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A photochemical synthesis of biologically relevant benzyl oxindoles is presented via electron‐donor acceptor (EDA) complex strategy. This exogenous photocatalyst‐free method describes the formation of a new electron donor‐acceptor complex based on potassium carbonate and thianthrenium salts for C(sp2)−C(sp3) bond formation. This transition‐metal free reaction allows a rapid increase in oxindoles molecular complexity chemical space, tolerating different functional groups as well as sophisticated biomolecules. The scalability and sustainability of this method is highlighted by an important waste recovery protocol. Mechanistic investigations support the formation of an EDA complex that induces a radical chain, and the applicability of this method is showcased by straightforward derivatization reactions. [ABSTRACT FROM AUTHOR]

Hydroxytrifluoroethyl and trifluoroacetyl groups are of utmost importance in biologically active compounds, but methods to tether these motifs to organic architectures have been limited. Typically, the preparation of these compounds relied on the use of strong bases or multistep routes. The renaissance of radical chemistry in photocatalytic, transition metal mediated, and hydrogen atom transfer (HAT) processes have allowed the installation of these medicinally relevant fluorinated motifs. This review provides an overview of the methods available for the direct synthesis of hydroxytrifluoroethyl‐ and trifluoroacetyl‐derived compounds governed by single‐electron transfer processes. [ABSTRACT FROM AUTHOR]

Summary: Background: Hepatic steatosis is a common finding in liver histopathology and the hallmark of metabolic dysfunction‐associated steatotic liver disease (MASLD), formerly known as non‐alcoholic fatty liver disease (NAFLD), whose global prevalence is rising. Aims: To review the histopathology of hepatic steatosis and its mechanisms of development and to identify common and rare disease associations. Methods: We reviewed literature on the basic science of lipid droplet (LD) biology and clinical research on acute and chronic liver diseases associated with hepatic steatosis using the PubMed database. Results: A variety of genetic and environmental factors contribute to the development of chronic hepatic steatosis or steatotic liver disease, which typically appears macrovesicular. Microvesicular steatosis is associated with acute mitochondrial dysfunction and liver failure. Fat metabolic processes in hepatocytes whose dysregulation leads to the development of steatosis include secretion of lipoprotein particles, uptake of remnant lipoprotein particles or free fatty acids from blood, de novo lipogenesis, oxidation of fatty acids, lipolysis and lipophagy. Hepatic insulin resistance is a key feature of MASLD. Seipin is a polyfunctional protein that facilitates LD biogenesis. Assembly of hepatitis C virus takes place on LD surfaces. LDs make important, functional contact with the endoplasmic reticulum and other organelles. Conclusions: Diverse liver pathologies are associated with hepatic steatosis, with MASLD being the most important contributor. The biogenesis and dynamics of LDs in hepatocytes are complex and warrant further investigation. Organellar interfaces permit co‐regulation of lipid metabolism to match generation of potentially toxic lipid species with their LD depot storage. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) is becoming increasingly important in nuclear medicine and drug discovery. To date, the development of many potential PET tracers is hampered by the lack of suitable synthetic pathways for their preparation. This is particularly true for the highly desired radiolabeling of compounds bearing [18F]CF3‐groups. For instance, S(O)nCF3‐groups (n=0, 1, 2) serve as structural motif in a range of biologically active compounds, but their radiosynthesis remains largely unprecedented (for n=1, 2). Herein, we describe general methods for the radiosynthesis of 18F‐labeled aryl trifluoromethyl sulfones, ‐sulfoxides, and ‐sulfides. All three methods are operationally straightforward, start from widely available precursors, i.e., sulfonyl fluorides and thiophenols, and make use of the recently established [18F]Ruppert‐Prakash reagent. Further, the syntheses display good functional group tolerance as demonstrated by the 18F‐labeling of more than 40 compounds. The applicability of the new method is demonstrated by the radiolabeling of three bioactive molecules, optionally to be used as PET tracers. In a broader context, this work presents a substantial expansion of the chemical space of radiofluorinated structural motifs to be used for the development of new PET tracers. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) is becoming increasingly important in nuclear medicine and drug discovery. To date, the development of many potential PET tracers is hampered by the lack of suitable synthetic pathways for their preparation. This is particularly true for the highly desired radiolabeling of compounds bearing [18F]CF3‐groups. For instance, S(O)nCF3‐groups (n=0, 1, 2) serve as structural motif in a range of biologically active compounds, but their radiosynthesis remains largely unprecedented (for n=1, 2). Herein, we describe general methods for the radiosynthesis of 18F‐labeled aryl trifluoromethyl sulfones, ‐sulfoxides, and ‐sulfides. All three methods are operationally straightforward, start from widely available precursors, i.e., sulfonyl fluorides and thiophenols, and make use of the recently established [18F]Ruppert‐Prakash reagent. Further, the syntheses display good functional group tolerance as demonstrated by the 18F‐labeling of more than 40 compounds. The applicability of the new method is demonstrated by the radiolabeling of three bioactive molecules, optionally to be used as PET tracers. In a broader context, this work presents a substantial expansion of the chemical space of radiofluorinated structural motifs to be used for the development of new PET tracers. [ABSTRACT FROM AUTHOR]

The feasibility to discriminate potentially asbestos‐containing components from asbestos‐free concrete based on camera images using the example of wall demolition waste is investigated. For this, three types of asbestos substitute materials and two types of concrete are crushed and photographed. The classification of the fragment images is carried out with a) morphological and texture features and b) with features automatically extracted by the pretrained MobileNetV3 network. Feret diameters, circularity, and others served as morphological descriptors. The texture was described by measures of grey‐level intensity, as obtained from the grey‐level co‐occurrence matrix. Support vector machines are found to achieve classification accuracies above 99 % based on the automatically extracted features. The presented identification approach is promising to automate the treatment process of asbestos‐containing materials from construction and demolition waste, which is effortful and requires expert knowledge to this day. [ABSTRACT FROM AUTHOR]

The amyotrophic lateral sclerosis (ALS) functional rating scale‐revised (ALSFRS‐R) has become the most widely utilized measure of disease severity in patients with ALS, with change in ALSFRS‐R from baseline being a trusted primary outcome measure in ALS clinical trials. This is despite the scale having several established limitations, and although alternative scales have been proposed, it is unlikely that these will displace ALSFRS‐R in the foreseeable future. Here, we discuss the merits of delta FS (ΔFS), the slope or rate of ALSFRS‐R decline over time, as a relevant tool for innovative ALS study design, with an as yet untapped potential for optimization of drug effectiveness and patient management. In our view, categorization of the ALS population via the clinical determinant of post‐onset ΔFS is an important study design consideration. It serves not only as a critical stratification factor and basis for patient enrichment but also as a tool to explore differences in treatment response across the overall population; thereby, facilitating identification of responder subgroups. Moreover, because post‐onset ΔFS is derived from information routinely collected as part of standard patient care and monitoring, it provides a suitable patient selection tool for treating physicians. Overall, post‐onset ΔFS is a very attractive enrichment tool that is, can and should be regularly incorporated into ALS trial design. [ABSTRACT FROM AUTHOR]

Summary: Background and Objective: The aim was assessing a short training for healthcare providers on patient‐focused counselling to treat childhood obesity in primary care, along with dietitian‐led workshops and educational materials. Methods: Randomized clustered trial conducted with paediatrician‐nurse pairs (Basic Care Units [BCU]) in primary care centres from Tarragona (Spain). BCUs were randomized to intervention (MI) (motivational interview, dietitian‐led education, and educational materials) or control group (SC, standard care). Participants were 8–14‐year‐old children with obesity, undergoing 1–11 monthly treatment visits during 1 year at primary care centres. The primary outcome was BMI z‐score reduction. Results: The study included 44 clusters (23 MI). Out of 303 allocated children, 201 (n = 106 MI) completed baseline, final visits, and at least one treatment visit and were included in the analysis. BMI z‐score reduction was −0.27 (±0.31) in SC, versus −0.36 (±0.35) in MI (p = 0.036). Mixed models with centres as random effects showed greater reductions in BMI in MI than SC; differences were B = −0.11 (95% CI: −0.20, −0.01, p = 0.025) for BMI z‐score, and B = −2.06 (95% CI: −3.89, −0.23, p = 0.028) for BMI %. No severe adverse events related to the study were notified. Conclusion: Training primary care professionals on motivational interviewing supported by dietitians and educational materials, enhanced the efficacy of childhood obesity therapy. [ABSTRACT FROM AUTHOR]

For aging‐related research, there is a pressing need to attend to the dissemination and implementation of evidence‐based interventions. Some aging‐related interventions with established effectiveness may be poorly disseminated and implemented due to behavioral, organizational, payment, or other constraints. To provide insight into the beginning to end process of translation and implementation, we present a case history of the three‐decade progression of Hospital at Home (HaH) now nearing national dissemination. We summarize research at various phases with particular attention to implementation considerations. Reviewing over three decades of HaH‐related research dating from initial discovery to translation and implementation, we found that the content and importance of different constructs (e.g., inner practice vs. outer environmental setting) and the choice of implementation strategies differed depending on implementation context (testing of effectiveness, scaling, or sustainability). Early effectiveness studies mostly examined implementation issues related to the intervention, the practice setting, and the individuals involved. However, explicit and early consideration of scale and sustainment was not the primary focus. For example, HaH program intake is primarily through hospital emergency departments (ED). Initial efforts would have benefited from incorporating strategies (e.g., incorporating ED leadership into program leadership) to address night and weekend admissions. Many regulatory barriers did not surface during initial considerations. Considering implementation issues late may contribute to delay in bringing discoveries to population impact. The experience with HaH suggests that scale and sustainability bear earlier consideration because barriers and facilitators to implementation are likely to be different in content and importance at different phases of implementation. [ABSTRACT FROM AUTHOR]

Plasma‐derived medicinal products (PDMPs) are recognized internationally as essential medicines required to treat various acute and chronic conditions including congenital deficiencies of plasma proteins in haemophilia and primary immune deficiency. Global provision of these medicines is dominated by a small number of commercial companies, influencing the price and availability of the products. Achieving a level of strategic independence from this dominance is now seen as a public health priority in many countries. During the Regional Congress of the International Society for Blood Transfusion (ISBT) in Cape Town, South Africa, in November 2023, around 50 delegates from 24 countries participated in a workshop (WS) organized jointly by the International Plasma and Fractionation Association (IPFA) and the ISBT Working Party on Global Blood Safety on pathways towards provision of PDMPs from domestic plasma independent of commercial purchase in the open market. The WS was structured around three themes, each addressed by a separate group: Quality/safety requirements for plasma for fractionation (PfF) Stepwise access for safe plasma proteins Approaching contract fractionation A synthesis of conclusions from these groups included the following: The need to acquire support from government authorities for a national plasma policy, recognizing the difficulties posed by unstable political and bureaucratic environments. The value of embedding plasma and PDMPs within a patient blood management (PBM) paradigm to promote optimal clinical use of PDMPs. Training of blood/plasma collection personnel in the relevant principles of Good Manufacturing Practice (GMP), coupled with regulatory oversight of plasma product production in the engaged jurisdictions. Appreciation that limited access to contract fractionation may necessitate a stepwise approach, which may include small‐scale preparation of versions of essential plasma proteins as an intermediate phase towards the manufacture of industrial‐scale PDMPs from domestic plasma. [ABSTRACT FROM AUTHOR]

This study investigates the germination requirements of 12 plant species native to the Argyle region of the east Kimberley, a biodiverse monsoonal tropical region characterized by high temperatures, high evaporation, and episodic seasonal rainfall. The research involved quality assessment of mature seeds, followed by dormancy alleviation and laboratory‐based germination to determine the responses of seeds to a range of temperatures (5–40°C) in terms of germination speed (T10), mean germination time, and maximum germination proportion. Data were then modeled to calculate the optimal temperature to support germination for each species. The results showed that germination rapidly commences in response to a wide range of temperatures typical of the wet season (November–February) in the east Kimberley, though germination for most species was still high (>50%) after exposure to temperatures as low as 15°C. Mean optimal temperature for germination across all species was 25.8 ± 1.5°C, with minimal variation between most species, the exception being Dodonaea physocarpa, which preferred cooler temperatures (Topt = 14.0°C). The speed of germination was also rapid (T10 = 1–3 days) across all species at the optimal germination temperature. The findings suggest that temperature is not a limiting factor for germination in this region and that the onset and intensity of the wet season are the most significant factors determining successful germination, emergence, and seedling establishment. The study underscores the importance of species‐specific understanding of environmental temperatures required for seed germination in seed‐based restoration efforts and informs the planning of direct seeding works, thus enhancing restoration outcomes. [ABSTRACT FROM AUTHOR]

Electron delocalization and aromaticity was comparatively evaluated in recently synthesized figure‐eight molecules made of two condensed U‐shaped polycyclic aromatic hydrocarbon moieties connected either by two single bonds or by two para‐phenylene groups. The selected examples include molecules that incorporate eight‐membered and sixteen‐membered rings, as well as a doubly [5]helicene‐bridged (1,4)cyclophane. We probe whether some electron delocalization could occur through the stereogenic single bonds in these molecules: Is aromaticity purely (semi‐)local, or possibly also global in these molecules? It was concluded that the situation can go from a purely (semi‐)local character when the dihedral angle at the connecting single bonds is large, such as in biphenyl, to a predominantly (semi‐)local character with a minor global contribution when the dihedral angle is small, such as in the para‐phenylene connectors of the [5] helicene‐bridged cyclophane. [ABSTRACT FROM AUTHOR]

Summary: Multiagent chemoimmunotherapy remains the standard of care treatment for Burkitt lymphoma leading to a cure in the majority of cases. However, frontline treatment regimens are associated with a significant risk of treatment related toxicity especially in elderly and immunocompromised patients. Additionally, prognosis remains dismal in refractory/relapsed Burkitt lymphoma. Thus, novel therapies are required to not only improve outcomes in relapsed/refractory Burkitt lymphoma but also minimize frontline treatment related toxicities. Recurrent genomic changes and signalling pathway alterations that have been implicated in the Burkitt lymphomagenesis include cell cycle dysregulation, cell proliferation, inhibition of apoptosis, epigenetic dysregulation and tonic B‐cell receptor‐phosphatidylinositol 3‐kinase (BCR‐PI3K) signalling. Here, we will discuss novel targeted therapy approaches using small molecule inhibitors that could pave the way to the future treatment landscape based on the understanding of recurrent genomic changes and signalling pathway alterations in the lymphomagenesis of adult Burkitt lymphoma. [ABSTRACT FROM AUTHOR]

Aim Methods and Results Conclusions Recommendations for surveillance after colonoscopy are based on risk factors for metachronous advanced colorectal neoplasia (AN) and colorectal cancer (CRC). The value of these risk factors remains unclear in populations enriched by individuals with a positive faecal immunochemical test and were investigated in a modern setting.This population‐based cohort study included all individuals in the Netherlands of ≥55 years old with a first adenoma diagnosis in 2015. A total of 22,471 patients were included. Data were retrieved from the Dutch Nationwide Pathology Databank (Palga). Primary outcomes were metachronous AN and CRC. Patient and polyp characteristics were evaluated by multivariable Cox regression analyses. During follow‐up, 2416 (10.8%) patients were diagnosed with AN, of which 557 (2.5% from the total population) were CRC. Adenomas with high‐grade dysplasia (hazard ratio [HR] 1.60, 95% confidence interval [CI] 1.40–1.83), villous histology (HR 1.91, 95% CI 1.59–2.28), size ≥10 mm (HR 1.12, 95% CI 1.02–1.23), proximal location (HR 1.12, 95% CI 1.02–1.23), two or more adenomas (HR 1.28, 95% CI 1.16–1.41), and serrated polyps ≥10 mm (HR 1.67, 95% CI 1.42–1.97) were independent risk factors for metachronous AN. In contrast, only adenomas with high‐grade dysplasia (HR 2.49, 95% CI 1.92–3.24) were an independent risk factor for metachronous CRC.Risk factors for metachronous AN and CRC were identified for populations with access to a faecal immunochemical test (FIT)‐based screening programme. If only risk factors for metachronous CRC are considered, a reduction in criteria for surveillance seems reasonable. [ABSTRACT FROM AUTHOR]

The current density–voltage characteristic (J–V) is a critical tool for understanding the behavior of solar cells. This study presents an overview of the key aspects of J–V analysis and introduces a user‐friendly flowchart that facilitates the swift identification of the most probable limiting process in a solar cell, based mainly on the outcomes of light‐intensity‐dependent J–V measurements. The flowchart is developed through extensive drift‐diffusion simulations and a rigorous review of the literature, with a specific focus on perovskite and organic solar cells. Moreover, the flowchart proposes supplementary experiments that can be conducted to obtain a more precise prediction of the primary performance losses. It therefore serves as an optimal starting point to analyse performance losses of solar cells. [ABSTRACT FROM AUTHOR]

The recent complexity of the university system, with diverse academic trajectories and varying socio‐demographic characteristics of students, has led to increased access for historically underrepresented students. This has resulted in a rising number of adult learners, students with external responsibilities and individuals returning to education. However, despite this enhanced access, it remains unclear whether it has improved graduation. This uncertainty stems from the fact that students' social circumstances and external responsibilities differ significantly based on when they enter university. From a life course perspective, the aim of this paper is to explore the interactive effects of age at university entrance and employment status on the probability of graduating of an entire cohort of new students who entered the Catalan Higher Education System in 2012 (N = 29,463). The results show an interaction effect between age and employment status on the probability of graduation where working decreases the probability of graduation among students younger than 42 years old. Conversely, the negative impact of employment on university graduation diminishes among students entering university at an older age. This underscores the importance of adopting a life course perspective to comprehend students' educational experiences and outcomes within higher education. [ABSTRACT FROM AUTHOR]

This combined experimental and theoretical study illustrates the profound consequences of non‐planarity on the electronic properties of polycyclic arenes. Three isomeric [10]fibonacene tetraesters were synthesized through a robust and regiocontrolled Perkin/Mallory approach: a nearly planar [10]phenacene derivative, a moderately twisted [10]semicircle derivative, and a 3D non‐planar [10]helicene derivative. The photophysical properties of the 3D [10]helicene isomer were found to be dramatically different from the comparable ones of the [10]phenacene and [10]semicircle isomers. The aromatic properties of the [10]phenacene and [10]semicircle isomers conform well with their predictive Kekulé and Clar analyses, but the [10]helicene isomer deviates from these general topological rules, which appears to be a general phenomenon for [n]fibonacenes with n≥9. [ABSTRACT FROM AUTHOR]

This combined experimental and theoretical study illustrates the profound consequences of non‐planarity on the electronic properties of polycyclic arenes. Three isomeric [10]fibonacene tetraesters were synthesized through a robust and regiocontrolled Perkin/Mallory approach: a nearly planar [10]phenacene derivative, a moderately twisted [10]semicircle derivative, and a 3D non‐planar [10]helicene derivative. The photophysical properties of the 3D [10]helicene isomer were found to be dramatically different from the comparable ones of the [10]phenacene and [10]semicircle isomers. The aromatic properties of the [10]phenacene and [10]semicircle isomers conform well with their predictive Kekulé and Clar analyses, but the [10]helicene isomer deviates from these general topological rules, which appears to be a general phenomenon for [n]fibonacenes with n≥9. [ABSTRACT FROM AUTHOR]

Aims: To investigate the exposure–response (E‐R) relationship, including exposure–efficacy and exposure–safety, of ropeginterferon alfa‐2b treatment in patients with polycythaemia vera (PV). Methods: Based on the results of the phase II trial A20‐202 regarding ropeginterferon alfa‐2b in patients with PV, E‐R analyses were performed to evaluate the efficacy and safety of the given dosing regimen. The E‐R analyses were based on logistic and linear regression and the relationship between exposure to ropeginterferon alfa‐2b and key efficacy and safety variables. The key efficacy variables included complete haematologic response (CHR) and reduction of the driver mutation JAK2V617F. The safety variable was treatment‐related adverse events (TRAEs). Results: A clear relationship between the exposure to ropeginterferon alfa‐2b and CHR was observed, with an increase in drug exposure resulting in an increased probability of achieving CHR. Similar CHR probabilities were observed in the third and fourth quantiles of the average concentration at Week 24. The results from the exposure–JAK2V617F model indicated that the JAK2V617F allele burden decreased with increasing exposure to ropeginterferon alfa‐2b and baseline body surface area. Exposure–safety analysis revealed a risk of AEs associated with transaminase abnormalities, which were not associated with clinical significance. Conclusions: Our analyses have shown that patients with PV treated with ropeginterferon alfa‐2b had an increased probability of achieving CHR and a molecular response with acceptable safety risks at the 250–350–500 μg titration dosing regimen. This study has provided the relevant data for the application of a biologics licence of ropeginterferon alfa‐2b for PV treatment in China. [ABSTRACT FROM AUTHOR]

Purpose: Myopia is the most important risk factor for developing retinal tears and retinal detachment (RD). Due to altered lifestyle factors myopia is increasing in the world. In this study, the correlation between educational level and risk for retinal detachment were analysed. Methods: A case–control registry study was conducted including a total of 10 268 individuals. Data were collected from registries of the Swedish National Board of Health and Welfare as well as the Swedish Central Bureau of Statistics. Cases were defined as ICD‐10 H33 (retinal detachments and breaks). For each case, a matched control was selected with the same age and sex, living in the same county at the time of diagnosis. The study population was divided into seven groups with regard to educational level and compared using conditional logistic regression. Results: In the total population, the odds ratio (OR) increased in a proportional fashion with a higher level of education. The odds ratio for the total population at the highest education level was 1.77 and increased to 2.00 when excluding individuals with diabetes. Out of the 5134 cases, 72% were men and 28% women. A statistically significant difference between sexes was only confirmed for the second highest education level. Conclusion: Individuals with a longer education have a significantly higher risk for retinal complications in the form of RD and breaks. Higher education is a risk factor for retinal complications in both sexes but seemingly more strongly in men. [ABSTRACT FROM AUTHOR]

Developing the technique of Acoustic travel time TOMography (ATOM) for monitoring the indoor air temperature and airflow measurements represents a significant breakthrough for modern buildings especially those prioritizing thermal comfort. While conventional measurement methods are limited to individual measuring points, ATOM technique can measure the climatic parameters' distribution across the entire room with high spatial resolution utilizing sound velocity measurements along various propagation sound paths. This research outlines the ongoing development of the ATOM technique for simultaneous measuring the indoor air temperature and airflow velocity at the Department of Building Physics at the Bauhaus‐University Weimar. It presents both the challenges confronted and the solutions developed in establishing a straightforward measuring system that can optimally fulfil the requirements of the indoor climate projects. [ABSTRACT FROM AUTHOR]

Carbon‐11 (11C) is a widely used radionuclide for positron emission tomography (PET) owing to the omnipresence of carbon atoms in organic molecules. While its half‐life of 20.4 min is ideal for imaging and dosimetry, it also limits the synthetic possibilities. As such, the development of fast and easy, high‐yielding synthesis methods is crucial for the application of 11C‐labeled tracers in humans. In this study, we present a novel and efficient method for the reaction of [11C]CO2 with amine precursors using benzotriazole‐1‐yl‐oxy‐tris‐(dimethylamino)‐phosphonium hexafluorophosphate (BOP) to access 11C‐labeled ureas. Our method is extremely fast as it only requires transfer of [11C]CO2 into a solution with precursor and BOP at room temperature, where it reacts momentary into the desired 11C‐labeled urea. This simple procedure makes it possible to radiolabel urea directly from [11C]CO2 without the need for advanced equipment, making the method applicable for all laboratories where [11C]CO2 is available. We synthesized a small series of aliphatic symmetrical and non‐symmetrical 11C‐labeled ureas using this method, and achieved good to excellent yields. The novelty of our study lies in the fact that peptide coupling reagent BOP is used for the first time in radiochemistry to activate [11C]CO2, facilitating its reaction with amines to obtain 11C‐labeled ureas. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions Common genetic variations in the nitric oxide synthase‐1 adaptor protein (NOS1AP) gene are associated with QT‐interval prolongation. In a previous study, we observed an association between the rs10494366 variant of this gene and an increased QT‐interval shortening in digoxin users. As QT‐interval shortening is a risk factor for sudden cardiac death (SCD), in this study, we investigated whether the association between digoxin use and risk of SCD differs in participants with different NOS1AP rs10494366 genotypes.We included 11 377 individuals from the prospective population‐based cohort of the Rotterdam Study. We used Cox proportional hazard regression analysis with digoxin as time‐dependent exposure to estimate the associations between current digoxin use and the risk of SCD among different rs10494366 genotype groups in the adjusted models. We also studied whether such an association was dose‐dependent, comparing high dosage (≥ 0.250 mg), moderate dosage (0.125 mg ≤ dose< 0.250 mg) and low dosage (< 0.125 mg) digoxin users with non‐users.The median baseline age of the total study population was 62 (interquartile range [IQR] 58–71) years. The cumulative incidence of SCD was 4.1% (469 cases), and among them, 74 (15.7%) individuals were current digoxin users at the time of death, during a median follow‐up of 11.5 (IQR 6.5–17) years. Current digoxin users had an increased risk of SCD (multivariable adjusted model hazard ratio [HR]: 3.07; 95% confidence interval [CI]: 2.38–3.98), with no significant differences between the three genotype groups. The adjusted HRs were 4.03 [95% CI: 1.98–8.21] in the minor homozygous GG, 3.46 [95% CI: 2.37–5.04] in the heterozygous TG and 2.56 [95%CI: 1.70–3.86] in the homozygous TT genotype groups. Compared to low‐ and moderate‐dose, high‐dose digoxin users with GG genotype had the highest risk of SCD (HR: 5.61 [95% CI: 1.34–23.47]).Current use of digoxin is associated with a significantly increased risk of SCD. The NOS1AP gene rs10494366 variant did not modify the digoxin‐associated risk of SCD in a population of European ancestry. [ABSTRACT FROM AUTHOR]

Introduction Aim Methods Results Conclusion In patients with an increased bleeding tendency, extensive diagnostic blood testing is often performed. When results of tier 1 assays of primary haemostasis are normal, protocols recommend additional testing to rule out rare disorders including coagulation factor XIII (FXIII) and α2‐antiplasmin (α2AP) deficiency.To evaluate the added diagnostic value of FXIII and α2AP levels in patients with a bleeding disorder of unknown cause (BDUC).A retrospective monocentre cohort study between August 2011 and August 2023 was conducted. In all patients with bleeding tendencies and normal diagnostic tests for von Willebrand disease and platelet function, FXIII and α2AP were measured.We included 158 consecutive patients; mean ISTH‐BAT scores were 8.2 (SD ± 3.7) in children, 6.2 (SD ± 2.1) in men and 10.6 (SD ± 3.3) in women. Median age was 37 (range 5–79) years, 88.6% of patients were female. Patients displayed median FXIII activity of 111% (IQR = 97–131) and median α2AP activity of 112% (IQR = 103–119).Three (1.9%) patients had FXIII levels < 50%, respectively 43%, 45% and 46%. Corresponding ISTH‐BAT scores were 7, 12 and 14. No α2AP levels < 60% was observed. No significant association was found between FXIII levels and ISTH‐BAT scores.In our cohort of BDUC patients, no clinical relevant FXIII deficiencies were detected; absolute values were well above the 30% cutoff considered adequate for normal haemostasis. No α2AP deficiencies were detected. These data suggest that in BDUC patients, measuring FXIII or AP activity is of limited value. [ABSTRACT FROM AUTHOR]

Objective Design Setting Population Methods Main outcome measures Results Conclusions To investigate how reproductive history was associated with urinary incontinence in midlife.A follow‐up study.Denmark.A total of 39 977 mothers who participated in the Maternal Follow up (2013–2014) in the Danish National Birth Cohort. National registries provided their reproductive history.How parity, mode of birth and obstetric tears associated with urinary incontinence were estimated with adjusted odds ratios (OR) and 95% CI using logistic regression.Self‐reported urinary incontinence including subtypes stress, urge and mixed urinary incontinence.At an average age of 44 years, the prevalence of any urinary incontinence was 32% (21% stress, 2% urge, and 8% mixed urinary incontinence). Women with two births more often had urinary incontinence than women with one birth (OR 1.20, 95% CI 1.10–1.31). Compared with women with only spontaneous births, a history of only caesarean sections was associated with much lower odds of urinary incontinence (OR 0.39, 95% CI 0.35–0.42) and a history of instrumental births with slightly lower odds (OR 0.92, 95% CI 0.86–0.98). Compared with no tear/first‐degree tear as the largest tear, episiotomy was associated with less urinary incontinence (OR 0.91, 95% CI 0.86–0.97) whereas third/fourth‐degree tears were associated with more (OR 1.14, 95% CI 1.04–1.25). Findings were mainly explained by similar associations with stress and mixed urinary incontinence.Vaginal birth was associated with a higher risk of long‐term urinary incontinence, but our results indicate that this risk may be reduced by shortening the second stage of birth. [ABSTRACT FROM AUTHOR]

The haloform reaction from methyl ketones to carboxylic acids is one of the oldest known synthetic organic reactions, which has been used in myriad applications over the decades. The corresponding reaction to produce esters is, however, less developed, as the reaction is generally limited to simple, primary alcohols that are used in solvent‐level quantities, thereby restricting the complexity of esters that can be directly formed. Herein, we detail the development of a general ester‐forming haloform coupling reaction using one equivalent of alcohol. Mechanistic and kinetic modelling studies demonstrated that the key intermediates are formed under equilibrium, which facilitated the development of conditions that are amenable to secondary alcohols. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Abnormalities in ataxin‐2 associated with spinocerebellar ataxia type 2 (SCA2) may lead to widespread disruptions in the proteome. This study was performed to identify dysregulated proteome in SCA2 and to explore its clinical‐radiological correlations.Cerebrospinal fluid (CSF) samples from 21 genetically confirmed SCA2 were subjected to shotgun proteome analysis using mass spectrometry (MS) and tandem mass tag (TMT)‐based multiplexing. Proteins with at least 1.5‐fold change in abundance were identified. Their relative abundance was measured using parallel reaction monitoring (PRM) and correlated against disease‐related factors.Eleven proteins were significantly upregulated in SCA2. They belonged to the family of cell adhesion molecules and granins. Their fold changes showed significant clinical, genetic, and radiological correlations.Significant dysregulation of CSF proteome is seen in SCA2. The dysregulated protein may have potential use in clinical evaluation of patients with SCA2. © 2024 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

The haloform reaction from methyl ketones to carboxylic acids is one of the oldest known synthetic organic reactions, which has been used in myriad applications over the decades. The corresponding reaction to produce esters is, however, less developed, as the reaction is generally limited to simple, primary alcohols that are used in solvent‐level quantities, thereby restricting the complexity of esters that can be directly formed. Herein, we detail the development of a general ester‐forming haloform coupling reaction using one equivalent of alcohol. Mechanistic and kinetic modelling studies demonstrated that the key intermediates are formed under equilibrium, which facilitated the development of conditions that are amenable to secondary alcohols. [ABSTRACT FROM AUTHOR]

Implantable medical devices require protective encapsulation to isolate them from the biological environment. Parylene‐C (PaC) is a prevalent encapsulation polymer but is susceptible to cracking, delamination, oxidation, and moisture penetration over time. This study demonstrates that 3D micro‐anchors fabricated by direct laser writing (DLW) greatly enhance PaC lifetime and encapsulation properties. The PaC film is vapor deposited onto these anchor points, followed by ultraviolet radiation (UV)‐curing‐induced shrinkage. Electrochemical impedance spectroscopy (EIS) during accelerated aging tests in reactive solutions (87 °C, 15 mM H2O2) is performed to monitor film degradation over time. Unpatterned PaC films failed before reaching the 3.25 accelerated year benchmark, while 100 µm spaced micro‐anchors extended encapsulation up to 5.5 equivalent years. Subsequent improvements are achieved with a spacing of 50 µm, demonstrating viability up to ≈6 equivalent years. This research demonstrates the benefit of engineering anchor points for preventing delamination of the PaC layer and significantly enhancing encapsulation properties. Printed 3D micro‐anchors are an extremely flexible platform, with many different shapes and sizes possible which can further enhance longevity. The success in increasing coating lifetimes offers a promising direction for improving long‐term implantable medical devices, potentially revolutionizing their longevity and reliability. [ABSTRACT FROM AUTHOR]

A vast amount of media‐related text data is generated daily in the form of social media posts, news stories or academic articles. These text data provide opportunities for researchers to analyse and understand how substance‐related issues are being discussed. The main methods to analyse large text data (content analyses or specifically trained deep‐learning models) require substantial manual annotation and resources. A machine‐learning approach called 'zero‐shot learning' may be quicker, more flexible and require fewer resources. Zero‐shot learning uses models trained on large, unlabelled (or weakly labelled) data sets to classify previously unseen data into categories on which the model has not been specifically trained. This means that a pre‐existing zero‐shot learning model can be used to analyse media‐related text data without the need for task‐specific annotation or model training. This approach may be particularly important for analysing data that is time critical. This article describes the relatively new concept of zero‐shot learning and how it can be applied to text data in substance use research, including a brief practical tutorial. [ABSTRACT FROM AUTHOR]

Coherent X-ray imaging is an active field at synchrotron sources. The images rely on the available coherent flux over a limited field of view. At many synchrotron beamlines a double-crystal monochromator (DCM) is employed in a standard nondispersive arrangement. For coherent diffraction imaging it is advantageous to increase the available field of view by increasing the spatial coherence length (SCL) of a beam exiting such a DCM. Here, Talbot interferometry data together with ray-tracing simulations for a (+ - - +) four-reflection experimental arrangement are presented, wherein the first two reflections are in the DCM and the final fourth reflection is asymmetric at grazing exit. Analyses of the interferometry data combined with the simulations show that compared with the beam exiting the DCM a gain of 76% in the SCL was achieved, albeit with a factor of 20 reduction in flux density, which may not be a severe penalty at a synchrotron beamline. Previous efforts reported in the literature to increase the SCL that employed asymmetric crystal diffraction at grazing incidence are also discussed. A much reduced SCL is found presently in simulations wherein the same asymmetric crystal is set for grazing incidence instead of grazing exit. In addition, the present study is compared and contrasted with two other means of increasing the SCL. These are (i) focusing the beam onto an aperture to act as a secondary source, and (ii) allowing the beam to propagate in vacuum an additional distance along the beamline. [ABSTRACT FROM AUTHOR]

Summary: Cancer progression can be restrained by tumor‐infiltrating lymphocytes in a process termed cancer immunosurveillance. Based on how lymphocytes are activated and recruited to the tumor tissue, cancer immunity is either pre‐wired, in which innate lymphocytes and innate‐like T cells are directly recruited to and activated in tumors following their differentiation in primary lymphoid organs; or priming‐dependent, in which conventional adaptive T cells are first primed by cognate antigens in secondary lymphoid organs before homing to and reactivated in tumors. While priming‐dependent cancer immunity has been a focus of cancer immunology research for decades, in part due to historical preconception of cancer theory and tumor model choice as well as clinical success of conventional adaptive T cell‐directed therapeutic programs, recent studies have revealed that pre‐wired cancer immunity mediated by tissue‐resident type 1 innate lymphoid cells (ILC1s) and killer innate‐like T cells (ILTCKs) is an integral component of the cancer immunosurveillance process. Herein we review the distinct ontogenies and cancer‐sensing mechanisms of ILC1s and ILTCKs in murine genetic cancer models as well as the conspicuously conserved responses in human malignancies. How ILC1s and ILTCKs may be targeted to broaden the scope of cancer immunotherapy beyond conventional adaptive T cells is also discussed. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic has accelerated the spread of conspiracy theories. Previous research has found that individuals who struggle with emotion regulation are more prone to believing in conspiracy theories. Emotional granularity, or the ability to differentiate between nuanced emotional states, is a key component of effective emotion regulation, yet its relationship with conspiracy beliefs has not been explored thoroughly. Thus, we conducted an experience‐sampling study (165 participants, mean age = 26.32 years) including measures of emotion regulation and differentiation. The findings revealed that individuals who endorse conspiracy theories engage in repetitive thinking about the causes and consequences of events and exhibit a reduced ability to distinguish between negative emotions. This effect, however, was observed only in the performance‐based measure of emotion differentiation, not in the self‐report measures. This suggests that enhancing emotional granularity may help individuals in regulating their emotions more effectively, thereby reducing their vulnerability to adopt conspiracy beliefs. [ABSTRACT FROM AUTHOR]

The potential for climate change to disrupt phenology‐mediated interactions in interaction networks has attracted considerable attention in recent decades. Frequently, studies emphasize the fragility of ephemeral seasonal interactions, and the risks posed by phenological asynchrony. Here, we argue that the fitness consequences of asynchrony in phenological interactions may often be more buffered than is typically acknowledged. We identify three main forms that buffering may take: (i) mechanisms that reduce asynchrony between consumer and resource; (ii) mechanisms that reduce the costs of being asynchronous; and (iii) mechanisms that dampen interannual variance in performance across higher organizational units. Using synchrony between the hatching of winter moth caterpillars and the leafing of their host‐plants as a case study, we identify a wide variety of buffers that reduce the detrimental consequences of phenological asynchrony on caterpillar individuals, populations, and meta‐populations. We follow this by drawing on examples across a breadth of taxa, and demonstrate that these buffering mechanisms may be quite general. We conclude by identifying key gaps in our knowledge of the fitness and demographic consequences of buffering, in the context of phenological mismatch. Buffering has the potential to substantially alter our understanding of the biotic impacts of future climate change—a greater recognition of the contribution of these mechanisms may reveal that many trophic interactions are surprisingly resilient, and also serve to shift research emphasis to those systems with fewer buffers and towards identifying the limits of those buffers. [ABSTRACT FROM AUTHOR]

Unsustainable wildlife trade is a major contributor to biodiversity loss; however, trade regulations have failed to prevent the decline of high‐profile species. Where wildlife is traded legally, opportunities exist to launder protected species through legal channels. The legal commercialization of olive ridley sea turtle eggs from Ostional, Costa Rica, has been criticized with some suggesting that the legal trade stimulates illegal extraction and sale of eggs. We aimed to identify whether the traceability rules, under which the Ostional project operates, were suitably robust. We surveyed markets across Costa Rica, by purchasing openly available sea turtle eggs and recording qualitative and quantitative data at the point of sale. We found that 378 (80%) of turtle eggs openly sold in the market were from olive ridley sea turtles. Green (n = 5) and leatherback (n = 6) turtle eggs were only on offer on three occasions, but no vendor referred to Ostional. Vendors frequently breached trade regulations, which appeared to be due to these regulations misaligning with consumer demand. Although the Ostional traceability rules are regularly flouted, we found no evidence that Ostional is being used as a cover to sell eggs from other turtle species. [ABSTRACT FROM AUTHOR]

The present paper reports a remote carbon‐to‐carbon boryl migration via an intramolecular 1,4‐B/Cu shift, which establishes an in situ stereospecific electrophilic trap on the alkene moiety. The synthetic application is developed to prepare functionalized cyclopentenes by means of a palladium‐catalyzed regioselective intramolecular coupling that completes a strategic cyclopropanation and generates valuable structural bicyclic systems. The mechanism is characterized by DFT (density functional theory) calculations which showed that the 1,4‐migration proceeds through an intramolecular, nucleophilic attack of the copper‐alkyl moiety on the boron atom bonded to the C(sp2), leading to a 5‐membered boracycle structure. The computation of the 1,3‐ and 1,4‐B/Cu shifts is also compared as is the impact of the endo‐ or exocyclic alkene on the reaction kinetics. [ABSTRACT FROM AUTHOR]

We executed this study to determine if chemerin‐like receptor 1 (CMKLR1), a Gi/o protein‐coupled receptor expressed by leukocytes and non‐leukocytes, contributes to the development of phenotypic features of non‐atopic asthma, including airway hyperresponsiveness (AHR) to acetyl‐β‐methylcholine chloride, lung hyperpermeability, airway epithelial cell desquamation, and lung inflammation. Accordingly, we quantified sequelae of non‐atopic asthma in wild‐type mice and mice incapable of expressing CMKLR1 (CMKLR1‐deficient mice) following cessation of acute inhalation exposure to either filtered room air (air) or ozone (O3), a criteria pollutant and non‐atopic asthma stimulus. Following exposure to air, lung elastic recoil and airway responsiveness were greater while the quantity of adiponectin, a multi‐functional adipocytokine, in bronchoalveolar lavage (BAL) fluid was lower in CMKLR1‐deficient as compared to wild‐type mice. Regardless of genotype, exposure to O3 caused AHR, lung hyperpermeability, airway epithelial cell desquamation, and lung inflammation. Nevertheless, except for minimal genotype‐related effects on lung hyperpermeability and BAL adiponectin, we observed no other genotype‐related differences following O3 exposure. In summary, we demonstrate that CMKLR1 limits the severity of innate airway responsiveness and lung elastic recoil but has a nominal effect on lung pathophysiology induced by acute exposure to O3. [ABSTRACT FROM AUTHOR]

Cold atmospheric plasma (CAP) is a source of cell‐damaging oxidant molecules that may be used as low‐cost cancer treatment with minimal side effects. Liquids treated with cold plasma and enriched with oxidants are a modality for non‐invasive treatment of internal tumors with cold plasma via injection. However, liquids are easily diluted with body fluids which impedes high and localized delivery of oxidants to the target. As an alternative, plasma‐treated hydrogels (PTH) emerge as vehicles for the precise delivery of oxidants. This study reports an optimal protocol for the preparation of injectable alginate PTH that ensures the preservation of plasma‐generated oxidants. The generation, storage, and release of oxidants from the PTH are assessed. The efficacy of the alginate PTH in cancer treatment is demonstrated in the context of cancer cell cytotoxicity and immunogenicity–release of danger signals and phagocytosis by immature dendritic cells, up to now unexplored for PTH. These are shown in osteosarcoma, a hard‐to‐treat cancer. The study aims to consolidate PTH as a novel cold plasma treatment modality for non‐invasive or postoperative tumor treatment. The results offer a rationale for further exploration of alginate‐based PTHs as a versatile platform in biomedical engineering. [ABSTRACT FROM AUTHOR]

Introduction: Liver disease is a leading cause of morbidity and mortality among persons living with HIV (PLHIV). While chronic viral hepatitis has been extensively studied in low‐ and middle‐income countries (LMICs), there is limited information about the burden of metabolic disorders on liver disease in PLHIV. Methods: We conducted a cross‐sectional analysis of baseline data collected between October 2020 and July 2022 from the IeDEA‐Sentinel Research Network, a prospective cohort enrolling PLHIV ≥40 years on antiretroviral treatment (ART) for ≥6 months from eight clinics in Asia, Americas, and central, East, southern and West Africa. Clinical assessments, laboratory testing on fasting blood samples and liver stiffness measurement (LSM)/controlled attenuation parameter (CAP) by vibration‐controlled transient elastography were performed. Multivariable logistic regression models assessed factors associated with liver fibrosis (LSM ≥7.1 kPa) and steatosis (CAP ≥248 dB/m). Population attributable fraction (PAF) of each variable associated with significant liver fibrosis was estimated using Levin's formula. Results: Overall, 2120 PLHIV (56% female, median age 50 [interquartile range: 45−56] years) were included. The prevalence of obesity was 19%, 12% had type 2 diabetes mellitus (T2DM), 29% had hypertension and 53% had dyslipidaemia. The overall prevalence of liver fibrosis and steatosis was 7.6% (95% confidence interval [CI] 6.1−8.4) and 28.4% (95% CI 26.5−30.7), respectively, with regional variability. Male sex at birth (odds ratio [OR] 1.62, CI 1.10−2.40), overweight/obesity (OR = 2.50, 95% CI 1.69−3.75), T2DM (OR 2.26, 95% CI 1.46−3.47) and prolonged exposure to didanosine (OR 3.13, 95% CI 1.46−6.49) were associated with liver fibrosis. Overweight/obesity and T2DM accounted for 42% and 11% of the PAF for liver fibrosis, while HBsAg and anti‐HCV accounted for 3% and 1%, respectively. Factors associated with steatosis included overweight/obesity (OR 4.25, 95% CI 3.29−5.51), T2DM (OR 2.06, 95% CI 1.47−2.88), prolonged exposure to stavudine (OR 1.69, 95% CI 1.27−2.26) and dyslipidaemia (OR 1.68, 95% CI 1.31−2.16). Conclusions: Metabolic disorders were significant risk factors for liver disease among PLHIV in LMICs. Early recognition of metabolic disorders risk factors might be helpful to guide clinical and lifestyle interventions. Further prospective studies are needed to determine the causative natures of these findings. [ABSTRACT FROM AUTHOR]

A systematic procedure is introduced for modeling charge‐neutral non‐polar surfaces of ionic minerals containing polyatomic anions. By integrating distance‐ and charge‐based clustering to identify chemical species within the mineral bulk, our pipeline, PolyCleaver, renders a variety of theoretically viable surface terminations. As a demonstrative example, this approach was applied to forsterite (Mg2SiO4), unveiling a rich interface landscape based on interactions with formaldehyde, a relevant multifaceted molecule, and more particularly in prebiotic chemistry. This high‐throughput method, going beyond techniques traditionally applied in the modeling of minerals, offers new insights into the potential catalytic properties of diverse surfaces, enabling a broader exploration of synthetic pathways in complex mineral systems. [ABSTRACT FROM AUTHOR]

Although CH2FCl (HCFC‐31) recently became of great atmospheric importance, studies concerning its excited states are almost nonexistent. Several excited singlet states were studied (valence nσ* and Rydberg n3s, n3p, σ3s, and σ3p) through highly correlated multireference configuration interaction with singles and doubles, including extensivity correction. Comparison with the states of CH3Cl indicates a strong influence of the F atom. Potential energy curves suggest formation of an electrostatically bound complex that relaxes to a hydrogen‐bonded contact ion‐pair (HBCIP) which can decay yielding CH2F + Cl or to the ground state minimum of CH2FCl. The HBCIP has a dipole moment of 9.57 D, a CI wavefunction described as 0.65ionic + 0.20biradical and it is strongly bonded by 4.72 eV. Its H bond has characteristics of moderate and strong H bonds. The simulated absorption spectrum confirms the nσ* assignment for the first and suggests the n3s + n3pσ assignment for the second band. [ABSTRACT FROM AUTHOR]

Rationale: SLAP is one of the two calibration materials for the isotopic water scale. By consensus the established δ18O value is −55.5‰, although several expert laboratories measure significantly more negative δ18OSLAP values. The real δ18OSLAP value as such does not influence the isotopic water scale; however, knowledge of the size of isotopic scale contraction in stable isotope measurements is vital for second‐order isotopes. This study describes the quantification of δ18OSLAP with respect to δ18OVSMOW. Methods: SLAP‐like water was quantitatively mixed with highly 18O‐enriched water to mimic VSMOW. The 18O concentration was determined using an electron ionization quadrupole mass spectrometer. The isotopic composition of the SLAP‐like and VSMOW‐like waters was measured using an optical spectrometer, alongside original VSMOW and SLAP. Results: This study resulted in a much more negative δ18O value for SLAP than expected. The averaged outcome of seven independent experiments is δ18OSLAP = −56.33 ± 0.03‰. There is a large discrepancy between the actual isotopic measurements of even the most carefully operating isotope laboratories and the true δ18O value. Conclusions: Although this finding as such does not influence the use of the VSMOW–SLAP scale, it raises the intriguing question of what we actually measure with our instruments and why even a fully corrected measurement can be so far off. Our result has consequences for issues like the transfer of δ18O from and to the VPDB scale, various fractionation factors, and Δ17O. The absolute 18O abundance for SLAP was calculated as (1887.98 ± 0.43) × 10−6 based on the absolute 18O abundance of VSMOW and the presented δ18OSLAP in this paper. [ABSTRACT FROM AUTHOR]

Tunability in electronic and optical properties has been intensively explored for developing conjugated polymers and their applications in organic and perovskite‐based electronics. Particularly, the charge carrier mobility of conjugated polymer semiconductors has been deemed to be a vital figure‐of‐merit for achieving high‐performance organic field‐effect transistors (OFETs). In this study, the systematic hole carrier mobility improvement of benzo[1,2‐b:4,5‐b']dithiophene‐based conjugated polymer in perovskite‐functionalized organic transistors is demonstrated. In conventional OFETs with a poly(methyl methacrylate) (PMMA) gate dielectric, improvements in hole mobility of 0.019 cm2 V−1 s−1 are measured using an off‐center spin‐coating technique, which exceeds those of on‐center counterparts (0.22 ± 0.07 × 10−2 cm2 V−1 s−1). Furthermore, the mobility drastically increases by adopting solid‐state electrolyte gating, corresponding to 2.99 ± 1.03 cm2 V−1 s−1 for the control, and the best hole mobility is 8.03 cm2 V−1 s−1 (average ≈ 6.94 ± 0.59 cm2 V−1 s−1) for perovskite‐functionalized OFETs with a high current on/off ratio of >106. The achieved device performance would be attributed to the enhanced film crystallinity and charge carrier density in the hybrid perovskite‐functionalized organic transistor channel, resulting from the high‐capacitance electrolyte dielectric. [ABSTRACT FROM AUTHOR]

The recycling of polyolefins for multiple life cycles is becoming a legislative requirement in the South African plastics industry. This study shows that this cannot be a blanket requirement for all polyolefins. While HDPE displays good resistance to weathering, the decrease in molecular weight limits the maximum number of life cycles before which the resultant product has lost all integrity. Impact polypropylenes fare much worse during weathering and more than 50% of impact properties are lost within the first 12 months of exposure. The blending of virgin material into degraded material can recover some properties of HDPE but not in the case of impact polypropylenes. The same legislation can therefore not be applied to all plastics and specific targets should depend on polymer composition. [ABSTRACT FROM AUTHOR]

In this research, we propose an environmentally friendly method for producing hematite nanoparticles (H‐NPs) from natural hematite ore, focusing on their application as efficient contrast agents in x‐ray and computed tomography (CT) imaging for medical purposes. The process involves the reduction of iron oxide within the ore to attain the desired hematite phase, crucial for synthesizing H‐NPs. To ensure sustainability, we adopted a Green Chemistry approach, utilizing a combination of carbon soot and limestone for the purification process, thereby achieving eco‐conscious production. The produced H‐NPs were thoroughly characterized using various analytical techniques, such as x‐ray fluorescence (XRF), x‐ray diffraction (XRD), Fourier transmission infrared spectroscopy (FT‐IR), and FESEM‐EDX (field emission scanning electron microscopy‐energy‐dispersive x‐ray spectroscopy). XRD analysis confirmed the crystalline rhombohedral hexagonal lattice structure, while FT‐IR spectra indicated the presence of characteristic Fe–O stretching modes in line with the expected molecular composition. FESEM‐EDX imaging unveiled agglomerated particles, ranging in size from 54.6 to 149.9 nm for iron ore and 22 nm for H‐NPs. These particles were primarily composed of iron (Fe) and oxygen (O). The magnetic properties of the H‐NPs were investigated through vibrating sample magnetometer (VSM) studies, highlighting their distinct ferromagnetic behavior. Of particular significance, the H‐NPs demonstrated exceptional performance as contrast agents in both x‐ray and CT imaging. Even at minimal concentrations, they exhibited remarkable x‐ray absorption capabilities. CT scans further validated their exceptional absorptive capacity. These findings emphasize the potential of H‐NPs as valuable assets in medical imaging, serving as sustainable tools for enhanced diagnostic applications. The study showcases an eco‐conscious approach to harnessing natural resources, paving the way for a greener and more effective utilization of H‐NPs in the medical imaging landscape. [ABSTRACT FROM AUTHOR]

Raman spectroscopy and laser ablation‐inductively coupled plasma‐mass spectrometry were used to characterize the chemical composition of 34 red garnet beads from Lower Nubian sites, dated between about 3200 BCE and 600 CE. All beads from the A‐Group to the Meroitic period feature a similar calcium‐poor almandine composition (69%–78% almandine, 15%–22% pyrope, 2%–6% grossular, 3%–9% spessartine), which differs from other calcium‐poor almandine garnet types, sourced mostly from Indian deposits in Antiquity. The Nubian beads constitute a new garnet type, named “cluster I”, featuring high yttrium (180 to 1205 ppm), moderately low chromium (13–70 ppm), and high scandium (119–213 ppm) concentrations. Their compositions match with previous and two new analyses from two alluvial garnet deposits, Wadi El‐Haraz and Wadi Abu Dom, near the Fourth Cataract of the Nile in Upper Nubia, about 670 km as the crow flies from the Lower Nubian graves. Garnet trade between the Bayuda desert and Lower Nubia sites, and possibly even Egypt, flourished for almost four millennia. Northeastern Africa is the cradle for the oldest use of a gemstone that is harder than quartz—the red almandine garnet.A Post‐Meroitic bead, the youngest in the assembly, displays an unusual faceting, a diamond tipped drill hole, excellent polish, distinct short‐ and long‐prismatic colorless mineral inclusions, and a calcium‐ and manganese‐poor pyrope composition. This suggests that it was not of a local, Nubian, production, but imported, most probably from a South Asian site. [ABSTRACT FROM AUTHOR]

The road from transcription to protein synthesis is paved with many obstacles, allowing for several modes of post-transcriptional regulation of gene expression. A fundamental player in mRNA biology is DDX3X, an RNA binding protein that canonically regulates mRNA translation. By monitoring dynamics of mRNA abundance and translation following DDX3X depletion, we observe stabilization of translationally suppressed mRNAs. We use interpretable statistical learning models to uncover GC content in the coding sequence as the major feature underlying RNA stabilization. This result corroborates GC content-related mRNA regulation detectable in other studies, including hundreds of ENCODE datasets and recent work focusing on mRNA dynamics in the cell cycle. We provide further evidence for mRNA stabilization by detailed analysis of RNA-seq profiles in hundreds of samples, including a Ddx3x conditional knockout mouse model exhibiting cell cycle and neurogenesis defects. Our study identifies a ubiquitous feature underlying mRNA regulation and highlights the importance of quantifying multiple steps of the gene expression cascade, where RNA abundance and protein production are often uncoupled. Synopsis: Monitoring the dynamics of mRNA changes after DDX3X depletion indicates translation suppression followed by mRNA stabilization. GC content in the CDS is a strong predictor of mRNA stabilization and it is detectable in multiple transcriptomics datasets, with a potential link to cell-cycle regulation. RNA-seq and Ribo-seq on a time course of DDX3X depletion show regulation of translation and mRNA levels. Intron-exon count modeling and SLAM-seq demonstrate post-transcriptional mRNA stabilization. Random Forest and Lasso show GC content in the CDS (GCcds) as a main predictor of mRNA stabilization. ENCODE RBP knockdowns and in vivo datasets show widespread GCcds-dependent mRNA stabilization. Monitoring the dynamics of mRNA changes after DDX3X depletion indicates translation suppression followed by mRNA stabilization. GC content in the CDS is a strong predictor of mRNA stabilization and it is detectable in multiple transcriptomics datasets, with a potential link to cell-cycle regulation. [ABSTRACT FROM AUTHOR]

Introduction: Tenofovir‐based oral pre‐exposure prophylaxis is currently approved for HIV prevention; however, adherence in women has been low. A vaginal gel containing tenofovir (TFV) demonstrated partial protection to HIV but protection was not confirmed in additional studies. Vaginal rings offer user‐controlled long‐acting HIV prevention that could overcome adherence and protection challenges. TFV may also help prevent herpes simplex virus type 2 acquisition when delivered intravaginally. We evaluated the pharmacokinetics, safety, adherence and acceptability of a 90‐day TFV ring. Methods: Between January and June 2019, Microbicide Trials Network (MTN)‐038 enrolled 49 HIV‐negative participants into a phase 1, randomized (2:1) trial comparing a 90‐day ring containing 1.4 grams (g) TFV to a placebo ring. TFV concentrations were quantified in plasma, cervicovaginal fluid (CVF), rectal fluid and cervical tissue, and TFV‐diphosphate (TFV‐DP) in cervical tissue. Used rings were analysed for residual TFV. Safety was assessed by adverse events (AEs); acceptability and adherence by self‐report. Results: Mean age was 29.5; 46 identified as cisgender‐female and three gender non‐conforming. There were no differences in the proportion of participants with grade ≥2 genitourinary AEs in the TFV versus placebo arms (p = 0.41); no grade ≥3 AEs were reported. Geometric mean TFV concentrations increased through day 34 in CVF/rectal fluid and day 59 in plasma, but declined across compartments by day 91. Geometric mean TFV‐DP tissue concentrations exceeded the 1000 fmol/mg target through day 56, but fell to 456 fmol/mg at day 91. Among 32 rings returned at the end of the study, 13 had no or low (<0.1 g) residual TFV. Residual TFV did not differ by socio‐demographics, sexual activity, Nugent Score or vaginal microbiota. Most participants reported being fully adherent to ring use: 85% and 81% in the TFV and placebo arms, respectively (p = 1.00). A majority of participants reported liking the ring (median 8 on a 10‐point Likert scale) and reported a high likelihood of using the ring in the future, if effective (median 9). Conclusions: The 90‐day TFV ring was well‐tolerated, acceptable and exceeded target cervical tissue concentrations through day 56, but declined thereafter. Additional studies are needed to characterize the higher release from TFV rings in some participants and the optimal duration of use. [ABSTRACT FROM AUTHOR]

Most people coreside with other kin in private households while others live alone. The incidence of coresidence with kin and solo living varies noticeably across societies. Scholars have long theorized about the role of modernization and cultural change for living arrangements, suggesting a trend toward the nuclearization of households (coresidence only with primary kin) or solo living as societies attain higher levels of development. There is little empirical evidence about global variations in living arrangements and about how such variations unfold at different levels of development. Here we address these fundamental questions. Using IPUMS census microdata for 279 samples and 90 countries, we develop a new metric for assessing the part of the lifetime a person can expect to reside with primary kin, nonprimary kin, or alone assuming exposure rates, from birth to death, to the living arrangements observed in a given year. Results show that coresidence patterns differ substantially across societies, with exposure to primary kin alone and to solo living substantially higher at higher levels of development (as measured with Human Development Index [HDI]). They also reveal a sustained decline in coresidence with nonprimary kin and/or with others nearly everywhere, supporting the idea of an increasing importance of nuclear living arrangements. This trend is most pronounced at medium levels of HDI. At very high levels of development, nuclear family coresidence tends to be stalling or is in decline in favor of more time spent living alone and, rather unexpectedly, to a modest increase in exposure to nonprimary kin within the household. We suggest different interpretations for these results. [ABSTRACT FROM AUTHOR]