliflozin does not appear to affect skeletal muscle FFA or glucose uptake. [ABSTRACT FROM AUTHOR]

Background: Investigations assessing how oral health status affects school performance and attendance considering individual and community variables are lacking. Aim: To analyze the association of school contextual factors and oral conditions with school performance and absenteeism in early adolescence. Design: This cross‐sectional study was carried out with 593 12‐year‐old students from 20 schools in Passo Fundo, a southern city in Brazil. The caregivers provided sociodemographic information by means of a questionnaire. Oral health status was clinically examined for dental caries and gingival bleeding. Students answered the CPQ11‐14 questionnaire to assess the oral health‐related quality of life (OHRQoL). Information on contextual factors was obtained from the schools' administrators. "School performance" was measured by Portuguese and Mathematic tests' scores, and "school absenteeism" by the number of school days missed. Descriptive statistics was conducted, followed by unadjusted and adjusted multilevel linear regression. Results: At the individual level, low OHRQoL was associated with lower school performance and higher absenteeism. At the contextual level, students from private schools had higher school performance and lower mean of school days missed. Conclusions: The type of school and OHRQoL were associated with school performance and attendance of adolescents. [ABSTRACT FROM AUTHOR]

Background: High positive end‐expiratory pressure (PEEP>10 cmH2O) is commonly used in mechanically ventilated hypoxemic patients with COVID‐19. However, some epidemiological and physiological studies indirectly suggest that using a lower PEEP may primarily and beneficially decrease lung hyperinflation in this population. Herein we directly quantified the effect of decreasing PEEP from 15 to 10 cmH2O on lung hyperinflation and collapse in mechanically ventilated patients with COVID‐19. Methods: Twenty mechanically ventilated patients with COVID‐19 underwent a lung computed tomography (CT) at PEEP of 15 and 10 cmH2O. The effect of decreasing PEEP on lung hyperinflation and collapse was directly quantified as the change in the over‐aerated (density below −900 HU) and non‐aerated (density above −100 HU) lung volumes. The net response to decreasing PEEP was computed as the sum of the change in those two compartments and expressed as the change in the "pathologic" lung volume. If the pathologic lung volume decreased (i.e., hyperinflation decreased more than collapse increased) when PEEP was decreased, the net response was considered positive; otherwise, it was considered negative. Results: On average, the ratio of arterial tension to inspiratory fraction of oxygen (PaO2:FiO2) in the overall study population was 137 (119–162) mmHg. In 11 (55%) patients, the net response to decreasing PEEP was positive. Their over‐aerated lung volume decreased by 159 (98–186) mL, while the non‐aerated lung volume increased by only 58 (31–91) mL. In nine (45%) patients, the net response was negative. Their over‐aerated lung volume decreased by 46 (18–72) mL, but their non‐aerated lung volume increased by 107 (44–121) mL. Conclusion: In 20 patients with COVID‐19 the net response to decreasing PEEP, as assessed with lung CT, was variable. In approximately half of them it was positive (and possibly beneficial), with a decrease in hyperinflation larger than the increase in collapse. [ABSTRACT FROM AUTHOR]

Obesity over‐activates the classical arm of the renin‐angiotensin system (RAS), impairing skeletal muscle remodeling. We aimed to compare the effect of exercise training and enalapril, an angiotensin‐converting enzyme inhibitor, on RAS modulation in the skeletal muscle of obese animals. Thus, we divided C57BL/6 mice into two groups: standard chow (SC) and high‐fat (HF) diet for 16 weeks. At the eighth week, the HF‐fed animals were divided into four subgroups—sedentary (HF), treated with enalapril (HF‐E), exercise training protocol (HF‐T), and combined interventions (HF‐ET). After 8 weeks of treatment, we evaluated body mass and index (BMI), body composition, exercise capacity, muscle morphology, and skeletal muscle molecular markers. All interventions resulted in lower BMI and attenuation of overactivation in the classical arm, while favoring the B2R in the bradykinin receptors profile. This was associated with reduced apoptosis markers in obese skeletal muscles. The HF‐T group showed an increase in muscle mass and expression of biosynthesis markers and a reduction in expression of degradation markers and muscle fiber atrophy due to obesity. These findings suggest that the combination intervention did not have a synergistic effect against obesity‐induced muscle remodeling. Additionally, the use of enalapril impaired muscle's physiological adaptations to exercise training. [ABSTRACT FROM AUTHOR]

Schizophrenia (SCZ) response to pharmacological treatment is highly variable. Quetiapine (QTP) administered as QTP lipid core nanocapsules (QLNC) has been shown to modulate drug delivery to the brain of SCZ phenotyped rats (SPR). In the present study, we describe the brain concentration–effect relationship after administrations of QTP as a solution or QLNC to SPR and naïve animals. A semimechanistic pharmacokinetic (PK) model describing free QTP concentrations in the brain was linked to a pharmacodynamic (PD) model to correlate the drug kinetics to changes in dopamine (DA) medial prefrontal cortex extracellular concentrations determined by intracerebral microdialysis. Different structural models were investigated to fit DA concentrations after QTP dosing, and the final model describes the synthesis, release, and elimination of DA using a pool compartment. The results show that nanoparticles increase QTP brain concentrations and DA peak after drug dosing to SPR. To the best of our knowledge, this is the first study that combines microdialysis and PK/PD modeling in a neurodevelopmental model of SCZ to investigate how a nanocarrier can modulate drug PK and PD, contributing to the development of new treatment strategies for SCZ. [ABSTRACT FROM AUTHOR]

Waste edible oils are an alternative source of high‐value natural compounds. Vitamin E can be recovered from palm oil refining residues by molecular distillation. However, the presence of other lipophilic molecules compromises the selective separation of vitamin E. Esterification of the free fatty acids can enhance the selective separation of vitamin E by molecular distillation, but the conditions for carrying out the reaction need to be investigated to simultaneously ensure the conversion of free fatty acids and the reduction of vitamin E losses. Thus, this study investigated the effect of the esterification of the industrial waste on the recovery of vitamin E by molecular distillation. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and analysis for fats and oils preconized by the American Oil Chemists' Society (AOCS) were used in the characterization of the industrial waste. Determination of the best condition to carry out the reaction was obtained by a central composite rotational design (CCRD) using the response surface methodology (RSM) and the desirability profile. The results showed that the best condition for the esterification was at 64°C, 213 min, 2 wt.% sulphuric acid, and a 10/1 methanol/free fatty acids molar ratio. This reaction condition achieved 97.9% conversion of free fatty acids and less than 3% of vitamin E loss. The esterification promoted concentration of vitamin E in the residue stream (145.4%) and reduction in the distillate stream (87.8%). Therefore, the obtained results presented a suitable route to obtaining vitamin E concentrate and adding value to an industrial residue. [ABSTRACT FROM AUTHOR]

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Although considerable gains in survival have been observed in developed countries, particularly in the last stretch of life, part of these additional years of life are lived in bad health. In this context, a number of actions/inactions that limit or may limit life span are becoming increasingly common. Demography and quantitative sociology are well‐positioned to make a significant contribution to the measurement of the consistency of different end‐of‐life interventions, to the examination of differences over time, space and among different social groups, and to the analysis of the behaviors and attitudes of different stakeholders (the sufferers, their relatives, health care personnel, public opinion). We focus here on euthanasia and assisted suicide (EAS). First, we discuss changes in public opinion on EAS in developed countries. Second, we analyze the diffusion and temporal trends of EAS, with a particular focus on Switzerland, the Netherlands, and Belgium; three countries for which it is also possible to consider the connections between the diffusion of EAS and palliative care. Third, we consider several differential aspects of the spread of EAS (mainly by sex, age, and cause of death). [ABSTRACT FROM AUTHOR]

We have studied the reduction reactions of two cytosolic human peroxiredoxins (Prx) in their disulfide form by three thioredoxins (Trx; two human and one bacterial), with the aim of better understanding the rate and mechanism of those reactions, and their relevance in the context of the catalytic cycle of Prx. We have developed a new methodology based on stopped‐flow and intrinsic fluorescence to study the bimolecular reactions, and found rate constants in the range of 105–106 m−1 s−1 in all cases, showing that there is no marked kinetic preference for the expected Trx partner. By combining experimental findings and molecular dynamics studies, we found that the reactivity of the nucleophilic cysteine (CN) in the Trx is greatly affected by the formation of the Prx–Trx complex. The protein–protein interaction forces the CN thiolate into an unfavorable hydrophobic microenvironment that reduces its hydration and results in a remarkable acceleration of the thiol‐disulfide exchange reactions by more than three orders of magnitude and also produces a measurable shift in the pKa of the CN. This mechanism of activation of the thiol disulfide exchange may help understand the reduction of Prx by alternative reductants involved in redox signaling. [ABSTRACT FROM AUTHOR]

The past ∼200 million years of Earth's geomagnetic field behavior have been recorded within oceanic basalts, many of which are only accessible via scientific ocean drilling. Obtaining the best possible paleomagnetic measurements from such valuable samples requires an a priori understanding of their magnetic mineralogies when choosing the most appropriate protocol for stepwise demagnetization experiments (either alternating field or thermal). Here, we present a quick, and non‐destructive method that utilizes the amplitude‐dependence of magnetic susceptibility to screen submarine basalts prior to choosing a demagnetization protocol, whenever conducting a pilot study or other detailed rock‐magnetic characterization is not possible. We demonstrate this method using samples acquired during International Ocean Discovery Program Expedition 391. Our approach is rooted in the observation that amplitude‐dependent magnetic susceptibility is observed in basalt samples whose dominant magnetic carrier is multidomain titanomagnetite (∼TM60–65, (Ti0.60–0.65Fe0.35–0.40)Fe2O4). Samples with low Ti contents within titanomagnetite or samples that have experienced a high degree of oxidative weathering do not display appreciable amplitude dependence. Due to their low Curie temperatures, basalts that possess amplitude‐dependence should ideally be demagnetized either using alternating fields or via finely‐spaced thermal demagnetization heating steps below 300°C. Our screening method can enhance the success rate of paleomagnetic studies of oceanic basalt samples. Plain Language Summary: Oceanic basalts are ideal recorders of the Earth's magnetic field. To decipher magnetic histories recorded in rocks, paleomagnetists need to isolate the magnetization directions and intensities within rocks by one of two possible methods. One method typically involves progressively heating the samples to high temperatures. The other method involves exposing samples to alternating magnetic fields with increasing peak field intensities. Both of these methods are ultimately destructive to the original magnetization preserved within rocks. However, without knowledge of a given rock's magnetic mineralogy, randomly choosing thermal or alternating field demagnetization methods may result in high failure rates. We developed a pre‐screening method to help decide which cleaning method will likely be more successful for a given sample based on low‐field magnetic susceptibility measurements. These measurements do not affect the original magnetic information recorded in a rock, thereby permitting subsequent paleomagnetic studies on the same sample. Our technique can be performed as rapidly as 2 min per sample, is non‐destructive, and does not require complicated sample preparation. Key Points: Paleomagnetic studies utilize either alternating field or thermal demagnetization, but it is difficult to choose the best protocol a prioriAmplitude‐dependence of magnetic susceptibility measurements permits preliminary magnetic mineralogy characterization in submarine basaltsRapid amplitude‐dependence measurements may aid in deciding upon the best demagnetization protocol for submarine basalt samples [ABSTRACT FROM AUTHOR]

Aim: To provide a preliminary evaluation of the accuracy and safety of Gluclas decision support system suggestions in a hypoglycaemic clamp study. Methods: This analysis was performed using data from 32 participants (four groups with different glucose‐insulin regulation: post Roux‐en‐Y gastric bypass with and without postprandial hypoglycaemia syndrome, postsleeve gastrectomy and non‐operated controls) undergoing Gluclas‐assisted hypoglycaemic clamps (target: 2.5 mmol/L for 20 minutes at 150 minutes after oral glucose ingestion). Gluclas provided glucose infusion rate suggestions upon manual entry of blood glucose values (every 5 minutes), which were either followed or overruled by investigators after critical review. Accuracy and safety were evaluated by mean absolute error (MAE), mean absolute percentage error (MAPE), average glucose level, coefficient of variation (CV) and minimal glucose level during the 20‐minute hypoglycaemic period. Results: Investigators accepted 84% of suggestions, with a mean deviation of 30.33 mg/min. During the hypoglycaemic period, the MAE was 0.16 (0.12‐0.24) (median [interquartile range]) mmol/L and the MAPE was 6.12% (4.80%‐9.29%). CV was 4.90% (3.58%‐7.27%), with 5% considered the threshold for sufficient quality. The minimal glucose level was 2.40 (2.30‐2.50) mmol/L. Conclusions: Gluclas achieved sufficiently high accuracy with minimal safety risks in a population with differences in glucose‐insulin dynamics, underscoring its applicability to various patient groups. [ABSTRACT FROM AUTHOR]

The use of supplementary cementitious materials is currently the most favorable strategy for reducing CO2 emissions in cements. Limestone Calcined Clay Cements, LC3, are a type of cement that allows the reduction of CO2 emissions up to 40%. The proportions of the mixtures can vary, but the most investigated combination, LC3‐50, contains about 50 wt% clinker, 30 wt% calcined kaolinitic clay, 15 wt% limestone and an optimised calcium sulphate content. However, the mechanical strengths of LC3 at early ages are not good enough and they should be improved. One way of doing this is by employing commercial strength‐enhancing (accelerator) admixtures based on C‐S‐H nucleation seeding. For this work, LC3‐50 cements were prepared with clays with varying kaolinite contents. Mortars and pastes were fabricated using a new PCE‐based superplasticizer developed to avoid the loss of fluidity at early ages typical of LC3 binders. The selected accelerator for this study was Master X‐Seed STE53. The results show that the loss of fluidity of LC3 mortars during the first hours could be solved by a recently developed PCE‐based superplasticizer. The compressive strengths at 1 day for LC3 mortars strikingly improved by using the C‐S‐H seeding admixture and this behavior was maintained for up to 28 days. [ABSTRACT FROM AUTHOR]

Metawebs (networks of potential interactions within a species pool) are a powerful abstraction to understand how large‐scale species interaction networks are structured.Because metawebs are typically expressed at large spatial and taxonomic scales, assembling them is a tedious and costly process; predictive methods can help circumvent the limitations in data deficiencies, by providing a first approximation of metawebs.One way to improve our ability to predict metawebs is to maximize available information by using graph embeddings, as opposed to an exhaustive list of species interactions. Graph embedding is an emerging field in machine learning that holds great potential for ecological problems.Here, we outline how the challenges associated with inferring metawebs line‐up with the advantages of graph embeddings; followed by a discussion as to how the choice of the species pool has consequences on the reconstructed network, specifically as to the role of human‐made (or arbitrarily assigned) boundaries and how these may influence ecological hypotheses. [ABSTRACT FROM AUTHOR]

Background. β-cell dysfunction and insulin resistance are the main mechanisms causing glucose intolerance in type 2 diabetes (T2D). Bariatric surgeries, i.e., sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), are procedures both known to induce weight loss, increase insulin action, and enhance β-cell function, but hepatic insulin extraction and glucose effectiveness may also play a role. Methods. To determine the contribution of these regulators on glucose tolerance after bariatric surgery, an oral glucose tolerance test (OGTT) was performed before and 2 months after surgery in 9 RYGB and 7 SG subjects. Eight healthy subjects served as metabolic controls. Plasma glucose, insulin, C-peptide, GLP-1, and GIP were measured during each OGTT. Insulin sensitivity and secretion, glucose effectiveness, and glucose rate of appearance were determined via oral minimal models. Results. RYGB and SG resulted in similar weight reductions (13%, RYGB (p < 0.01); 14%, SG (p < 0.05)). Two months after surgery, insulin secretion (p < 0.05) and glucose effectiveness both improved equally in the two groups (11%, RYGB (p < 0.01); 8%, SG (p > 0.05)), whereas insulin sensitivity remained virtually unaltered. Bariatric surgery resulted in a comparable increase in the GLP-1 response during the OGTT, whereas GIP concentrations remained unaltered. Following surgery, oral glucose intake resulted in a comparable increase in hepatic insulin extraction, the response in both RYGB and SG patients significantly exceeding the response observed in the control subjects. Conclusions. These results demonstrate that the early improvement in glucose tolerance in obese T2D after RYGB and SG surgeries is attributable mainly to increased insulin secretion and glucose effectiveness, while insulin sensitivity seems to play only a minor role. This trial is registered with NCT02713555. [ABSTRACT FROM AUTHOR]

Familial Renal Glucosuria (FRG) is a co‐dominantly inherited trait characterized by orthoglycaemic glucosuria. From 2003 to 2015 we have reported several cohorts validating SLC5A2 (16p11.2), encoding SGLT2 (Na+/glucose cotransporter family member 2), as the gene responsible for FRG. The aim of this work was to validate the variants identified in our extended FRG cohort of published, as well more recent unreported cases, according to the ACMG‐AMP 2015 criteria. Forty‐six variants were evaluated, including 16 novel alleles first described in this study. All are rare, ultra‐rare or absent from population databases and most are missense changes. According to the ACMG‐AMP standards, only 74% of the variants were classified as P/LP. The lack of descriptions of unrelated patients with similar variants or failing to test additional affected family members, averted a conclusion for pathogenicity in the alleles that scored VUS, highlighting the importance of both family testing and variant reporting. Finally, the cryo‐EM structure of the hSGLT2–MAP17 complex in the empagliflozin‐bound state improved the ACMG‐AMP pathogenicity score by identifying critical/functional protein domains. [ABSTRACT FROM AUTHOR]

Background: The affective expression of sexual behaviour in individuals with Williams syndrome can lead to risky behaviours, especially if parents do not have information on how to provide sex education or support from specialised professionals. Method: The Attitudes to Sexuality Questionnaire for Individuals with Intellectual Disabilities was used to identify parental beliefs, attitudes and concerns about the sexuality and sex education of individuals with intellectual disabilities. The sample comprised 35 parents of individuals with Williams syndrome (mean age 12.8 years (SD = 4.5), 57.1% male). Results: Parents believe in the possibility of marriage and sexual relationships for individuals with intellectual disability when they are older and agree with sexual reproduction in adulthood. Parents consider that sex education, in addition to parental guidance, should be provided by professionals. Conclusions: This data highlights the need for parents to have clear guidelines on interventions in respect of the sexuality of individuals with intellectual disability. [ABSTRACT FROM AUTHOR]