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Extant analyses identified the various channels through which the ongoing Russia‐Ukraine war is hurting Africa's aspiration toward sustainable food security. They however acknowledged that the crisis presents a viable opportunity to kickstart the process of reversing Africa's food dependence and minimizing the continent's vulnerabilities to future external food shocks. It is however feared that the well‐known leadership deficit in the continent poses significant impediment for exploiting opportunities offered by such 'good crisis'. The international community is, therefore, called upon to help Africa to better prepare for the next crisis. Taking this as our point of departure, we argue that the onus of reversing Africa's food dependence rests squarely on Africa's political leaders and policy makers and not on any external intervention. We then propose a residual option for tackling the leadership challenge and for launching Africa on the path of sustainable food security in line with the target of SDG‐2. The study relied on qualitative descriptive analysis of both primary and secondary data. [ABSTRACT FROM AUTHOR]

Background: Lenvatinib (LEN) and atezolizumab + bevacizumab (A + B) have drastically changed the treatment paradigm for advanced hepatocellular carcinoma (HCC). Before these landmark trials, sorafenib (SOR) served as the standard first‐line treatment for a decade. Our study aimed to assess the outcomes of HCC patients treated during the SOR era (2008–2018) in contrast to those in the post‐SOR era (2018–2021), of which the predominant first‐line treatments were LEN or A + B. Methods: Inclusion criteria of the study were all HCC patients in the Canadian province of Alberta who started first‐line systemic therapy at cancer centers between 1 January 2008 and 31 December 2021. Survival outcomes, including overall survival (OS) and progression‐free survival (PFS), along with clinician‐assessed response rate (RR), were subject to retrospective analysis. Results: Of 372 total patients, 230 received treatment in the SOR era and 142 in the post‐SOR era. The demographic and clinical characteristics for the SOR era and post‐SOR era groups are as follows, respectively: the median age was 63 and 64 years, 80% and 81% were male, and 24% and 11% were of East Asian ethnicity. Before receiving systemic treatment, 40% and 33% received TACE, 7% and 9% received TARE, and 3% and 14% received SBRT in the two eras, respectively. In the post‐SOR era, patients received A + B (23%), LEN (51%), and SOR (23%) as first‐line treatment. There was a statistically significant improvement in RR (15% vs. 26%; p = 0.02), median PFS (3.8 months vs. 7.9 months; p < 0.0001), and median OS (9.8 months vs. 17.0 months; p < 0.0001). Conclusions: In this retrospective multicenter real‐world study, HCC patients treated in the post‐SOR era, where LEN and A + B were commonly used first‐line treatments, exhibited superior OS, PFS, and RR compared to patients treated in the SOR era. The findings of this study affirm the tangible progress achieved in the real world in enhancing outcomes for HCC patients through advancements in treatments over the past 15 years. [ABSTRACT FROM AUTHOR]

Telomere length (TL) is an important indicator of cellular aging. Shorter TL is associated with several age‐related diseases including coronary heart disease, heart failure, diabetes, osteoporosis, and cancer. Recently, a DNA methylation‐based TL (DNAmTL) estimator has been developed as an alternative method for directly measuring TL. In this study, we examined the association of DNAmTL with cancer prevalence and mortality risk among people with and without HIV in the Veterans Aging Cohort Study Biomarker Cohort (VACS, N = 1917) and Women's Interagency HIV Study Cohort (WIHS, N = 481). We profiled DNAm in whole blood (VACS) or in peripheral blood mononuclear cells (WIHS) using an array‐based method. Cancer prevalence was estimated from electronic medical records and cancer registry data. The VACS Index was used as a measure of physiologic frailty. Models were adjusted for self‐reported race and ethnicity, batch, smoking status, alcohol consumption, and five cell types (CD4, CD8, NK, B cell, and monocyte). We found that people with HIV had shorter average DNAmTL than those without HIV infection [beta = −0.25, 95% confidence interval (−0.32, −0.18), p = 1.48E‐12]. Greater value of VACS Index [beta = −0.002 (−0.003, −0.001), p = 2.82E‐05] and higher cancer prevalence [beta = −0.07 (−0.10, −0.03), p = 1.37E‐04 without adjusting age] were associated with shortened DNAmTL. In addition, one kilobase decrease in DNAmTL was associated with a 40% increase in mortality risk [hazard ratio: 0.60 (0.44, 0.82), p = 1.42E‐03]. In summary, HIV infection, physiologic frailty, and cancer are associated with shortening DNAmTL, contributing to an increased risk of all‐cause mortality. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Blood protein biomarkers demonstrate potential for Alzheimer's disease (AD) diagnosis. Limited studies examine the molecular changes in AD blood cells. METHODS: Bulk RNA‐sequencing of blood cells was performed on AD patients of Chinese descent (n = 214 and 26 in the discovery and validation cohorts, respectively) with normal controls (n = 208 and 38 in the discovery and validation cohorts, respectively). Weighted gene co‐expression network analysis (WGCNA) and deconvolution analysis identified AD‐associated gene modules and blood cell types. Regression and unsupervised clustering analysis identified AD‐associated genes, gene modules, cell types, and established AD classification models. RESULTS: WGCNA on differentially expressed genes revealed 15 gene modules, with 6 accurately classifying AD (areas under the receiver operating characteristics curve [auROCs] > 0.90). These modules stratified AD patients into subgroups with distinct disease states. Cell‐type deconvolution analysis identified specific blood cell types potentially associated with AD pathogenesis. DISCUSSION: This study highlights the potential of blood transcriptome for AD diagnosis, patient stratification, and mechanistic studies. Highlights: We comprehensively analyze the blood transcriptomes of a well‐characterized Alzheimer's disease cohort to identify genes, gene modules, pathways, and specific blood cells associated with the disease.Blood transcriptome analysis accurately classifies and stratifies patients with Alzheimer's disease, with some gene modules achieving classification accuracy comparable to that of the plasma ATN biomarkers.Immune‐associated pathways and immune cells, such as neutrophils, have potential roles in the pathogenesis and progression of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Background: Medial temporal lobe atrophy (MTA) is a diagnostic marker for mild cognitive impairment (MCI) and Alzheimer's disease (AD), but the accuracy of quantitative MTA (QMTA) in diagnosing early AD is unclear. This study aimed to investigate the accuracy of QMTA and its related components (inferior lateral ventricle [ILV] and hippocampus) with MTA in the early diagnosis of MCI and AD. Method s : This study included four groups: normal (NC), MCI stable (MCIs), MCI converted to AD (MCIs), and mild AD (M‐AD) groups. Magnetic resonance image analysis software was used to quantify the hippocampus, ILV, and QMTA. MTA was rated by two experienced neurologists. Receiver operating characteristic area under the curve (AUC) analysis was performed to compare their capability in differentiating AD from NC and MCI, and optimal thresholds were determined using the Youden index. Results: QMTA distinguished M‐AD from NC and MCI with higher diagnostic accuracy than MTA, hippocampus, and ILV (AUCNC = 0.976, AUCMCI = 0.836, AUCMCIs = 0.894, AUCMCIc = 0.730). The diagnostic accuracy of QMTA was superior to that of MTA, the hippocampus, and ILV in differentiating MCI from AD. The diagnostic accuracy of QMTA was found to remain the best across age, sex, and pathological subgroups analyzed. The sensitivity (92.45%) and specificity (90.64%) were higher in this study when a cutoff value of 0.635 was chosen for QMTA. Conclusions: QMTA may be a better choice than the MTA scale or the associated quantitative components alone in identifying AD patients and MCI individuals with higher progression risk. [ABSTRACT FROM AUTHOR]

Visual tracking of road cracks in unstructured road environment was, is, and remains a crucial and challenging task, which plays a vital role in accurate crack sealing for automated road cracks repair. However, many problems have not been well solved in existing automated road cracks repair, such as the low automation due to partial dependence on manual and the interrupted traffic flow caused by the heavy equipment used. In this article, a cross-entropy-based adaptive fuzzy control (CEAFC) method is proposed, which reaches visual tracking with unmanned mobile robot (VT-UMbot) for road cracks. Specifically, the CEAFC method uses cross-entropy optimization iteration to tune parameters for the tracking controller, and fuzzy logic is constructed to explore robustness improvement. Moreover, a framework of VT-UMbot based on a four-wheel independent differential drive is established, and visual servo and tracking control are integrated into the system. Our experiment shows that the proposed method is extensively evaluated on three road cracks scenarios and achieves state-of-the-art performance with high efficiency. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Existing blood‐based biomarkers for Alzheimer's disease (AD) mainly focus on its pathological features. However, studies on blood‐based biomarkers associated with other biological processes for a comprehensive evaluation of AD status are limited. METHODS: We developed a blood‐based, multiplex biomarker assay for AD that measures the levels of 21 proteins involved in multiple biological pathways. We evaluated the assay's performance for classifying AD and indicating AD‐related endophenotypes in three independent cohorts from Chinese or European‐descent populations. RESULTS: The 21‐protein assay accurately classified AD (area under the receiver operating characteristic curve [AUC] = 0.9407 to 0.9867) and mild cognitive impairment (MCI; AUC = 0.8434 to 0.8945) while also indicating brain amyloid pathology. Moreover, the assay simultaneously evaluated the changes of five biological processes in individuals and revealed the ethnic‐specific dysregulations of biological processes upon AD progression. DISCUSSION: This study demonstrated the utility of a blood‐based, multi‐pathway biomarker assay for early screening and staging of AD, providing insights for patient stratification and precision medicine. Highlights: The authors developed a blood‐based biomarker assay for Alzheimer's disease.The 21‐protein assay classifies AD/MCI and indicates brain amyloid pathology.The 21‐protein assay can simultaneously assess activities of five biological processes.Ethnic‐specific dysregulations of biological processes in AD were revealed. [ABSTRACT FROM AUTHOR]

Summary: Type 2 diabetes (T2D), obesity, and nonalcoholic fatty liver disease/nonalacoholic steatohepatitis (NAFLD/NASH) share mutual causalities. Medications that may offer clinical benefits to all three conditions are being developed. Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) are approved for the management of T2D and obesity and there is great interest in evaluating higher doses of available GLP‐1RAs and developing novel GLP‐1RA‐based co‐agonists to provide greater reductions in glycated hemoglobin (HbA1c) and body weight as well as modifying NAFLD/NASH complications in clinically meaningful ways. High‐dose GLP‐1RAs and multi‐hormonal strategies including GLP‐1R agonism have either already been approved or are in development for managing T2D, obesity, or NASH. We provide a mechanistic outline with a detailed summary of the available clinical data and ongoing trials that are adjudicating the impact of high‐dose GLP‐1RAs, unimolecular, and multimolecular GLP‐1R‐based co‐agonists in populations living with T2D, obesity, or NASH. The available trial findings are aligned with preclinical observations, showing clinical efficacy and safety thus providing optimism for the expansion of GLP‐1R‐based drug classes for managing the triad of T2D, obesity and NASH. Development, access, and wide‐spread utilization of these new therapeutic approaches will offer important opportunities to markedly improve the collective global burden of T2D, obesity, and NASH. [ABSTRACT FROM AUTHOR]

Polythermal glaciers can trap considerable volumes of liquid water with the potential to generate devastating outburst floods. This study aims to identify water‐filled subglacial reservoirs from ambient seismic noise collected by moderate‐cost surveys. The horizontal‐to‐vertical spectral ratio technique is highly sensitive to impedance contrasts at interfaces, thus commonly used to estimate glacier thickness. Here, we focus on the inverse ratio, that is, the V/H spectral ratio (VHSR), whose high values indicate a low impedance volume beneath the surface, suggesting subglacial cavities. We analyze VHSR peaks from a seismic array of 60 nodes installed on the Tête‐Rousse Glacier (Mont Blanc massif, French Alps); data were gathered over 15 days. Mapping the VHSR amplitude over the free surface reveals the main cavity locations and the basal areas affected by melting within the glacier. Results obtained in the field are supported by a conceptual model based on 3D finite‐element simulations. Plain Language Summary: Considerable volumes of liquid water may be trapped within cavities in polythermal glaciers. If these cavities rupture, the resulting outburst flood has the potential to cause devastation in populated mountain areas. With the aim of testing methods to locate such cavities, we installed 60 small 3‐component seismic sensors on the Tête‐Rousse Glacier (Mont Blanc massif, French Alps), which is known to contain such cavities. We used these sensors to test a detection method based on ambient seismic noise. For 3 weeks, the sensors recorded vibrations within the glacier. On a glacier without cavities, these vibrations ought to be predominantly in the horizontal direction. In the presence of a cavity, we expect the ice above the cavity to vibrate mostly vertically—like a bridge. In this paper, we highlight areas on the glacier where vertical vibrations were stronger than horizontal vibrations. These areas fit well with the locations of the main known cavities in this glacier, and with areas affected by basal melting. We supported our field observations with modeling based on 3D simulations, paving the way to a new method to locate water‐filled cavities within glaciers. Key Points: Spectral analysis from ambient seismic noise is complementary to other geophysical methods for investigating glaciers at depthResults suggest that the vertical‐to‐horizontal spectral ratio is a reliable proxy to locate subglacial cavitiesExperimental results were confirmed using a simplified numerical model [ABSTRACT FROM AUTHOR]

This article, published in Aging Cell, explores the topic of healthy aging and the various factors that influence it. The authors emphasize the need for a holistic approach to understanding and promoting healthy aging, considering biological pathways, holistic approaches, and interventions targeting multiple organ systems and mechanistic pathways. The article discusses specific topics such as senescent cells, NAD metabolism, genetic variants in centenarians, the African killifish as a model organism, organ crosstalk, cardiorespiratory fitness, and behavioral interventions. The authors also highlight the challenges and future directions in the field of healthy aging research. [Extracted from the article]

Background: Contingency management (CM) is an evidence‐based approach for reducing alcohol use; however, its implementation into routine HIV primary care‐based settings has been limited. We evaluated perspectives on implementing CM to address unhealthy alcohol use and associated conditions for people with HIV in primary care settings. Methods: From May 2021 to August 2021, we conducted two focus groups with staff involved in delivering the intervention (n = 5 Social Workers and n = 4 Research Coordinators) and individual interviews (n = 13) with a subset of participants involved in the multi‐site Financial Incentives, Randomization, and Stepped Treatment (FIRST) trial. Qualitative data collection and analyses were informed by the Promoting Action on Research Implementation in Health Service (PARIHS) implementation science framework, including evidence (perception of CM), context (HIV primary care clinic and CM procedures), and facilitation (feasibility outside the research setting). Results: Several major themes were identified. Regarding the evidence, participants lacked prior experience with CM, but the intervention was well received and, by some, perceived to lead to lasting behavior change. Regarding the clinical context for the reward schedule, the use of biochemical testing, specifically fingerstick phosphatidylethanol testing, and the reward process were perceived to be engaging and gratifying for both staff and patients. Participants indicated that the intervention was enhanced by its co‐location within the HIV clinic. Regarding facilitation, participants suggested addressing the intervention's feasibility for non‐research use, simplifying the reward structure, and rewarding non‐abstinence in alcohol use. Conclusions: Among patients and staff involved in a clinical trial, CM was viewed as a helpful, positive, and feasible approach to addressing unhealthy alcohol use and related conditions. To enhance implementation, future efforts may consider simplified approaches to the reward structure and expanding rewards to non‐abstinent reductions in alcohol consumption. [ABSTRACT FROM AUTHOR]

Aim: The aim of this work was to investigate the value of rectal cancer T‐staging on MRI after chemoradiotherapy (ymrT‐staging) in relation to the degree of fibrotic transformation of the tumour bed as assessed using the pathological tumour regression grade (pTRG) of Mandard as a standard of reference. Method: Twenty two radiologists, including five rectal MRI experts and 17 'nonexperts' (general/abdominal radiologists), evaluated the ymrT stage on the restaging MRIs of 90 rectal cancer patients after chemoradiotherapy. The ymrT stage was compared with the final ypT stage at histopathology; the percentages of correct staging (ymrT = ypT), understaging (ymrT < ypT) and overstaging (ymrT > ypT) were calculated and compared between patients with predominant tumour at histopathology (pTRG4–5) and patients with predominant fibrosis (pTRG1–3). Interobserver agreement (IOA) was computed using Krippendorff's alpha. Results: Average ymrT/ypT stage concordance was 48% for the experts and 43% for the nonexperts; ymrT/ypT stage concordance was significantly higher in the pTRG4–5 subgroup (58% vs. 41% for the pTRG1–3 group; p = 0.01), with the best results for the MRI experts. Overstaging was the main source of error, especially in the pTRG1–3 subgroup (average overstaging rate 38%–44% vs. 13%–55% in the pTRG4–5 subgroup). IOA was higher for the expert versus nonexpert readers (α = 0.67 vs. α = 0.39). Conclusions: ymrT‐staging is moderately accurate; accuracy is higher in poorly responding patients with predominant tumour but low in good responders with predominant fibrosis, resulting in significant overstaging. Radiologists should shift their focus from ymrT‐staging to detecting gross residual (and progressive) disease, and identifying potential candidates for organ preservation who would benefit from further clinical and endoscopic evaluation to guide final treatment planning. [ABSTRACT FROM AUTHOR]

Basal sliding of glaciers and ice sheets remains a source of uncertainty in simulating the long‐term evolution of ice masses. In particular, the response of ice flow to changes in driving stress depends strongly on the value of the exponent m in nonlinear friction laws (e.g., Weertman's law), which is poorly constrained by observations. Here we constrain the friction law at a natural scale on Argentière Glacier (French Alps, hard‐bed), taking advantage of well‐resolved observations of glacier mass balance, geometry and basal sliding over time spans that include large changes in driving stress. By combining three different independent methods based on (a) surface velocity inversion, (b) transient length change modeling, and (c) direct local sliding measurements, we consistently find a value of m = 3.1 ± 0.3. We suggest that Weertman's law is suitable for modeling the long‐term evolution of hard‐bedded glaciers and ice sheets. Plain Language Summary: Modeling the evolution of glaciers and ice sheets under climate variability requires accurate estimation of ice flow velocities by numerical models. One of the most challenging components of these models is the representation of basal sliding at the rock‐ice interface, generally described by relationships between stress and sliding speed. These relationships are mainly derived from laboratory experiments and theoretical studies, and their ability to represent nature still needs to be evaluated. Because direct observation beneath glaciers and ice sheets is difficult, few studies have attempted to validate sliding models from natural scale observations. In this context, our study provides a rare constraint, based on observations on an alpine glacier, on the law that should be used to model glacier sliding on clean bedrock (so‐called hard‐bed glaciers). We show that a simple power law performs well in explaining long‐term glacier behavior for a power exponent of ∼3.1. We suggest that this exponent should be adopted in non‐linear power laws incorporated into ice flow models that perform future projections of hard‐bedded glaciers and ice sheet evolution. Key Points: We suggest that a Weertman friction law is suitable for multi‐decadal simulations of the hard‐bedded glaciersCombining three independent methods and data sets we infer a Weertman's friction exponent of 3.1 ± 0.3The temporal evolution of glacier fronts is found to be strongly sensitive to the friction law exponent [ABSTRACT FROM AUTHOR]

Introduction: Recent advances in long-acting antiretroviral therapy (LA-ART) could provide new options for HIV treatment and reduce adherence barriers, if regimens are acceptable to patients. We elicited preferences for key attributes of potential LA-ART regimens among people with HIV (PWH) in the United States, focusing on four treatment modes (oral tablets, subcutaneous injections, intramuscular injections, and implants), product characteristics and location of administration. Methods: A discrete choice experiment was conducted among PWH aged ≥18 years recruited from HIV clinics in Washington State and Atlanta, Georgia from March 2021 to June 2022. Participants responded to 17 choice scenarios, each with three options: two systematically generated hypothetical LA-ART regimens and a constant opt-out (their current daily oral treatment). LA-ART regimen descriptions included treatment mode, pain, dosing frequency, location, pre-treatment time with undetectable viral load, pre-treatment negative reaction testing and "late-dose leeway" (i.e. flexibility or forgiveness in timing the next dose). We used conditional logistic regression, with an interaction between treatment mode and pain, to estimate preference weights for all attribute levels. Results: Seven hundred participants (350 at each site) enrolled, with median age 51 years (range 18-73); 70% identified as cisgender male, 24% as cisgender female and 6% as non-binary or transgender. LA oral tablets were the only mode preferred over current daily oral treatment, with annual implants and injections the next most preferred LA-ART option. Longer time between doses was preferred, and administration at home was preferred to clinics, which were preferred to pharmacies. Attributes with less impact on preferences included oral lead-in treatment to achieve viral suppression or test for negative reactions and late-dose leeway around the prescribed dosing interval. Participants in Atlanta were more likely to prefer their current daily oral ART than participants from Seattle. Conclusions: PWH in the United States may soon have several options for LA-ART. Our results suggest that LA oral tablets will be preferred by many patients over their current daily oral treatment, while implants and injections with longer duration may be acceptable to some. Future research should investigate sources of preference heterogeneity and actual uptake of and adherence to LA-ART products, when available. [ABSTRACT FROM AUTHOR]

Objectives: Cerebral microbleeds are associated with the risks of ischemic stroke and intracranial hemorrhage, causing clinical dilemmas for antithrombotic treatment decisions. We aimed to evaluate the risks of intracranial hemorrhage and ischemic stroke associated with microbleeds in patients with atrial fibrillation treated with vitamin K antagonists, direct oral anticoagulants, antiplatelets, and combination therapy (i.e. concurrent oral anticoagulant and antiplatelet). Methods: We included patients with documented atrial fibrillation from the pooled individual patient data analysis by the Microbleeds International Collaborative Network. Risks of subsequent intracranial hemorrhage and ischemic stroke were compared between patients with and without microbleeds, stratified by antithrombotic use. Results: A total of 7,839 patients were included. The presence of microbleeds was associated with an increased relative risk of intracranial hemorrhage (adjusted hazard ratio [aHR] = 2.74, 95% confidence interval = 1.76–4.26) and ischemic stroke (aHR = 1.29, 95% confidence interval = 1.04–1.59). For the entire cohort, the absolute incidence of ischemic stroke was higher than intracranial hemorrhage regardless of microbleed burden. However, for the subgroup of patients taking combination of anticoagulant and antiplatelet therapy, the absolute risk of intracranial hemorrhage exceeded that of ischemic stroke in those with 2 to 4 microbleeds (25 vs 12 per 1,000 patient‐years) and ≥ 11 microbleeds (94 vs 48 per 1,000 patient‐years). Interpretation: Patients with atrial fibrillation and high burden of microbleeds receiving combination therapy have a tendency of higher rate of intracranial hemorrhage than ischemic stroke, with potential for net harm. Further studies are needed to help optimize stroke preventive strategies in this high‐risk group. ANN NEUROL 2023;94:61–74 [ABSTRACT FROM AUTHOR]

Mn‐redox‐based oxides and oxyfluorides are considered the most promising earth‐abundant high‐energy cathode materials for next‐generation lithium‐ion batteries. While high capacities are obtained in high‐Mn content cathodes such as Li‐ and Mn‐rich layered and spinel‐type materials, local structure changes and structural distortions (often lead to voltage fade, capacity decay, and impedance rise, resulting in unacceptable electrochemical performance upon cycling. In the present study, structural transformations that exploit the high capacity of Mn‐rich oxyfluorides while enabling stable cycling, in stark contrast to commonly observed structural changes that result in rapid performance degradation, are reported. It is shown that upon cycling of a cation‐disordered rocksalt (DRX) cathode (Li1.1Mn0.8Ti0.1O1.9F0.1, an ultrahigh capacity of ≈320 mAh g−1 (energy density of ≈900 Wh kg−1) can be obtained through dynamic structural rearrangements upon cycling , along with a unique voltage profile evolution and capacity rise. At high voltage, the presence of Mn4+ and Li+ vacancies promotes local cation ordering, leading to the formation of domains of a "δ phase" within the disordered framework. On deep discharge, Mn4+ reduction, along with Li+ insertion transform the structure to a partially ordered DRX phase with a β′‐LiFeO2‐type arrangement. At the nanoscale, domains of the in situ formed phases are randomly oriented, allowing highly reversible structural changes and stable electrochemical cycling. These new insights not only help explain the superior electrochemical performance of high‐Mn DRXbut also provide guidance for the future development of Mn‐based, high‐energy density oxide, and oxyfluoride cathode materials. [ABSTRACT FROM AUTHOR]

Lithium‐rich transition metal oxides with a cation‐disordered rocksalt structure (disordered rocksalt oxides or DRX) are promising candidates for sustainable, next‐generation Li‐ion cathodes due to their high energy densities and compositional flexibility, enabling Co‐ and Ni‐free battery chemistries. However, current methods to synthesize DRX compounds require either high temperature (≈1000 °C) sintering for several hours, or high energy ball milling for several days in an inert atmosphere. Both methods are time‐ and energy‐intensive, limiting the scale up of DRX production. The present study reports the rapid synthesis of various DRX compositions in ambient air via a microwave‐assisted solid‐state technique resulting in reaction times as short as 5 min, which are more than two orders of magnitude faster than current synthesis methods. The DRX compounds synthesized via microwave are phase‐pure and have a similar short‐ and long‐range structure as compared to DRX materials synthesized via a standard solid‐state route, resulting in nearly identical electrochemical performance. In some cases, microwave heating allows for better particle size and morphology control. Overall, the rapid and energy‐efficient microwave technique provides a more sustainable route to produce DRX materials, further incentivizes the development of next‐generation DRX cathodes, and is key to accelerating their optimization via high‐throughput studies. [ABSTRACT FROM AUTHOR]

Intronic single‐nucleotide polymorphisms (SNPs) in FOXO3A are associated with human longevity. Currently, it is unclear how these SNPs alter FOXO3A functionality and human physiology, thereby influencing lifespan. Here, we identify a primate‐specific FOXO3A transcriptional isoform, FOXO3A‐Short (FOXO3A‐S), encoding a major longevity‐associated SNP, rs9400239 (C or T), within its 5′ untranslated region. The FOXO3A‐S mRNA is highly expressed in the skeletal muscle and has very limited expression in other tissues. We find that the rs9400239 variant influences the stability and functionality of the primarily nuclear protein(s) encoded by the FOXO3A‐S mRNA. Assessment of the relationship between the FOXO3A‐S polymorphism and peripheral glucose clearance during insulin infusion (Rd clamp) in a cohort of Danish twins revealed that longevity T‐allele carriers have markedly faster peripheral glucose clearance rates than normal lifespan C‐allele carriers. In vitro experiments in human myotube cultures utilizing overexpression of each allele showed that the C‐allele represses glycolysis independently of PI3K signaling, while overexpression of the T‐allele represses glycolysis only in a PI3K‐inactive background. Supporting this finding inducible knockdown of the FOXO3A‐S C‐allele in cultured myotubes increases the glycolytic rate. We conclude that the rs9400239 polymorphism acts as a molecular switch which changes the identity of the FOXO3A‐S‐derived protein(s), which in turn alters the relationship between FOXO3A‐S and insulin/PI3K signaling and glycolytic flux in the skeletal muscle. This critical difference endows carriers of the FOXO3A‐S T‐allele with consistently higher insulin‐stimulated peripheral glucose clearance rates, which may contribute to their longer and healthier lifespans. [ABSTRACT FROM AUTHOR]

Cation‐disordered rocksalt (DRX) cathodes have recently emerged as a promising class of cobalt‐free, high‐capacity cathodes for lithium‐ion batteries. To facilitate their commercialization, the development of scalable synthesis techniques providing control over composition and morphology is critical. To this end, a sol‐gel synthesis route to prepare Mn‐rich DRX cathodes with high capacities is presented here. Several compositions with varied Mn content and nominal F doping are successfully prepared using this technique. In‐situ X‐ray diffraction measurements demonstrate that DRX formation proceeds at moderate temperature (800 °C) through the sol‐gel route, which enables intimate mixing among reactive intermediate phases that form at lower temperatures. All synthesized compositions possess cation short‐range order, as evidenced by neutron pair distribution function and electron diffraction analysis. These DRX materials demonstrate promising electrochemical performance with reversible capacities up to 275 mAh g. Compared to the baseline oxide (Li1.2Mn0.4Ti0.4O2), the Mn‐rich compositions exhibit improved cycling stability, with some showing an increase in capacity upon cycling. Overall, this study demonstrates the feasibility of preparing high‐capacity DRX cathodes through a sol‐gel based synthesis route, which may be further optimized to provide better control over the product morphology compared to traditional synthesis methods. [ABSTRACT FROM AUTHOR]

The particulate methane monooxygenase (pMMO) is a copper monooxygenase that converts methane into methanol in methanotrophic bacteria. As this enzyme converts methane into methanol efficiently and selectively under ambient conditions, it has become the paradigm for understanding the design of nature to facilitate this process so that we could develop a biomimetic catalyst to accomplish this difficult C1 chemistry in the laboratory. With the advent of the recent 2.5 Å cryo‐electron microscopy structure of the pMMO from Methylococcus capsulatus (Bath), it is now evident that the catalytic site of hydroxylation in pMMO is a CuICuICuI tricopper cluster (CuI: copper ions) sequestered within the transmembrane domain of this protein complex. With three reducing equivalents embodied in this structural motif, the tricopper cluster can react with O2 to irreversibly cleave the OO bond to harness the highly reactive oxene for rapid and direct insertion into the CH bonds of methane. Here, we review the structural, biochemical, and biophysical studies over the past three decades that have culminated in this important advance in the chemistry of methane oxidation. [ABSTRACT FROM AUTHOR]

Practitioners and researchers in geoscience education embrace collaboration applying ICON (Integrated, Coordinated, Open science, and Networked) principles and approaches which have been used to create and share large collections of educational resources, to move forward collective priorities, and to foster peer‐learning among educators. These strategies can also support the advancement of coproduction between geoscientists and diverse communities. For this reason, many authors from the geoscience education community have co‐created three commentaries on the use and future of ICON in geoscience education. We envision that sharing our expertise with ICON practice will be useful to other geoscience communities seeking to strengthen collaboration. Geoscience education brings substantial expertise in social science research and its application to building individual and collective capacity to address earth sustainability and equity issues at local to global scales The geoscience education community has expanded its own ICON capacity through access to and use of shared resources and research findings, enhancing data sharing and publication, and leadership development. We prioritize continued use of ICON principles to develop effective and inclusive communities that increase equity in geoscience education and beyond, support leadership and full participation of systemically non‐dominant groups and enable global discussions and collaborations. Plain Language Summary: The Geoscience Education community describes the value, use, and future of ICON collaboration through three independent, community‐produced commentaries focused on the practice of geoscience education; geoscience education research; and diversity, equity, inclusion, and justice. Each commentary offers ideas important to building inclusive and effective communities. These ideas apply to science‐community collaboration broadly and inform coproduction and network building activities within and across geoscience‐public boundaries. The expansion of inclusive and effective networks is needed for equitable outcomes. Key Points: Integrated, Coordinated, Open science, and Networked (ICON) principles and practices are widely used in geoscience education to improve both research and practiceStrengthened capacity for ICON practices is needed to advance current educational prioritiesA priority must be placed on full participation by that are systemically non‐dominant groups and improving global interactions [ABSTRACT FROM AUTHOR]

Objectives: HIV virological failure remains a major threat to programme success in sub‐Saharan Africa. While HIV drug resistance (HIVDR) and inadequate adherence are the main drivers of virological failure, the individual, clinical and health system characteristics that lead to poor outcomes are not well understood. The objective of this paper is to identify those characteristics among people failing first‐line antiretroviral therapy (ART). Methods: We enrolled a cohort of adults in HIV care experiencing virological failure on first‐line ART at five sites and used standard statistical methods to characterize them with a focus on three domains: individual/demographic, clinical, and health system, and compared each by country of enrolment. Results: Of 840 participants, 51% were women, the median duration on ART was 3.2 years [interquartile range (IQR) 1.1, 6.4 years] and the median CD4 cell count prior to failure was 281 cells/µL (IQR 121, 457 cells/µL). More than half of participants [53%; 95% confidence interval (CI) 49–56%] stated that they had > 90% adherence and 75% (95% CI 72–77%) took their ART on time all or most of the time. Conversely, the vast majority (90%; 95% CI 86–92%) with a completed genotypic drug resistance test had any HIV drug resistance. This population had high health system use, reporting a median of 3 (IQR 2.6) health care visits and a median of 1 (IQR 1.1) hospitalization in the preceding 6 months. Conclusions: Patients failing first‐line ART in sub‐Saharan Africa generally report high rates of adherence to ART, have extremely high rates of HIV drug resistance and utilize significant health care resources. Health systems interventions to promptly detect and manage treatment failure will be a prerequisite to establishing control of the HIV epidemic. [ABSTRACT FROM AUTHOR]

The standard argument to the conclusion that artificial intelligence (AI) constitutes an existential risk for the human species uses two premises: (1) AI may reach superintelligent levels, at which point we humans lose control (the 'singularity claim'); (2) Any level of intelligence can go along with any goal (the 'orthogonality thesis'). We find that the singularity claim requires a notion of 'general intelligence', while the orthogonality thesis requires a notion of 'instrumental intelligence'. If this interpretation is correct, they cannot be joined as premises and the argument for the existential risk of AI turns out invalid. If the interpretation is incorrect and both premises use the same notion of intelligence, then at least one of the premises is false and the orthogonality thesis remains itself orthogonal to the argument to existential risk from AI. In either case, the standard argument for existential risk from AI is not sound.—Having said that, there remains a risk of instrumental AI to cause very significant damage if designed or used badly, though this is not due to superintelligence or a singularity. [ABSTRACT FROM AUTHOR]

Due to global biodiversity declines, conservation programmes have increasingly had to consider reintroducing captive animals into the wild. However, reintroductions often fail as captive individuals may be naïve to predators and do not recognise or respond appropriately to predatory cues, contributing to high mortality rates soon after release. This study evaluates differences in predator‐response behaviours between individuals from three experimental groups, a captive population (n = 13), a semi‐wild population (i.e. raised in captivity and successfully released; n = 6) and a wild population (n = 2) of cheetah (Acinonyx jubatus) to an artificially simulated auditory threat of lions (Panthera leo), a larger, natural predator in South Africa. Such comparisons improve our understanding of differences between captive and wild behaviours and provide an aspect to evaluating the relative success of reintroduction programmes. Changes in the proximal distance, the latency of approach and hesitation towards both control (African bush cricket, Acanthoplus discoidalis) and treatment (lion) auditory cues were observed for 29 cheetah from captive, semi‐wild and wild populations in at least three trial replicates each. Overall, captive individuals consistently displayed poor predatory‐response behaviours, approaching the treatment as often as the control, as well as spending more time near the stimulus (<10 m) and hesitating more often than semi‐wild cheetah, which could distinguish between the control and treatment, consistently fleeing from the latter with little hesitation. Repeatability analyses indicated that these behavioural responses to predatory cues could not be explained by individual personality and between‐trial learning comparisons showed no evidence of habituation. Our findings demonstrate how a priori testing for predator naïvety could inform future introductory decisions and thereby increase post‐release survival rates, significantly improving the efficacy of reintroduction strategies. We, therefore, emphasise the importance of such research and screening in highly threatened species, such as cheetah, where reintroduction from captivity has become a necessary consideration. [ABSTRACT FROM AUTHOR]

The nickel chloride complex of the Schiff base N2,N2′‐propanediylbis(2,3‐butanedione‐2‐imine‐3‐oxime), namely, chlorido(3,9‐dimethylundeca‐3,8‐diene‐2,10‐dione 10‐oxime 2‐oximato‐κ4N,N′,N′′,N′′′)nickel(II), [NiCl(C11H19N4O2)], at 100 K crystallizes in the orthorhombic space group Cmce. The structure exhibits mirror disorder of the main molecule that is not present in the bromide analogue. The relatively small number of unique reflections in the data set and the disorder imposed by the crystallographic mirror plane present a challenging educational case study. [ABSTRACT FROM AUTHOR]

Introduction: Blood proteins are emerging as candidate biomarkers for Alzheimer’s disease (AD). We systematically profiled the plasma proteome to identify novel AD blood biomarkers and develop a high-performance, blood-based test for AD. Methods: We quantified 1160 plasma proteins in a Hong Kong Chinese cohort by high-throughput proximity extension assay and validated the results in an independent cohort. In subgroup analyses, plasma biomarkers for amyloid, tau, phosphorylated tau, and neurodegeneration were used as endophenotypes of AD. Results: We identified 429 proteins that were dysregulated in AD plasma. We selected 19 “hub proteins” representative of the AD plasma protein profile, which formed the basis of a scoring system that accurately classified clinical AD (area under the curve = 0.9690–0.9816) and associated endophenotypes. Moreover, specific hub proteins exhibit disease stage-dependent dysregulation, which can delineate AD stages. Discussion: This study comprehensively profiled the AD plasma proteome and serves as a foundation for a high-performance, blood-based test for clinical AD screening and staging. [ABSTRACT FROM AUTHOR]

Introduction: Cerebral small vessel disease (SVD) is an important cause of dementia that lacks effective treatment. We evaluated the efficacy and safety of cilostazol, an antiplatelet agent with potential neurovascular protective effects, in slowing the progression of white matter hyperintensities (WMHs) in stroke- and dementia-free subjects harboring confluentWMHon magnetic resonance imaging (MRI). Methods: In this single-center, randomized, double-blind, placebo-controlled study, we randomized stroke- and dementia-free subjects with confluent WMHs to receive cilostazol or placebo for 2 years in a 1:1 ratio. The primary outcome was change in WMH volume over 2 years. Secondary outcomes were changes in brain volumes, lacunes, cerebral microbleeds, perivascular space, and alterations in white matter microstructural integrity, cognition, motor function, and mood. Results: We recruited 120 subjects from October 27, 2014, to January 21, 2019. A total of 55 subjects in the cilostazol group and 54 subjects in the control group were included for intention-to-treat analysis. At 2-year follow-up, the changes in WMH volume were not statistically different between cilostazol treatment and placebo (0.3±1.0 mL vs -0.1±0.8 mL, p = 0.167). Secondary outcomes, bleeding and vascular events, were also not statistically different between the two groups. Discussion: In this trialwith stroke- and dementia-free subjects with confluentWMHs, cilostazol did not impact WMH progression but demonstrated an acceptable safety profile. Future studies should address the treatment effects of cilostazol on subjects at different clinical stages of SVD. [ABSTRACT FROM AUTHOR]

Ruxolitinib is a US Food and Drug Administration–approved orally administered Janus kinase (1/2) inhibitor that reduces cytokine‐induced inflammation. As part of a randomized, phase 2, open‐label trial, ruxolitinib (10 mg twice daily) was administered to HIV‐positive, virologically suppressed individuals (33 men, 7 women) on antiretroviral therapy (ART) for 5 weeks. Herein, we report the population PK subsequently determined from this study. Plasma concentrations of ruxolitinib (294 samples) and antiretroviral agents were measured at week 1 (N = 39 participants) and week 4 or 5 (N = 37). Ruxolitinib PK was adequately described with a 2‐compartment model with first‐order absorption and elimination with distribution volumes normalized to mean body weight (91.5 kg) and a separate typical clearance for participants administered efavirenz (a known cytochrome P450 3A4 inducer). Participants administered an ART regimen with efavirenz had an elevated typical apparent oral clearance versus the integrase inhibitor regimen group (22.5 vs 12.9 L/hr; N = 14 vs 25). Post hoc predicted apparent oral clearance was likewise more variable and higher (P <.0001) in those administered efavirenz. There was an ≈25% variation in ruxolitinib plasma exposures between week 1 and week 4/5. ART plasma concentrations resembled those from PK studies without ruxolitinib. Therefore, integrase inhibitor–based ART regimens may be preferred over efavirenz‐based regimens when ruxolitinib is administered to HIV‐positive individuals. [ABSTRACT FROM AUTHOR]

Introduction: Tenofovir diphosphate (TFV‐DP) in dried blood spots (DBS), a measure of cumulative antiretroviral therapy (ART) adherence, is associated with viral suppression and predicts future viremia in persons with HIV (PWH). However, its utility to identify those at risk for virologic failure (VF) and drug resistance is unknown. To address this, we aimed to establish the association between this adherence biomarker and VF with drug resistance in a cohort of PWH initiating first‐line ART in KwaZulu‐Natal, South Africa. Methods: PWH initiating TFV disoproxil fumarate (TDF)‐based ART within a parent prospective cohort were evaluated. Using a nested design, DBS for TFV‐DP were collected from cases who developed VF (HIV‐1 RNA ≥1000 copies/ml) after ≥5 months on ART versus controls, matched 1:2 by site, age, gender, race and ART duration. Cases were categorized as having VF with or without resistance using genotyping. One‐way analysis of variance (ANOVA) was used to compare TFV‐DP for controls, cases with VF and resistance, and cases with VF without resistance. Data are presented as mean (standard deviation, SD) or geometric mean [95% confidence interval, 95% CI]. Results and discussion: One thousand participants were enrolled in the parent study between 2014 and 2016, of which 288 (29%) had DBS available. Of these, 94 (33%) were cases and 194 (67%) were controls; 59% were women. Mean age of our population was 33 (SD 8) years. Genotyping was available in 50 (53%) of the 94 cases. Geometric mean TFV‐DP in DBS from controls was 708 [95% CI; 647–773] fmol/punch, which was higher compared to participants having VF with resistance (n = 36), 386 [95% CI; 241–617] fmol/punch and VF without resistance (n = 14), 61 [95% CI; 22–164] fmol/punch; p<0.001. Genotype could not be obtained in 44 (47%) cases. Conclusions: TFV‐DP in DBS showed a stepwise association with VF and drug resistance in South African PWH. Participants having VF with resistance had mid‐range concentrations of TFV‐DP, which were higher than those for PWH without resistance. Future research on the clinical utility of TFV‐DP concentrations in DBS to predict and prevent the development of VF and drug resistance is needed. [ABSTRACT FROM AUTHOR]

Tonotopy is a prominent feature of the vertebrate auditory system and forms the basis for sound discrimination, but the molecular mechanism that underlies its formation remains largely elusive. Ephrin/Eph signaling is known to play important roles in axon guidance during topographic mapping in other sensory systems, so we investigated its possible role in the establishment of tonotopy in the mouse cochlear nucleus. We found that ephrin‐A3 molecules are differentially expressed along the tonotopic axis in the cochlear nucleus during innervation. Ephrin‐A3 forward signaling is sufficient to repel auditory nerve fibers in a developmental stage‐dependent manner. In mice lacking ephrin‐A3, the tonotopic map is degraded and isofrequency bands of neuronal activation upon pure tone exposure become imprecise in the anteroventral cochlear nucleus. Ephrin‐A3 mutant mice also exhibit a delayed second wave in auditory brainstem responses upon sound stimuli and impaired detection of sound frequency changes. Our findings establish an essential role for ephrin‐A3 in forming precise tonotopy in the auditory brainstem to ensure accurate sound discrimination. [ABSTRACT FROM AUTHOR]

Background: Dietary protein and phosphorus (P) restriction is the mainstay for nutritional management of chronic kidney disease (CKD). However, adequate restriction levels for cats with early CKD remain unclear. Objectives: To investigate responses in cats with early CKD to varying dietary protein, P, and calcium (Ca) : P ratio. Animals Nineteen research colony cats with International Renal Interest Society stages 1‐2 CKD. Methods: In an opportunistic longitudinal case study, cats were fed a low protein (59 g/Mcal), low P (0.84 g/Mcal) dry diet (LP‐LP; Ca : P = 1.9) for 18 months and later transitioned onto a moderate protein (76‐98 g/Mcal), moderate P (1.4‐1.6 g/Mcal) dry‐wet diet regimen (MP‐MP; Ca : P = 1.4‐1.6) for 22 months. Fold‐changes in serum creatinine, total Ca (tCa) and P (primary outcomes) and fibroblast growth factor 23 (FGF23) were assessed by linear‐mixed models. Results: While feeding LP‐LP, mean serum creatinine decreased (0.87‐fold, 95% confidence interval [CI] 0.81, 0.93, P <.001) to within reference range after 6 months, while increases in total Ca (tCa; 1.16‐fold, 95% CI 1.11, 1.22, P <.001) and FGF23 (2.72‐fold, 95% CI 1.72, 4.31, P <.001), but not in P (1.03‐fold, 95% CI 0.945, 1.124, P =.94), were observed after 17 months. On MP‐MP, mean creatinine, tCa and P remained within reference ranges and did not significantly change (P =.11, P =.98, and P = 1, respectively), while FGF23 significantly decreased (0.58‐fold, 95% CI 0.36, 0.95, P =.02) after 22 months. Conclusions and Clinical Importance: Cats with early CKD developed hypercalcemia after long‐term feeding of a highly P‐restricted diet. Increasing dietary P and reducing Ca : P ratio maintained renal markers, while improving Ca‐P balance. Cats with early CKD could benefit from moderately protein‐ and P‐restricted diets. [ABSTRACT FROM AUTHOR]

Introduction: The Department of Veterans Affairs (VA) is the largest provider of HIV care in the United States. Changes in healthcare delivery became necessary with the COVID‐19 pandemic. We compared HIV healthcare delivery during the first year of the COVID‐19 pandemic to a prior similar calendar period. Methods: We included 27,674 people with HIV (PWH) enrolled in the Veterans Aging Cohort Study prior to 1 March 2019, with ≥1 healthcare encounter from 1 March 2019 to 29 February 2020 (2019) and/or 1 March 2020 to 28 February 2021 (2020). We counted monthly general medicine/infectious disease (GM/ID) clinic visits and HIV‐1 RNA viral load (VL) tests. We determined the percentage with ≥1 clinic visit (in‐person vs. telephone/video [virtual]) and ≥1 VL test (detectable vs. suppressed) for 2019 and 2020. Using pharmacy records, we summarized antiretroviral (ARV) medication refill length (<90 vs. ≥90 days) and monthly ARV coverage. Results: Most patients had ≥1 GM/ID visit in 2019 (96%) and 2020 (95%). For 2019, 27% of visits were virtual compared to 64% in 2020. In 2019, 82% had VL measured compared to 74% in 2020. Of those with VL measured, 92% and 91% had suppressed VL in 2019 and 2020. ARV refills for ≥90 days increased from 39% in 2019 to 51% in 2020. ARV coverage was similar for all months of 2019 and 2020 ranging from 76% to 80% except for March 2019 (72%). Women were less likely than men to be on ARVs or to have a VL test in both years. Conclusions: During the COVID‐19 pandemic, the VA increased the use of virtual visits and longer ARV refills, while maintaining a high percentage of patients with suppressed VL among those with VL measured. Despite decreased in‐person services during the pandemic, access to ARVs was not disrupted. More follow‐up time is needed to determine whether overall health was impacted by the use of differentiated service delivery and to evaluate whether a long‐term shift to increased virtual healthcare could be beneficial, particularly for PWH in rural areas or with transportation barriers. Programmes to increase ARV use and VL testing for women are needed. [ABSTRACT FROM AUTHOR]

Theoretical descriptions of ice‐bed friction beneath glaciers and ice sheets are key to predict changes in sea level. Applicability of these theories at the natural landscape scale and over long periods has however not been tested. Here we test hard bed friction laws by analyzing a unique data set of in‐situ basal sliding measurements collected over three decades under an Alpine glacier enduring large changes in geometry. We report many observational features that are in striking agreement with theoretical predictions. However, we also observe an undocumented behavior where the basal stress state stabilizes near Iken's limit under meltwater input, which suggests the basal effective pressure is primarily set by bed shear stress rather than by water input and drainage specifics as commonly thought. As a result, long‐term changes in year‐averaged sliding velocities follow a simple power law scaling with bed shear stress as opposed to more complex pressure‐dependent relationships. Plain Language Summary: Basal sliding is an important component of glacier motion. However, our knowledge of the physics that controls basal sliding is incomplete. This causes large uncertainties in the contribution to sea‐level rise predicted for ice sheets over the coming century. Here, we test our understanding of basal sliding against particularly unique observations, made via a rotating bicycle wheel that has been continuously measuring glacier basal motion over three decades within excavated tunnels under the Argentière Glacier in the French Alps. Due to stress changes from significant glacier thinning over the multi‐decadal period we are able to establish an observationally derived sliding law and compare it with expectations from theory. We report many observational features that are in striking agreement with theoretical predictions from glacier sliding over bedrock beds. However, we also observe an undocumented behavior of stress stabilization during the melting period at a specific stress state known as the Iken's limit. This behavior causes long term sliding velocities to follow a simple power law scaling with bed shear stress. This finding has the potential of strongly simplifying and reducing uncertainty on predicting glaciers response to climate change. Key Points: We use unique basal sliding observations collected over three decades to test basal friction theoriesThe observations show striking agreement with theory, although we report an unexpected stress stabilization near Iken's limitStress stabilization causes basal effective pressure to scale with bed shear stress, and long‐term sliding speeds to follow a simple law [ABSTRACT FROM AUTHOR]

Background: Chinese medicine (CM) modalities, including acupuncture and Chinese herbal medicine (CHM), are popular palliative interventions among patients with cancer, but further clinical research is required to assess their effectiveness and safety. Objective: To prioritize top ten important CM clinical research questions from patients with cancer, cancer survivors and caregivers' perspectives via a face‐to‐face prioritization workshop in Hong Kong. Methods: A list of 25 CM clinical research questions for cancer palliative care, which were identified from existing systematic reviews (SRs) and overview of SRs, was presented to 17 participants (patients with cancer [n = 5], cancer survivors [n = 6] and caregivers [n = 6]). The participants were then invited to establish consensus on prioritizing top ten research questions. Results: Among the top ten priorities, five (50%) focused on acupuncture and related therapies, while five (50%) were on CHM. The three most important research priorities were (i) manual acupuncture plus opioids for relieving pain; (ii) CHM for improving quality of life among patients receiving chemotherapy; and (iii) concurrent use of CHM plus loperamide for reducing stomatitis. Conclusion: The top ten participant‐endorsed CM clinical research priorities for cancer palliative care can guide local researchers on future direction. They can also inform local research funders on patient‐centred allocation of limited funding. Under limited research funding, the most important co‐prioritized research question from professional and patient perspectives may be addressed first. Patient or Public Contribution: Patients with cancer, cancer survivors and caregivers participated in conduct of the study to prioritize CM clinical research questions. [ABSTRACT FROM AUTHOR]

There is an apparent reciprocal relationship between magnesium ammonium phosphate (MAP, struvite) and calcium oxalate (CaOx) urolithiasis incidence rate in cats. The number of struvite uroliths submitted for analysis over the past 35 years has been decreasing, with an increase in CaOx urolith submissions. Commercial diets aimed to dissolve struvite uroliths are typically acidified, and it has been suggested that dietary acidification increases urinary calcium excretion and the risk of CaOx crystallization. The objective of this study was to assess the effect of urine acidification on the relative supersaturation (RSS) of CaOx in cats, as a representation of crystallization risk. Four diets were extruded to contain identical nutrient contents, but with gradual acidification (0, 0.6, 1.3 and 1.9% sodium bisulphate substituted sodium chloride in diets A, B, C and D respectively). Thirteen adult cats were fed each diet sequentially for a minimum of 10 days. Average urine pH was 6.4, 6.2, 6.0 and 5.9 on diets A, B, C and D respectively (p < 0.0001). Struvite RSS decreased on diets inducing more acidic urine pH (p < 0.0001). Urinary calcium excretion and concentration increased with diets inducing lower urine pH (p < 0.0001), but oxalate excretion and concentration decreased (p < 0.001). CaOx RSS was not different between diets (p = 0.63). These results suggest that a lower diet base excess and resulting urine pH to support struvite dissolution do not increase the risk for CaOx crystallization in the range of urine pH representative of most commercial feline diets. Long‐term studies are needed to confirm this. [ABSTRACT FROM AUTHOR]

The recovery of muscle oxygen consumption (mV˙O2) after exercise measured using near‐infrared spectroscopy (NIRS) provides a measure of skeletal muscle mitochondrial capacity. Nevertheless, due to sex differences in factors that can influence scattering and thus penetration depth of the NIRS signal in the tissue, e.g., subcutaneous adipose tissue thickness and intramuscular myoglobin and hemoglobin, it is unknown whether results in males can be extrapolated to a female population. Therefore, the aim of this study was to measure skeletal muscle mitochondrial capacity in females at different levels of aerobic fitness to test whether NIRS can measure relevant differences in mitochondrial capacity. Mitochondrial capacity was analyzed in the gastrocnemius muscle and the wrist flexors of 32 young female adults, equally divided in relatively high (V˙O2peak ≥ 47 ml/kg/min) and relatively low aerobic fitness group (V˙O2peak ≤ 37 ml/kg/min). mV˙O2 recovery was significantly faster in the high‐ compared to the low‐fitness group in the gastrocnemius, but not in the wrist flexors (p = 0.009 and p = 0.0528, respectively). Furthermore, V˙O2peak was significantly correlated to mV˙O2 recovery in both gastrocnemius (R2 = 0.27, p = 0.0051) and wrist flexors (R2 = 0.13, p = 0.0393). In conclusion, NIRS measurements can be used to assess differences in mitochondrial capacity within a female population and is correlated to V˙O2peak. This further supports NIRS assessment of muscle mitochondrial capacity providing additional evidence for NIRS as a promising approach to monitor mitochondrial capacity, also in an exclusively female population. [ABSTRACT FROM AUTHOR]

Post‐translational protein modifications derived from metabolic intermediates, such as acyl‐CoAs, have been shown to regulate mitochondrial function. Patients with a genetic defect in the propionyl‐CoA carboxylase (PCC) gene clinically present symptoms related to mitochondrial disorders and are characterised by decreased mitochondrial respiration. Since propionyl‐CoA accumulates in PCC deficient patients and protein propionylation can be driven by the level of propionyl‐CoA, we hypothesised that protein propionylation could play a role in the pathology of the disease. Indeed, we identified increased protein propionylation due to pathologic propionyl‐CoA accumulation in patient‐derived fibroblasts and this was accompanied by defective mitochondrial respiration, as was shown by a decrease in complex I‐driven respiration. To mimic pathological protein propionylation levels, we exposed cultured fibroblasts, Fao liver cells and C2C12 muscle myotubes to propionate levels that are typically found in these patients. This induced a global increase in protein propionylation and histone protein propionylation and was also accompanied by a decrease in mitochondrial respiration in liver and fibroblasts. However, in C2C12 myotubes propionate exposure did not decrease mitochondrial respiration, possibly due to differences in propionyl‐CoA metabolism as compared to the liver. Therefore, protein propionylation could contribute to the pathology in these patients, especially in the liver, and could therefore be an interesting target to pursue in the treatment of this metabolic disease. [ABSTRACT FROM AUTHOR]

We report on a long‐term evaluation of biological control of an invasive cactus, Opuntia stricta, in the Kruger National Park, South Africa. By forming large impenetrable thickets, this weed species posed a major threat to the integrity and biodiversity of the park, and to agroecosystems more widely.Over 22 years, from 1992 to 2013, counts were made along fixed transects at four different sites to measure the abundance of O. stricta and the prevalence of two of its biological control agents: (a) Cactoblastis cactorum, whose larvae feed in the plants' cladodes and (b) a sap‐sucking cochineal insect, Dactylopius opuntiae. With only C. cactorum present, the numbers of O. stricta cladodes and fruit remained unchanged at two of the sites but increased annually at the other two. Within 5 years of the introduction of D. opuntiae, the numbers of cladodes and fruit decreased substantially at all the sites and the residual cactus populations have been held at inconsequentially low levels ever since.Both the C. cactorum and D. opuntiae populations on O. stricta in South Africa were sourced from founder stocks in Australia. This allows direct comparisons of biological control of O. stricta in South Africa with the world‐famous program against O. stricta, in Queensland and in New South Wales, that peaked in the 1920s and 1930s.Synthesis and applications. Almost all accounts acclaim Cactoblastis cactorum as the dominant contributor to the sustained decline of populations of prickly pears in Australia in the 1930s. Our results provide evidence that this now widely accepted conclusion is incorrect and that cochineal was and is the key role player. Managers and biological control practitioners concerned with the apparent underperformance of C. cactorum in the suppression of invasive Opuntia cacti should interpret the entrenched reports in the literature with circumspection. There may also be less cause for concern about the anticipated devastation of native Opuntia prickly pear species in the southern United States where C. cactorum has become an invasive pest species. [ABSTRACT FROM AUTHOR]

The biomimetic synthesis of aromatic polyketides from macrocyclic substrates by means of catalyst‐controlled transannular cyclization cascades is described. The macrocyclic substrates, which feature increased stability and fewer conformational states, were thereby transformed into several distinct polyketide scaffolds. The catalyst‐controlled transannular cyclizations selectively led to aromatic polyketides with a defined folding and oxygenation pattern, thus emulating β‐keto‐processing steps of polyketide biosynthesis. [ABSTRACT FROM AUTHOR]

Background: We sought to compare self‐reported alcohol consumption using Timeline Followback (TLFB) to biomarker‐based evidence of significant alcohol use (phosphatidylethanol [PEth] > 20 ng/ml). Using data from patients with HIV (PWH) entering a clinical trial, we asked whether TLFB could predict PEth > 20 ng/ml and assessed the magnitude of association between TLFB and PEth level. Methods: We defined unhealthy alcohol use as any alcohol use in the presence of liver disease, at‐risk drinking, or alcohol use disorder. Self‐reported alcohol use obtained from TLFB interview was assessed as mean number of drinks/day and number of heavy drinking days over the past 21 days. Dried blood spot samples for PEth were collected at the interview. We used logistic regression to predict PEth > 20 ng/ml and Spearman correlation to quantify the association with PEth, both as a function of TLFB. Results: Among 282 individuals (99% men) in the analytic sample, approximately two‐thirds (69%) of individuals had PEth > 20 ng/ml. The proportion with PEth > 20 ng/ml increased with increasing levels of self‐reported alcohol use; of the 190 patients with either at‐risk drinking or alcohol use disorder based on self‐report, 82% had PEth > 20 ng/ml. Discrimination was better with number of drinks per day than heavy drinking days (AUC: 0.80 [95% CI: 0.74 to 0.85] vs. 0.74 [95% CI: 0.68 to 0.80]). The number of drinks per day and PEth were significantly and positively correlated across all levels of alcohol use (Spearman's R ranged from 0.29 to 0.56, all p values < 0.01). Conclusions: In this sample of PWH entering a clinical trial, mean numbers of drinks per day discriminated individuals with evidence of significant alcohol use by PEth. PEth complements self‐report to improve identification of self‐reported unhealthy alcohol use among PWH. [ABSTRACT FROM AUTHOR]

This study evaluates the performance and benefits of kilometre‐ and subkilometre‐scale convection‐permitting simulations over tropical Australia. Focusing on an extended monsoon break period, we can directly compare Unified Model (UM) and Weather Research and Forecasting model (WRF) simulations to C‐band polarimetric radar observations and soundings. We show that the two models have different behaviour, and both are different to observations. Whereas WRF produces daily squall lines whether or not they occurred in observations, the UM primarily generates small but intense storms. The UM and WRF produce qualitatively different surface density currents at different times in the diurnal cycle. Once the density currents are present, the models also show different behaviour in relation to convective initiation. While higher resolution helps in the distribution of total precipitation over the domain, most characteristics do not change with higher resolutions, and model differences are always larger than resolution differences. While Convective Available Potential Energy/Convective Inhibition (CAPE/CIN) does not seem to be important to explain model differences, our findings point to the evolution of density currents in the boundary layer as the most important source of model errors and differences. [ABSTRACT FROM AUTHOR]