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We investigate how the neural processing in auditory cortex is shaped by the statistics of natural sounds. Hypothesising that auditory cortex (A1) represents the structural primitives out of which sounds are composed, we employ a statistical model to extract such components. The input to the model are cochleagrams which approximate the non-linear transformations a sound undergoes from the outer ear, through the cochlea to the auditory nerve. Cochleagram components do not superimpose linearly, but rather according to a rule which can be approximated using the max function. This is a consequence of the compression inherent in the cochleagram and the sparsity of natural sounds. Furthermore, cochleagrams do not have negative values. Cochleagrams are therefore not matched well by the assumptions of standard linear approaches such as sparse coding or ICA. We therefore consider a new encoding approach for natural sounds, which combines a model of early auditory processing with maximal causes analysis (MCA), a sparse coding model which captures both the non-linear combination rule and non-negativity of the data. An efficient truncated EM algorithm is used to fit the MCA model to cochleagram data. We characterize the generative fields (GFs) inferred by MCA with respect to in vivo neural responses in A1 by applying reverse correlation to estimate spectro-temporal receptive fields (STRFs) implied by the learned GFs. Despite the GFs being non-negative, the STRF estimates are found to contain both positive and negative subfields, where the negative subfields can be attributed to explaining away effects as captured by the applied inference method. A direct comparison with ferret A1 shows many similar forms, and the spectral and temporal modulation tuning of both ferret and model STRFs show similar ranges over the population. In summary, our model represents an alternative to linear approaches for biological auditory encoding while it captures salient data properties and links inhibitory subfields to explaining away effects.

Sparse coding is a popular approach to model natural images but has faced two main challenges: modelling low-level image components (such as edge-like structures and their occlusions) and modelling varying pixel intensities. Traditionally, images are modelled as a sparse linear superposition of dictionary elements, where the probabilistic view of this problem is that the coefficients follow a Laplace or Cauchy prior distribution. We propose a novel model that instead uses a spike-and-slab prior and nonlinear combination of components. With the prior, our model can easily represent exact zeros for e.g. the absence of an image component, such as an edge, and a distribution over non-zero pixel intensities. With the nonlinearity (the nonlinear max combination rule), the idea is to target occlusions; dictionary elements correspond to image components that can occlude each other. There are major consequences of the model assumptions made by both (non)linear approaches, thus the main goal of this paper is to isolate and highlight differences between them. Parameter optimization is analytically and computationally intractable in our model, thus as a main contribution we design an exact Gibbs sampler for efficient inference which we can apply to higher dimensional data using latent variable preselection. Results on natural and artificial occlusion-rich data with controlled forms of sparse structure show that our model can extract a sparse set of edge-like components that closely match the generating process, which we refer to as interpretable components. Furthermore, the sparseness of the solution closely follows the ground-truth number of components/edges in the images. The linear model did not learn such edge-like components with any level of sparsity. This suggests that our model can adaptively well-approximate and characterize the meaningful generation process.

This study quantified the effect of major factors affecting the milk production in buffaloes. The important factors considered for the estimation of milk production included the value of dry fodder, the value of green fodder, the value of concentrate, number of lactations and the value of labour hours. A production function for milk was estimated by employing Ordinary Least Square (OLS) regression. In the estimated model among all the relevant variables, green fodder, lactation number and labour hours were found to be the influential factors affecting milk production in this species.

Purpose: To share our recent experience of the pattern and demography of endemic bladder calculi in children and the outcomes of current management strategies for the removal of bladder calculi in a peri-urban setting., Material and Methods: This retrospective longitudinal study was carried out at a dedicated urology centre. All patients with endemic bladder stones from January 2020 to December 2021 managed at our centre were included in this study. After discharge, each patient was followed up for 1 year. Data analysis was carried out with IBM SPSS v23. Mean and standard deviation were calculated for normally distributed continuous variables; for non-normally distributed continuous variables, median and IQR were calculated; frequency and percentage were calculated for categorical variables., Results: This study included 254 patients, with a male-to-female ratio of 10.5:1. The mean age of the patients was 4.80 ± 2.86 years. Ninety-one percent of the patients belonged to rural areas. Open cystolithotomy (OC) was performed in 11 (4.3%) patients, transurethral cystolithotripsy (TUCL) in 165 (65.0%), and percutaneous cystolithotomy (PCCL) in 78 (30.7%). The mean operative time was 48.8 ± 4.34 minutes for TUCL, 36.18 ± 7.4 minutes for open cystolithotomy, and 38.6 ± 5.2 minutes for PCCL. The most common stone composition was ammonium urate + calcium phosphate (33.1%). The complication rate was 4.8% in TUCL, 12.8% in PCCL, and 27.3% in open cystolithotomy. Stone clearance was 98.1% for TUCL and 100% for both PCCL and OC., Conclusion: Paediatric bladder calculus is still endemic in rural areas of Sindh with poor socioeconomic backgrounds. Timely diagnosis and early intervention with preventive measures can lead to better outcomes and fewer complications. Minimally invasive methods of cystolithotomy have a shorter hospital stay, are more cost-effective, and have fewer complications as compared to open cystolithotomy.

The process of developing of new drugs is greatly hampered by their inadequate physicochemical, pharmacokinetic, and intrinsic characteristics. In this regard, the selected chloro indolinone, (Z)-6-chloro-3-(2-chlorobenzylidene)indolin-2-one (C1), and nitro indolinone, (Z)-6-chloro-3-(2-nitrobenzylidene)indolin-2-one (C2), were subjected to SwissADME and density function theory (DFT) analysis. For compounds C1 and C2, the BOILED-Egg pharmacokinetic model predicted intestinal absorption, blood-brain barrier (BBB) penetration, and p-glycoprotein interaction. According to the physicochemical analysis, C1 has exceptional drug-like characteristics suitable for oral absorption. Despite only being substrates for some of the major CYP 450 isoforms, compounds C1 and C2 were anticipated to have strong plasma protein binding and efficient distribution and block these isoforms. The DFT study using the B3LYP/6-311G(d,p) approach with implicit water effects was performed to assess the structural features, electronic properties, and global reactivity parameters (GRP) of C1 and C2. The DFT results provided further support for other studies, implying that C2 is more water-soluble than C1 and that both compounds can form hydrogen bonds and (weak) dispersion interactions with other molecules, such as solvents and biomolecules. Furthermore, the GRP study suggested that C1 should be more stable and less reactive than C2. A concentration-dependent 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity was shown by both C1 and C2. In brief, this finding has provided a strong foundation to explore further the therapeutic potential of these molecules against a variety of human disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pirzada, Khan, Alam, Darwish, Elhenawy, Kuznetsov and Daglia.)

Focal cortical dysplasia (FCD) is a prominent neurological disorder characterized by disruptions in localized brain cell organization and development. This narrative review delineates the multi-faceted nature of FCD, emphasizing its correlation with drug-resistant epilepsy, predominantly in children and young adults. We explore the historical context of FCD, highlighting its indispensable role in shaping our comprehension of epilepsy and cortical anomalies. The clinical spectrum of FCD is broad, encompassing diverse seizure patterns, cognitive impairments, and associated neuropsychiatric disorders. We underscore the importance of differential diagnosis, with techniques ranging from electroencephalogram (EEG) interpretations to microscopic evaluations, and discuss advanced diagnostic modalities, such as the 3T magnetic resonance imaging (MRI) epilepsy protocols. Therapeutically, while anti-seizure medications are often first-line interventions, surgically refractory cases necessitate more invasive procedures, underscoring the importance of individualized treatment. Furthermore, the review touches upon the prognostic aspects of FCD, highlighting the importance of personalized care regimens, and provides insights into emerging therapeutic avenues, including the potential of the mammalian target of rapamycin (mTOR) pathway. Conclusively, this review accentuates the complex relationship between brain development and epileptogenicity inherent to FCD and underscores the promise of future research in enhancing patient outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Mohsin et al.)

The burgeoning field of epigenetics offers transformative insights into the complex landscape of neurological and psychiatric disorders. By unraveling the intricate interplay between genetic, epigenetic, environmental, and lifestyle factors, this comprehensive review highlights the multifaceted nature of mental health. The exploration reveals the potential of epigenetic modifications to revolutionize our understanding, diagnosis, treatment, and prevention of these disorders. Emphasizing the importance of multidisciplinary collaborations, large-scale studies, technological advancements, and ethical considerations, the review asserts the promise of epigenetics as a vital tool for personalized medicine, early intervention, and public health strategies. While acknowledging the challenges in a still-emerging field, the review paints an optimistic picture of epigenetics as a groundbreaking approach that can reshape mental healthcare, offering hope for those affected by neurological and psychiatric conditions. The future trajectory of the field relies on interdisciplinary efforts, ethical diligence, innovative technologies, and translating scientific insights into real-world applications, thereby unlocking the vast potential of epigenetics in mental health., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Grezenko et al.)

Computational pharmacology and chemistry of drug-like properties along with pharmacokinetic studies have made it more amenable to decide or predict a potential drug candidate. 4-Hydroxyisoleucine is a pharmacologically active natural product with prominent antidiabetic properties. In this study, ADMETLab 2.0 was used to determine its important drug-related properties. 4-Hydroxyisoleucine is compliant with important drug-like physicochemical properties and pharma giants' drug-ability rules like Lipinski's, Pfizer, and GlaxoSmithKline (GSK) rules. Pharmacokinetically, it has been predicted to have satisfactory cell permeability. Blood-brain barrier permeation may add central nervous system (CNS) effects, while a very slight probability of being CYP2C9 substrate exists. None of the well-known toxicities were predicted in silico , being congruent with wet lab results, except for a "very slight risk" for respiratory toxicity predicted. The molecule is non ecotoxic as analyzed with common indicators such as bioconcentration and LC 50 for fathead minnow and daphnia magna . The toxicity parameters identified 4-hydroxyisoleucine as non-toxic to androgen receptors, PPAR-γ, mitochondrial membrane receptor, heat shock element, and p53. However, out of seven parameters, not even a single toxicophore was found. The density functional theory (DFT) study provided support to the findings obtained from drug-like property predictions. Hence, it is a very logical approach to proceed further with a detailed pharmacokinetics and drug development process for 4-hydroxyisoleucine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ahmad, Kuznetsov, Pirzada, Alsharif, Daglia and Khan.)

The current study was planned to examine the nephroprotective effect of the crude extract and its various fractions of Viola serpense Wall against paracetamol-induced toxicity in rabbits. The serum creatinine levels of all fractions, as well as the crude extract, were found to have a greater effect. The effect on urine urea by the n-hexane, ethyl acetate, n-butanol and aqueous fraction in high doses (300 mg/kg b.wt.) and crude extract and chloroform in low doses (150 mg/kg bwts.) were comparatively more effective and comparable to silymarin. The creatinine clearance of the fractions except for chloroform, aqueous at 300 mg/kg and the hydro-methanolic extracts at both doses were highly significant. The histological structures of kidneys in crude extract and chloroform-treated groups showed more improvement at the lower doses. The fractions n-hexane, ethyl acetate and n-butanolic exhibited an inverse dose relationship in the histology of the kidney. However, the aqueous fraction showed a dose-dependent nephroprotective effect. Finally, the crude extract and fractions significantly improved paracetamol-induced nephrotoxicity in rabbits.

Caralluma edulis is a well-known species of the genus Caralluma from Apocynaceae, commonly known as chunga. Caralluma species are mostly succulent perennial herbs, several of which are edible species. The plant has an outstanding therapeutic background in the traditional system of treatment. It has been recommended for the treatment of a number medical disorders such as hypertension, Alzheimer's disease, rheumatism, gastric problems and leprosy. Traditionally the stem was boiled in water and this extract was then used to cure diabetes. The pharmacological effects of C. edulis have also been explored in various in vitro and in vivo experiments. In this regard, the extract of the plant exhibited strong antioxidant, and analgesic activity against inflammation as well as xylene-mediated ear edema as topical effects. The significant anti-hyperlipidemic effect of the plant extract is also reported. However, the extract was found insignificant in the reversal of alloxan-induced diabetes in the rabbit model at test doses. These pharmacological effects are strongly supported by the presence of different bioactive phytochemicals in the plant. These groups of compounds include sterols, terpenoids, flavonoids, and pregnane glycosides. C. edulis is a very potential member of the genus Caralluma with strong traditional history, phytochemistry and phytopharmacology, and needs further exploration for clinically used lead compounds. In this review, we have focused on combining different reported data on the traditional uses of the plant, its phytochemical profile and pharmacological effects in different experimental assay along with subsequent future prospects., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)