Search

Rare variants in the beta-glucocerebrosidase gene (GBA1) are common genetic risk factors for alpha synucleinopathy, which often manifests clinically as GBA-associated Parkinson's disease (GBA-PD). Clinically, GBA-PD closely mimics idiopathic PD, but it may present at a younger age and often aggregates in families. Most carriers of GBA variants are, however, asymptomatic. Moreover, symptomatic PD patients without GBA variant have been reported in families with seemingly GBA-PD. These observations obscure the link between GBA variants and PD pathogenesis and point towards a role for unidentified additional genetic and/or environmental risk factors or second hits in GBA-PD. In this study, we explored whether rare genetic variants may be additional risk factors for PD in two families segregating the PD-associated GBA1 variants c.115+1G>A (ClinVar ID: 93445) and p.L444P (ClinVar ID: 4288). Our analysis identified rare genetic variants of the HSP70 co-chaperone DnaJ homolog subfamily B member 6 (DNAJB6) and lysosomal protein prosaposin (PSAP) as additional factors possibly influencing PD risk in the two families. In comparison to the wild-type proteins, variant DNAJB6 and PSAP proteins show altered functions in the context of cellular alpha-synuclein homeostasis when expressed in reporter cells. Furthermore, the segregation pattern of the rare variants in the genes encoding DNAJB6 and PSAP indicated a possible association with PD in the respective families. The occurrence of second hits or additional PD cosegregating rare variants has important implications for genetic counseling in PD families with GBA1 variant carriers and for the selection of PD patients for GBA targeted treatments.

Background and Purpose: The recently introduced Pipeline Flex Embolization Device with Shield Technology (Pipeline Shield) is the third generation of Pipeline flow-diverter devices. It has a new stent-surface modification, which reduces thrombogenicity. We aimed to evaluate clinical and radiographic (safety and efficacy) outcomes of the Pipeline Shield., Materials and Methods: The 30-day and 1-year mortality and morbidity rates and the 6- and 18-month radiographic aneurysm occlusion outcomes for procedures performed between March 2016 and January 2018 were analyzed. 3D-TOF-MRA was used for follow-up., Results: Forty-four attempted Pipeline Shield procedures were performed for 41 patients with 44 target aneurysms (total of 52 aneurysms treated). A total of 88.5% of devices were inserted in the anterior circulation, and 11.5%, in the posterior circulation; 49/52 (94.2%) aneurysms were saccular; and 1/52 (1.9%) was fusiform. One (1.9%) aneurysm was an iatrogenic pseudoaneurysm, and 1 (1.9%) was a dissecting aneurysm. Seventy-one percent (35/49) of the saccular aneurysms were wide-neck (neck, >4 mm), 34.6% (18/52) were large (≥10 mm), and 3.8% (2/52) were giant (≥25 mm). The mean aneurysm sac maximal diameter was 9.0 mm, and the mean neck width was 5.0 mm. The cumulative mortality and morbidity rates were 2.3% and 6.8% at 1 year, respectively. The adequate occlusion rate was 78.8% at 6 months and 90.3% at 18 months., Conclusions: In this pragmatic and non-industry-sponsored study, the occlusion rates and safety outcomes were similar to those seen in previously published studies with flow-diverter devices and earlier generation Pipeline Embolization Devices., (© 2019 by American Journal of Neuroradiology.)

Atypical parkinsonian disorders (APDs) comprise a group of neurodegenerative diseases with heterogeneous clinical and pathological features. Most APDs are sporadic, but rare familial forms have also been reported. Epidemiological and post-mortem studies associated APDs with oxidative stress and cellular protein aggregates. Identifying molecular mechanisms that translate stress into toxic protein aggregation and neurodegeneration in APDs is an active area of research. Recently, ribonucleic acid (RNA) stress granule (SG) pathways were discussed to be pathogenically relevant in several neurodegenerative disorders including APDs. Using whole genome sequencing, mRNA expression analysis, transfection assays and cell imaging, we investigated the genetic and molecular basis of a familial neurodegenerative atypical parkinsonian disorder. We investigated a family with six living members in two generations exhibiting clinical symptoms consistent with atypical parkinsonism. Two affected family members suffered from parkinsonism that was associated with ataxia. Magnetic resonance imaging (MRI) of these patients showed brainstem and cerebellar atrophy. Whole genome sequencing identified a heterozygous stop-gain variant (c.C811T; p.R271X) in the Poly(A) binding protein, cytoplasmic 4-like (PABPC4L) gene, which co-segregated with the disease in the family. In situ hybridization showed that the murine pabpc4l is expressed in several brain regions and in particular in the cerebellum and brainstem. To determine the functional impact of the stop-gain variant in the PABPC4L gene, we investigated the subcellular localization of PABPC4L in heterologous cells. Wild-type PABPC4L protein localized predominantly to the cell nucleus, in contrast to the truncated protein encoded by the stop-gain variant p.R271X, which was found homogeneously throughout the cell. Interestingly, the wild-type, but not the truncated protein localized to RasGAP SH3 domain Binding Protein (G3BP)-labeled cytoplasmic granules in response to oxidative stress induction. This suggests that the PABPC4L variant alters intracellular distribution and possibly the stress granule associated function of the protein, which may underlie APD in this family. In conclusion, we present genetic and molecular evidence supporting the role of a stop-gain PABPC4L variant in a rare familial APD. Our data shows that the variant results in cellular mislocalization and inability of the protein to associate with stress granules.

Background and Objective: Modern sulfonylureas like glimepiride offer effective glycemic control with extrapancreatic benefits and good tolerability. The objective of the present study was to evaluate and compare safety and efficacy of glimepiride and sitagliptin in combination with metformin in patients with type 2 diabetes mellitus (T2DM)., Methods: In this open-label, randomized, comparative, multicenter study, a total of 305 T2DM patients who were either drug naïve or uncontrolled on metformin were randomized to glimepiride 1 or 2 mg/sustained-release metformin 1000 mg once daily (glimepiride group, n = 202) or sitagliptin 50 mg/metformin 500 mg twice daily (sitagliptin group, n = 103) for 12 weeks. Primary endpoint was change in glycosylated hemoglobin (HbA1c). Secondary endpoints were change in fasting plasma glucose (FPG), postprandial plasma glucose (PPG), body mass index (BMI) and to assess overall safety profile., Results: At 12 weeks, there was a statistically significant difference in the mean HbA1c reduction in glimepiride group (0.42%) as compared to sitagliptin group (0.30%) ( P = 0.001). Mean reduction in FPG and PPG was also statistically significant in the glimepiride group as compared to the sitagliptin group ( P = 0.008). There was no significant difference in terms of change in BMI (0.07 ± 0.39 kg/m 2 vs. 0.08 ± 0.31 kg/m 2 ) in glimepiride and sitagliptin groups, respectively, ( P = 0.644) between both the groups. The incidences of hypoglycemic events were also comparable among both the groups., Conclusion: In T2DM patients, glimepiride/metformin combination exhibited significant reduction in glycemic parameters as compared to sitagliptin/metformin combination. Moreover, there was no significant difference between both the groups in terms of change in BMI and incidence of hypoglycemia., Competing Interests: There are no conflicts of interest.

Interoception is the sensing of physiological signals originating inside the body, such as hunger, pain and heart rate. People with greater sensitivity to interoceptive signals, as measured by, for example, tests of heart beat detection, perform better in laboratory studies of risky decision-making. However, there has been little field work to determine if interoceptive sensitivity contributes to success in real-world, high-stakes risk taking. Here, we report on a study in which we quantified heartbeat detection skills in a group of financial traders working on a London trading floor. We found that traders are better able to perceive their own heartbeats than matched controls from the non-trading population. Moreover, the interoceptive ability of traders predicted their relative profitability, and strikingly, how long they survived in the financial markets. Our results suggest that signals from the body - the gut feelings of financial lore - contribute to success in the markets.

Context: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a poor prognosis. Although the majority of childhood ACC arises in the context of inherited cancer susceptibility syndromes, it remains less clear whether a hereditary tumor predisposition exists for the development of ACC in adults. Here, we report the first occurrence of familial ACC in a kindred with Lynch syndrome resulting from a pathogenic germline MSH2 mutation., Case: A 54-year-old female with a history of ovarian and colorectal malignancy was found to have an ACC. A detailed family history revealed her mother had died of ACC and her sister had previously been diagnosed with endometrial and colorectal cancers. A unifying diagnosis of Lynch syndrome was considered, and immunohistochemical analyses demonstrated loss of MSH2 and MSH6 expression in both AACs (proband and her mother) and in the endometrial carcinoma of her sister. Subsequent genetic screening confirmed the presence of a germline MSH2 mutation (resulting in deletions of exons 1-3) in the proband and her sister., Conclusion: Our findings provide strong support for the recent proposal that ACC should be considered a Lynch syndrome-associated tumor and included in the Amsterdam II clinical diagnostic criteria. We also suggest that screening for ACC should be considered in cancer surveillance strategies directed at individuals with germline mutations in DNA mismatch repair genes.

Background/Objectives: Type 2 diabetes mellitus (T2DM) is a disorder characterized by insulin resistance, hyperglycemia, and dyslipidemia. Myricetin, a flavonoid found in various plants, has shown potential anti-diabetic effects in murine studies. This meta-analysis aimed to evaluate the impact of myricetin supplementation on glucose metabolism and lipid profiles in mouse models of metabolic diseases. Methods: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines (PROSPERO: CRD42024591569). Studies involving mice with metabolic disease models and exclusively using myricetin supplementation were checked across four databases (Embase, Scopus, PubMed, and WoS) until 23rd September 2024. The primary outcomes assessed were blood glucose (BG), insulin levels, triacylglycerol (TAG), total cholesterol (TC), HDL, and LDL. A random-effects model was applied to estimate standardized mean differences (SMD), and SYRCLE's risk-of-bias tool for animal studies was used. Results: Twenty-one studies with 514 mice met the inclusion criteria. Myricetin supplementation significantly reduced BG (SMD = −1.45, CI: −1.91 to −0.99, p < 0.00001, I2 = 74%), insulin (SMD = −1.78, CI: −2.89 to −0.68, p = 0.002, I2 = 86%), TAG (SMD = −2.60, CI: −3.24 to −1.96, p < 0.00001, I2 = 81%), TC (SMD = −1.86, CI: −2.29 to −1.44, p < 0.00001, I2 = 62%), and LDL (SMD = −2.95, CI: −3.75 to −2.14, p < 0.00001, I2 = 74%). However, the effect on HDL was not statistically significant (SMD = 0.71, CI: −0.01 to 1.43, p = 0.05, I2 = 83%). Conclusions: Myricetin supplementation improved glucose metabolism and lipid profiles in mouse models, suggesting its potential as a therapeutic agent for managing T2DM. However, further research is needed to confirm these findings in human studies. [ABSTRACT FROM AUTHOR]

Background:Moringa oleifera leaf is used for diabetes due to its pharmacologic effects. Patients with hyperglycemia experience beta cell destruction. However, no research on risk awareness has been done to ascertain its safety. The present study describes the antidiabetic effect of Moringa oleifera leaf, such as the protection of pancreatic beta cells and the induction of glycogen synthesis, before addressing the secondary effects of diabetes, such as hepatic and renal toxicity. Methods: Forty‐five Wistar rats weighed 160 ± 10 g were divided into nine groups. All animal operations complied with the National Institute of Health (NIH) guidelines for the care and use of laboratory animals as approved by the Animal Ethical Committee, University of Jos. Group I was normal control and Group II was diabetic animals induced with alloxan. Insulin and extract doses of 200, 400, and 800 mg/kg were given to diabetic Groups III‐VI. Normal animals in Groups VII–IX were given extract at doses of 200, 400, and 800 mg/kg for 28 days. Tissues were retrieved for biochemical and histological investigations using standard techniques. Results: There was decrease relative body weight of diabetic animals (95.50 ± 5.50) when compared to normal control (142.75 ± 20.08) with increased levels of urea (control 6.13 ± 0.523 and diabetes 29.23 ± 1.267) and creatinine (control 0.70 ± 0.057 and diabetes 2.13 ± 0.185). Histology of the liver and pancreas also points to organ damage due to hyperglycemia. However, oral administration of extract showed antidiabetic effect with protection of pancreatic beta cells and the induction of glycogen synthesis, no glycogen was deposited in the liver, addressing the secondary effects of diabetes, such as hepatic and renal toxicity. Further discovery revealed that extract elevated antioxidant enzyme expression. Conclusion: Leaf extract from Moringa oleifera reduces blood sugar and lessens the damage caused by hyperglycemia in the pancreas and liver. [ABSTRACT FROM AUTHOR]

Building envelopes and indoor environments exhibit thermal inertia, forming a virtual energy storage system in conjunction with the building air conditioner (AC) system. This system represents a current demand response resource for building electricity use. Thus, this study centers on the CatBoost algorithm within machine learning (ML) technology, utilizing the LASSO regression model for feature selection and applying the Optuna framework for hyperparameter optimization (HPO) to develop a cost-optimal control method for minimizing building AC loads. This method addresses the challenges associated with traditional load forecasting and control methods, which are often impacted by environmental temperature, building parameters, and user behavior uncertainties. These methods struggle to accurately capture the complex dynamics and nonlinear relationships of AC operations, making it difficult to devise AC operation and virtual energy storage scheduling strategies effectively. The proposed method was applied and validated using a case study of an office building in Nanjing, China. The prediction results showed coefficient of variation in root mean square error (CV-RMSE) values of 6.4% and 2.2%. Compared with the original operating conditions, the indoor temperature remained within a comfortable range, the AC load was reduced by 5.25%, and the operating energy costs were reduced by 24.94%. These results demonstrate that the proposed method offers improved computational efficiency, enhanced model performance, and economic benefits. [ABSTRACT FROM AUTHOR]

In recent years, research has noted the increasing prevalence of mental health problems among university students. The current mental health needs of the university population, along with the multitude of stressors they face, have increased the importance of examining their psychological well-being and determining the personal resources that effectively promote it. In this context, the present research aims to analyze the roles of psychological capital (PsyCap) and coping strategies as personal resources that are significantly related to the psychological well-being (PWB) of university students. Specifically, the mediating roles of various coping strategies (both adaptive and maladaptive) in the relationship between PsyCap and PWB are explored. The study involves 391 university students from Spain. The results show partial mediation effects of adaptive coping strategies (cognitive restructuring and social support) on the relationship between PsyCap and PWB. Likewise, PsyCap is shown to be a direct positive predictor of adaptive coping strategies and PWB, as well as a direct negative predictor of maladaptive coping strategies (self-criticism). Therefore, it is concluded that PsyCap and some adaptive coping strategies serve as valuable personal resources that predict PWB in university students. PsyCap is also associated with a lower tendency to engage in maladaptive coping strategies, such as self-criticism. Similarly, the use of cognitive restructuring and/or social support is related to high levels of PWB among university students. [ABSTRACT FROM AUTHOR]

Background: Coccoloba uvifera L. (Family: Polygonaceae) known as sea grape is natively distributed in middle and south America. The aqueous leaf extract showed inhibitory activities against α-glucosidase and α-amylase in previous reports. Moreover, the hydroalcoholic leaves extract ameliorated hyperglycemia in the oral glucose tolerance test. Despite these promising results, the extracts used in these studies were not standardized, nor was their mechanism of action elucidated. The current study aims to standardize the ethanolic C. uvifera leaves extract (CU) using markers, and assess its ameliorative activity against diabetes and its hepatoprotective activity against diabetic complications. Results: Standardized leaves' ethanolic extract contained 0.09 ± 0.00057 and 0.23 ± 0.0011 mg/g gallic acid and rutin, respectively, as estimated by HPLC. Administration of CU (100, 200 and 400 mg/kg) for 6 weeks ameliorated DM manifestations in STZ-induced diabetic rats in a dose-dependent manner. The ethanolic extract reduced fasting blood glucose, increased serum insulin and reduced elevated liver enzymes. CU counteracted oxidative stress, promoted glucose metabolizing enzymes and reduced gluconeogenesis enzymes. The underlying mechanism involved increased expression of IR, IRS-1, IRS-2 and GLUT2 in liver tissue through activation of PI3K/AKT signaling. The histopathological study demonstrated reduced inflammation and hepatocyte degeneration. Conclusion: CU could be used as a promising antidiabetic drug with hepatoprotective activity in diabetes hepatic complications. The standardized CU ethanolic extract should be further assessed clinically alone or in combination with other antidiabetic remedies. [ABSTRACT FROM AUTHOR]

The current study proceeded to reduce the environmental hazards spreading worldwide due to synthetic dyes. To overcome these problems, eco-friendly natural dyes are introduced as alternative sources of synthetic dyes. The present study was focused on exploring the bio-colorant of the aqueous and acidic extract of the bark of Melia azedarach L. for the dyeing of both silk and cotton samples. The results of the extraction medium specified that the aqueous extract gave maximum colorant solubility and upon fabric dyeing produced higher color strength in contrast to the acidic medium. The optimization experimentation data showed that excellent color strength of silk fabric was found at 45 min dyeing time duration, in 35:1 mL dye extract, and using 2% salt (NaCl) as an exhausting agent, whereas cotton fabric showed the maximum K/S value at 60 min dyeing time, in a 45:1 mL liquor ratio, and with the use of 2% salt. Bio-mordants produce different shades on both fabrics. Bio-mordanting experiments on silk revealed that pre-mordanting with 2% turmeric and 3% pomegranate, and post-mordanting using 3% turmeric and 2% pomegranate produced a darker shade. In the case of cotton, the pre-mordanted samples with 2% turmeric and 3% pomegranate and the post-mordanted samples with 4% turmeric and 4% pomegranate gave the highest color strengths. All the mordanted samples gave excellent fastness ratings. Overall, it has been found that Bakain bark proved to be an excellent source of tannin. The result of this study showed that it could be a cost-effective and eco-friendly dye source for textile progress. [ABSTRACT FROM AUTHOR]

Spiking neural networks and neuromorphic hardware platforms that simulate neuronal dynamics are getting wide attention and are being applied to many relevant problems using Machine Learning. Despite a well-established mathematical foundation for neural dynamics, there exists numerous software and hardware solutions and stacks whose variability makes it difficult to reproduce findings. Here, we establish a common reference frame for computations in digital neuromorphic systems, titled Neuromorphic Intermediate Representation (NIR). NIR defines a set of computational and composable model primitives as hybrid systems combining continuous-time dynamics and discrete events. By abstracting away assumptions around discretization and hardware constraints, NIR faithfully captures the computational model, while bridging differences between the evaluated implementation and the underlying mathematical formalism. NIR supports an unprecedented number of neuromorphic systems, which we demonstrate by reproducing three spiking neural network models of different complexity across 7 neuromorphic simulators and 4 digital hardware platforms. NIR decouples the development of neuromorphic hardware and software, enabling interoperability between platforms and improving accessibility to multiple neuromorphic technologies. We believe that NIR is a key next step in brain-inspired hardware-software co-evolution, enabling research towards the implementation of energy efficient computational principles of nervous systems. NIR is available at neuroir.org Neuromorphic software and hardware solutions vary widely, challenging interoperability and reproducibility. Here, authors establish a representation for neuromorphic computations in continuous time and demonstrate support across 11 platforms. [ABSTRACT FROM AUTHOR]

This study addresses the magnetohydrodynamic flow of a squeezed ternary nanofluid between two horizontal parallel Riga plates. The importance of this problem lies in understanding the complex interactions between magnetic fields, nanofluid dynamics, and heat transfer, which are crucial for optimizing thermal management systems. This study utilizes a numerical approach, specifically a collocation method implemented in MATLAB, to solve the governing equations with high precision. Key results acquired indicate that the magnetic field and Riga plate actuator significantly enhance fluid velocity, whereas the variation in thermal conductivity, radiation, and viscous dissipation increases the temperature distribution. Quantitative analysis illustrates the impact of all these factors on skin friction and Nusselt number. Sensitivity analysis using the response surface methodology exhibits the conditions for optimized heat transfer. The novelty of this work lies in its comprehensive analysis of the magnetohydrodynamic flow in the presence of a microcantilever sensor, which provides deep understanding of optimization of heat transfer rates. This research offers a detailed examination of the combined effects of various physical phenomena and also validates them through graphical comparisons with existing studies. [ABSTRACT FROM AUTHOR]

Risk taking is central to human activity. Consequently, it lies at the focal point of behavioral sciences such as neuroscience, economics, and finance. Many influential models from these sciences assume that financial risk preferences form a stable trait. Is this assumption justified and, if not, what causes the appetite for risk to fluctuate? We have previously found that traders experience a sustained increase in the stress hormone cortisol when the amount of uncertainty, in the form of market volatility, increases. Here we ask whether these elevated cortisol levels shift risk preferences. Using a double-blind, placebo-controlled, cross-over protocol we raised cortisol levels in volunteers over 8 d to the same extent previously observed in traders. We then tested for the utility and probability weighting functions underlying their risk taking and found that participants became more risk-averse. We also observed that the weighting of probabilities became more distorted among men relative to women. These results suggest that risk preferences are highly dynamic. Specifically, the stress response calibrates risk taking to our circumstances, reducing it in times of prolonged uncertainty, such as a financial crisis. Physiology-induced shifts in risk preferences may thus be an underappreciated cause of market instability.

Context: Attainment of safe GH and IGF-1 levels is a central goal of acromegaly management., Objective: The aim of this study was to determine the extent to which reductions in GH and IGF-1 concentrations correlate with amelioration of radiological, metabolic, vascular, cardiac, and respiratory sequelae in a single unselected patient cohort., Study Design: This was a prospective, within-subject comparison in 30 patients with newly diagnosed acromegaly (15 women and 15 men: mean age, 54.3 years; range, 23-78 years) before and after 24 weeks of lanreotide Autogel (ATG) therapy., Results: Reductions in GH and IGF-1 concentrations and tumor volume were observed in all but 2 patients (median changes [Δ]: GH, -6.88 μg/L [interquartile range -16.78 to -3.32, P = .000001]; IGF-1, -1.95 × upper limit of normal [-3.06 to -1.12, P = .000002]; and pituitary tumor volume, -256 mm(3) [-558 to -72.5, P = .0002]). However, apnea/hypopnea index scores showed highly variable responses (P = .11), which were independent of ΔGH or ΔIGF-1, but moderately correlated with Δweight (R(2) = 0.42, P = .0001). Although systolic (P = .33) and diastolic (P = .76) blood pressure were unchanged, improvements in arterial stiffness (aortic pulse wave velocity, -0.4 m/s [-1.2 to +0.2, P = .046]) and endothelial function (flow mediated dilatation, +1.73% [-0.32 to +6.19, P = .0013]) were observed. Left ventricular mass index regressed in men (-11.8 g/cm(2) [-26.6 to -1.75], P = .019) but not in women (P = .98). Vascular and cardiac changes were independent of ΔGH or ΔIGF-1 and also showed considerable interindividual variation. Metabolic parameters were largely unchanged., Conclusions: Presurgical ATG therapy lowers GH and IGF-1 concentrations, induces tumor shrinkage, and ameliorates/reverses cardiac, vascular, and sleep complications in many patients with acromegaly. However, responses vary considerably between individuals, and attainment of biochemical control cannot be assumed to equate to universal complication control.

Glioblastoma is a highly aggressive tumour with marked heterogeneity at the morphological level in both the tumour cells and the associated highly prominent vasculature. As we begin to develop an increased biological insight into the underlying processes driving the disease, fewer attempts have thus far been made to understand these phenotypic differences. We sought to address this by carefully assessing the morphological characteristics of both the tumour cells and the associated vasculature, relating these observations to the IDH1/MGMT status, with a particular focus on the early onset population of young adults who develop primary glioblastoma. 276 primary glioblastoma specimens were classified into their predominant cell morphological type (fibrillary, gemistocytic, giant cell, small cell, oligodendroglial, sarcomatous), and assessed for specific tumour (cellularity, necrosis, palisades) and vascular features (glomeruloid structures, arcades, pericyte proliferation). IDH1 positive glioblastomas were associated with a younger age at diagnosis, better clinical outcome, prominent oligodendroglial and small cell tumour cell morphology, pallisading necrosis and glomeruloid vascular proliferation in the absence of arcade-like structures. These features widen the phenotype of IDH1 mutation-positive primary glioblastoma in young adults and provide correlative evidence for a functional role of mutant IDH1 in the differential nature of neo-angiogenesis in different subtypes of glioblastoma.

The article presents a study which examined rearing environment and husbandry practices of Coimbatore sheep in the field. The study showed that the examined sheep were reared by farmers under traditional method of rearing with less scientific management practices. The researchers recommend that farmers be given periodical training on improved scientific breeding and management practices.

A 29-year-old male university student, with no prior history of trauma, presented with a 1 year history of clear fluid leaking intermittently from his left nostril. His past medical history included bilateral gynaecomastia since age 12, and recent low libido. β2-transferrin analysis of the nasal fluid confirmed a diagnosis of cerebrospinal fluid (CSF) rhinorrhoea. The serum prolactin was grossly elevated at 42 700 mU/l and brain magnetic resonance imaging (MRI) revealed a large parasellar/sellar mass. A diagnosis of invasive macroprolactinoma complicated by spontaneous CSF rhinorrhoea was made. The patient was commenced on treatment with cabergoline, but while awaiting surgery to repair the CSF leak he developed streptococcus mitis and sanguis meningitis. He made an uncomplicated recovery with antibiotic treatment. Immediately following this episode, the CSF rhinorrhoea resolved spontaneously. Subsequently, a repeat MRI scan revealed dramatic involution of the pituitary mass and the serum prolactin had fallen to 604 mU/l.

A promising method of automating management tasks in computing systems is to formulate them as control or optimization problems in terms of performance metrics. For an online optimization scheme to be of practical value in a distributed setting, however, it must successfully tackle the curses of dimensionality and modeling. This paper develops a hierarchical control framework to solve performance management problems in distributed computing systems operating in a data center. Concepts from approximation theory are used to reduce the computational burden of controlling such large-scale systems. The relevant approximations are made in the construction of the dynamical models to predict system behavior and in the solution of the associated control equations. Using a dynamic resource-provisioning problem as a case study, we show that a computing system managed by the proposed control framework with approximation models realizes profit gains that are, in the best case, within 1% of a controller using an explicit model of the system.

Interoception plays an important role in emotion processing. However, the neurobiological substrates of the relationship between visceral responses and emotional experiences remain unclear. In the present study, we measured interoceptive sensitivity using the heartbeat discrimination task and investigated the effects of individual differences in interoceptive sensitivity on changes in pulse rate and insula activity in response to subjective emotional intensity. We found a positive correlation between heart rate and valence level when listening to music only in the high interoceptive sensitivity group. The valence level was also positively correlated with music-elicited anterior insula activity. Furthermore, a region of interest analysis of insula subregions revealed significant activity in the left dorsal dysgranular insula for individuals with high interoceptive sensitivity relative to individuals with low interoceptive sensitivity while listening to the high-valence music pieces. Our results suggest that individuals with high interoceptive sensitivity use their physiological responses to assess their emotional level when listening to music. In addition, insula activity may reflect the use of interoceptive signals to estimate emotions. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) algorithms hold the potential to revolutionize radiology. However, a significant portion of the published literature lacks transparency and reproducibility, which hampers sustained progress toward clinical translation. Although several reporting guidelines have been proposed, identifying practical means to address these issues remains challenging. Here, we show the potential of cloud-based infrastructure for implementing and sharing transparent and reproducible AI-based radiology pipelines. We demonstrate end-to-end reproducibility from retrieving cloud-hosted data, through data pre-processing, deep learning inference, and post-processing, to the analysis and reporting of the final results. We successfully implement two distinct use cases, starting from recent literature on AI-based biomarkers for cancer imaging. Using cloud-hosted data and computing, we confirm the findings of these studies and extend the validation to previously unseen data for one of the use cases. Furthermore, we provide the community with transparent and easy-to-extend examples of pipelines impactful for the broader oncology field. Our approach demonstrates the potential of cloud resources for implementing, sharing, and using reproducible and transparent AI pipelines, which can accelerate the translation into clinical solutions. A significant portion of the scientific literature on AI for radiology lacks transparency and reproducibility, which hampers sustained progress toward clinical translation. Here, the authors offer a blueprint for transparent AI pipelines on cloud platforms, focusing on lung cancer prediction and biomarker discovery. [ABSTRACT FROM AUTHOR]

The proliferation of battery-operated end-user electronic devices due to technological advancements, especially in medical image processing applications, demands low power consumption, high-speed operation, and efficient coding. The design of these devices is centered on the Application-Specific Integrated Circuits (ASIC), General Purpose Processors (GPP), and Field Programmable Gate Array (FPGA) frameworks. The need for low-power functional blocks arises from the growing demand for high-performance computational units that are part of high-speed processors operating at high clock frequencies. The operational speed of the processor is determined by the computational unit, which is the workhorse of high-speed processors. A novel approach to integrating Very Large-Scale Integration (VLSI) ASIC design and the concepts of low-power VLSI compatible with medical image compression was embraced in this research. The focus of this study was the design, development, and implementation of a Power Delay Product (PDP) optimized computational unit targeted for medical image compression using ASIC design flow. This stimulates the research community's quest to develop an ideal architecture, emphasizing on minimizing power consumption and enhancing device performance for medical image processing applications. The study uses area, delay, power, PDP, and Peak Signal-to-Noise Ratio (PSNR) as performance metrics. The research work takes inspiration from this and aims to enhance the efficiency of the computational unit through minor design modifications that significantly impact performance. This research proposes to explore the trade-off of high-performance adder and multiplier designs to design an ASIC-based computational unit using low-power techniques to enhance the efficiency in power and delay. The computational unit utilized for the digital image compression process was synthesized and implemented using gpdk 45 nm standard libraries with the Genus tool of Cadence. A reduced PDP of 46.87% was observed when the image compression was performed on a medical image, along with an improved PSNR of 5.89% for the reconstructed image. [ABSTRACT FROM AUTHOR]

Horses revolutionized human history with fast mobility1. However, the timeline between their domestication and their widespread integration as a means of transport remains contentious2–4. Here we assemble a collection of 475 ancient horse genomes to assess the period when these animals were first reshaped by human agency in Eurasia. We find that reproductive control of the modern domestic lineage emerged around 2200 bce, through close-kin mating and shortened generation times. Reproductive control emerged following a severe domestication bottleneck starting no earlier than approximately 2700 bce, and coincided with a sudden expansion across Eurasia that ultimately resulted in the replacement of nearly every local horse lineage. This expansion marked the rise of widespread horse-based mobility in human history, which refutes the commonly held narrative of large horse herds accompanying the massive migration of steppe peoples across Europe around 3000 bce and earlier3,5. Finally, we detect significantly shortened generation times at Botai around 3500 bce, a settlement from central Asia associated with corrals and a subsistence economy centred on horses6,7. This supports local horse husbandry before the rise of modern domestic bloodlines.Analyses of 475 ancient horse genomes show modern horses emerged around 2200 bce, coinciding with sudden expansion across Eurasia, refuting the narrative of large horse herds accompanying earlier migrations of steppe peoples across Europe. [ABSTRACT FROM AUTHOR]

This paper analyzes, designs and implements a reconfigurable phase-shifted full-bridge (PSFB) converter. It adopts the topology of the traditional PSFB converter and incorporates clamping circuits to solve some fundamental problems of conventional topology. In addition, auxiliary switches are employed for output reconfiguration, which allows expanding the output voltage range without compromising the system efficiency. Single pole double throw (SPDT) mechanical switches are used to realize series and parallel connections. In this paper, the characterization of the PSFB converter with clamping circuit and its design considerations are discussed. A 10 kW prototype with a power density of 0.485 W/cm3, 900 V input voltage and 400/800 V nominal output voltage was manufactured. The experimental results validated the analysis and confirmed the high conversion efficiency for a wide load range; an efficiency of 96.69% was obtained for the full load condition. [ABSTRACT FROM AUTHOR]

Anderson–Fabry disease (AFD) is a genetic sphingolipidosis involving virtually the entire body. Among its manifestation, the involvement of the central and peripheral nervous system is frequent. In recent decades, it has become evident that, besides cerebrovascular damage, a pure neuronal phenotype of AFD exists in the central nervous system, which is supported by clinical, pathological, and neuroimaging data. This neurodegenerative phenotype is often clinically characterized by an extrapyramidal component similar to the one seen in prodromal Parkinson's disease (PD). We analyzed the biological, clinical pathological, and neuroimaging data supporting this phenotype recently proposed in the literature. Moreover, we compared the neurodegenerative PD phenotype of AFD with a classical monogenic vascular disease responsible for vascular parkinsonism and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). A substantial difference in the clinical and neuroimaging features of neurodegenerative and vascular parkinsonism phenotypes emerged, with AFD being potentially responsible for both forms of the extrapyramidal involvement, and CADASIL mainly associated with the vascular subtype. The available studies share some limitations regarding both patients' information and neurological and genetic investigations. Further studies are needed to clarify the potential association between AFD and extrapyramidal manifestations. [ABSTRACT FROM AUTHOR]

Textile coloration is a complex process involving the interaction of dye molecules with fibers in a dye bath. Synthetic dyes pose environmental hazards, leading to increased interest in natural dyes sourced from plants, animals, and minerals. However, natural dyes often require mordants for application to textiles. Despite their eco‐friendliness, natural dyes can exhibit poor wash fastness on fabrics, necessitating further research to enhance their performance. This study investigates the use of mahogany sawdust extract as a natural dye for cotton coloration, focusing on the enhancement of fastness properties through metallic mordants and associated environmental risks. Mahogany sawdust, rich in flavonoids and tannins, shows promise as a sustainable alternative to synthetic dyes. The dyeing process involves the extraction of natural dyes from sawmill bio‐waste and subsequent application onto cotton fabrics using various metallic mordants. Evaluation of colorfastness properties, color strength, color coordinates, tensile strength, FTIR, and SEM analysis provides insights into the dye‐fiber interactions and fabric properties. Environmental risk assessment considers metal exhaustion onto fabric surfaces, residual metal concentrations in mordant baths, and metal content in dyeing wastewater. Overall, this study contributes to the development of sustainable dyeing processes and highlights the importance of environmental considerations in textile coloration. Highlights: Mahogany sawdust extract: potential natural dye for sustainable cotton coloration.Metallic mordants enhance colorfastness and fabric durability in dyeing processes.Comprehensive analysis reveals the intricate dynamics of dye‐fiber interactions.Environmental risk evaluation guides sustainable textile manufacturing practices.Research paves the way for greener, more sustainable textile industry practices globally. [ABSTRACT FROM AUTHOR]

This paper presents the algorithmic framework for a multimodal hearing aid (HA) prototype designed on a Field Programmable Gate Array (FPGA), specifically the RFSOC4*2 AMD FPGA, and evaluates the transmitter performance through simulation studies. The proposed architecture integrates audio and video inputs, processes them using advanced algorithms, and employs the 5G New Radio (NR) communication protocol for uploading the processed signal to the cloud. The core transmission utilizes Orthogonal Frequency Division Multiplexing (OFDM), an algorithm that effectively multiplexes the processed signals onto various orthogonal frequencies, enhancing bandwidth efficiency and reducing interference. The design is divided into different modules such as Sound reference signal (SRS), demodulation reference signal (DMRS), physical broadcast channel (PBCH), and physical uplink shared channel (PUSCH). The modulation algorithm has been optimized for FPGA parallel processing capabilities, making it better suited for the hearing aid requirements for low latency. The optimized algorithm achieves a transmission time of only 4.789 ms and uses fewer hardware resources, enhancing performance in a cost-effective and energy-efficient manner. [ABSTRACT FROM AUTHOR]

Simple Summary: Color and body size traits are considered the key parameters influence the economic value of animals. In recent years, advancement in the genetic basis of coat colors in equines has received considerable attention among animal breeders. In addition, coat color plays a significant role in breed identification and selection, as well as animal health and disease. The current review concisely provides information on the role of melanin pigments and key candidate genes associated with coat color phenotypes in equines. Furthermore, the review also highlights the importance of coat color in equine breeding and health. Variation in coat color among equids has attracted significant interest in genetics and breeding research. The range of colors is primarily determined by the type, concentration, and distribution of melanin pigments, with the balance between eumelanin and pheomelanin influenced by numerous genetic factors. Advances in genomic and sequencing technologies have enabled the identification of several candidate genes that influence coat color, thereby clarifying the genetic basis of these diverse phenotypes. In this review, we concisely categorize coat coloration in horses and donkeys, focusing on the biosynthesis and types of melanin involved in pigmentation. Moreover, we highlight the regulatory roles of some key candidate genes, such as MC1R, TYR, MITF, ASIP, and KIT, in coat color variation. Moreover, the review explores how coat color relates to selective breeding and specific equine diseases, offering valuable insights for developing breeding strategies that enhance both the esthetic and health aspects of equine species. [ABSTRACT FROM AUTHOR]

Binary transition metal oxide complexes (BTMOCs) in three-dimensional (3D) layered structures show great promise as electrodes for supercapacitors (SCs) due to their diverse oxidation states, which contribute to high specific capacitance. However, the synthesis of BTMOCs with 3D structures remains challenging yet crucial for their application. In this study, we present a novel approach utilizing a single-step hydrothermal technique to fabricate flower-shaped microspheres composed of a NiCo-based complex. Each microsphere consists of nanosheets with a mesoporous structure, enhancing the specific surface area to 23.66 m2 g−1 and facilitating efficient redox reactions. When employed as the working electrode for supercapacitors, the composite exhibits remarkable specific capacitance, achieving 888.8 F g−1 at 1 A g−1. Furthermore, it demonstrates notable electrochemical stability, retaining 52.08% capacitance after 10,000 cycles, and offers a high-power density of 225 W·kg−1, along with an energy density of 25 Wh·kg−1, showcasing its potential for energy storage applications. Additionally, an aqueous asymmetric supercapacitor (ASC) was assembled using NiCo microspheres-based complex and activated carbon (AC). Remarkably, the NiCo microspheres complex/AC configuration delivers a high specific capacitance of 250 F g−1 at 1 A g−1, with a high energy density of 88 Wh kg−1, for a power density of 800 W kg−1. The ASC also exhibits excellent long-term cyclability with 69% retention over 10,000 charge–discharge cycles. Furthermore, a series of two ASC devices demonstrated the capability to power commercial blue LEDs for a duration of at least 40 s. The simplicity of the synthesis process and the exceptional performance exhibited by the developed electrode materials hold considerable promise for applications in energy storage. [ABSTRACT FROM AUTHOR]

Changes in risk preference have been reported when making a series of independent risky choices or non-foraging economic decisions. Behavioral economics has put forward various explanations for specific effects on risk preference in non-foraging tasks, but a consensus regarding the general principle underlying these effects has not been reached. In contrast, recent studies have investigated human economic risky choices using tasks adapted from foraging theory, which require consideration of past choices and future opportunities to make optimal decisions. In these foraging tasks, human economic risky choices are explained by the ethological principle of fitness maximization, which naturally leads to dynamic risk preference. Here, we conducted two online experiments to investigate whether the principle of fitness maximization can explain risk preference dynamics in a non-foraging task. Participants were asked to make a series of independent risky economic decisions while the environmental richness changed. We found that participants' risk preferences were influenced by the current and past environments, making them more risk-averse during and after the rich environment compared to the poor environment. These changes in risk preference align with fitness maximization. Our findings suggest that the ethological principle of fitness maximization might serve as a generalizable principle for explaining dynamic preferences, including risk preference, in human economic decision-making. Author summary: Decision-making involving probabilistic outcomes (i.e., under risk) is an integral part of our daily lives. Empirical studies have shown that risky behavior often deviates from standard economic theory, and peoples' risk preferences change depending on their psychological and physiological states, and the context of the decision. While previous studies have developed empirical mathematical models to provide mechanistic explanations of these effects, there is no unifying principle that explains why human risky decision-making is tuned this way. Here, we document one such context effect and suggest that this effect can be explained by the ethological principle of fitness maximization. In our study, participants made sequential independent risky decisions in different environments. We found that environments in which it was easy to get large rewards (rich environment) increased participants' risk-aversiveness both during and after experiencing them, and experiencing poor environments increased risk taking behavior. The foregoing modulations of risk-aversiveness are predicted if participants make decisions to satisfy some internal threshold for minimum reward gain, akin to reaching a minimum threshold for survival, rather than to maximize reward gain. Our results suggest that a better understanding of human economic behavior may be achieved under the principle of fitness maximization. [ABSTRACT FROM AUTHOR]

One of today's main concerns is to bring artificial intelligence capabilities to embedded systems for edge applications. The hardware resources and power consumption required by state-of-the-art models are incompatible with the constrained environments observed in edge systems, such as IoT nodes and wearable devices. Spiking Neural Networks (SNNs) can represent a solution in this sense: inspired by neuroscience, they reach unparalleled power and resource efficiency when run on dedicated hardware accelerators. However, when designing such accelerators, the amount of choices that can be taken is huge. This paper presents SpikExplorer, a modular and flexible Python tool for hardware-oriented Automatic Design Space Exploration to automate the configuration of FPGA accelerators for SNNs. SpikExplorer enables hardware-centric multiobjective optimization, supporting target factors such as accuracy, area, latency, power, and various combinations during the exploration process. The tool searches the optimal network architecture, neuron model, and internal and training parameters leveraging Bayesian optimization, trying to reach the desired constraints imposed by the user. It allows for a straightforward network configuration, providing the full set of explored points for the user to pick the trade-off that best fits their needs. The potential of SpikExplorer is showcased using three benchmark datasets. It reaches 95.8% accuracy on the MNIST dataset, with a power consumption of 180 mW/image and a latency of 0.12 ms/image, making it a powerful tool for automatically optimizing SNNs. [ABSTRACT FROM AUTHOR]

Adrenocortical carcinoma (ACC) and pheochromocytoma/paraganglioma (PPGL) are two rare types of adrenal gland malignancies. Regarding hereditary tumors, some patients with ACC are associated with with Li-Fraumeni syndrome (LFS), and those with PPGL with multiple endocrine neoplasia type 2. Recent studies have expanded this spectrum to include other types of hereditary tumors, such as Lynch syndrome or familial adenomatous polyposis. Individuals harboring germline TP53 pathogenic variants that cause LFS have heterogeneous phenotypes depending on the respective variant type. As an example, R337H variant found in Brazilian is known as low penetrant. While 50–80% of pediatric ACC patients harbored a LFS, such a strong causal relationship is not observed in adult patients, which suggests different pathophysiologies between the two populations. As for PPGL, because multiple driver genes, such as succinate dehydrogenase (SDH)-related genes, RET, NF1, and VHL have been identified, universal multi-gene germline panel testing is warranted as a comprehensive and cost-effective approach. PPGL pathogenesis is divided into three molecular pathways (pseudohypoxia, Wnt signaling, and kinase signaling), and this classification is expected to result in personalized medicine based on genomic profiles. It remains unknown whether clinical characteristics differ between cases derived from genetic predisposition syndromes and sporadic cases, or whether the surveillance strategy should be changed depending on the genetic background or whether it should be uniform. Close cooperation among medical genomics experts, endocrinologists, oncologists, and early investigators is indispensable for improving the clinical management for multifaceted ACC and PPGL. [ABSTRACT FROM AUTHOR]

The generation of test vectors is a key technique that affects the efficiency and fault detection rate of the boundary scan test. Aiming at the local optimal solution problem of the current common test vectors generation algorithm, this paper proposes a test vectors generation algorithm based on improved GA-AO* model, through which the test vectors are generated by using the idea of heuristic search and backtracking correction. In order to speed up the heuristic search, this paper designed a heuristic function with both prior and posterior parameters to describe the influence of typical faults on the failure probability index of the test vectors. At the same time, this paper used a genetic algorithm (GA) to determine the specific values of the posterior parameters iteratively. Finally, through theoretical analysis and physical verification, compared with the test vector generated by the traditional method, the test vector generated by this method is optimized on the prior failure probability index and performs better in the physical experiment. [ABSTRACT FROM AUTHOR]

Simple Summary: Since horses were domesticated, human selection has introduced new coat colors and patterns, which have become a feature of added value in many current breeds. The wild population generally exhibit a basic coat color set (Bay, Black and Chestnut) due to a lack of crossbreeding with domestic breeds and mating with subjects carrying the same color set. Sometimes, visual identification of the coat color is difficult due to several individual and environmental conditions, leading to incorrect registration. However, it is crucial to identify coat colors accurately and to correctly report them in the Stud Book for legal and medical certification. Furthermore, Grays are horses born with an original basic coat color, but, gradually, hair graying leads to the complete loss of coat pigmentation with age. Therefore, it becomes very difficult to predict what color foals will be born from a Gray parent. Indeed, many other traits, like behavior, athletic skills, and genetic diseases, could be influenced by coat color. For breeders who want to produce foals with specific coats, this feature is also central. For all these reasons, molecular analysis of two major genes involved in the basic coat color definition (MC1R and ASIP genes) was conducted on 90 Sarcidano Horses, to correctly identify and assign individual coat colors. This study aimed to evaluate the discrepancies between genetic and visual coat color assignment in the Sarcidano Horse and to elucidate potential reasons. Individual DNA from 90 Sarcidano Horses was used for genetic assignment of coat color to explore the correspondence with individual forms containing phenotypical traits. The MC1R exon 1 and ASIP exon 3 have been genotyped and sequenced to obtain a picture of the coat color distribution in this breed. Surprisingly, once we compared the genetic results with the individual forms reporting the phenotypic data for each subject, a certain degree of non-correspondence between the phenotypic and genetic data in relation to coat color emerged. From the genetic analysis, Chestnuts (n = 58) resulted the most common Sarcidano Horse (n = 58), followed by a quite large number of Blacks (n = 28) and a very small number of Bays (n = 4), whereas phenotypic distribution resulted in 38 Chestnuts, 40 Bays, only 2 Blacks, and 10 Grays (without the possibility of recognizing the true color they carried). Chestnut resulted a very representative coat color, while many horses that visually identified as Bays were genetically Blacks. This discrepancy, that could be due to a variety of individual and external factors, including age, time of year, living situation and dietary condition, suggesting the importance of accurate coat color identification to ensure adequate features registration and reliable prediction of offspring's coat color. [ABSTRACT FROM AUTHOR]

Images obtained in low-light scenes are often accompanied by problems such as low visibility, blurred details, and color distortion, enhancing them can effectively improve the visual effect and provide favorable conditions for advanced visual tasks. In this study, we propose a Multi-Technology Fusion of Low-light Image Enhancement Network (MTIE-Net) that modularizes the enhancement task. MTIE-Net consists of a residual dense decomposition network (RDD-Net) based on Retinex theory, an encoder-decoder denoising network (EDD-Net), and a parallel mixed attention-based self-calibrated illumination enhancement network (PCE-Net). The low-light image is first decomposed by RDD-Net into a lighting map and reflectance map; EDD-Net is used to process noise in the reflectance map; Finally, the lighting map is fused with the denoised reflectance map as an input to PCE-Net, using the Fourier transform for illumination enhancement and detail recovery in the frequency domain. Numerous experimental results show that MTIE-Net outperforms the comparison methods in terms of image visual quality enhancement improvement, denoising, and detail recovery. The application in nighttime face detection also fully demonstrates its promise as a pre-processing means in practical applications. [ABSTRACT FROM AUTHOR]

An environmentally friendly method using real or artificial bovine milk permeate to both depilate and preserve sheepskins has been reported which completely and cleanly removed the wool from the hair follicle and had no detrimental effects on the skin. A proteomic analysis, assessing the relative abundance of proteins in matched permeate-depilated and chemically depilated (sulfide) sheepskins, showed variations in the levels of specific collagen types in the skin's basement membrane and other proteins associated with the follicles. These findings were corroborated by biochemical analyses of matched permeate depilated and raw skin samples, and provide clues to the mechanism of non-invasive and complete depilation. They also support the observation that permeate-depilated skins were smoother than their sulfide-depilated counterparts and resulted in leather with a superior surface. [ABSTRACT FROM AUTHOR]

Myrica rubra (Lour.) Siebold & Zucc bark is a traditional natural medicine used by the people of the Dong minority in western Hunan in China. In this study, the main compounds in Myrica rubra bark including epigallocatechin gallate, myricetrin, myricetin, taraxerol, myricanol, and 11-O-acetylmyricanol were separated using both silica gel column chromatography and high-speed countercurrent chromatography (HSCCC). Notably, it is the first report of discovering 11-O-acetylmyricanol from Myrica rubra bark. The results of the bioactivity studies suggested that epigallocatechin gallate showed the highest α-glucosidase inhibitory activity, while myricetin exhibited the highest reactive oxygen species (ROS) scavenging ability in zebrafish embryos. Intriguingly, myricanol exhibited strong apoptosis-inducing activity on HepG2 cells, and further studies revealed that myricanol was capable of promoting the cleavage of caspase 3, 8, and 9, then resulting in the apoptosis in HepG2 cells. The findings of the present study have important implications for the separation of the main compounds in Myrica rubra and will provide credence to the ethnomedicinal application of the isolated compounds against cardiovascular disease and cancer. [ABSTRACT FROM AUTHOR]

The number of electric vehicles (EVs) is growing exponentially, which presents the power grid with new challenges to turn their reliance to renewable energy sources (RESs). Coordination between the available generations from RESs and the charging time should be managed to optimally utilize the available generation from RESs. The dispatch scheduling of EVs can significantly reduce the impact of these challenges on power systems. Three different technologies can be used to manage the dispatch of EV batteries which are unregulated charging (UC), unidirectional grid-to-vehicle (G2V), and bidirectional vehicle-to-grid (V2G) technologies. This study aims to address the primary reason for EV owners' disbelief in the accuracy of battery wear models, which is impeding their involvement in V2G technology. This paper introduces a novel accurate EV battery wear model considering the instantaneous change in the operation of the EV battery. Moreover, an effective musical chairs algorithm (MCA) is used to reduce everyday expenses and increase revenue for V2G technologies in a short convergence time with accurate determination of optimal power dispatch scheduling. The results obtained from these three strategies are compared and discussed. The salient result from this comparison is that V2G technology increases wear and reduces the battery lifespan in comparison with the UC and G2V. The yearly expenses of G2V are reduced by 33% compared to the one associated with the UC. Moreover, the use of V2G technology provides each EV owner with USD 3244.4 net yearly profit after covering the charging and wear costs. The superior results extracted from the proposed model showed the supremacy of V2G usage, which is advantageous for both EV owners and the power grid. [ABSTRACT FROM AUTHOR]

We comprised metabolites of gut microbiota (GM; endogenous species) and dietary plant-derived natural flavonoids (DPDNFs; exogenous species) were known as potent effectors against non-alcoholic fatty liver disease (NAFLD) via network pharmacology (NP). The crucial targets against NAFLD were identified via GM and DPDNFs. The protein interaction (PPI), bubble chart and networks of GM or natural products-metabolites-targets-key signalling (GNMTK) pathway were described via R Package. Furthermore, the molecular docking test (MDT) to verify the affinity was performed between metabolite(s) and target(s) on a key signalling pathway. On the networks of GNMTK, Enterococcus sp. 45, Escherichia sp.12, Escherichia sp.33 and Bacterium MRG-PMF-1 as key microbiota; flavonoid-rich products as key natural resources; luteolin and myricetin as key metabolites (or dietary flavonoids); AKT Serine/Threonine Kinase 1 (AKT1), CF Transmembrane conductance Regulator (CFTR) and PhosphoInositide-3-Kinase, Regulatory subunit 1 (PIK3R1) as key targets are promising components to treat NAFLD, by suppressing cyclic Adenosine MonoPhosphate (cAMP) signalling pathway. This study shows that components (microbiota, metabolites, targets and a key signalling pathway) and DPDNFs can exert combinatorial pharmacological effects against NAFLD. Overall, the integrated pharmacological approach sheds light on the relationships between GM and DPDNFs. [ABSTRACT FROM AUTHOR]

In this study, non-toxic mercury nanoparticle was synthesized as per "Prakash theory of metal drugs" and nanoparticle's characters has been demonstrated by employing several nanotechnological tools including XPS, XRD, EDAX. The size of the Prakasine nanoparticles (PRK-NP) ranged from 90-100 nm, confirmed using TEM, SEM, DLS and along with zeta potential of -29.5mV before storage and -8.5mV after storage. The FTIR provided information regarding the nanoparticle capping and functional groups. The study was further elaborated for determining PRK-NPs toxicity, genotoxicity, in-vivo toxicity, immunological anti-tumour activity, immunogenicity potential, gene expression profiling and confirmed by MTT and apoptosis assays, cancer zebrafish model studies and WBC proliferation assay. PRK-NPs revealed no cytotoxicity where cell viability was observed 99% in L6 mouse fibroblasts and 99% in MCF-7 cell lines. Also, the cell viability was to be 89.47% at a very high concentration of 320 μg/ml in HEK 293 cells. The PRK-NPs significantly reduced the tumour in zebrafish at dose of 90 lg/g by up regulating IL-1α, IL-1β, IL-2-ITK, IL-6, IL-8, IL-12, TNF-α and IFN-γ, and down regulating IL-4, IL-5, IL-10 and TGF-β compared to untreated controls without any adverse effects and toxicity. Thus, the current study beholds anticipation PRK-NPs may play a vital role in therapeutic. [ABSTRACT FROM AUTHOR]

Sulfonylureas (SU) continue to be a vital therapeutic category of oral hypoglycemic agents (OHAs) for the management of type 2 diabetes mellitus (T2DM). Physicians consider modern SU (gliclazide and glimepiride) as "safe and smart" choices for T2DM management. The presence of multiple international guidelines and scarcity of a national guideline may contribute to the challenges faced by few physicians in choosing the right therapeutic strategy. The role of SU in diabetes management is explicit, and the present consensus aims to emphasize the benefits and reposition SU in India. This pragmatic, practical approach aims to define expert recommendations for the physicians to improve caregivers' knowledge of the management of T2DM, leading to superior patient outcomes. [ABSTRACT FROM AUTHOR]