Key Points Research Articles

[Multidistrict atherosclerotic disease: epidemiological and clinical framework].

Atherosclerosis is a systemic disease that can involve different arterial districts. Traditionally, the focus of cardiologists has been on the diagnosis and treatment of atherosclerotic coronary artery disease (CAD). However, atherosclerosis localization in other districts is increasingly common and is associated with an increased risk of CAD and, more generally, of adverse cardiovascular events. Although the term peripheral arterial disease (PAD) commonly refers to the localization of atherosclerotic disease in the arterial districts of the lower limbs, in this document, in accordance with the European Society of Cardiology guidelines, the term PAD will be used for all the locations of atherosclerotic disease excluding coronary and aortic ones. The aim of this review is to report updated data on PAD epidemiology, with particular attention to the prevalence and its prognostic impact on patients with CAD. Furthermore, the key points for an appropriate diagnostic framework and a correct pharmacological therapeutic approach are summarized, while surgical/interventional treatment goes beyond the scope of this review.

Climate change and plant health: impact, implications and the role of research for mitigation and adaptation

Climate change is a pressing issue requiring bold innovations using an integrated and systematic approach. As part of the CGIAR Webinar Series for the International Year of Plant health 2020 a webinar took place in 2021 entitled ‘Climate change and plant health: impact, implications, and the role of research for adaptation and mitigation’. The purpose of this paper is to share the discussions of the webinar and to show how CGIAR, working closely with partners, can contribute to better management of plant health in a climate crisis. The global research community has an enormous opportunity to collaborate on innovations, partnerships, capacity development and policy engagement to scale up solutions for plant health and agricultural resilience in a climate crisis, embedded within social and economic frameworks. Key action points were identified related to surveillance, big data and predictive models; integrated pest management (IPM) tools; a new paradigm for research to deliver end-to-end, sustainable solutions; fostering of an enabling environment; gender research; delivery of research at ecosystem and landscape scale through bundling and digital tools; and leveraging partnerships, including with the private sector. Through leveraging collaboration opportunities embedded within social and economic frameworks, the global research community has to scale up solutions for plant health and agricultural resilience under a changing climate.

The photoionization of methoxymethanol: Fingerprinting a reactive C2 oxygenate in a complex reactive mixture.

Methoxymethanol (CH3OCH2OH) is a reactive C2 ether-alcohol that is formed by coupling events in both heterogeneous and homogeneous systems. It is found in complex reactive environments-for example those associated with catalytic reactors, combustion systems, and liquid-phase mixtures of oxygenates. Using tunable synchrotron-generated vacuum-ultraviolet photons between 10.0 and 11.5eV, we report on the photoionization spectroscopy of methoxymethanol. We determine that the lowest-energy photoionization process is the dissociative ionization of methoxymethanol via H-atom loss to produce [C2H5O2]+, a fragment cation with a mass-to-charge ratio (m/z) = 61.029. We measure the appearance energy of this fragment ion to be 10.24 ± 0.05eV. The parent cation is not detected in the energy range examined. To elucidate the origin of the m/z = 61.029 (C2H5O2) fragment, we used automated electronic structure calculations to identify key stationary points on the cation potential energy surface and compute conformer-specific microcanonical rate coefficients for the important unimolecular processes. The calculated H-atom dissociation pathway results in a [C2H5O2]+ fragment appearance at 10.21eV, in excellent agreement with experimental results.

An Integrated Framework with ADD-LSTM and DeepLabCut for Dolphin Behavior Classification

Caring for dolphins is a delicate process that requires experienced caretakers to pay close attention to their behavioral characteristics. However, caretakers may sometimes lack experience or not be able to give their full attention, which can lead to misjudgment or oversight. To address these issues, a dolphin behavior analysis system has been designed to assist caretakers in making accurate assessments. This study utilized image preprocessing techniques to reduce sunlight reflection in the pool and enhance the outline of dolphins, making it easier to analyze their movements. The dolphins were divided into 11 key points using an open-source tool called DeepLabCut, which accurately helped mark various body parts for skeletal detection. The AquaAI Dolphin Decoder (ADD) was then used to analyze six dolphin behaviors. To improve behavior recognition accuracy, the long short-term memory (LSTM) neural network was introduced. The ADD and LSTM models were integrated to form the ADD-LSTM system. Several classification models, including unidirectional and bidirectional LSTM, GRU, and SVM, were compared. The results showed that the ADD module combined with a double-layer bidirectional LSTM method achieved high accuracy in dolphin behavior analysis. The accuracy rates for each behavior exceeded 90%.

Motor unit modes in the calf muscles during a submaximal isometric contraction are changed by brief stretches.

The purpose of our study was to investigate the influence of a stretch intervention on the common modulation of discharge rate among motor units in the calf muscles during a submaximal isometric contraction. The current report comprises a computational analysis of a motor unit dataset that we published previously (Mazzo etal., 2021). Motor unit activity was recorded from the three main plantar flexor muscles while participants performed an isometric contraction at 10% of the maximal voluntary contraction force before and after each of two interventions. The interventions were a control task (standing balance) and static stretching of the plantar flexor muscles. A factorization analysis on the smoothed discharge rates of the motor units from all three muscles yielded three modes that were independent of the individual muscles. The composition of the modes was not changed by the standing-balance task, whereas the stretching exercise reduced the average correlation in the second mode and increased it in the third mode. A centroid analysis on the correlation values showed that most motor units were associated with two or three modes, which were presumed to indicate shared synaptic inputs. The percentage of motor units adjacent to the seven centroids changed after both interventions: Control intervention, mode 1 decreased and the shared mode 1+2 increased; stretch intervention, shared modes either decreased (1+2) or increased (1+3). These findings indicate that the neuromuscular adjustments during both interventions were sufficient to change the motor unit modes when the same task was performed after each intervention. KEY POINTS: Based on covariation of the discharge rates of motor units in the calf muscles during a submaximal isometric contraction, factor analysis was used to assign the correlated discharge trains to three motor unit modes. The motor unit modes were determined from the combined set of all identified motor units across the three muscles before and after each participant performed a control and a stretch intervention. The composition of the motor unit modes changed after the stretching exercise, but not after the control task (standing balance). A centroid analysis on the distribution of correlation values found that most motor units were associated with a shared centroid and this distribution, presumably reflecting shared synaptic input, changed after both interventions. Our results demonstrate how the distribution of multiple common synaptic inputs to the motor neurons innervating the plantar flexor muscles changes after a brief series of stretches.

Optimizing Retention Bunkers in Copper Mines with Numerical Methods and Gradient Descent

This study examines the optimization of ore receiving bins in underground copper mines, targeting the reduction of rapid wear and tear on bin components. The investigation identifies the primary wear contributors as the force exerted by the accumulated ore and the velocity at which ore particles move. By altering design and operational parameters, the objective is to decrease wear at key points such as transfer areas, thereby improving the efficiency and service life of retention bunkers. A Discrete Element Method (DEM) model of the bin was created and validated against actual mining conditions to study the impact of material flow on wear. The optimization approach used a constrained gradient descent algorithm to minimize factors like particle velocity and pressure force, while maintaining the efficiency of the bin. The findings provide valuable insights for the future design enhancements, potentially improving the operational performance of retention bunkers in the mining industry.

The Impact of Social Vulnerability on Substance Use Detection Practices in Pregnancy.

This study aimed to synthesize current literature regarding the impact of social vulnerability on pregnancy-related substance use detection in the United States and highlight disparities in substance use detection practices. Clinicaltrials.gov, Google Scholar, PubMed (includes MEDLINE), and Cochrane Library databases were searched using the following Medical Subject Headings (MeSH): (["pregnancy" or "prenatal"] AND ["substance use screening" or "urine toxicology testing" or "toxicology testing" or "urine drug screening" or "CRAFFT" or "4P's" or "4P's Plus" or "NIDA Quick Screen" or "DAST-10" or "SURP-P" or "WIDUS"], AND ("bias" or "disparities" or "social vulnerability"]). The search included systematic reviews, prospective and retrospective studies, randomized controlled trials, case studies, and qualitative and quantitative research from January 2014 through November 2023. Selected literature was limited to studies published in English, which included a study population of either pregnant individuals or pregnancy health care providers in the United States, and that were focused on inequities in pregnancy substance use detection. Using Covidence, three authors screened abstracts, and two screened full articles for inclusion. The included studies were evaluated for quality of evidence using the mixed methods appraisal tool. The search yielded 4,188 manuscripts; 37 were eligible for full review. A total of 18 manuscripts were included based on the relevancy of the topic. The most common social vulnerability domain identified was minority status (17/18), followed by socioeconomic status (11/18), household characteristics (8/18), and housing type (1/18). Social vulnerability plays a role in substance use detection among pregnant individuals. Most notably, race and ethnicity, age, and public insurance lead to increased rates of detection, though most individual factors need to be studied in greater depth. This study was registered with PROSPERO (PROSPERO ID CRD42022352598), the International Prospective Register of Systematic Reviews. KEY POINTS: · Socially vulnerable pregnant individuals are more likely to receive substance use screening or urine toxicology testing.. · Race, ethnicity, age, and insurance influence substance use detection disparities.. · More research is needed to understand how other characteristics influence disparities in substance use detection..

Spatiotemporal pattern evolution and influencing factors of population spatial distribution in Changsha-Zhuzhou-Xiangtan urban agglomeration, China

<p class="MsoNormal" style="text-align: justify;"><span lang="EN-US" style="font-family: 'times new roman', times, serif; font-size: 14pt;">Population, as a fundamental element in urban development, often reflects a city's economic development pattern through its spatial distribution and dynamic changes. Studying population spatial distribution is pivotal for bolstering the economic activity capacity in urban agglomerations and guiding regional economic health. Using the Changsha-Zhuzhou-Xiangtan urban agglomeration as a case study, this paper analyzes its overall spatial structure and the spatiotemporal evolution of population at the district and county levels. This analysis utilizes population density, population redistribution index, and population geographic concentration as key indices. Additionally, a spatial econometric model is constructed to assess the impact of economic, social, and environmental factors on population spatial patterns. Findings reveal several key points: (1) Furong District serves as the primary central area, boasting a population geographic concentration of 25.1% in 2021. Tianxin District, Kaifu District, Yuhua District, Shifeng District, Yuelu District, and Hetang District constitute the secondary central areas, while Yutang District, Tianyuan District, Lusong District, Yuhu District, Wangcheng District, and Changsha County form the tertiary level areas. (2) Population density within the Changsha-Zhuzhou-Xiangtan urban agglomeration gradually decreases from Furong District outward. The first central area and sub-central areas experience increasing population density, highlighting a polarization trend in the population distribution. (3) The overall Moran's index for the spatial distribution of population in the Changsha-Zhuzhou-Xiangtan urban agglomeration is significantly positive, indicating a strong spatial autocorrelation and a deepening spatial agglomeration of population distribution. (4) Per capita disposable income, financial expenditure, and education level positively influence the geographical concentration of population in the urban agglomeration, while GDP per capita, road area per capita, and environmental quality exert a negative impact. Notably, the most influential factors shaping population spatial distribution are GDP per capita, disposable income per capita, and air quality.</span></p>

A machine-learning tool to identify bistable states from calcium imaging data.

Mapping neuronal activation using calcium imaging in vivo during behavioural tasks has advanced our understanding of nervous system function. In almost all of these studies, calcium imaging is used to infer spike probabilities because action potentials activate voltage-gated calcium channels and increase intracellular calcium levels. However, neurons not only fire action potentials, but also convey information via intrinsic dynamics such as by generating bistable membrane potential states. Although a number of tools for spike inference have been developed and are currently being used, no tool exists for converting calcium imaging signals to maps of cellular state in bistable neurons. Purkinje neurons in the larval zebrafish cerebellum exhibit membrane potential bistability, firing either tonically or in bursts. Several studies have implicated the role of a population code in cerebellar function, with bistability adding an extra layer of complexity to this code. In the present study, we develop a tool, CaMLSort, which uses convolutional recurrent neural networks to classify calcium imaging traces as arising from either tonic or bursting cells. We validate this classifier using a number of different methods and find that it performs well on simulated event rasters as well as real biological data that it had not previously seen. Moreover, we find that CaMLsort generalizes to other bistable neurons, such as dopaminergic neurons in the ventral tegmental area of mice. Thus, this tool offers a new way of analysing calcium imaging data from bistable neurons to understand how they participate in network computation and natural behaviours. KEY POINTS: Calcium imaging, compriising the gold standard of inferring neuronal activity, does not report cellular state in neurons that are bistable, such as Purkinje neurons in the cerebellum of larval zebrafish. We model the relationship between Purkinje neuron electrical activity and its corresponding calcium signal to compile a dataset of state-labelled simulated calcium signals. We apply machine-learning methods to this dataset to develop a tool that can classify the state of a Purkinje neuron using only its calcium signal, which works well on real data even though it was trained only on simulated data. CaMLsort (Calcium imaging and Machine Learning based tool to sort intracellular state) also generalizes well to bistable neurons in a different brain region (ventral tegmental area) in a different model organism (mouse). This tool can facilitate our understanding of how these neurons carry out their functions in a circuit.

Data analysis of tactical wargaming based on data mining

In order to effectively solve the problem of acquiring knowledge from tactical wargaming data, an overall analysis framework is designed based on the standard process of data mining. The data is analyzed from four aspects: time, space, maneuver path and multi-operator behavior correlation. The behavioral characteristics of single operators at different stages and the spatial distribution of key points such as shooting points, hit points and hidden points, and the association rules of movement, shooting, and occupation between multiple operators are obtained. This will provide commanders with experience and knowledge, help them to quickly accumulate combat experience, and provide behavior rules and action modes for the development of wargaming AI, effectively improving its intelligent level.

Circadian patterns of behaviour change during pregnancy in mice.

Food intake and activity adapt during pregnancy to meet the increased energy demands. In comparison to non-pregnant females, pregnant mice consume more food, eating larger meals during the light phase, and reduce physical activity. How pregnancy changes the circadian timing of behaviour was less clear. We therefore randomised female C57BL/6J mice to mating for study until early (n=10), mid- (n=10) or late pregnancy (n=11) or as age-matched, non-pregnant controls (n=12). Mice were housed individually in Promethion cages with a 12h light-12h dark cycle [lights on at 07.00h, Zeitgeber (ZT)0] for behavioural analysis.Food intake between ZT10 and ZT11 was greater in pregnant than non-pregnant mice on days 6.5-12.5 and 12.5-17.5. In mice that exhibited a peak in the last 4h of the light phase (ZT8-ZT12), peaks were delayed by 1.6h in the pregnant compared with the non-pregnant group. Food intake immediately after dark-phase onset (ZT13-ZT14) was greater in the pregnant than non-pregnant group during days 12.5-17.5. Water intake patterns corresponded to food intake. From days 0.5-6.5 onwards, the pregnant group moved less during the dark phase, with decreased probability of being awake, in comparison to the non-pregnant group. The onset of dark-phase activity, peaks in activity, and wakefulness were all delayed during pregnancy. In conclusion, increased food intake during pregnancy reflects increased amplitude of eating behaviour, without longer duration. Decreases in activity also contribute to positive energy balance in pregnancy, with delays to all measured behaviours evident from mid-pregnancy onwards. KEY POINTS: Circadian rhythms synchronise daily behaviours including eating, drinking and sleep, but how these change in pregnancy is unclear. Food intake increased, with delays in peaks of food intake behaviour late in the light phase from days 6.5 to 12.5 of pregnancy, in comparison to the non-pregnant group. The onset of activity after lights off (dark phase) was delayed in pregnant compared with non-pregnant mice. Activity decreased by ∼70% in the pregnant group, particularly in the dark (active) phase, with delays in peaks of wakefulness evident from days 0.5-6.5 of pregnancy onwards. These behavioural changes contribute to positive energy balance during pregnancy. Delays in circadian behaviours during mouse pregnancy were time period and pregnancy stage specific, implying different regulatory mechanisms.

FGF2 gene's antisense protein, NUDT6, plays a depressogenic role by promoting inflammation and suppressing neurogenesis without altering FGF2 signalling.

Fibroblast growth factor-2 (FGF2) is involved in the regulation of affective behaviour and shows antidepressant effects through the Akt and extracellular signal regulated kinase (ERK) 1/2 pathways. Nudix hydrolase 6 (NUDT6) protein is encoded from FGF2 gene's antisense strand and its role in the regulation of affective behaviour is unknown. Here, we overexpressed NUDT6 in the hippocampus and investigated its behavioural effects and the underlying molecular mechanisms affecting the behaviour. We showed that increasing hippocampal NUDT6 results in depression-like behaviour in rats without changing FGF2 levels or activating its downstream effectors, Akt and ERK1/2. Instead, NUDT6 acted by inducing inflammatory signalling, specifically by increasing S100 calcium binding protein A9 (S100A9) levels, activating nuclear factor-kappa B-p65 (NF-κB-p65), and elevating microglia numbers along with a reduction in neurogenesis. Our results suggest that NUDT6 could play a role in major depression by inducing a proinflammatory state. This is the first report of an antisense protein acting through a different mechanism of action than regulationof its sense protein. The opposite effects of NUDT6 and FGF2 on depression-like behaviour may serve as a mechanism to fine-tune affective behaviour. Our findings open up new venues for studying the differential regulation and functional interactions of sense and antisense proteins in neural function and behaviour, as well as in neuropsychiatric disorders. KEY POINTS: Hippocampal overexpression of nudix hydrolase 6 (NUDT6), the antisense protein of fibroblast growth factor-2 (FGF2), increases depression-like behaviour in rats. Hippocampal NUDT6 overexpression triggers a neuroinflammatory cascade by increasing S100 calcium binding proteinA9 (S100A9) expression and nuclear NF-κB-p65 translocation in neurons, in addition to microglial recruitment and activation. Hippocampal NUDT6 overexpression suppresses neurogenesis. NUDT6 exerts its actions without altering the levels or downstream signalling pathways of FGF2.

The Credit Card of Murabaha & Ijarah (Leasing) of Benefits and Services in the Palestinian Islamic Bank: A Critical and Analaytical Jurisprudential Study

The research attempts to answer a crucial question: To what extent does the Mastercard issued by the Palestinian Islamic Bank adhere to Sharia principles and regulations related to agency contracts, Murabaha (cost-plus financing), and Ijarah (leasing)? The research followed a descriptive-analytical approach, examining everything related to the mentioned card and its application, along with the Sharia principles it is based on, through discussion, analysis, and critique. The research is distinguished by its analytical and critical jurisprudential study, producing a new Islamic banking product, amidst the scarcity of Sharia studies on it. The research was divided into two sections and a conclusion: the first dealt with defining the card, its application in the Palestinian Islamic Bank, and its Sharia adaptation. The second section addressed the most significant jurisprudential issues concerning it. The research concluded several key points, including genuine jurisprudential issues with the card undermining its legitimacy, such as violating agency and leasing rules regarding responsibility and guarantee, selling, and leasing in the seller's knowledge of the market value, and the client's acceptance of purchasing or leasing from the bank itself occurring in the card issuance agreement before the bank's ownership. It also noted the absence of genuine Sharia oversight ensuring Sharia compliance in operations and their regulations, which could lead to significant harm to Islamic banks in their form and differentiation from interest-based banks.

ESR Essentials: Imaging of sacroiliitis-practice recommendations by ESSR.

Sacroiliitis is commonly seen in patients with axial spondyloarthritis, in whom timely diagnosis and treatment are crucial to prevent irreversible structural damage. Imaging has a prominent place in the diagnostic process and several new imaging techniques have been examined for this purpose. We present a summary of updated evidence-based practice recommendations for imaging of sacroiliitis. MRI remains the imaging modality of choice for patients with suspected sacroiliitis, using at least four sequences: coronal oblique T1-weighted and fluid-sensitive sequences, a perpendicular axial oblique sequence, and a sequence for optimal evaluation of the bone-cartilage interface. Both active inflammatory and structural lesions should be described in the report, indicating location and extent. Radiography and CT, especially low-dose CT, are reasonable alternatives when MRI is unavailable, as patients are often young. This is particularly true to evaluate structural lesions, at which CT excels. Dual-energy CT with virtual non-calcium images can be used to depict bone marrow edema. Knowledge of normal imaging features in children (e.g., flaring, blurring, or irregular appearance of the articular surface) is essential for interpreting sacroiliac joint MRI in children because these normal processes can simulate disease. CLINICAL RELEVANCE STATEMENT: Sacroiliitis is a potentially debilitating disease if not diagnosed and treated promptly, before structural damage to the sacroiliac joints occurs. Imaging has a prominent place in the diagnostic process. We present a summary of practice recommendations for imaging of sacroiliitis, including several new imaging techniques. KEY POINTS: • MRI is the modality of choice for suspected inflammatory sacroiliitis, including a joint-line-specific sequence for optimal evaluation of the bone-cartilage interface to improve detection of erosions. • Radiography and CT (especially low-dose CT) are reasonable alternatives when MRI is unavailable. • Knowledge of normal imaging features in children is mandatory for interpretation of MRI of pediatric sacroiliac joints.

LEGAL CHALLENGES OF ARTIFICIAL INTELLIGENCE AND ROBOTICS: A COMPREHENSIVE REVIEW

The paper presents an insightful overview of the intricate legal challenges posed by the proliferation of Artificial Intelligence (AI) and Robotics. This comprehensive review explores the multifaceted dimensions of the evolving legal landscape, addressing issues at the intersection of technology and law. Key focal points include the accountability and liability frameworks for autonomous AI systems, ethical considerations in the deployment of intelligent machines, and the complex dynamics of data privacy in the age of pervasive automation. The review delves into the intricate legal nuances surrounding intellectual property rights, particularly as AI systems contribute to creative outputs and innovation. It navigates the blurred lines between human and machine authorship, raising fundamental questions about ownership and protection in this digital era. Moreover, the paper emphasizes the global nature of these challenges, highlighting the imperative for international cooperation to formulate harmonized legal standards. As AI and robotics revolutionize industries and societal frameworks, the analysis underscores the critical need for adaptive and anticipatory legal frameworks. It explores how existing legal paradigms are grappling with the unprecedented speed of technological advancements and the ethical dilemmas arising from the delegation of decision-making to intelligent algorithms. The paper sets the stage for a thorough examination of the legal intricacies surrounding AI and robotics. It advocates for a proactive and collaborative approach, involving legal experts, technologists, ethicists, and policymakers in crafting robust frameworks that balance innovation with ethical, privacy, and accountability considerations. This review serves as a foundational resource for understanding and addressing the legal challenges inherent in the transformative era of Artificial Intelligence and Robotics.
 Keywords: Artificial intelligence, Robotics, Legal, AI challenges, Ethics, Review.

Effects of inoculation and dry matter content on microbiome dynamics and metabolome profiling of sorghum silage

Sorghum forage was ensiled for 90 days at two dry matter (DM) contents (27 vs. 39%) without or with Lactiplantibacillus plantarum inoculation. On day 90 of fermentation, silages were sampled to assess the microbial community dynamics and metabolome profile. L. plantarum inoculation improved silage quality, as shown by a lower pH and greater acetic acid concentration. Loss of DM remained unaffected by L. plantarum inoculation but was greater in low- vs. high-DM sorghum silages (14.4 vs. 6.62%). The microbiome analysis revealed that Pseudomonas congelans represented the dominant species of the epiphytic microbiota in both low- and high-DM sorghum forage before ensiling. However, L. buchneri represented the dominant species at the end of ensiling. Ensiling fermentation resulted in distinct metabolic changes in silages with varying DM content. In low-DM silages, ensiling fermentation led to the accumulation of 24 metabolites and a reduction in the relative concentration of 13 metabolites. In high-DM silages, ensiling fermentation resulted in an increase in the relative concentration of 26 metabolites but a decrease in the concentration of 8 metabolites. Compared to non-inoculated silages, L. plantarum inoculation resulted in an increased concentration of 3 metabolites and a reduced concentration of 5 metabolites in low-DM silages. Similarly, in high-DM silages, there was an elevation in the relative concentration of 3 metabolites, while a decrease in 7 other metabolites. Ten metabolites with bio-functional activity were identified, including chrysoeriol, isorhamnetin, petunidin 3-glucoside, apigenin, caffeic acid, gallic acid, p-coumaric acid, trans-cinnamic acid, herniarin, and 3,4-dihydroxy-trans-cinnamate. This study presents a comprehensive analysis of microbiome and metabolome profiling of sorghum forage during ensiling as a function of DM content and L. plantarum inoculation, with a particular emphasis on identifying metabolites that may possess bio-functional properties.Key points• DM loss was not different by L. plantarum but higher in low- vs. high-DM silage.• L. buchneri dominated ensiling, regardless of DM level.• 10 metabolites with bio-functional activity were identified.

Reduction of left ventricular diastolic pressure as a key regulator of infarct coronary flow under mechanical left ventricular support.

Restoring ischaemic myocardial tissue perfusion is crucial for minimizing infarct size. Acute mechanical left ventricular (LV) support has been suggested to improve infarct tissue perfusion. However, its regulatory mechanism remains unclear. We investigated the physiological mechanisms in six Yorkshire pigs, which were subjected to 90-min balloon occlusion of the left anterior descending artery. During the acute reperfusion phase, LV support using an Impella heart pump was initiated. LV pressure, coronary flow and pressure of the infarct artery were simultaneously recorded to evaluate the impact of LV support on coronary physiology. Coronary wave intensity was calculated to understand the forces regulating coronary flow. Significant increases in coronary flow velocity and its area under the curve were found after mechanical LV support. Among the coronary flow-regulating factors, coronary pressure was increased mainly during the late diastolic phase with less pulsatility. Meanwhile, LV pressure was reduced throughout diastole resulting in significant and consistent elevation of coronary driving pressure. Interestingly, the duration of diastole was prolonged with LV support. In the wave intensity analysis, the duration between backward suction and pushing waves was extended, indicating that earlier myocardial relaxation and delayed contraction contributed to the extension of diastole. In conclusion, mechanical LV support increases infarct coronary flow by extending diastole and augmenting coronary driving pressure. These changes were mainly driven by reduced LV diastolic pressure, indicatingthat the key regulator of coronary flow under mechanical LV support is downstream of the coronary artery, rather than upstream. Our study highlights the importance of LV diastolic pressure in infarct coronary flow regulation. KEY POINTS: Restoring ischaemic myocardial tissue perfusion is crucial for minimizing infarct size. Although mechanical left ventricular (LV) support has been suggested to improve infarct coronary flow, its specific mechanism remains to be clarified. LV support reduced LV pressure, and elevated coronary pressure during the late diastolic phase, resulting in high coronary driving pressure. This study demonstrated for the first time that mechanical LV support extends diastolic phase, leading to increased infarct coronary flow. Future studies should evaluate the correlation between improved infarct coronary flow and resulting infarct size.

Ocular surface information seen from the somatosensory thalamus and cortex.

Ocular Surface (OS) somatosensory innervation detects external stimuli producing perceptions, such as pain or dryness, the most relevant symptoms in many OS pathologies. Nevertheless, little is known about the central nervous system circuits involved in these perceptions, and how they integrate multimodal inputs in general. Here, we aim to describe the thalamic and cortical activity in response to OS stimulation of different modalities. Electrophysiological extracellular recordings in anaesthetized rats were used to record neural activity, while saline drops at different temperatures were applied to stimulate the OS. Neurons were recorded in the ophthalmic branch of the trigeminal ganglion (TG, 49 units), the thalamic VPM-POm nuclei representing the face (Th, 69 units) and the primary somatosensory cortex (S1, 101 units). The precise locations for Th and S1 neurons receiving OS information are reported here for the first time. Interestingly, all recorded nuclei encode modality both at the single neuron and population levels, with noxious stimulation producing a qualitatively different activity profile from other modalities. Moreover, neurons responding to new combinations of stimulus modalities not present in the peripheral TG subsequently appear in Th and S1, being organized in space through the formation of clusters. Besides, neurons that present higher multimodality display higher spontaneous activity. These results constitute the first anatomical and functional characterization of the thalamocortical representation of the OS. Furthermore, they provide insight into how information from different modalities gets integrated from the peripheral nervous system into the complex cortical networks of the brain. KEY POINTS: Anatomical location of thalamic and cortical ocular surface representation. Thalamic and cortical neuronal responses to multimodal stimulation of the ocular surface. Increasing functional complexity along trigeminal neuroaxis. Proposal of a new perspective on how peripheral activity shapes central nervous system function.

The Role of Astrocytes and Alpha-Synuclein in Parkinson’s Disease: A Review

The search for new therapies to reduce symptoms and find a cure for Parkinson’s disease has focused attention on two key points: the accumulation of alpha-synuclein aggregates and astrocytes. The former is a hallmark of the disease, while the latter corresponds to a type of glial cell with an important role in both the prevention and development of this neurodegenerative disorder. Traditionally, research has focused on therapies targeting dopaminergic neurons. Currently, as more is known about the genetic and molecular factors and the neuroglial interaction in the disease, great emphasis has been placed on the neuroprotective role of astrocytes in the early stages of the disease and on the astrocytic capture of alpha-synuclein under both physiological and pathological conditions. This review aims to analyze the contribution of alpha-synuclein and astrocytes to the development and progression of Parkinson’s disease, as well as to evaluate recent therapeutic proposals specifically focused on synucleopathies and astroglial cells as potential therapies for the disease.

Ethyl Methanesulfonate Mutant Library Construction in Tartary Buckwheat with Agronomic Trait and Flavonoid Screening for Germplasm Innovation

As a nutrient-rich multigrain crop, buckwheat is a typical “medicinal food homology” crop that is rich in flavonoids, including rutin and various vitamins. It has positive anti-oxidant and anti-tumour properties and lowers blood pressure. However, due to strict self-crossing characteristics, slow progress has been made in Tartary buckwheat (TB) cross-breeding, resulting in the slow breeding of new varieties of new TB varieties, which has limited the improvement of yield and quality. Therefore, mutant breeding is a rapid and effective technique for broadening and innovating TB breeding. In recent years, improving qualities related to yield, lodging resistance, and stability have become key points in TB breeding. Based on the above findings, excellent, potentially valuable TB lines with rich phenotypes were obtained for the TB mutation library via ethyl methanesulfonate (EMS), laying a foundation for creating new TB germplasms. In this study, we systematically investigated more than 10 agronomic traits of JQ2 and JQ4 mutants, including plant type, leaf colour, grain type, grain colour, grain number per plant, grain length, grain width, grain weight per plant, and 1000-grain weight. The results show that the maximum number of grains per plant was 1956, the weight was 32.84 g, and the 1000-grain weight was 30.89 g. The maximum number of grains per JQ4 plant was 2308, and the weight was 44.82 g. The maximum 1000-grain weight was 24.7 g. Among the 295 JQ2 mutants and 153 JQ4 mutants, 10 flavonoids (orientin, morin, quercetin, kaempferol, luteolin, naringin, hesperetin, myricetin, hesperidin, and rutin) were detected with near infrared spectroscopy (NIR). The mutants were divided into five groups according to the flavonoid content of the JQ2 mutants, of which the first group included 31 individual lines. and the second to fifth groups included 70, 69, 72, and 53 lines, respectively. The JQ4 mutants were divided into four classes, of which 41, 50, 32, and 30 were individual lines, respectively, with the highest rutin content being 82.06 mg/g. In summary, through systematic analysis and screening of the agronomic traits and flavonoid contents of JQ2 and JQ4 mutant seeds, we obtained three lines with a high 1000-grain weight, including two JQ2 mutant lines (30.89 g) and one JQ4 mutant line, which reached 24.70 g and ten lines with high grain weight per plant. This included 8 JQ2 mutants and 2 JQ4 mutants, as well as 72 high-rutin mutants (including 31 lines from JQ2 and 41 lines from JQ4 mutants). These elite lines provide the material basis for creating TB germplasms with excellent qualities and cultivation characteristics.