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The conversion of biobased feedstocks into energy and value-added chemicals is one main approach to address the current global challenge for waste mitigation through the biorefinery mode. Corncob biomass which is one of the most abundant agricultural residue in India with a high hemicellulose content, can serve as a potential low-cost raw material for food-grade xylitol production. The present study demonstrates a process for xylitol production from corncob biomass with detailed energy and life cycle analysis for viability assessment. The major highlight of the process is the use of microbial fermentation, where biomass-derived D-xylose is converted to xylitol with high selectivity. Overall, 0.502 kg of xylitol crystals could be produced from 3.5 kg of corncob biomass. Simulation analysis revealed that the evaporators are the primary consumers of energy, and the process of heat integration can significantly reduce the energy requirements of the overall process. Environmental impacts of the system evaluated showed emission results of 8.68 kg CO 2 equivalent and revealed that marine aquatic and freshwater eco-toxicity are the only possible contributors to the environment. The results suggest that the process would have favourable energy balances, which can be used in pilot plant and heat exchanger network design and operation for xylitol production scale up to 500 L. Image 1 [ABSTRACT FROM AUTHOR]

To myelinate axons, oligodendrocyte precursor cells (OPCs) must stop dividing and differentiate into premyelinating oligodendrocytes (preOLs). PreOLs are thought to survey and begin ensheathing nearby axons, and their maturation is often stalled at human demyelinating lesions. Lack of genetic tools to visualize and manipulate preOLs has left this critical differentiation stage woefully understudied. Here, we generated a knock-in mouse line that specifically labels preOLs across the central nervous system. Genetically labeled preOLs exhibit distinct morphology, unique transcriptomic and electrophysiological features, and do not overlap with OPCs. PreOL lineage tracing revealed that subsets of them undergo prolonged maturation and that different brain regions initiate oligodendrogenesis with the spatiotemporal specificity. Lastly, by fate mapping preOLs under sensory deprivation, we find that neuronal activity functions within a narrow time window of preOL maturation to promote their survival and successful integration. Our work provides a new tool to probe this critical cell stage during axon ensheathment, allowing for fine dissection of axon-oligodendrocyte interactions., Competing Interests: DECLARATION OF INTERESTS There are no competing or conflicting interests of any authors.

Background: Obesity has emerged as a major health challenge globally in the last two decades. Dysregulated fatty acid metabolism and de novo lipogenesis are prime causes for obesity development which ultimately trigger other co-morbid pathological conditions thereby risking life longevity. Fatty acid metabolism and de novo lipogenesis involve several biochemical steps both in cytosol and mitochondria. Reportedly, the high catalytically active mitochondrial carbonic anhydrases (CAVA/CAVB) regulate the intercellular depot of bicarbonate ions and catalyze the rapid carboxylation of pyruvate and acetyl-co-A to acetyl-co-A and malonate respectively, which are the precursors of fatty acid synthesis and lipogenesis. Several in vitro and in vivo investigations indicate inhibition of mitochondrial carbonic anhydrase isoforms interfere in the functioning of pyruvate, fatty acid and succinate pathways. Targeting of mitochondrial carbonic anhydrase isoforms (CAVA/CAVB) could thereby modulate gluconeogenetic as well as lipogenetic pathways and pave way for designing of novel leads in the development pipeline of anti-obesity medications., Methods: The present review unveils a diverse chemical space including synthetic sulphonamides, sulphamates, sulfamides and many natural bioactive molecules which selectively inhibit the mitochondrial isoform CAVA/CAVB with an emphasis on major state-of-art drug design strategies., Results: More than 60% similarity in the structural framework of the carbonic anhydrase isoforms has converged the drug design methods towards the development of isoform selective chemotypes. While the benzene sulphonamide derivatives selectively inhibit CAVA/CAVB in low nanomolar ranges depending on the substitutions on the phenyl ring, the sulpamates and sulpamides potently inhibit CAVB. The virtual screening and drug repurposing methods have also explored many non-sulphonamide chemical scaffolds which can potently inhibit CAVA., Conclusion: The review could pave way for the development of novel and effective anti-obesity drugs which can modulate the energy metabolism., Competing Interests: Declarations Competing interests The authors declare no conflicts of interest., (© 2024. The Author(s), under exclusive licence to Tehran University of Medical Sciences.)

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a central nervous system demyelinating disease that has become a major source of morbidity among children and adults. In the first case, we present an 18-year-old Hispanic female with a recently resolved upper respiratory infection who presented with fever, headache, progressive quadriparesis, urinary retention, and encephalopathy. The hospital course involved autonomic dysfunction and prolonged intubation requiring tracheostomy and gastrostomy. Cerebrospinal fluid (CSF) showed pleocytosis and a positive MOG titer (1:40). Magnetic resonance imaging (MRI) showed longitudinally extensive cervicothoracic T2 hyperintensity and brain multifocal T2 hyperintensities. After high-dose intravenous methylprednisolone (IVMP) and intravenous immunoglobulin (IVIG), she had full neurological recovery by the last follow-up. The second case is of a 22-year-old Hispanic male who presented with progressive lower extremity paresthesia and weakness over six weeks. CSF demonstrated pleocytosis, elevated protein, oligoclonal bands, and MOG antibody. MRI revealed multiple subcortical T2-hyperintense lesions and enhancing midcervical and lower thoracic lesions. Treatment with IVMP led to minor improvement with discharge on steroid taper and azathioprine. The patient's disease progressed with a fluctuating course requiring two readmissions with upper extremity weakness, right optic neuritis, and urinary sphincteric dysfunction with neuroradiologic worsening. Treatment throughout multiple admissions included intravenous steroids, IVIG, plasmapheresis, mycophenolate mofetil, and rituximab with minimal improvement, symptom recurrence, and progression of multifocal lesions. The patient died four months after the symptom onset. These cases had markedly different treatment responses despite similar baseline characteristics. The difference in morbidity and disability burden highlights the importance of further investigation of this condition through clinical trials., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Human Research Protection Program Institutional Review Board issued approval N/A. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Frade et al.)

Aims and Background: Midazolam is commonly used as a preanesthetic medication for behavior management of children. The current study is conducted to find out the effect of midazolam through nasal and oral routes as a premedicament in pediatric patients treated under general anesthesia. The main aims of the study were: to compare the effect of oral syrup and intranasal spray as preanesthetic medication; to record the undesirable side effects of midazolam by both routes., Materials and Methods: The patients aged 2-6 years of either sex were randomly divided into two equal groups of 30 each-group I: oral; group II: intranasal., Results: The oral and intranasal routes of midazolam were found to be equally effective and provided adequate sedation for easy separation from the parents and cooperation from children during the induction of anesthesia with minimal side effects., Conclusion: Based on the study results, we can conclude that both oral and intranasal midazolam can be used as preanesthetic medication for pediatric dental patients treated under general anesthesia., Clinical Significance: In pediatric patients, the oral route should be preferred for midazolam premedication in comparison to the intranasal route., How to Cite This Article: Swati, Shah RK, Tandon S, et al . Comparative Evaluation of Oral and Intranasal Administration of Midazolam as Preanesthetic Medication in Pediatric Dental Patients Treated under General Anesthesia. Int J Clin Pediatr Dent 2024;17(8):881-886., Competing Interests: Source of support: Nil Conflict of interest: NoneConflict of interest: None, (Copyright © 2024; The Author(s).)

In clinical research, it is crucial to segment the magnetic resonance (MR) brain image for studying the internal tissues of the brain. To address this challenge in a sustainable manner, a novel approach has been proposed leveraging the power of unsupervised clustering while integrating conditional spatial properties of the image into intuitionistic clustering technique for segmenting MRI images of brain scans. In the proposed technique, an Intuitionistic-based clustering approach incorporates a nuanced understanding of uncertainty inherent in the image data. The measure of uncertainty is achieved through calculation of hesitation degree. The approach introduces a conditional spatial function alongside the intuitionistic membership matrix, enabling the consideration of spatial relationships within the image. Furthermore, by calculating weighted intuitionistic membership matrix, the algorithm gains the ability to adapt its smoothing behavior based on the local context. The main advantages are enhanced robustness with homogenous segments, lower sensitivity to noise, intensity inhomogeneity and accommodation of degree of hesitation or uncertainty that may exist in the real-world datasets. A comparative analysis of synthetic and real datasets of MR brain images proves the efficiency of the suggested approach over different algorithms. The paper investigates how the suggested research methodology performs in medical industry under different circumstances including both qualitative and quantitative parameters such as segmentation accuracy, similarity index, true positive ratio, false positive ratio. The experimental outcomes demonstrate that the suggested algorithm outperforms in retaining image details and achieving segmentation accuracy., 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 Arora, Altuwaijri, Nauman, Tushir, Sharma, Gupta and Kim.)

Staphylococcus aureus, the most frequent cause of skin infections, is more common in men than women and selectively colonizes the skin during inflammation. Yet, the specific cues that drive infection in these settings remain unclear. Here we show that the host androgens testosterone and dihydrotestosterone promote S. aureus pathogenesis and skin infection. Without the secretion of these hormones, skin infection in vivo is limited. Testosterone activates S. aureus virulence in a concentration dependent manner through stimulation of the agr quorum sensing system, with the capacity to circumvent other inhibitory signals in the environment. Taken together, our work defines a previously uncharacterized inter-kingdom signal between the skin and the opportunistic pathogen S. aureus and identifies the mechanism of sex-dependent differences in S. aureus skin infection., One-Sentence Summary: Testosterone promotes S. aureus pathogenesis through activation of the agr quorum sensing system.

Objectives: Medical tourism is expanding globally, with patients seeking cosmetic procedures abroad. To date, little information is known regarding the risks and outcomes of cosmetic tourism, especially potential stroke complications. Here, we present a case of fungal meningitis in the setting of medical tourism leading to ischemic strokes and vasospasm., Material and Methods: We describe an immunocompetent 29-year-old female patient who initially presented with intractable headaches and an abnormal cerebrospinal fluid (CSF) profile who was eventually diagnosed with Fusarium solani meningitis as a part of a common source outbreak in Matamoros, Mexico. These patients were part of a cohort who underwent cosmetic procedures requiring spinal anesthesia. This report also highlights the unusual clinical course leading to poor outcomes in such conditions., Results: The patient initially presented with headaches, papilledema, elevated opening pressure on the spinal tap, abnormal CSF studies, and eventually developed ischemic strokes and hydrocephalus. CSF showed positive beta D-Glucan with repeated negative CSF fungal cultures. A cerebral angiogram revealed extensive basilar artery vasospasm that led to ischemic strokes. Continued clinical worsening and lack of response to antifungal treatment prompted further imaging that revealed significant non-obstructive hydrocephalus subsequently complicated by spontaneous intracranial hemorrhage. CSF PCR for Fusarium solani species was positive days after her passing., Conclusion: This novel case highlights fungal meningitis caused by Fusarium solani complicated by bilateral ischemic strokes stemming from basilar artery vasospasm. Complications from medical tourism impact not only individual patients but also the health systems of both countries. Professional and regulatory entities for cosmetic surgeries must highlight and educate patients on the risks and complications of cosmetic surgeries happening abroad. Physicians should be aware of ongoing outbreaks and possible complications of these procedures., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Aims: The liver is remarkably regenerative and can completely recover even when 80% of its mass is surgically removed. Identification of secreted factors that regulate liver growth would help us understand how organ size and regeneration are controlled but also provide candidate targets to promote regeneration or impair cancer growth., Approach and Results: To enrich for secreted factors that regulate growth control, we induced massive liver overgrowth with either YAP or MYC . Differentially expressed secreted factors were identified in these livers using transcriptomic analysis. To rank candidates by functionality, we performed in vivo CRISPR screening using the Fah knockout model of tyrosinemia. We identified secreted phosphoprotein-2 (SPP2) as a secreted factor that negatively regulates regeneration. Spp2 -deficient mice showed increased survival after acetaminophen poisoning and reduced fibrosis after repeated carbon tetrachloride injections. We examined the impact of SPP2 on bone morphogenetic protein signaling in liver cells and found that SPP2 antagonized bone morphogenetic protein signaling in vitro and in vivo. We also identified cell-surface receptors that interact with SPP2 using a proximity biotinylation assay coupled with mass spectrometry. We showed that SPP2's interactions with integrin family members are in part responsible for some of the regeneration phenotypes., Conclusions: Using an in vivo CRISPR screening system, we identified SPP2 as a secreted factor that negatively regulates liver regeneration. This study provides ways to identify, validate, and characterize secreted factors in vivo., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Cancer is a serious disease that has been around for a long time but currently has no sustainable solution. Several medications currently available offer an opportunity for the manifestation of cancer treatment; however, the "search for better" has led to the development and study of a variety of new scaffolds. Dihydropyrimidinones (DHPMs) are a privileged scaffold, prominent for their versatile range of biological activities. In recent years, the anticancer potential of these unsaturated pyrimidine ring systems has been traversed, along with their synthesis methods and the interlinked mechanisms leading to the anticancer activity. This review summarizes the structure-activity relationship of DHPMs as potential anticancer agents. This study is a short review of their synthesis, mechanism of action, and structure-activity relationships (SARs) that are answerable for the anticancer activity of DHPMs and have been thoroughly researched and assessed., (© 2023 Deutsche Pharmazeutische Gesellschaft.)

Somatic mutations in non-malignant tissues accumulate with age and insult, but whether these mutations are adaptive on the cellular or organismal levels is unclear. To interrogate mutations found in human metabolic disease, we performed lineage tracing in mice harboring somatic mosaicism subjected to non-alcoholic steatohepatitis (NASH). Proof-of-concept studies with mosaic loss of Mboat7 , a membrane lipid acyltransferase, showed that increased steatosis accelerated clonal disappearance. Next, we induced pooled mosaicism in 63 known NASH genes, allowing us to trace mutant clones side-by-side. This in vivo tracing platform, which we coined MOSAICS, selected for mutations that ameliorate lipotoxicity, including mutant genes identified in human NASH. To prioritize new genes, additional screening of 472 candidates identified 23 somatic perturbations that promoted clonal expansion. In validation studies, liver-wide deletion of Bcl6, Tbx3, or Smyd2 resulted in protection against NASH. Selection for clonal fitness in mouse and human livers identifies pathways that regulate metabolic disease., Highlights: Mosaic Mboat7 mutations that increase lipotoxicity lead to clonal disappearance in NASH. In vivo screening can identify genes that alter hepatocyte fitness in NASH. Mosaic Gpam mutations are positively selected due to reduced lipogenesis. In vivo screening of transcription factors and epifactors identified new therapeutic targets in NASH.

Nutrient deficiency has resulted in impaired growth and development of the population globally. Microgreens are considered immature greens (required light for photosynthesis and growing medium) and developed from the seeds of vegetables, legumes, herbs, and cereals. These are considered "living superfood/functional food" due to the presence of chlorophyll, beta carotene, lutein, and minerals like magnesium (Mg), Potassium (K), Phosphorus (P), and Calcium (Ca). Microgreens are rich at the nutritional level and contain several phytoactive compounds (carotenoids, phenols, glucosinolates, polysterols) that are helpful for human health on Earth and in space due to their anti-microbial, anti-inflammatory, antioxidant, and anti-carcinogenic properties. Microgreens can be used as plant-based nutritive vegetarian foods that will be fruitful as a nourishing constituent in the food industryfor garnish purposes, complement flavor, texture, and color to salads, soups, flat-breads, pizzas, and sandwiches (substitute to lettuce in tacos, sandwich, burger). Good handling practices may enhance microgreens'stability, storage, and shelf-life under appropriate conditions, including light, temperature, nutrients, humidity, and substrate. Moreover, the substrate may be a nutritive liquid solution (hydroponic system) or solid medium (coco peat, coconut fiber, coir dust and husks, sand, vermicompost, sugarcane filter cake, etc. ) based on a variety of microgreens. However integrated multiomics approaches alongwith nutriomics and foodomics may be explored and utilized to identify and breed most potential microgreen genotypes, biofortify including increasing the nutritional content (macro-elements:K, Ca and Mg; oligo-elements: Fe and Zn and antioxidant activity) and microgreens related other traits viz., fast growth, good nutritional values, high germination percentage, and appropriate shelf-life through the implementation of integrated approaches includes genomics, transcriptomics, sequencing-based approaches, molecular breeding, machine learning, nanoparticles, and seed priming strategiesetc., 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 Gupta, Sharma, Singh, Bhardwaj, Srivastava and Kumar.)

One of the most well-known anti-targets defining medication cardiotoxicity is the voltage-dependent hERG K + channel, which is well-known for its crucial involvement in cardiac action potential repolarization. Torsades de Pointes, QT prolongation, and sudden death are all caused by hERG (the human Ether-à-go-go-Related Gene) inhibition. There is great interest in creating predictive computational ( in silico ) tools to identify and weed out potential hERG blockers early in the drug discovery process because testing for hERG liability and the traditional experimental screening are complicated, expensive and time-consuming. This study used 2D descriptors of a large curated dataset of 6766 compounds and machine learning approaches to build robust descriptor-based QSAR and predictive classification models for KCNH2 liability. Decision Tree, Random Forest, Logistic Regression, Ada Boosting, kNN, SVM, Naïve Bayes, neural network and stochastic gradient classification classifier algorithms were used to build classification models. If a compound's IC 50 value was between 10 μM and less, it was classified as a blocker (hERG-positive), and if it was more, it was classified as a non-blocker (hERG-negative). Matthew's correlation coefficient formula and F1score were applied to compare and track the developed models' performance. Molecular docking and dynamics studies were performed to understand the cardiotoxicity relating to the hERG-gene. The hERG residues interacting after 100 ns are LEU:697, THR:708, PHE:656, HIS:674, HIS:703, TRP:705 and ASN:709 and the hERG-ligand-16 complex trajectory showed stable behaviour with lesser fluctuations in the entire simulation of 200 ns.Communicated by Ramaswamy H. Sarma.

Identifying new pathways that regulate mammalian regeneration is challenging due to the paucity of in vivo screening approaches. We employed pooled CRISPR knockout and activation screening in the regenerating liver to evaluate 165 chromatin regulatory proteins. Both screens identified the imitation-SWI chromatin remodeling components Baz2a and Baz2b, not previously implicated in regeneration. In vivo sgRNA, siRNA, and knockout strategies against either paralog confirmed increased regeneration. Distinct BAZ2-specific bromodomain inhibitors, GSK2801 and BAZ2-ICR, resulted in accelerated liver healing after diverse injuries. Inhibitor-treated mice also exhibited improved healing in an inflammatory bowel disease model, suggesting multi-tissue applicability. Transcriptomics on regenerating livers showed increases in ribosomal and cell cycle mRNAs. Surprisingly, CRISPRa screening to define mechanisms showed that overproducing Rpl10a or Rpl24 was sufficient to drive regeneration, whereas Rpl24 haploinsufficiency was rate limiting for BAZ2 inhibition-mediated regeneration. The discovery of regenerative roles for imitation-SWI components provides immediate strategies to enhance tissue repair., Competing Interests: Declaration of interests H.Z. has a sponsored research agreement with Alnylam Pharmaceuticals, consults for Flagship Pioneering, and serves on the SAB of Ubiquitix. These interests are not directly related to the contents of this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)