JURNAL AGROTEKNOLOGI
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    John Keats in the season of mists

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    Allylic alcohols and amines by carbenoid eliminative cross-coupling using epoxides or aziridines

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    α-Lithiated terminal epoxides and N-(tert-butylsulfonyl)aziridines undergo eliminative cross-coupling with α-lithio ethers, to give convergent access to allylic alcohols and allylic amines, respectively. The process can be considered as proceeding by selective strain-relieving attack (ring-opening) of the lithiated three-membered heterocycle by the lithio ether and then selective β-elimination of lithium alkoxide

    A qualitative exploration of men's perceptions of the terms “male sterilization” versus “vasectomy” in the southern United States

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    Objectives Clinical literature and contraception information guides use the terms “male sterilization” and “vasectomy” interchangeably. We investigate the meanings men attach to “sterilization” and how those meanings compare to perceptions of “vasectomy.” Study design Cisgender, heterosexual men, ages 25 to 67, living across seven U.S. southern states participated in individual telephone interviews from May to December 2019. Interviews explored men's experiences with contraception, including their perception of the term “sterilization.” We audio-recorded and transcribed the interviews and conducted thematic analyses using an inductive approach. Results While most participants described “vasectomy” as a relatively benign procedure, they described “sterilization” as “sinister,” “bleak,” and “barbaric.” Participants’ discussions of sterilization invoked associations with eugenicist practices and specific historical examples of forced sterilization. While some participants recognized that vasectomy is a means of achieving sterilization, most viewed the term “sterilization” as incongruous with the modern medical procedure of “vasectomy,” precisely because sterilization has been used as a form of reproductive oppression. Conclusion Our findings suggest that men have strong affective responses to the term “sterilization.” Participants’ knowledge of historical eugenicist practices has implications for the acceptability of vasectomy as a permanent contraceptive option in our contemporary context. Implications The phrase “male sterilization” can be associated with eugenics and coercive reproductive practices. Using the term for reproductive counselling, education, or research purposes may have implications for the acceptability of vasectomy as a permanent contraceptive option

    A prospective study of the relationships between change in body composition and cardiovascular risk factors across the menopause

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    Objective: Menopause increases the risk of cardiovascular disease (CVD) which in part has been attributed to the rises in cholesterol and blood pressure (BP). This study examined the hypothesis that menopausal changes in body composition and regional fat depots relate to the change in CVD risk factors. Methods: A prospective recall study was designed to capture premenopausal women to be reexamined soon after menopause. A total of 97 women from the Oxford Biobank underwent dual x-ray absorptiometry, blood biochemistry and BP readings pre- and post-menopause. Results: Despite minimal changes in body weight over the 5.1±0.9 year follow-up period, there was an increase in total fat mass and a decline in lean mass, where the proportional change of regional fat mass was the greatest for the visceral fat depot (+22%, p<0.01). Plasma ApoB (+12%, p<0.01) and CRP (+45%, p<0.01) increased as did systolic (+7%, p<0.001) and diastolic BP (+5%, p<0.001). Plasma NEFA decreased (-20%, p<0.05) which may reflect on a change in adipose tissue function across the menopause. PCSK-9 decreased (-26%, p<0.01) which suggests a compensation for the postmenopausal reduction in LDL receptor activity. Using a multilinear regression analyses the changes in ApoB and DBP were associated with visceral fat mass change, but this association was lost when adjusted for total fat mass change. Conclusion: The increase in CVD risk factor burden across menopause may not be driven by changes in body composition, rather by functional changes in end organs such as adipose tissue and liver

    Prediction models for child and adolescent mental health: A systematic review of methodology and reporting in recent research

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    Background There has been a rapid growth in the publication of new prediction models relevant to child and adolescent mental health. However, before their implementation into clinical services, it is necessary to appraise the quality of their methods and reporting. We conducted a systematic review of new prediction models in child and adolescent mental health, and examined their development and validation. Method We searched five databases for studies developing or validating multivariable prediction models for individuals aged 18 years old or younger from 1 January 2018 to 18 February 2021. Quality of reporting was assessed using the Transparent Reporting of a multivariable prediction models for Individual Prognosis Or Diagnosis checklist, and quality of methodology using items based on expert guidance and the PROBAST tool. Results We identified 100 eligible studies: 41 developing a new prediction model, 48 validating an existing model and 11 that included both development and validation. Most publications (k = 75) reported a model discrimination measure, while 26 investigations reported calibration. Of 52 new prediction models, six (12%) were for suicidal outcomes, 18 (35%) for future diagnosis, five (10%) for child maltreatment. Other outcomes included violence, crime, and functional outcomes. Eleven new models (21%) were developed for use in high-risk populations. Of development studies, around a third were sufficiently statistically powered (k = 16%, 31%), while this was lower for validation investigations (k = 12, 25%). In terms of performance, the discrimination (as measured by the C-statistic) for new models ranged from 0.57 for a tool predicting ADHD diagnosis in an external validation sample to 0.99 for a machine learning model predicting foster care permanency. Conclusions Although some tools have recently been developed for child and adolescent mental health for prognosis and child maltreatment, none can be currently recommended for clinical practice due to a combination of methodological limitations and poor model performance. New work needs to use ensure sufficient sample sizes, representative samples, and testing of model calibration

    Faropenem reacts with serine and metallo-β-lactamases to give multiple products

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    Penems have demonstrated potential as antibacterials and β-lactamase inhibitors; however, their clinical use has been limited, especially in comparison with the structurally related carbapenems. Faropenem is an orally active antibiotic with a C2 tetrahydrofuran (THF) ring, which is resistant to hydrolysis by some β-lactamases. We report studies on the reactions of faropenem with carbapenem-hydrolysing β-lactamases, focusing on the class A serine βlactamase KPC-2 and the metallo β-lactamases (MBLs) VIM-2 (a subclass B1 MBL) and L1 (a B3 MBL). Kinetic studies show that faropenem is a substrate for all three β-lactamases, though it is less efficiently hydrolysed by KPC-2. Crystallographic analyses on faropenemderived complexes reveal the opening of the β-lactam ring with formation of an imine with KPC-2, VIM-2, and L1. In the cases of the KPC-2 and VIM-2 structures, the THF ring is opened to give an alkene, but with L1 the THF ring remains intact. Solution state studies, employing NMR, were performed on L1, KPC-2, VIM-2, VIM-1, NDM-1, OXA-23, OXA-10, and OXA-48. The solution results reveal, in all cases, formation of imine products in which the THF ring is opened; formation of a THF ring-closed imine product was only observed with VIM-1 and VIM-2. An enamine product with a closed THF ring was also observed in all cases, at varying levels. Combined with previous reports, the results exemplify the potential for different outcomes in the reactions of penems with MBLs and SBLs and imply further structure-activity relationship studies are worthwhile to optimise the interactions of penems with β-lactamases. They also exemplify how crystal structures of β-lactamase substrate/inhibitor complexes do not always reflect reaction outcomes in solution

    Low parasite connectivity among three malaria hotspots in Thailand

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    Identifying sources and sinks of malaria transmission is critical for designing effective intervention strategies particularly as countries approach elimination. The number of malaria cases in Thailand decreased 90% between 2012 and 2020, yet elimination has remained a major public health challenge with persistent transmission foci and ongoing importation. There are three main hotspots of malaria transmission in Thailand: Ubon Ratchathani and Sisaket in the Northeast; Tak in the West; and Yala in the South. However, the degree to which these hotspots are connected via travel and importation has not been well characterized. Here, we develop a metapopulation model parameterized by mobile phone call detail record data to estimate parasite flow among these regions. We show that parasite connectivity among these regions was limited, and that each of these provinces independently drove the malaria transmission in nearby provinces. Overall, our results suggest that due to the low probability of domestic importation between the transmission hotspots, control and elimination strategies can be considered separately for each region

    Plakophilin-2 truncating variants impair cardiac contractility by disrupting sarcomere stability and organization

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    Progressive loss of cardiac systolic function in arrhythmogenic cardiomyopathy (ACM) has recently gained attention as an important clinical consideration in managing the disease. However, the mechanisms leading to reduction in cardiac contractility are poorly defined. Here, we use CRISPR gene editing to generate human induced pluripotent stem cells (iPSCs) that harbor plakophilin-2 truncating variants (PKP2tv), the most prevalent ACM-linked mutations. The PKP2tv iPSC–derived cardiomyocytes are shown to have aberrant action potentials and reduced systolic function in cardiac microtissues, recapitulating both the electrical and mechanical pathologies reported in ACM. By combining cell micropatterning with traction force microscopy and live imaging, we found that PKP2tvs impair cardiac tissue contractility by destabilizing cell-cell junctions and in turn disrupting sarcomere stability and organization. These findings highlight the interplay between cell-cell adhesions and sarcomeres required for stabilizing cardiomyocyte structure and function and suggest fundamental pathogenic mechanisms that may be shared among different types of cardiomyopathies

    Vertically migrating Isoxys and the early Cambrian biological pump

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    The biological pump is crucial for transporting nutrients fixed by surface-dwelling primary producers to demersal animal communities. Indeed, the establishment of an efficient biological pump was likely a key factor enabling the diversification of animals over 500 Myr ago during the Cambrian explosion. The modern biological pump operates through two main vectors: the passive sinking of aggregates of organic matter, and the active vertical migration of animals. The coevolution of eukaryotes and sinking aggregates is well understood for the Proterozoic and Cambrian; however, little attention has been paid to the establishment of the vertical migration of animals. Here we investigate the morphological variation and hydrodynamic performance of the Cambrian euarthropod Isoxys. We combine elliptical Fourier analysis of carapace shape with computational fluid dynamics simulations to demonstrate that Isoxys species likely occupied a variety of niches in Cambrian oceans, including vertical migrants, providing the first quantitative evidence that some Cambrian animals were adapted for vertical movement in the water column. Vertical migration was one of several early Cambrian metazoan innovations that led to the biological pump taking on a modern-style architecture over 500 Myr ago

    Colorimetric metal-free detection of carbon monoxide: reversible CO uptake by a BNB frustrated Lewis pair

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    We report two BNB-type frustrated Lewis pairs which feature an acceptor-donor-acceptor functionalized cavity, and which differ in the nature of the B-bound fluoroaryl group (C6F5 vs. C6H3(CF3)2-3,5, Arf). These receptor systems are capable of capturing gaseous CO, and in the case of the -BArf2 system this can be shown to occur in reversible fashion at/above room temperature. For both systems, the binding event is accompanied by migration of one of the aryl substituents to the electrophilic carbon of the CO guest. Experiments utilizing an additional equivalent of PtBu3 allow the initially formed (non-migrated) CO adduct to be identified and trapped (via demethylation), while also establishing the reversibility of the B-to-C migration process. When partnered with the slightly less Lewis acidic -BArf2 substituent, this reversibility allows for release of the captured carbon monoxide in the temperature range 40–70 °C, and the possibility for CO sensing, making use of the associated colourless to orange/red colour change

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