Control Functions Research Articles

Reliability of irrigation water and farm-level productivity: Evidence from semi-arid farming systems in northern Ethiopia

CONTEXTAccess to sufficient amount of irrigation water enables farmers to intensify cultivation, leading to increased productivity. The type, application level of irrigation infrastructure, and water use management conditions affect the extent of water supply and farm-level productivity. Despite this, much of the literature on the impact of irrigation water on farm-level productivity considers the dichotomous concept of access to irrigation without accounting for differences in the reliability of access to irrigation water. OBJECTIVEBeyond the dichotomous effect of access to irrigation, this study examined the impact of reliable irrigation water on farm-level productivity in semi-arid agricultural systems. METHODSUsing data from 462 irrigated farm plots from northern Ethiopia, we estimated the impact of reliability of irrigation water on plot-level productivity based on the control function approach to address the potential endogeneity associated with the reliability of irrigation water in the productivity model. RESULTS AND CONCLUSIONResults show that reliability of irrigation water positively and significantly affects farm-level productivity. The implication is that beyond access to irrigation water, reliability in access and use of irrigation water remains crucial to productivity. In this regard, it is vital to work on strengthening the village-level water management systems and enhancing their institutional efficiency to ensure water use reliability and sustain future investments in irrigation systems to enhance plot-level productivity. SIGNIFICANCEThe bulk of the literature is restricted to documentation of knowledge on the dichotomous effect of access to irrigation that could mask the more realistic impact on plot-level productivity. This study extends the literature by modeling not only access to but also reliability of access to unmask the differential impact of access to and reliability of irrigation water on plot-level productivity. It can also provide policy a useful direction in promoting the need to invest, beyond access, on ensuring the reliability of irrigation water for enhancing productivity.

Finding Safety Violations of AI-Enabled Control Systems through the Lens of Synthesized Proxy Programs

Given the increasing adoption of modern AI-enabled control systems, ensuring their safety and reliability has become a critical task in software testing. One prevalent approach to testing control systems is falsification, which aims to find an input signal that causes the control system to violate a formal safety specification using optimization algorithms. However, applying falsification to AI-enabled control systems poses two significant challenges: (1) it requires the system to execute numerous candidate test inputs, which can be time-consuming, particularly for systems with AI models that have many parameters, and (2) multiple safety requirements are typically defined as a conjunctive specification, which is difficult for existing falsification approaches to comprehensively cover. This paper introduces Synthify , a falsification framework tailored for AI-enabled control systems, i.e., control systems equipped with AI controllers. Our approach performs falsification in a two-phase process. At the start, Synthify synthesizes a program that implements one or a few linear controllers to serve as a proxy for the AI controller. This proxy program mimics the AI controller's functionality but is computationally more efficient. Then, Synthify employs the \(\epsilon\) -greedy strategy to sample a promising sub-specification from the conjunctive safety specification. It then uses a Simulated Annealing-based falsification algorithm to find violations of the sampled sub-specification for the control system. To evaluate Synthify , we compare it to PSY-TaLiRo , a state-of-the-art and industrial-strength falsification tool, on 8 publicly available control systems. On average, Synthify achieves a 83.5% higher success rate in falsification compared to PSY-TaLiRo with the same budget of falsification trials. Additionally, our method is 12.8 \(\times\) faster in finding a single safety violation than the baseline. The safety violations found by Synthify are also more diverse than those found by PSY-TaLiRo , covering 137.7% more sub-specifications.

Improving Emotion Regulation, Internalizing Symptoms and Cognitive Functions in Adolescents at Risk of Executive Dysfunction—A Controlled Pilot VR Study

Executive functions (EFs) are essential cognitive processes involved in concentration, planning, decision-making, and impulse control during adolescence. Executive Dysfunction (ED) can lead to significant academic and socio-emotional difficulties, particularly with impairments in emotion regulation (ER). This study aims to assess a virtual reality (VR) cognitive training intervention on EFs, ER, and internalizing symptoms in adolescents at risk for ED. Thirty-eight adolescents aged 12–14 years, identified as being at moderate to high risk for ED, were randomly assigned to two groups. The experimental group (n = 22) received gamified VR cognitive training, while the control group (n = 16) received VR nature-based relaxation training. Both interventions lasted five weeks, twice a week for 30 min each. Pre- and post-assessments included ER skills, internalizing symptoms, and cognitive performance measures. Two-way mixed ANOVAs showed significant group × time interactions (p < 0.05) in measures of depression and internalizing symptoms. The experimental group showed significant reductions in these symptoms compared with the control group. Significant main effects of time (p < 0.05) were also found on some measures. Both groups experienced reduced anxiety, improved emotional control and cognitive functioning, and VR cognitive training was particularly effective in reducing internalizing symptoms, while both interventions showed promising results in improving some ER skills and cognitive performance. The findings demonstrate the preliminary effects of VR-based cognitive training in improving the psychological and cognitive well-being of adolescents at risk for ED and suggest that integrating VR technologies into educational settings can effectively address the cognitive and emotional challenges faced by these students.

Insights from a Career at the Border of Developmental Psychology and Cognitive Neuroscience

Much has changed since I started my PhD research in 1980. Neither the field of developmental cognitive neuroscience nor the term “executive functions” existed then. In some ways this piece is backward-looking, such as discussing how our research introduced the importance of the executive function of inhibitory control for cognitive development and that infants and young children are much smarter than we thought. The way our field has queried infants and young children often prevented us from seeing their competencies. That is still too true in studying children from different backgrounds. In other ways, this piece is forward-looking, such as when discussing evidence that the conceptualization of working memory as an executive function and as the key function of dorsolateral prefrontal cortex has been too narrow. It is not just separation in time that must be bridged (traditionally the province of working memory) but also separations in space, and the latter are just as important for cognitive development and just as dependent on the executive function brain network, including dorsolateral prefrontal cortex. It is also forward-looking in discussing the critical importance of motor, social, and emotional development for cognitive development and executive functions, as well as bidirectional relations among these different facets of development. Study of the different aspects of human development are still far too siloed, as are the different fields of science. Examples are provided of how the fields of neuroscience (including neurochemistry and molecular genetics) and child development inform and complement one another. Implications for educators, parents, and researchers are interwoven throughout.

The bisexual branching processes affected by viral infectivity and with random control functions in random environments

Abstract In this paper, the model of bisexual branching processes affected by viral infectivity and with random control functions in independent and identically distributed (i.i.d.) random environments is established and the Markov property is given firstly. Then the relations of the probability generating functions of this model are studied, and some sufficient conditions for process extinction under common mating functions are presented. Finally, the limiting behaviors of the considered model after proper normalization, such as the sufficient conditions for the convergence in L1 and L2 and almost everywhere convergence, are investigated under the condition that the random control functions are super additive.

Development of intelligent traction machine for tensioning and paying off construction of transmission lines

Monitoring the traction force and speed of the traction machine is crucial for timely discovering construction problems and avoiding accidents during the construction process of tension wire laying. The existing monitoring methods have low accuracy, are susceptible to environmental interference, and cannot achieve real-time monitoring. Therefore, this article has developed an intelligent traction machine suitable for tension line construction.The design scheme includes three modules: data acquisition and processing, data transmission, and software design. The data acquisition and processing module is responsible for real-time monitoring of traction force and traction speed, and converting the monitored data into digital signals through pressure sensors and speed sensors, and then processing them through a microcontroller. The data transmission module transmits monitoring data to the construction site terminal equipment and remote command center through LoRa wireless transmission technology, displays monitoring data on the terminal equipment, and realizes warning and control functions. At present, the intelligent traction machine has been applied in the tension wire laying construction of a 750 kV transmission line project in Guangdong, China and has achieved good results. Through continuous optimization and improvement, intelligent traction machines have practical conditions and broad application prospects.

Genomic and Methylomic Signatures Associated With the Maintenance of Genome Stability and Adaptive Evolution in Two Closely Allied Wolf Spiders.

Pardosa spiders, belonging to the wolf spider family Lycosidae, play a vital role in maintaining the health of forest and agricultural ecosystems due to their function in pest control. This study presents chromosome-level genome assemblies for two allied Pardosa species, P. laura and P. agraria. Both species' genomes show a notable expansion of helitron transposable elements, which contributes to their large genome sizes. Methylome analysis indicates that P. laura has higher overall DNA methylation levels compared to P. agraria. DNA methylation may not only aids in transposable element-driven genome expansion but also positively affects the three-dimensional organisation of P. laura after transposon amplification, thereby potentially enhancing genome stability. Genes associated with hyper-differentially methylated regions in P. laura (compared to P. agraria) are enriched in functions related to mRNA processing and energy production. Furthermore, combined transcriptome and methylome profiling has uncovered a complex regulatory interplay between DNA methylation and gene expression, emphasising the important role of gene body methylation in the regulation of gene expression. Comparative genomic analysis shows a significant expansion of cuticle protein and detoxification-related gene families in P. laura, which may improve its adaptability to various habitats. This study provides essential genomic and methylomic insights, offering a deeper understanding of the relationship between transposable elements and genome stability, and illuminating the adaptive evolution and species differentiation among allied spiders.

HMGB1 secretion by resveratrol in NSCLC: A pathway to ferroptosis-mediated platelet activation suppression.

Cancer-associated venous thromboembolism (CAT) is a frequent and serious complication in cancer patients. Resveratrol, a natural compound with reported anti-tumor effects, is not fully understood in its role regarding CAT in lung cancer. This study aims to explore resveratrol's potential to diminish platelet activation induced by lung adenocarcinoma cells and uncover the underlying mechanisms. Clinical data on coagulation function in non-small cell lung cancer (NSCLC) patients were gathered. A549 human lung cancer cells and Lewis mouse lung cancer cells were employed to assess tumor-induced platelet activation and the impact of resveratrol on this process. Western blotting analyzed protein expression, electron microscopy examined extracellular vesicle (EV) morphology, flow cytometry measured platelet activation, reactive oxygen species (ROS), and exocrine protein expression, while ELISA quantified secretory proteins. Tumor control and platelet function were studied in tumor-bearing mice. We identified that hematological profiles of NSCLC patients frequently manifest a hypercoagulable state relative to healthy controls and lung cancer cells could instigate platelet activation, yet resveratrol could attenuate this phenomenon induced by lung cancer. Resveratrol stimulates lung cancer cells to release HMGB1-enriched EVs, promoting platelet ferroptosis and inhibiting platelet activation through increased ROS, lipid peroxidation, and disrupted cystine transporters. In vivo studies confirm that resveratrol inhibits lung cancer cell growth and suppresses tumor-induced platelet activation in mice. Our studies revealed that resveratrol alleviated lung cancer-induced ferroptosis associated platelet activation. This suggests a potential pharmacological approach for preventing and treating both lung cancer and CAT.

Foldable, Stretchable, Superelastic, and Tunable Wettability Aramid Nanofiber Aerogels for Efficient Thermal Insulation and Oil-Water Separation.

Aerogels hold great potential in thermal insulation, catalytic supports, adsorption, and separation, due to their low density, high porosity, and low thermal conductivity. However, their inherent mechanical fragility and limited control functionality pose substantial challenges that hinder their practical use. In this study, a strategy is developed for the fabrication of cross-linked aramid nanofiber aerogels (cANFAs) by combining internanofiber surface cross-linking with ice-templating techniques. This approach enables the production of cANFAs with an ultralow density of 6.3 mg/cm3 while exhibiting robust mechanical properties, including exceptional mechanical resilience, withstanding 90% compression in air and 80% compression underwater for 100 cycles, and high stretchability with a tensile strain of 34%. The cANFAs demonstrate remarkable thermal insulation properties, with low thermal conductivities of 0.03816 W/(m·K) at room temperature and 0.03518 W/(m·K) at -40 °C. Additionally, the cANFAs exhibit tunable wettability, being hydrophilic and oleophilic in air while becoming superhydrophobic underwater, which enables efficient gravity-driven oil-water separation performance. This study presents a promising route to create robust and functional aramid nanofiber aerogels for practical applications across various fields.

Theta and beta power in the subthalamic nucleus respond to conflict across subregion and hemisphere

Abstract The subthalamic nucleus is thought to play a crucial role in controlling impulsive actions. Networked among the basal ganglia and receiving input from several cortical areas, the subthalamic nucleus is well-positioned to influence action selection when faced with competing and conflicting action outcomes. The purpose of this study was to test the dissociable roles of the dorsal and ventral aspects of the subthalamic nucleus during action conflict in patients with Parkinson’s disease undergoing intraoperative neurophysiological recording and to explore a potential mechanism for this inhibitory control. We hypothesized that modulations of neurophysiological activity during action conflict would be more pronounced in the dorsal subthalamic nucleus compared to the ventral subthalamic nucleus, due to the dissociation of cortical afferents to subthalamic nucleus subregions and previous findings of deep brain stimulation targeting subthalamic nucleus subregions in Parkinson’s disease. We recorded neurophysiological activity while ten participants with Parkinson’s disease performed the Simon task during deep brain stimulation surgery. Response-locked local field potentials in the theta and beta band (associated with conflict control and movement inhibition, respectively) were analyzed across subthalamic nucleus subregions and hemispheres relative to the motor response (ipsilateral/contralateral). In the presence of action conflict, the dorsal subthalamic nucleus, connected to cortical motor regions, exhibited larger theta power relative to the ventral subthalamic nucleus subregion which is linked to the limbic circuits (P<0.05). This evidence supports independent subregion function in conflict control. However, both subregions had relatively increased beta power for conflict trials compared to non-conflict in the hemisphere ipsilateral to the motor response. The conflict related beta modulation was not present in the contralateral hemisphere. This indicates the importance of the ipsilateral hemisphere in the inhibition of incorrect action impulses. Additionally, higher inter-trial beta power in the ventral subregion correlated with reduced accuracy on conflict trials, which we propose could serve as a biomarker for impaired task performance. The results of the study support the existence of a functional dissociation within subthalamic nucleus subregions, emphasizing the role of the dorsal subthalamic nucleus in modulating action conflict.

Contextual cues facilitate dynamic value encoding in the mesolimbic dopamine system.

Adaptive behavior in a dynamic environmental context often requires rapid revaluation of stimuli that deviates from well-learned associations. The divergence between stable value-encoding and appropriate behavioral output remains a critical component of theories of dopamine's function in learning, motivation, and motor control. Yet, how dopamine neurons are involved in the revaluation of cues when the world changes, to alter our behavior, remains unclear. Here, we make use of a complementary set of invivo approaches to clarify the contributions of the mesolimbic dopamine system to the dynamic reorganization of reward- seeking behavior. Male and female rats were trained to discriminate when a conditioned stimulus would be followed by a sucrose reward by exploiting the prior, non-overlapping presentation of a another discrete cue-an occasion setter. Only when the occasion setter's presentation preceded the conditioned stimulus did the conditioned stimulus predict sucrose delivery, dissociating the average value of the conditioned stimulus from its immediate value, on a trial-to-trial basis. Activity of ventral tegmental area dopamine neurons was essential for rats to successfully update behavioral response to the occasion setter. Moreover, dopamine release in the nucleus accumbens following the conditioned stimulus only occurred when the occasion setter indicated it would predict reward and did not reflect its average expected value. Downstream of dopamine release, we found that neurons in the nucleus accumbens dynamically tracked the value of the conditioned stimulus. Together, these results help refine notions of dopamine function, revealing a prominent contribution of the mesolimbic dopamine system to the rapid revaluation of motivation.

State of Change-Related Hybrid Energy Storage System Integration in Fuzzy Sliding Mode Load Frequency Control Power System with Electric Vehicles

In the context of the integration of hybrid energy storage systems (HESSs) and electric vehicles (EVs), this paper investigates the load frequency control (LFC) issue of the power system. Weighting coefficients are set for the generators, HESSs and EVs, respectively, to show their different abilities to regulate the power system. A fuzzy logic-based sliding mode control approach is designed to ensure the stable performance of the LFC power system integrated with HESSs and EVs. The improvement of the proposed method is the application of the linear matrix inequality (LMI) toolbox in fuzzy controller design, which solves the limitations and uncertainties caused by trial-error or experience in common fuzzy controllers. There is no general form for the membership function of the fuzzy control. This paper presents a design approach for the membership function based on the calculation results of LMI. Simulations are tested on an IEEE 39-bus system integrated with HESSs and EVs. The simulation results prove that the proposed method reduces the time required for the power system frequency to reach stability by approximately 8.8%, demonstrating the superiority and usability of the proposed approach.

A novel small RNA regulates Locus of Enterocyte Effacement and site-specific colonization of enterohemorrhagic Escherichia coli O157:H7 in gut

Enterohemorrhagic Escherichia coli (EHEC) is a contagious foodborne pathogen that specifically colonizes the human large intestine, which is regulated by different environmental stimuli within the gut. Transcriptional regulation of EHEC virulence and infection has been extensively studied, while the posttranscriptional regulation of these processes by small RNAs (sRNAs) remains not fully understood. Here we present a virulence-regulating pathway in EHEC O157:H7, in which the sRNA EvrS binds to and destabilizes the mRNA of Z2269, a novel transcriptional regulator. In turn, Z2269 indirectly activates the expression of LEE (locus of enterocyte effacement) pathogenicity island through the master regulator Ler. Importantly, the expression of EvrS is modulated by environmental oxygen levels. EvrS also exhibits lower expression in the colon compared to the ileum, influencing the site-specific colonization of EHEC O157:H7 in mice. These results indicate that the oxygen status within the intestine may regulate the expression of EvrS, thereby modulating virulence factors of EHEC and contributing to successful infection in vivo. This study has broader implications for understanding sRNA functions in spatiotemporal virulence control of EHEC and may provide novel strategies to prevent EHEC infections.

The lateralized cerebellum: insights into motor, cognitive, and affective functioning across ages: a scoping review.

Research on the cerebellum and its functional organization has significantly expanded over the last decades, expanding our comprehension of its role far beyond motor control, including critical contributions to cognition and affective processing. Notably, the cerebellar lateralization mirrors contralateral brain lateralization, a complex phenomenon that remains unexplored, especially across different stages of life. The present work aims to bridge this gap by providing a comprehensive scoping review of the lateralization of motor, cognitive, and affective functioning within the cerebellum across the lifespan. A methodical search in electronic databases (i.e., PubMed, Embase, and PsycINFO) was conducted up to October 2024, focusing on neuroimaging studies with healthy participants of all ages performing motor, cognitive, or affective tasks. Our selection process, which involved multiple independent reviewers, identified 128 studies reporting cerebellar asymmetries in individuals from early childhood to older age, with a significant portion of studies regarding young-middle adults (19-45years old). The majority of the findings confirmed established lateralization patterns in motor and language processing, such as ipsilateral motor control and right-lateralized language functions. However, less attention has been paid to other cognitive functions and affective processing where more heterogeneous and less consistent asymmetries have been observed. To the best of our knowledge, this scoping review is the first to comprehensively investigate the motor, cognitive, and affective functional lateralization of the cerebellum across lifespan, highlighting previously overlooked dimensions of cerebellar contributions.

An Investigation of Hand Gestures for Controlling Video Games in a Rehabilitation Exergame System

Musculoskeletal disorders (MSDs) can significantly impact individuals’ quality of life (QoL), often requiring effective rehabilitation strategies to promote recovery. However, traditional rehabilitation methods can be expensive and may lack engagement, leading to poor adherence to therapy exercise routines. An exergame system can be a solution to this problem. In this paper, we investigate appropriate hand gestures for controlling video games in a rehabilitation exergame system. The Mediapipe Python library is adopted for the real-time recognition of gestures. We choose 10 easy gestures among 32 possible simple gestures. Then, we specify and compare the best and the second-best groups used to control the game. Comprehensive experiments are conducted with 16 students at Andalas University, Indonesia, to find appropriate gestures and evaluate user experiences of the system using the System Usability Scale (SUS) and User Experience Questionnaire (UEQ). The results show that the hand gestures in the best group are more accessible than in the second-best group. The results suggest appropriate hand gestures for game controls and confirm the proposal’s validity. In future work, we plan to enhance the exergame system by integrating a diverse set of video games, while expanding its application to a broader and more diverse sample. We will also study other practical applications of the hand gesture control function.

Control (Supervisory) Powers of the Eurasian Economic Commission and the European Commission: Comparative Legal Aspect

Introduction. The article examines the powers of the Eurasian Economic Commission (hereinafter referred to as the EEC) and the European Commission (hereinafter referred to as the EC) in the field of control (supervision) over the implementation of integration legal orders by member states and business entities, their scope, limits of competence, and impact on the development of integration processes in the Eurasian Economic Union (hereinafter referred to as the EAEU) and the European Union (hereinafter referred to as the EU), as well as the role of the courts of the relevant integration associations in the implementation of the function under consideration by the Commissions. In addition, the author reviewed and analyzed the relevant law enforcement practice of the EEC and the EC, as well as the legal positions of the courts of the integration associations in question.Materials and methods. This study uses the works of both Russian and foreign experts in the field of European law and the law of the EAEU, as well as analyzes the legal acts of the EU and the EAEU. The research used general scientific methods of cognition – analysis, synthesis, induction, deduction. Special legal methods were also used in the work – formal legal, technical legal, the method of legal analogy, as well as the comparative legal method.Results of the study. As a result of the conducted research, it was revealed that despite the functioning of the EAEU for more than 10 years, there are certain problems in the activities of the EEC for the control (supervision) of the implementation by member States and economic entities of the EAEU law. In particular: the inability to apply to the EAEU Court with an application to bring to justice a member state that violated the norms of the EAEU law; the absence of a procedure in the law of the EAEU for prior notification of the EEC on acts adopted by the member States; the presence of fragmentation in the legal regulation of the EEC's control (supervisory) function over the implementation of the EAEU law by economic entities. The identified problems make it difficult for the EEC to effectively perform its duties in the part under consideration, and therefore they can be resolved through, inter alia, using the positive experience of the European Commission in exercising control (supervisory) powers over the implementation of European Union law.Discussion and conclusion. The presence of the problems indicated in the article in the field of the EEC's control (supervisory) powers necessitates the introduction of comprehensive amendments to the EAEU Treaty, acts of the EAEU bodies, as well as the issuance of new acts that will regulate issues that have not been regulated by the EAEU law to date. Thus, based on the results of a comparative legal analysis of the powers, the author identified problems and formulated conclusions on the similarities and differences in the legal status of the EEC and the EC in terms of their exercise of control (supervisory) powers. The trends in the development of the law enforcement practice of the Commissions in terms of the fulfillment by member States and business entities of obligations within the framework of relevant integration associations are determined. The ways of improving the implementation of the control (supervisory) function by the Eurasian Economic Commission on the basis of the identified positive experience of the European Union are presented.

Integrated Microneedles and Hydrogel Biosensor Platform: Toward a Diagnostic Device for Collection and Dual-Mode Sensing of Monkeypox Virus A29 Protein.

The outbreak of the monkeypox epidemic underscores the importance of developing a rapid and sensitive virus detection technique. Microneedles (MNs) offer minimally invasive sampling capabilities, providing a solution for the development of integrated extraction and diagnostic portable devices. Here, we report an integrated MNs and hydrogel biosensor (IMHB) platform, composed of an electronic device, an MN patch, and a hydrogel patch. The IMHB allowed for specific extraction of monkeypox virus (MPXV) directly from lesional skin and virus detection in both electrochemical and colorimetric modes. A bifunctional signal probe 3,3',5,5'-tetramethylbenzidine (TMB) was loaded in a hydrogel patch, providing measurable signals for dual-mode sensing. Additionally, a control area was designed in this platform to collect blank samples from normal skin, enabling ratio analysis and quality control functions. This dual-mode ratiometric sensing strategy exhibited a wide range of 10-1000 ng/mL for MPXV A29 protein, with detection limits of 0.1632 and 0.3017 ng/mL for electrochemical and colorimetric assay, respectively. The developed IMHB platform provides a novel way for rapid on-site determination of MPXV, demonstrating the potential for quick intervention in the early stages of infectious diseases.

Farm production, marketing, and children's nutritional outcomes in rural Zambia

AbstractDespite increasing agricultural productivity, malnutrition remains high among food producers in many developing countries. This study examines how the difference between agricultural household nutrition requirements and production kept for home consumption, the Nutritient deficiency from own production (NDOP), impacts children's height‐for‐age z‐scores (HAZ) using a unique survey of 528 households in Zambia. The study also investigates the relationship between NDOP and market‐bought nutrition and the role of intra‐season price changes in nutrition. To address the endogeneity of NDOP, we use a control function approach. We find that NDOP is associated with lower HAZ. Both energy (calories) NDOP and nutrient‐specific NDOP, resulting from underproduction relative to nutritional requirements and from selling more than surplus food crops, are negatively correlated with HAZ. This result suggests that higher productivity and market participation do not always lead to better nutrition. We also find that crop sales (commercialization) only benefit nutrition if the household only sells surplus output relative to its nutritional requirements. Finally, we also find that NDOP does not correlate with market food purchases, and that the seasonal price increases for cereals further dampens market food purchases. The findings highlight that policies promoting smallholder commercialisation may overlook detrimental nutrition trade‐offs when own‐production falls short of household needs. Accounting for post‐harvest allocation of nutrients between own‐consumption, sales, and purchases can help ensure agricultural interventions improve farmer livelihoods and child nutrition.

Comparative efficacy and safety of sitagliptin or gliclazide combined with metformin in treatment-naive patients with type 2 diabetes: A single-center, prospective, randomized, controlled, noninferiority study with genetic polymorphism analysis.

This study evaluates the efficacy and safety of sitagliptin versus gliclazide, combined with metformin, in treatment-naive patients with type 2 diabetes mellitus (T2DM) and glucotoxicity. In this single-center, randomized, controlled noninferiority trial, 129 treatment-naive patients with T2DM with glucotoxicity (fasting plasma glucose [FPG] ≥ 200 mg/dL and glycated hemoglobin ≥ 9.0%) were randomized to receive sitagliptin plus metformin (n = 66) or gliclazide plus metformin (n = 63) for 12 weeks. Sitagliptin and gliclazide were given for the first 4 weeks, followed by metformin monotherapy for 8 weeks. Efficacy end points included changes in glycemic control, body weight, and β-cell function at baseline, 4 weeks, and 12 weeks. After 12 weeks, mean glycated hemoglobin reductions were 4.03% in the sitagliptin group and 4.13% in the gliclazide group, with a mean difference of -0.097 (95% confidence interval, -0.648 to 0.453), confirming noninferiority. Both groups showed significant FPG reductions at 4 weeks (P < .05). The sitagliptin group achieved faster glycemic targets, greater FPG and body weight reductions, and higher rates of FPG < 6.1 mmol/L (26.2% vs 5.7%; P = .012). No significant differences were observed in β-cell function or hypoglycemia incidence (P > .05). Genetic analysis showed specific single-nucleotide polymorphisms affected drug efficacy: dipeptidyl peptidase-4 rs2909451 TT and rs4664443 GG genotypes showed lower efficacy with sitagliptin, while GLP1R rs3765467 AG and KCNJ11 rs2285676 CC genotypes responded better to sitagliptin. Sitagliptin combined with metformin is noninferior to gliclazide combined with metformin in treatment-naive patients with T2DM with glucotoxicity. Genetic polymorphisms significantly affect drug efficacy, highlighting the importance of personalized medicine. The sitagliptin group achieved glycemic targets more quickly and had greater weight reductions without increased adverse effects.

Pharmacological reduction of lipid hydroperoxides as a potential modulator of sarcopenia.

We previously reported that elevated expression of phospholipid hydroperoxide glutathione peroxidase 4, an enzyme that regulates membrane lipid hydroperoxides, can mitigate sarcopenia in mice. However, it is still unknown whether a pharmacological intervention designed to modulate lipid hydroperoxides might be an effective strategy to reduce sarcopenia in aged mice. Here we asked whether a newly developed compound, CMD-35647 (CMD), can reduce muscle atrophy induced by sciatic nerve transection. We treated mice daily with vehicle or CMD (15mg/kg, i.p. injection) starting 1day prior to denervation. CMD treatment reduced hydroperoxide generation and blunted muscle atrophy by over 17% in denervated muscle. To test whether CMD can reduce ageing-induced muscle atrophy and weakness, we treated mice with either vehicle or CMD (15mg/kg, i.p. injection) 3days per week for 8months, starting at 18months of age until 26months of age. We measured muscle mass, functional status of neuromuscular junctions, muscle contractile function and mitochondrial function in control and CMD-treated 26-month-old female mice. Treatment with CMD conferred protection against muscle atrophy in both tibialis anterior and extensor digitorum longus that was associated with maintenance of fibre size of MHC 2b and 2x fibres. Mitochondrial respiration was also protected in CMD-treated mice. We also found that muscle force generation was protected with CMD treatment despite denervation in ∼25% of the muscle fibres. Overall, this study shows that pharmacological interventions designed to reduce lipid hydroperoxides might be effective for preventing sarcopenia. KEY POINTS: Sarcopenia in aged mice is associated with muscle loss, contractile dysfunction, denervation, and reduced mitochondrial respiration. CMD-35647 is a pharmocological compound that can neutralize lipid hydroperoxides. 8 month treatment of CMD-35647 mitigated muscle atrophy in tibialis anterior and extensor digitorum longus. 8 month treatment of CMD-35647 improved muscle function in aged mice independent of the neuromuscular junction. Aged mice treated with CMD-35647 had greater respiration in red gastrocnemius muscle when compared to vehicle treated mice.