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Background: Emerging clinical and epidemiological data indicates that human immunodeficiency virus (HIV) is associated with an increased risk of stroke and aggravated brain damage. We aimed to develop a reproducible murine model of photothrombotic-stroke with HIV infection that mimics the clinical situation., Method: To evaluate the impact of HIV infection on stroke, male C57BL/6 mice were infected with EcoHIV (p24 2-4 × 10 6 /mouse; i.v.) or mock control. Four weeks post-infection, a stroke was induced by the photothrombotic method (pt-MCAO). After 72 h, a catwalk test was performed for gait impairments, and mice were euthanized for stroke outcomes., Results: EcoHIV-infection exhibited a larger infarction, brain edema, higher IgG extravasation, hemorrhagic transformation, and gait impairments following pt-MCAO vs mock control. EcoHIV-infected mice showed higher levels of IFN-y and lower levels of IL-6, indicating immune activation without affecting IL-1β and MCP-1 in plasma and brain compared to mock pt-MCAO, suggesting unaltered inflammation. EcoHIV-infection showed increased oxidative stress markers (nitrotyrosine, and 4-hydroxynonenal) and thioredoxin interacting protein expression. Further, EcoHIV-infection significantly activated the microglia and astrocyte cells., Conclusions: This animal model would be reliable and clinically relevant to future studies investigating pathophysiological mechanisms and developing new therapeutic approaches in stroke patients with HIV conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Catharanthus roseus, also known as Madagascar periwinkle, is a perennial plant renowned for its extensive pharmacological properties. It produces vital chemotherapeutic compounds, including vinblastine and vincristine, and exhibits anti-inflammatory, antidiabetic, and antioxidant activities. In this study, we utilized a range of two-dimensional (2D) nuclear magnetic resonance (NMR) techniques, such as 1 H- 1 H correlation spectroscopy (COSY), 1 H- 1 H J-resolved NMR, and 1 H- 13 C heteronuclear single quantum coherence (HSQC) sensitivity-enhanced NMR spectroscopy, to identify key metabolites in C. roseus leaf extracts. Given the presence of numerous metabolites with closely spaced multiplet resonances, the 1 H NMR spectra often exhibit significant signal overlap, making metabolite identification difficult or even impossible. However, the use of 2D NMR techniques effectively overcame this challenge, allowing for the precise identification of important alkaloids, such as vindoline, vinblastine, serpentine, and ajmalicine, along with essential metabolites like organic acids, amino acids, and carbohydrates. The extract contained a variety of bioactive compounds, including organic acids crucial for the tricarboxylic acid (TCA) cycle, branched-chain amino acids vital for metabolic functions, and alkaloids with substantial therapeutic potential. This comprehensive study underscores the continued significance of C. roseus in both traditional and modern medicine, emphasizing its intricate metabolic network and its potential in the development of novel therapeutics., (© 2024 John Wiley & Sons Ltd.)

Developing asymmetric transformations using electroredox and N-heterocyclic carbene (NHC)-catalyzed radical pathways is still desirable and challenging. Herein, we report an iodide-promoted β-carbon activation (LUMO-lowering process) of enals via electroredox carbene catalysis coupled with a hydrogen evolution reaction (HER). This strategy offers an environmentally friendly and sustainable route for rapidly assembling synthetically useful chiral naphthopyran-3-one in good to excellent yield and enantioselectivity using traceless electrons as inexpensive and greener oxidants. The mechanistic studies and cyclic voltammetry suggest that the reaction proceeds via direct single electron transfer (SET) of the in situ-generated Breslow intermediate.

Multicellular organisms control environmental interactions through specialized barriers in specific cell types. A conserved barrier in plant roots is the endodermal Casparian strip (CS), a ring-like structure made of polymerized lignin that seals the endodermal apoplastic space. Most angiosperms have another root cell type, the exodermis, that is reported to form a barrier. Our understanding of exodermal developmental and molecular regulation and function is limited as this cell type is absent from Arabidopsis thaliana. We demonstrate that in tomato (Solanum lycopersicum), the exodermis does not form a CS. Instead, it forms a polar lignin cap (PLC) with equivalent barrier function to the endodermal CS but distinct genetic control. Repression of the exodermal PLC in inner cortical layers is conferred by the SlSCZ and SlEXO1 transcription factors, and these two factors genetically interact to control its polar deposition. Several target genes that act downstream of SlSCZ and SlEXO1 in the exodermis are identified. Although the exodermis and endodermis produce barriers that restrict mineral ion uptake, the exodermal PLC is unable to fully compensate for the lack of a CS. The presence of distinct lignin structures acting as apoplastic barriers has exciting implications for a root's response to abiotic and biotic stimuli., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: Interventions that combat obesity and its associated metabolic perturbations may decrease incidence and improve outcomes of endometrial cancer (EC). Potential options for weight loss include pharmacotherapeutic interventions such as tirzepatide, a dual-acting glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) receptor agonist. Given this, we explored the anti-obesity and anti-tumorigenic effects of tirzepatide in our pre-clinical mouse model of endometrioid EC., Methods: Starting at 4 weeks of age, Lkb1 fl/fl p53 fl/fl mice were fed a low-fat diet vs a high-fat diet to generate a lean or obese phenotype. Nine weeks after induction of EC, obese and lean mice were randomized to receive tirzepatide for 4 weeks. Body and tumor weights, tumor transcriptomic and metabolomic profiles, and serum metabolic markers and chemokines were assessed., Results: Both obese and lean mice began to lose body weight after 2 weeks of tirzepatide treatment, ultimately achieving a significant weight loss of 20.1 % in obese mice and 16.8 % in lean mice. Tirzepatide improved obesity-induced serum adiponectin, leptin, GIP, and C-reactive protein levels. Furthermore, tirzepatide relative to vehicle, effectively reduced tumor growth in obese and lean mice, inhibited the ErbB signaling and glycolysis/gluconeogenesis in tumors of obese mice, and increased O-linked glycosylation biosynthesis and phospholipase D signaling in tumors of lean mice., Conclusion: Tirzepatide decreased both mouse weight and tumor growth via effects on metabolic and immune pathways in the EC tumors that differed between obese and lean mice. This novel weight loss treatment deserves further evaluation as an innovative strategy in the management of EC., Competing Interests: Declaration of competing interest The authors did not disclose potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Metabolomics is emerging as a significant approach to reflect the individual's response to pathophysiological conditions. Nuclear magnetic resonance (NMR) spectroscopy has evolved as a tool to identify metabolic dysregulations in critically ill patients afflicted with conditions like acute respiratory distress syndrome (ARDS), severe acute pancreatitis (SAP), acute kidney injury (AKI), and sepsis. The spectral data from the serum sample of the study and control group are recorded using an 800 MHz NMR spectrometer and processed using NMR processing and analysis tools. Furthermore, a rigorous statistical analysis, such as univariate and multivariate tests, is performed to pinpoint significant metabolites, which are then accurately identified and quantified using NMR metabolite quantification software. Additionally, pathway analysis highlights the deranged biochemical cycles that result in the severity of illness. Through this comprehensive approach, researchers aim to gain deeper insights into the metabolic alterations associated with these critical illnesses, potentially paving the way for a better understanding of the disease and improved diagnostics and treatment strategies.

Pure and chromium (Cr) doped L-asparagine monohydrate (LAM) single crystals were grown by using evaporation controlled solution growth technique. XRD analysis confirmed the orthorhombic crystal system with space group P2 1 2 1 2 1 of grown crystals. Cr-incorporation decreased the cell parameters and unit cell volume of the crystals. Intermolecular interactions were analysed through Hirshfeld and fingerprint studies. SEM analysis showed the appearance of pits on the smooth surface of pure crystal due to Cr-addition. UV-Vis analysis showed high transparency, low cut-off and direct band gap of 5.42 eV and 5.51 eV for pure and Cr doped crystals, respectively. Fundamental functional groups were identified by FTIR and Raman spectroscopy. The thermal stability and melting point of the crystals were investigated using TGA/DSC analysis. The dielectric constant for doped LAM was increased to 44 as compare to dielectric constant of pure crystal which was 32. Both crystals showed low dielectric loss, having values 0.04 and 0.006 for pure LAM and doped crystals, respectively. In Vickers microhardness test, Cr doping was found to change the nature of pure LAM crystal from 'soft' to 'hard' as Meyer's index changed from 2.48 to 1.24., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cerebellar patients exhibit various motor impairments, but the sequence of primary and compensatory processes leading to these deficits remains unclear. To investigate this, we reversibly blocked cerebellar outflow in monkeys performing planar reaching. The block caused a spatially tuned reduction in hand velocity due to decreased muscle torque, especially in movements with high coupling torques. Examining repeated movements to the same target revealed that during multi-joint reaching movements, the reduced velocity was driven by an acute deficit superimposed on a gradually emergent strategic slowing aimed at minimizing passive inter-joint interactions. However, the reduced velocity did not explain the decomposed and variable trajectories observed during the cerebellar block. Our findings suggest that loss of cerebellar signals leads to motor impairments through insufficient muscle torques and an altered control strategy to compensate for the impaired control of limb dynamics. However, impaired feedforward control also increases motor noise, which cannot be strategically eliminated.

Subjective tinnitus, characterized by the perception of phantom sounds in the absence of external stimuli, presents significant challenges in both audiology and neurology. Once thought to primarily involve aberrant neural activity within auditory pathways, it is now understood to engage a broader array of neuroanatomical structures. This study investigated the connections between auditory, cognitive, and sensory processing regions, which are crucial for unraveling the complex neurobiological basis of tinnitus. Using high-resolution T1-weighted magnetic resonance imaging, we compared 52 individuals with subjective tinnitus with 52 age-matched healthy controls, focusing on cerebral cortex features, including fractal dimensionality, gyrification, and sulcal depth. Covariate analyses were conducted to explore the relationships between tinnitus duration, Tinnitus Handicap Inventory scores, anxiety score, and neuroanatomical changes. We found significant alterations in key brain regions involved in sensory processing, cognition, and emotional regulation, including the insula, lateral occipital cortex, middle frontal gyrus, and superior parietal lobule. These neuroanatomical changes were strongly correlated with the severity and chronicity of tinnitus symptoms. Our findings reveal profound structural changes in the brain associated with subjective tinnitus, offering valuable insights into the condition's underlying mechanisms and providing a potential framework for guiding future research and therapeutic interventions., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Drought stress is a key limitation for plant growth and colonization of arid habitats. We study the evolution of gene expression response to drought stress in a wild tomato, Solanum chilense, naturally occurring in dry habitats in South America. We conduct a transcriptome analysis under standard and drought experimental conditions to identify drought-responsive gene networks and estimate the age of the involved genes. We identify two main regulatory networks corresponding to two typical drought-responsive strategies: cell cycle and fundamental metabolic processes. The metabolic network exhibits a more recent evolutionary origin and a more variable transcriptome response than the cell cycle network (with ancestral origin and higher conservation of the transcriptional response). We also integrate population genomics analyses to reveal positive selection signals acting at the genes of both networks, revealing that genes exhibiting selective sweeps of older age also exhibit greater connectivity in the networks. These findings suggest that adaptive changes first occur at core genes of drought response networks, driving significant network re-wiring, which likely underpins species divergence and further spread into drier habitats. Combining transcriptomics and population genomics approaches, we decipher the timing of gene network evolution for drought stress response in arid habitats., (© 2024 The Author(s). Molecular Ecology published by John Wiley & Sons Ltd.)

Objective: Intracranial EEG can identify epilepsy-related networks in patients with focal epilepsy; however, the association between network organization and post-surgical seizure outcomes remains unclear. Hubness serves as a critical metric to assess network organization by identifying brain regions that are highly influential to other regions. In this study, we tested the hypothesis that favorable post-operative seizure outcomes are associated with the surgical removal of interictal network hubs, measured by the novel metric "Resection-Hub Alignment Degree (RHAD).", Methods: We analyzed Phase II interictal intracranial EEG from 69 patients with epilepsy who were seizure-free (n = 45) and non-seizure-free (n = 24) 1 year post-operatively. Connectivity matrices were constructed from intracranial EEG recordings using imaginary coherence in various frequency bands, and centrality metrics were applied to identify network hubs. The RHAD metric quantified the congruence between hubs and resected/ablated areas. We used a logistic regression model, incorporating other clinical factors, and evaluated the association of this alignment regarding post-surgical seizure outcomes., Results: There was a significant difference in RHAD in fast gamma (80-200 Hz) interictal network between patients with favorable and unfavorable surgical outcomes (p = .025). This finding remained similar across network definitions (i.e., channel-based or region-based network) and centrality measurements (Eigenvector, Closeness, and PageRank). The alignment between surgically removed areas and other commonly used clinical quantitative measures (seizure-onset zone, irritative zone, high-frequency oscillations zone) did not reveal significant differences in post-operative outcomes. This finding suggests that the hubness measurement may offer better predictive performance and finer-grained network analysis. In addition, the RHAD metric showed explanatory validity both alone (area under the curve [AUC] = .66) and in combination with surgical therapy type (resection vs ablation, AUC = .71)., Significance: Our findings underscore the role of network hub surgical removal, measured through the RHAD metric of interictal intracranial EEG high gamma networks, in enhancing our understanding of seizure outcomes in epilepsy surgery., (© 2024 International League Against Epilepsy.)

Background: Tuberculomas are prevalent in developing countries and demonstrate variable signals on MRI resulting in the overlap of the conventional imaging phenotype with other entities including glioma and brain metastasis. An accurate MRI diagnosis is important for the early institution of anti-tubercular therapy, decreased patient morbidity, mortality, and prevents unnecessary neurosurgical excision. This study aims to assess the potential of radiomics features of regular contrast images including T1W, T2W, T2W FLAIR, T1W post contrast images, and ADC maps, to differentiate between tuberculomas, high-grade-gliomas and metastasis, the commonest intra parenchymal mass lesions encountered in the clinical practice., Methods: This retrospective study includes 185 subjects. Images were resampled, co-registered, skull-stripped, and zscore-normalized. Automated lesion segmentation was performed followed by radiomics feature extraction, train-test split, and features reduction. All machine learning algorithms that natively support multiclass classification were trained and assessed on features extracted from individual modalities as well as combined modalities. Model explainability of the best performing model was calculated using the summary plot obtained by SHAP values., Results: Extra tree classifier trained on the features from ADC maps was the best classifier for the discrimination of tuberculoma from high-grade-glioma and metastasis with AUC-score of 0.96, accuracy-score of 0.923, Brier-score of 0.23., Conclusion: This study demonstrates that radiomics features are effective in discriminating between tuberculoma, metastasis, and high-grade-glioma with notable accuracy and AUC scores. Features extracted from the ADC maps surfaced as the most robust predictors of the target variable., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

For better bone regeneration, precise control over the architecture of the scaffolds is necessary. Because the shape of the pore may affect the bone regeneration, therefore, additive manufacturing has been used in this study to fabricate magnetic bioactive glass (MBG) scaffolds with three different architectures, namely, grid, gyroid, and Schwarz D surface with 15 × 15 × 15 mm 3 dimensions and 70% porosity. These scaffolds have been fabricated using an in-house-developed material-extrusion-based additive manufacturing system. The composition of bioactive glass was selected as 45% SiO 2 , 20% Na 2 O, 23% CaO, 6% P 2 O 5 , 2.5% B 2 O 3 , 1% ZnO, 2% MgO, and 0.5% CaF 2 (wt %), and additionally 0.4 wt % of iron carbide nanoparticles were incorporated. Afterward, MBG powder was mixed with a 25% (w/v) Pluronic F-127 solution to prepare a slurry for fabricating scaffolds at 23% relative humidity. The morphological characterization using microcomputed tomography revealed the appropriate pore size distribution and interconnectivity of the scaffolds. The compressive strengths of the fabricated grid, gyroid, and Schwarz D scaffolds were found to be 14.01 ± 1.01, 10.78 ± 1.5, and 12.57 ± 1.2 MPa, respectively. The in vitro study was done by immersing the MBG scaffolds in simulated body fluid for 1, 3, 7, and 14 days. Darcy's law, which describes the flow through porous media, was used to evaluate the permeability of the scaffolds. Furthermore, an anticancer drug (Mitomycin C) was loaded onto these scaffolds, wherein these scaffolds depicted good release behavior. Overall, gyroid-structured scaffolds were found to be the most suitable among the three scaffolds considered in this study for bone tissue engineering and drug-delivery applications.

Atherosclerotic plaque formation is a leading cause of arterial thrombosis that significantly impacts global health by instigating major adverse cardiovascular events (MACE) like myocardial infarction (MI) and stroke. Platelets are central to this process, leading to the development of antiplatelet therapies, to mitigate MACE risks. The combination of aspirin with a potent P2Y 12 inhibitor known as dual antiplatelet therapy (DAPT) is the standard for post-percutaneous coronary intervention (PCI) aimed at reducing ischemic events. However, DAPT's associated bleeding risks, particularly in high bleeding risk (HBR) patients, require a balanced approach to optimize therapeutic outcomes. Recent advancements have led to the exploration of ticagrelor monotherapy as a promising strategy after short-term DAPT to reduce bleeding risks while preserving ischemic protection. This review manuscript focuses on ticagrelor monotherapy for HBR patients with discussion on optimal timing, patient selection, and treatment duration. It highlights ticagrelor's broad efficacy in diverse patient sub-groups and outlines its superiority over aspirin (ASA) and clopidogrel monotherapies. Trials such as TICO, TWILIGHT, GLOBAL LEADERS, and ULTIMATE-DAPT as well as literature meta -analyses validate ticagrelor monotherapy's role in lowering mortality and clinical adverse events versus conventional DAPT. The review endorses a personalized treatment regimen, beginning with DAPT before moving to ticagrelor monotherapy, as a balanced method for managing both bleeding and ischemic risks in post-PCI acute coronary syndrome (ACS) patients, especially those facing higher bleeding threats., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: High-risk strains of HPV are known to cause cervical cancer. Multiple clinical studies have emphasized that smoking and drinking are critical risk factors for cervical cancer and its high-grade precursors. In this study, we investigated if smoking and/or drinking augment the molecular mechanisms of cervical carcinogenesis and defined a potential therapeutic approach for their attenuation., Methods: The impact of benzo[a]pyrene (B[a]P) and/or ethanol (EtOH) exposure on cervical cancer cells was assessed by measuring changes in their cell migration and invasion characteristics. Expression of HPV16 E6/E7, NF-κB, cytokines, and inflammation mediators was determined using qRT-PCR, immunoblotting, ELISA, luciferase reporter assay, and confocal microscopy. Herein, we used curcumin (Cur), and PLGA nanoparticle formulation of curcumin (PLGA-Cur) and determined effectiveness of free Cur and PLGA-Cur formulation on smoking and drinking activated NF-κB/IL-6 mediated inflammatory signaling pathways using in vitro cervical cancer models., Results: Treatments with B[a]P and/or EtOH altered the expression of HPV16 E6/E7 oncogenes and EMT markers in cervical cancer cells; it also enhanced migration and invasion. In addition, B[a]P and/or EtOH exposure promoted inflammation pathways through TNF-α and NF-κB signaling, leading to IL-6 upregulation and activation of VEGF. The molecular effects caused by B[a]P and/or EtOH exposure were effectively attenuated by curcumin (Cur)/PLGA-Cur treatment., Conclusions: These data suggest a molecular link between smoking, drinking, and HPV infectivity in cervical carcinogenesis. In addition, attenuation of these effects by treatment with Cur/PLGA-Cur treatment, implies the role of curcumin in cervical cancer prevention and treatment., (© 2024. The Author(s).)

Idiopathic macular hole (IMH) is a condition that arises from a combination of interactions among several forces on the fovea, remarkably from vitreous traction in the anteroposterior and tangential directions. Recent studies have highlighted the significance of microincision vitrectomy surgery, and IMH surgery was performed with minimal invasiveness, and visual improvement was an expected outcome. This study aimed to observe the pre-operative optical coherence tomography (OCT) indices correlated with visual acuity in the closure of IMH after surgery. Primarily, the findings were associated with clinical characteristics, including OCT indices, change in best corrected visual acuity (BCVA), clinical factors associated with IMH closure, and prognostic factors for the visual outcomes. This retrospective study included pre- and post-operative BCVA and OCT indices of 110 eyes with IMH. Each OCT variable was subjected to stepwise regression analysis regarding therapeutic factors that predict the need for IMH closure. Our results revealed that the hole form factor (HFF, r = 0.196), macular hole index (MHI, r = 0.669), and tractional hole index (THI, r = 0.085) had a positive correlation with visual acuity. However, basal hole diameter (BHD, r = -0.696) and minimum hole diameter (MHD, r = -0.407) showed a negative correlation. Out of them, HFF, MHI, BHD, and MHD were observed to be statistically significant (p < 0.05). The mean follow-up time was 149 ± 63.22 (85-300) days. The mean baseline BCVA was 0.75 ± 0.44 logMAR (Logarithm of the Minimum Angle of Resolution) units, which was improved to 0.29 ± 0.27 logMAR units at the final follow-up. The surgical success closure rate was 100 % among subjects with IMH. In conclusion, OCT indices were significant indicators of visual success rates in IMH, and OCT measurement could be employed as a single key index in predicting the IMH closure rate. Also, our findings suggested that OCT indices could be utilized as a safe and effective predictor of visual and anatomical outcomes in the case of IMH., Competing Interests: All authors have declared no conflict of interest and substantially contributed for this work., (© 2024 The Authors.)

Acute respiratory distress syndrome (ARDS) is associated with high mortality rates, which are further exacerbated when accompanied by acute kidney injury (AKI). Presently, there is a lack of comprehensive studies thoroughly elucidating the metabolic dysregulation in ARDS patients with AKI leading to poor outcomes. We hypothesized that metabolomics can be a potent tool to highlight the differences in the metabolic profile unraveling unidentified pathophysiological mechanisms of ARDS patients with and without AKI. 1 H nuclear magnetic resonance spectroscopy was used to identify key metabolites in the serum samples of 75 patients. Distinct clusters of both groups were obtained as the study's primary outcome using multivariate analysis. Notable alternations in the levels of nine metabolites were identified. Pathway analysis revealed the dysregulation of five significant cycles, which resulted in various complications, such as hyperammonemia, higher energy requirements, and mitochondrial dysfunction causing oxidative stress. Identified metabolites also showed a significant correlation with clinical scores, indicating severity. This study shows the alterations in the metabolite concentration highlighting the difference in the pathophysiology of both patient groups and its association with outcome, pointing in the direction of a personalized medicine approach and holding significant promise for application in critical care settings to improve clinical outcomes.

Background: In past 20 years, there is increase in mobile phone users from 12.4 million to about 5.6 billion i.e 70 % of the world's population.[1] Electromagnetic radiations emitted from mobile phone damages inner ear, cochlea and outer hair cells of inner ear and auditory pathway (AP).[2]., Materials and Methods: Case control study. Group 1, N=30 subjects, using mobile smart phones since past 1-5 years and exposure time more than 2 hours per day. Group II included 30 subjects, using mobile smart phones for more than 5 years and exposure time more than 2 hours per day. Headache, tinnitus, or sensations of burning around phone-using were excluded. Brainstem auditory evoked potential (BAEP) done. Student Unpaired t test was used for analysis and chisquare test., Results: Mean ± SD of absolute latencies (AL) of Brainstem evoked response auditory. (BERA) waves III, V and all interpeak latencies at 80 dB and 4,6,8 KHz in group 2 were delayed and significant as compared to group 1. All parameters were highly significant at 8KHz as compared to 4KHz in group 2., Conclusion: Brain stem evoked response audiometry (BERA) detects hearing loss in smart mobile phone using subjects at higher frequencies i.e at 8 KHz early. Hence central neural axis involvement can be detected early by BERA., (Copyright © 2024 Copyright: © 2024 Annals of African Medicine.)

Intracranial EEG is used for two main purposes: to determine (i) if epileptic networks are amenable to focal treatment and (ii) where to intervene. Currently, these questions are answered qualitatively and differently across centres. There is a need to quantify the focality of epileptic networks systematically, which may guide surgical decision-making, enable large-scale data analysis and facilitate multi-centre prospective clinical trials. We analysed interictal data from 101 patients with drug-resistant epilepsy who underwent pre-surgical evaluation with intracranial EEG at a single centre. We chose interictal data because of its potential to reduce the morbidity and cost associated with ictal recording. Sixty-five patients had unifocal seizure onset on intracranial EEG, and 36 were non-focal or multi-focal. We quantified the spatial dispersion of implanted electrodes and interictal intracranial EEG abnormalities for each patient. We compared these measures against the '5 Sense Score,' a pre-implant prediction of the likelihood of focal seizure onset, assessed the ability to predict unifocal seizure onset by combining these metrics and evaluated how predicted focality relates to subsequent treatment and outcomes. The spatial dispersion of intracranial EEG electrodes predicted network focality with similar performance to the 5-SENSE score [area under the receiver operating characteristic curve = 0.68 (95% confidence interval 0.57, 0.78)], indicating that electrode placement accurately reflected pre-implant information. A cross-validated model combining the 5-SENSE score and the spatial dispersion of interictal intracranial EEG abnormalities significantly improved this prediction [area under the receiver operating characteristic curve = 0.79 (95% confidence interval 0.70, 0.88); P < 0.05]. Predictions from this combined model differed between surgical- from device-treated patients with an area under the receiver operating characteristic curve of 0.81 (95% confidence interval 0.68, 0.85) and between patients with good and poor post-surgical outcome at 2 years with an area under the receiver operating characteristic curve of 0.70 (95% confidence interval 0.56, 0.85). Spatial measures of interictal intracranial EEG abnormality significantly improved upon pre-implant predictions of network focality by area under the receiver operating characteristic curve and increased sensitivity in a single-centre study. Quantified focality predictions related to ultimate treatment strategy and surgical outcomes. While the 5-SENSE score weighed for specificity in their multi-centre validation to prevent unnecessary implantation, sensitivity improvement found in our single-centre study by including intracranial EEG may aid the decision on whom to perform the focal intervention. We present this study as an important step in building standardized, quantitative tools to guide epilepsy surgery., Competing Interests: All authors declare no competing interest. E.C.C. consults for Epiminder, an EEG device company., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background In developing nations, the primary cause of death is trauma, and the prevalence of trauma is increasing as more vehicles are driven. Numerous trauma scoring systems have been created in order to predict the mortality rate and patients with trauma's prognosis. The purpose of the current study was to assess the prognostic ability of various trauma scoring systems for patients' mortality and morbidity in cases involving chest and abdominal injuries, as they are common in the surgery department. Methodology At Ranchi, Jharkhand's Rajendra Institute of Medical Sciences, a prospective observational study was conducted from June 2021 to September 2022. All patients who met the requirements for inclusion were older than 18 and reported chest and abdominal trauma totaling 204. Before any essential therapies, primary care and resuscitation, including airway maintenance, breathing, circulation, and hemorrhage control, were established. A comprehensive clinical evaluation was done based on each patient's needs. Radiological evaluation included chest X-ray and ultrasonography (USG) for chest trauma, whereas USG (FAST) and CT scans were for abdominal trauma. Trauma scores, such as the Revised Trauma Score (RTS), the Trauma Revised Injury Severity Score (TRISS), the New Injury Severity Score (NISS), and the Injury Severity Score (ISS), were computed and examined using IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp. Results Of the 204 patients, 14.7% were female and 85.3% were male. The age range of 21-30 years old accounted for the largest percentage of cases (28%). 50 percent of injuries were caused by automobile accidents, while 25% were the result of assaults. At 83.8% versus 16.2%, blunt injuries were substantially more common than penetrating ones. In comparison to the chest, the abdomen was more frequently involved. The study's findings demonstrated that, while every trauma scoring was statistically significant in predicting mortality, the New Injury Severity Score (NISS), as well as the Trauma Revised Injury Severity Score (TRISS), became the most effective in predicting mortality (p < 0.0001). Conclusion According to the results, the most precise trauma grading method for chest and abdominal injuries is the Trauma Revised Injury Severity Score (TRISS), even though all other trauma scoring systems are useful in predicting patient outcomes. Surgeons using these metrics to predict outcomes and make well-informed treatment decisions can benefit greatly., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Rajendra Institute of Medical Sciences issued approval 230/IEC/RIMS. The conduct of the study was authorized ethically by the Institutional Ethics Committee of the Rajendra Institute of Medical Sciences, Ranchi (memorandum no. 230, dated 19/05/2021). The Declaration of Helsinki was fully followed in the conduct of the study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. 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, Besra et al.)

The hypothalamus, composed of several nuclei, is essential for maintaining our body's homeostasis. The arcuate nucleus (ARC), located in the mediobasal hypothalamus, contains neuronal populations with eminent roles in energy and glucose homeostasis as well as reproduction. These neuronal populations are of great interest for translational research. To fulfill this promise, we used a robotic cell culture platform to provide a scalable and chemically defined approach for differentiating human pluripotent stem cells (hPSCs) into pro-opiomelanocortin (POMC), somatostatin (SST), tyrosine hydroxylase (TH) and gonadotropin-releasing hormone (GnRH) neuronal subpopulations with an ARC-like signature. This robust approach is reproducible across several distinct hPSC lines and exhibits a stepwise induction of key ventral diencephalon and ARC markers in transcriptomic profiling experiments. This is further corroborated by direct comparison to human fetal hypothalamus, and the enriched expression of genes implicated in obesity and type 2 diabetes (T2D). Genome-wide chromatin accessibility profiling by ATAC-seq identified accessible regulatory regions that can be utilized to predict candidate enhancers related to metabolic disorders and hypothalamic development. In depth molecular, cellular, and functional experiments unveiled the responsiveness of the hPSC-derived hypothalamic neurons to hormonal stimuli, such as insulin, neuropeptides including kisspeptin, and incretin mimetic drugs such as Exendin-4, highlighting their potential utility as physiologically relevant cellular models for disease studies. In addition, differential glucose and insulin treatments uncovered adaptability within the generated ARC neurons in the dynamic regulation of POMC and insulin receptors. In summary, the establishment of this model represents a novel, chemically defined, and scalable platform for manufacturing large numbers of hypothalamic arcuate neurons and serves as a valuable resource for modeling metabolic and reproductive disorders., Competing Interests: Conflict of Interest Statement The authors declare no competing interests.

Background: Methemoglobinemia requires early identification and treatment, but limited knowledge exists regarding the current therapeutic approach taken by clinicians as well as the outcomes that occur in children., Objectives: To determine the current prevalence of this rare disease in the pediatric population, evaluate the impact of methemoglobin and functional hemoglobin levels, and assess how this disease is approached by clinicians. We hypothesize that methemoglobinemia prevalence is low and more methylene blue use would be observed in subjects with functional hemoglobin levels less than 7 g/dL., Design: This was a retrospective observational cohort study utilizing deidentified TriNetX ® electronic health record (EHR) data., Methods: Using a multicenter EHR database, we evaluated subjective characteristics, diagnostic, laboratory results, medication, and procedural codes., Results: Ninety-eight children (mean age 5.3 ± 5.3 years) from 53 healthcare organizations were included. Methemoglobinemia prevalence was 0.0015% with an overall 30-day mortality of 6.1%. Subjects with methemoglobin percentages greater than 20% had a higher frequency of methylene blue administration (70.6% versus 24.7%, P  = .0005). Critical care service requirements and methylene blue administration were similar in the subjects with functional hemoglobin less than 7 g/dL and more than 7 g/dL groups. Overall, 13 (13.2%) subjects underwent glucose-6-phosphate dehydrogenase deficiency (G6PD) testing., Conclusion: In our study, we found methemoglobinemia prevalence in children is low, there is a low frequency of G6PD testing despite methylene blue hemolysis risk, and subjects appeared to be treated similarly despite a low functional hemoglobin. These findings highlight the continued critical nature of this disease and may highlight opportunities for education aimed at improving care in children diagnosed with methemoglobinemia, particularly related to G6PD testing., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Conrad Krawiec receives funding from the New England Journal of Medicine and Elsevier Osmosis for educational materials and content. This manuscript was presented as a poster presentation at the Pediatric Academic Societies on April 30th, 2023., (© The Author(s) 2024.)

In recognition, remember -responses are understood to be based on recollection, and know -responses are understood to be based on familiarity. Two kinds of models have been proposed for the process by which recognition decisions are made. In single-process models, familiarity and recollection are integrated, and there is a single criterion for recognition. In dual-process models, familiarity and recollection are segregated, and there are separate criteria for remember and know-judgments. Recent process models can account for the distribution of remember and know-responses (under a range of different assumptions) but do not address the time course of the recognition process. Paradoxical findings, indicating that familiarity is available faster than recollection but remember-responses are on average faster than know-responses, cannot be convincingly explained by any existing dual-process model. We propose a new model that resolves this paradox by analyzing in detail the time course of recollection and familiarity. Know-responses based on the high familiarity of the test item are faster than remember-responses based on recollection. However, low-familiarity, low-recollection responses are slow and are also categorized by participants as know-responses. Hence, the average know-response time is slower than average remember-response time because know-responses include both fast high-familiarity responses and slow low-familiarity, low-recollection responses. A 12-parameter quantitative model that describes the relationship among the effects of confidence, accuracy, and remember and know categorization on accuracy and reaction time provided the best fit between expected reaction time and observed reaction time among the models tested. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Advances in artificial intelligence have paved the way for leveraging hematoxylin and eosin-stained tumor slides for precision oncology. We present ENLIGHT-DeepPT, an indirect two-step approach consisting of (1) DeepPT, a deep-learning framework that predicts genome-wide tumor mRNA expression from slides, and (2) ENLIGHT, which predicts response to targeted and immune therapies from the inferred expression values. We show that DeepPT successfully predicts transcriptomics in all 16 The Cancer Genome Atlas cohorts tested and generalizes well to two independent datasets. ENLIGHT-DeepPT successfully predicts true responders in five independent patient cohorts involving four different treatments spanning six cancer types, with an overall odds ratio of 2.28 and a 39.5% increased response rate among predicted responders versus the baseline rate. Notably, its prediction accuracy, obtained without any training on the treatment data, is comparable to that achieved by directly predicting the response from the images, which requires specific training on the treatment evaluation cohorts., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Dr. Sidney Farber (Farber) was a distinguished pediatric pathologist and widely recognized pioneer of modern chemotherapy. In 1948, his influential study showed that various anti-folates, particularly 4-aminopteroylglutamic acid, also known as aminopterin, induced transient disease control in kids who had acute undifferentiated leukemia. The findings laid the basis for developing and using additional chemotherapies, individually or in combination, for treating pediatric and adult cancers. Farber also introduced actinomycin D to treat Wilms tumor in various stages. Underneath his oversight, the 'Jimmy Fund,' one of the earliest dedicated pediatric oncology centers, and the Children's Cancer Research Foundation, which subsequently evolved into the Dana-Farber Cancer Institute, was established. Farber is known as the "Founder of Pediatric Pathology" and the "Father of Modern Chemotherapy," citing his immense contributions. This article is a tribute to the great scientist Farber for his significant contributions to the scientific field and the countless individuals he has impacted., Competing Interests: 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, Kumar Upadhyay et al.)

An organophotocatalytic method has been described towards the synthesis of indolines and oxindoles starting from unusual α -chloro amide and N -(2-chlorophenyl)- N -alkyl methacrylamide substrates. This marks a notable improvement since the earlier syntheses utilized iridium and gold catalysts, and involved C-I or C-Br bond cleavage as the initial step. Our photocatalyst is a pincer ligand that can be easily deprotonated to make a very strong reducing agent. The reductive cleavage of the carbon-chloride bond, and subsequent 5- exo -trig ring cyclization, followed by hydrogen atom abstraction, prepare the desired heterocycles under very mild reaction conditions. An atom economic use of KO t Bu has been shown to demonstrate the unusual trifunctional role of the latter.

Purpose: Uterine serous carcinoma (USC) is a highly aggressive and frequently recurring subtype of endometrial cancer with limited treatment options for advanced or recurrent stages. Sulindac, a classic non-steroidal anti-inflammatory drug, has demonstrated anti-tumor activity in several pre-clinical tumor models. This study aims to evaluate the effect of sulindac on cell proliferation and invasion in USC cells., Methods: Human USC cell lines ARK-1 and SPEC2 were treated with different concentrations of sulindac. Cell proliferation was assessed using MTT and colony formation assays. ELISA assays measured cellular stress, cleaved caspase 3 activity, antioxidant ability, and adhesion. Cell cycle arrest was evaluated by Cellometer. The invasive capability was detected by wound healing assay. Western blotting was used to analyze the changes in protein expression induced by sulindac., Results: Exposure to sulindac decreased cellular viability in a dose-dependent manner in ARK-1 and SPEC2 cells. Sulindac effectively inhibited cell cycle progression, increased cellular stress, caused apoptosis, and reduced cell adhesion and invasion in USC cells. Additionally, sulindac decreased the expression of COX-2 and blocked phosphorylation of NF-κB induced by TNF-α., Conclusion: Sulindac is a potential therapeutic agent for USC that deserves further exploration in pre-clinical studies and potentially future clinical trials., (© 2024. The Author(s).)

The interactions between glycosaminoglycans (GAGs) and proteins are essential in numerous biochemical processes that involve ion-pair interactions. However, there is no evidence of direct and specific interactions between GAGs and collagen proteins in native cartilage. The resolution of solid-state NMR (ssNMR) can offer such information but the detection of GAG interactions in cartilage is limited by the sensitivity of the experiments when 13 C and 15 N isotopes are at natural abundance. In this communication, this limitation is overcome by taking advantage of dynamic nuclear polarization (DNP)-enhanced magic-angle spinning (MAS) experiments to obtain two-dimensional (2D) 15 N- 13 C and 13 C- 13 C correlations on native samples at natural abundance. These experiments unveiled inter-residue correlations in the aliphatic regions of the collagen protein previously unobserved. Additionally, our findings provide direct evidence of charge-pair salt-bridge interactions between negatively charged GAGs and positively charged arginine (Arg) residues of collagen protein. We also identified potential hydrogen bonding interactions between hydroxyproline (Hyp) and GAGs, offering atomic insights into the biochemical interactions within the extracellular matrix of native cartilage. Our approach may provide a new avenue for the structural characterization of other native systems.

Background: Having a child with a serious illness like cancer has a detrimental and negative impact on the parents' health-related quality of life (HRQOL). Many factors have been identified as being associated with poorer HRQOL. Acquiring knowledge about these factors is essential to enhancing the quality of life (QOL) of children as well as their parents., Aim: This study aims to analyze HRQOL in parents of children with cancer and to explore relationships between parent and child variables and parental quality of life., Materials and Methods: A total of 80 parents of children with cancer were enrolled in this cross-sectional study. To evaluate the parental HRQOL, the Short Form 36 Health Survey Questionnaire (SF-36) was used., Results: Child age and time since diagnosis showed a positive correlation with all domains of HRQOL on Spearman's correlation. A statistically significant difference in SF-36 scores across four cancer groups was seen on the Kruskal-Wallis test. Mothers showed poorer quality of life in the physical role functioning domain as compared to fathers ( U = 248, P < 0.01)., Conclusion: The present study shows poor HRQOL for parents of children with cancer, despite learning to cope and adjust over time. Parents of children with retinoblastoma demonstrate a poorer QOL as compared to other cancer groups. The study suggests close monitoring of parents' QOL and the provision of appropriate treatment and psychosocial support for parents along with the treatment of children., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Industrial Psychiatry Journal.)

Purpose: Meningioma is the most common intracranial tumor, graded on pathology using WHO criteria to predict tumor course and treatment. However, pathological grading via biopsy may not be possible in cases with poor surgical access due to tumor location. Therefore, our systematic review aims to evaluate whether diagnostic imaging features can differentiate high grade (HG) from low grade (LG) meningiomas as an alternative to pathological grading., Methods: Three databases were searched for primary studies that either use routine magnetic resonance imaging (MRI) or computed tomography (CT) to assess pathologically WHO-graded meningiomas. Two investigators independently screened and extracted data from included studies., Results: 24 studies met our inclusion criteria with 12 significant (p < 0.05) CT and MRI features identified for differentiating HG from LG meningiomas. Cystic changes in the tumor had the highest specificity (93.4%) and irregular tumor-brain interface had the highest positive predictive value (65.0%). Mass effect had the highest sensitivity (81.0%) and negative predictive value (90.7%) of all imaging features. Imaging feature with the highest accuracy for identifying HG disease was irregular tumor-brain interface (79.7%). Irregular tumor-brain interface and heterogenous tumor enhancement had the highest AUC values of 0.788 and 0.703, respectively., Conclusion: Our systematic review highlight imaging features that can help differentiate HG from LG meningiomas., (© 2024. The Author(s).)

Background and aim While the infiltration of surgical incisions with local anesthetics is not a new practice, it remains a crucial component of contemporary multimodal analgesia protocols. This study aimed to evaluate the efficacy and safety of using adjuvants in combination with local anesthetic wound infiltration for pain management in patients undergoing mastectomy surgery. Methods Eighty-one patients aged 18-60 years, classified as American Society of Anesthesiologists (ASA) grade I or II, were scheduled for unilateral mastectomy and randomly assigned to three groups of 27 each. The groups were designated as Group C (bupivacaine alone), Group D (bupivacaine with dexmedetomidine), and Group K (bupivacaine with ketamine). Group C received 0.25% bupivacaine alone, Group D received 0.25% bupivacaine with 1 mcg/kg dexmedetomidine, and Group K received 0.25% bupivacaine with 1 mg/kg ketamine. The time to achieve a Visual Analogue Scale (VAS) score of 3 following local wound infiltration was recorded for each group. Additionally, total postoperative fentanyl intake during the first 24 hours, as measured by the patient-controlled analgesia (PCA) pump, was compared among the groups. Sedation levels were assessed using the Ramsay Sedation Scale (RSS). Data were analyzed using the Chi-Square test and one-way ANOVA in IBM SPSS Statistics for Windows, Version 28.0 (Released 2021; IBM Corp., Armonk, NY, USA). Results Demographic factors were similar across the three groups. Analysis of the VAS scores revealed that the ketamine group provided better postoperative pain control than the dexmedetomidine group (p < 0.001). Groups D (71.72 ± 71.73) and K (3.53 ± 13.42) had significantly lower 24-hour fentanyl intake (in mcg) compared to Group C (the control group), as measured by PCA. Additionally, Group C had a significantly lower RSS at the sixth hour (p = 0.003) compared to both Groups D and K. Conclusion Ketamine, when used as an adjuvant to bupivacaine for local infiltration, enhances the effectiveness and prolongs postoperative analgesia more effectively than dexmedetomidine in patients undergoing mastectomy., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Committee, Rajendra Institute of Medical Sciences, Ranchi issued approval 231. The study was ethically cleared by the Institutional Ethical Committee (IEC) via letter no. 231, dated 19/5/21, and it was prospectively registered under the CTRI with registration number CTRI/2021/08/035933. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. 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, Raj et al.)

Antiretroviral drugs have made significant progress in treating HIV-1 and improving the quality of HIV-1-infected individuals. However, due to their limited permeability into the brain HIV-1 replication persists in brain reservoirs such as perivascular macrophages and microglia, which cause HIV-1-associated neurocognitive disorders. Therefore, it is highly desirable to find a novel therapy that can cross the blood-brain barrier (BBB) and target HIV-1 pathogenesis in brain reservoirs. A recently developed 2-amino-3-methylpentanoic acid [2-morpholin-4-yl-ethyl]-amide (LM11A-31), which is a p75 neutrotrophin receptor (p75 NTR ) modulator, can cross the BBB. In this study, we examined whether LM11A-31 treatment can suppress HIV-1 replication, oxidative stress, cytotoxicity, and inflammatory response in macrophages. Our results showed that LM11A-31 (100 nM) alone and/or in combination with positive control darunavir (5.5 µM) significantly suppresses viral replication and reduces cytotoxicity. Moreover, the HIV-1 suppression by LM11A-31 was comparable to the HIV-1 suppression by darunavir. Although p75 NTR was upregulated in HIV-1-infected macrophages compared to uninfected macrophages, LM11A-31 did not significantly reduce the p75 NTR expression in macrophages. Furthermore, our study illustrated that LM11A-31 alone and/or in combination with darunavir significantly suppress pro-inflammatory cytokines including IL-1β, IL-8, IL-18, and TNF-α and chemokines MCP-1 in HIV-induced macrophages. The suppression of these cytokines and chemokines by LM11A-31 was comparable to darunavir. In contrast, LM11A-31 did not significantly alter oxidative stress, expression of antioxidant enzymes, or autophagy marker proteins in U1 macrophages. The results suggest that LM11A-31, which can cross the BBB, has therapeutic potential in suppressing HIV-1 and inflammatory response in brain reservoirs, especially in macrophages., 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 Mirzahosseini, Sinha, Zhou, Godse, Kodidela, Singh, Ishrat and Kumar.)

Purpose: To determine the number of torque/reverse torque cycles attachment screws can withstand before fracture, and to record the magnitude of reverse torque values for each of the 10 cycles of screw tightening and loosening., Materials and Methods: The testing assemblies consisted of 30 temporary cylinder/multiunit abutment/internal connection implants (10 each from Dentsply Sirona Astra, Biohorizons, and Zimmer Biomet Dental). The assemblies were inserted into resin blocks, and temporary cylinders were connected to the multiunit abutments with new attachment screws and torqued to the recommended preload (15 Ncm Dentsply Sirona Astra; 15 Ncm Biohorizons; 10 Ncm Zimmer Biomet Dental) using a digital torque gauge instrument (Model 3, MARK-10 Corporation, New York, USA) at room temperature without lubrication. After 24 h, the attachment screws were reverse torqued with the same instrument and the values were recorded. The torque/reverse torque cycles were repeated every 24 h for 10 days. Data were analyzed using mixed model analysis. A second test included torquing the used screws (30) until fracture or stripping occurred. The reverse torque values were recorded and compared with new screws that were torqued until fracture or stripping. A sample of used and new attachment screws from each assembly were viewed under both laser microscope (LEXT OLS4000, 3D Measuring Laser Microscope, Olympus) and scanning electron microscope (JEOL-JSM6510, Tokyo, Japan). Data were analyzed using t-test., Results: Following 10 cycles of torquing and reverse torquing, the reverse torque values measured on day 10 were lesser compared with the reverse torque value measured on day 1 for 29/30 attachment screws (96.6%). According to the t-test used for the second test, the p-values among all three groups were ≥0.9 which were not statistically significant., Conclusion: The results of this study indicated that after 10 cycles of torquing and reverse torquing attachment screws, the reverse torque values decreased. There were no statistical differences between the magnitude of torque necessary to fracture new and used attachment screws., (© 2024 by the American College of Prosthodontists.)

Background: The piriform cortex has been implicated in the initiation, spread and termination of epileptic seizures. This understanding has extended to surgical management of epilepsy, where it has been shown that resection or ablation of the piriform cortex can result in better outcomes. How and why the piriform cortex may play such a crucial role in seizure networks is not well understood. To answer these questions, we investigated the functional and structural connectivity of the piriform cortex in both healthy controls and temporal lobe epilepsy (TLE) patients., Methods: We studied a retrospective cohort of 55 drug-resistant unilateral TLE patients and 26 healthy controls who received structural and functional neuroimaging. Using seed-to-voxel connectivity we compared the normative whole-brain connectivity of the piriform to that of the hippocampus, a region commonly involved in epilepsy, to understand the differential contribution of the piriform to the epileptogenic network. We subsequently measured the inter-piriform coupling (IPC) to quantify similarities in the inter-hemispheric cortical functional connectivity profile between the two piriform cortices. We related differences in IPC in TLE back to aberrations in normative piriform connectivity, whole brain functional properties, and structural connectivity., Results: We find that relative to the hippocampus, the piriform is functionally connected to the anterior insula and the rest of the salience ventral attention network (SAN). We also find that low IPC is a sensitive metric of poor surgical outcome (sensitivity: 85.71%, 95% CI: [19.12%, 99.64%]); and differences in IPC within TLE were related to disconnectivity and hyperconnectivity to the anterior insula and the SAN. More globally, we find that low IPC is associated with whole-brain functional and structural segregation, marked by decreased functional small-worldness and fractional anisotropy., Conclusions: Our study presents novel insights into the functional and structural neural network alterations associated with this structure, laying the foundation for future work to carefully consider its connectivity during the presurgical management of epilepsy., Competing Interests: Competing Interests The authors report no competing interests.

Patients with long-standing inflammatory bowel disease (IBD) face an increased risk of developing colitis-associated cancer (CAC). Although IBD-induced prolonged inflammation seems to be involved in CAC pathogenesis, the specific molecular changes that contribute remain unknown. Here, we applied digital spatial RNA profiling, RNAscope, and imaging mass cytometry to examine paired uninflamed, inflamed, and early dysplastic mucosa of patients with IBD. We observed robust type 3 (IL-17) responses during inflammation, accompanied by elevated JAK-STAT signaling and phosphorylated STAT3 (P-STAT3) levels, with both inflamed and dysplastic mucosa displaying immune cell activation. Higher stromal P-STAT3 was detected in uninflamed and inflamed mucosa of patients who eventually developed dysplasia. CD8a + T cells did not infiltrate inflamed or dysplastic epithelial regions in these patients, while control patients showed elevated CD8a in inflamed mucosa. Our study reveals distinct inflammatory patterns throughout CAC development, marked by an activated IL-17 pathway, engaged STAT3, and diminished cytotoxic T cell infiltration., Competing Interests: B.O. received research grants from AbbVie, Celltrion, Ferring, Takeda, Galapagos, and Pfizer and is a member of the advisory boards of Cablon, Pfizer, BMS, Janssen, MSD, Takeda, and Galapagos. Y.V. received a Public Private Partnership grant from Health Holland (#TKI2017), with TigaTx BV and received a research grant from Galapagos., (© 2024 The Author(s).)

Drs. John and Ford reported in biomedicines that a variant transcript encoding receptor tyrosine kinase-like orphan receptor 1 (ROR1), namely ENST00000545203 or variant 3 ( ROR1 V3 ), was a predominant ROR1 transcript of neoplastic or normal cells in the Bioinformatic database, including GTEx and the 33 datasets from TCGA. Unlike the full-length ROR1 transcript, Drs. John and Ford deduced that ROR1 V3 encoded a cytoplasmic ROR1 protein lacking an apparent signal peptide necessary for transport to the cell surface, which they presumed made it unlikely to function as a surface receptor for Wingless/Integrated (Wnt) factors. Moreover, they speculated that studies evaluating ROR1 via immunohistochemistry using any one of several anti-ROR1 mAbs actually may have detected cytoplasmic protein encoded by ROR1 V3 and that anti-cancer therapies targeting surface ROR1 thus would be ineffective against "cytoplasmic ROR1-positive" cancers that express predominately ROR1 V3 . We generated lentivirus vectors driving the expression of full-length ROR1 or the ROR1 v3 upstream of an internal ribosome entry site (IRES) of the gene encoding a red fluorescent reporter protein. Although we find that cells that express ROR1 have surface and cytoplasmic ROR1 protein, cells that express ROR1 v3 neither have surface nor cytoplasmic ROR1, which is consistent with our finding that ROR1 v3 lacks an in-frame initiation codon for ribosomal translation into protein. We conclude that the detection of ROR1 protein in various cancers cannot be ascribed to the expression of ROR1 v3 .

Background This study aims to investigate the potential association of the Chief Executive Officer (CEO)'s educational background on hospital safety metrics, specifically the Leapfrog safety grades. Methods A total of 172 academic and university-affiliated hospitals across the United States were included in the study. Information regarding a CEO's background was obtained through hospital websites, while the Leapfrog safety scores were found through the Leapfrog safety grade website. Hospital sizes were also noted. Results A total of 67 hospitals were led by Doctors of Medicine (MDs), 16 were led by Masters in Business Administration (MBAs), 14 were led by Masters in Healthcare Administration (MHAs), and 62 were led by CEOs with various other degree types. Of the 42 A-rated hospitals included, 17 were led by physicians and 25 by nonphysicians. The average Leapfrog grade point average was similar regardless of the CEO's background, ranging from 2.6 to 3.1. Conclusion The findings suggest that a CEO's educational background has less of an impact on the overall hospital safety performance than what may have previously been hypothesized., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. 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, Razick et al.)

Narrow spectrum nano-antibiotics are supposedly the future trouble-shooters to improve the efficacy of conventional antimicrobials for treatment of severe bacterial infections, remove contamination from water and diminish the development of antibiotic resistance. In this study, antimicrobial peptide functionalized boron-carbon-nitride nanosheets ((Ant)pep@BCN NSs) are developed that are a promising wastewater disinfector and antibiotic resistant bactericide agent. These nanosheets are developed for selective removal and effective inactivation of antibiotic resistant bacteria (ARB) from water in presence of two virulent bacteria. The (Ant)pep@BCN NSs provide reactive surface receptors specific to the ARB. They mimic muralytic enzymes to damage the cell membrane of ARB. These NSs demonstrate 3-fold higher antimicrobial efficiency against the targeted ARB compared to pristine BCN even at lower concentrations. To the best of our knowledge, this is the first time that functionalized BCN has been developed to remove ARB selectively from wastewater. Furthermore, the (Ant)pep@BCN selectively reduced the microbiological load and led to morphological changes in Gram negative ARB in a mixed bacterial inoculum. These ARBs excreted outer-inner membrane vesicles (OIMVs) of triangular shape as a stimuli response to (Ant)pep@BCN NSs. These novel antimicrobial peptide-NSs have potential to improve treatment efficacy against ARB infections and water contamination., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Obsessive compulsive disorder (OCD) is a clinically heterogeneous psychiatric disorder in terms of symptom content and insight., Aim: To study the various factors associated with insight in OCD., Materials and Methods: A cross-sectional hospital-based study was conducted among 40 patients with OCD who were evaluated on Yale-Brown Obsessive-Compulsive Scale, Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, Brown Assessment of Beliefs Scale, Meta-Cognitions Questionnaire, WHOQOL-BREF, and Sheehan Disability Scale. Statistical analysis was done using SPSS version 22., Results: Metacognition, severity of OCD, and associated disability were the significant predictors for insight in patients with OCD., Conclusion: Factors associated with insight in OCD can enhance our understanding in the management of OCD., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Indian Journal of Psychiatry.)

Background and Aims: Depression is a common and debilitant mental health disorder that is very common among young adults of the age group of 18-25 years. There is evidence that autonomic nervous system dysfunction associated with depression may play an important role in cardiovascular disease among patients with depression. HRV that is used to assess ANS function is found to be altered in depression. Since the HRV findings associated with depression remain inconsistent, this study is aimed to find HRV changes associated with depression so that the use of HRV as a diagnostic tool for depression can be validated., Methods: A total of 42 newly diagnosed patients of depression of the age group (18-26) years and 89 non-depressed volunteers matched for age, BMI and sex proportions were included in the study. Heart rate variability was recorded using five-minute stationary RR interval of Lead II by 4-channel Power Lab System (AD Instrument Ltd). HRV findings are summarized into Time-Domain parameters, Frequency-Domain parameters and Non-Linear parameters., Result: All HRV parameters are significantly reduced and the LF/HF ratio is significantly raised ( P < 0.05) in the group of depressive patients when compared to the group of healthy controls. The reduction of HRV parameters (SDRR, RMSSD, Total Power, SD1 and SD2) in the group of patients with depression is found to be highly significant ( P < 0.0001)., Conclusion: The findings of our study suggest that depression may be associated with alterations in ANS activities, which contribute to an increased risk of cardiovascular disease. Thus, HRV can serve as a potential bio-marker for depression., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Family Medicine and Primary Care.)

Background and Objectives: Postoperative seizure control in drug-resistant temporal lobe epilepsy (TLE) remains variable, and the causes for this variability are not well understood. One contributing factor could be the extensive spread of synchronized ictal activity across networks. Our study used novel quantifiable assessments from intracranial EEG (iEEG) to test this hypothesis and investigated how the spread of seizures is determined by underlying structural network topological properties., Methods: We evaluated iEEG data from 157 seizures in 27 patients with TLE: 100 seizures from 17 patients with postoperative seizure control (Engel score I) vs 57 seizures from 10 patients with unfavorable surgical outcomes (Engel score II-IV). We introduced a quantifiable method to measure seizure power dynamics within anatomical regions, refining existing seizure imaging frameworks and minimizing reliance on subjective human decision-making. Time-frequency power representations were obtained in 6 frequency bands ranging from theta to gamma. Ictal power spectrums were normalized against a baseline clip taken at least 6 hours away from ictal events. Electrodes' time-frequency power spectrums were then mapped onto individual T1-weighted MRIs and grouped based on a standard brain atlas. We compared spatiotemporal dynamics for seizures between groups with favorable and unfavorable surgical outcomes. This comparison included examining the range of activated brain regions and the spreading rate of ictal activities. We then evaluated whether regional iEEG power values were a function of fractional anisotropy (FA) from diffusion tensor imaging across regions over time., Results: Seizures from patients with unfavorable outcomes exhibited significantly higher maximum activation sizes in various frequency bands. Notably, we provided quantifiable evidence that in seizures associated with unfavorable surgical outcomes, the spread of beta-band power across brain regions is significantly faster, detectable as early as the first second after seizure onset. There was a significant correlation between beta power during seizures and FA in the corresponding areas, particularly in the unfavorable outcome group. Our findings further suggest that integrating structural and functional features could improve the prediction of epilepsy surgical outcomes., Discussion: Our findings suggest that ictal iEEG power dynamics and the structural-functional relationship are mechanistic factors associated with surgical outcomes in TLE.

Valproic acid (VPA), or sodium valproate, is a frequently prescribed medication for many psychiatric conditions, notably for the management of bipolar affective disorder. While its common side effects are well known and thoroughly documented in medical literature, the occurrence of cataracts as a side effect is exceedingly rare. There is evidence of cataract formation with long-term use of VPA in a few studies. Recognizing this potential adverse effect is crucial. It is important to recommend that patients undergo regular eye examinations if they experience any visual disturbances or as a preventative measure to ensure effective management. This case report examines the unusual occurrence of cataract development associated with valproate use., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. 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, Sinha et al.)

Aim The study aims to analyze the imaging findings of invasive rhino-orbital-cerebral mucormycosis (ROCM) in patients who had COVID-19. Materials and methods This retrospective descriptive study was done on confirmed (culture and histopathology) patients who had a COVID-19 infection. The data was collected from the record section from May 2021 to June 2021. Imaging data were analyzed, and findings were tabulated according to statistical methods. Results Radiological evaluation, including CT and MRI, was done in 48 cases. The ethmoid sinus was the most common sinus involved in 60.41% of cases, followed by the maxillary sinus (52.09%). Unilateral pansinusitis was observed in 21 cases (43.75%). Among periantral extensions, retroantral fat involvement was the most common finding, seen in 24 cases (50%). Lamina papyracea and the walls of the maxillary sinus were involved in eight cases (16.67%). A total of 38 cases (79.17%) exhibited involvement of the extraconal compartment, while 32 cases (66.67%) showed involvement of the intraconal compartment. In intracranial involvement, infarct was noted in 13 cases (27%), and cavernous sinus involvement in nine cases (18.75%). Conclusions ROCM is a life-threatening fungal infection in immunocompromised patients, especially diabetics. Imaging of ROCM plays a pivotal role in early diagnosis, the extent of disease, surgical planning, prognosis, and the response to treatment. Radiologists must know the imaging features and patterns of extension of ROCM., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Committee of Indira Gandhi Institute of Medical Sciences issued approval 294/IEC/IGIMS/2021. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. 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, Ranjan et al.)

Evolution-based neural architecture search methods have shown promising results, but they require high computational resources because these methods involve training each candidate architecture from scratch and then evaluating its fitness, which results in long search time. Covariance Matrix Adaptation Evolution Strategy (CMA-ES) has shown promising results in tuning hyperparameters of neural networks but has not been used for neural architecture search. In this work, we propose a framework called CMANAS which applies the faster convergence property of CMA-ES to the deep neural architecture search problem. Instead of training each individual architecture seperately, we used the accuracy of a trained one shot model (OSM) on the validation data as a prediction of the fitness of the architecture, resulting in reduced search time. We also used an architecture-fitness table (AF table) for keeping a record of the already evaluated architecture, thus further reducing the search time. The architectures are modeled using a normal distribution, which is updated using CMA-ES based on the fitness of the sampled population. Experimentally, CMANAS achieves better results than previous evolution-based methods while reducing the search time significantly. The effectiveness of CMANAS is shown on two different search spaces using four datasets: CIFAR-10, CIFAR-100, ImageNet, and ImageNet16-120. All the results show that CMANAS is a viable alternative to previous evolution-based methods and extends the application of CMA-ES to the deep neural architecture search field., (© 2023 Massachusetts Institute of Technology.)

Yawning is a normal physiological process that occurs naturally in all human beings in different settings, such as hunger, drowsiness, or stress. It is typically harmless, but abnormal yawning can be seen in many medical conditions. In psychiatry, it frequently occurs in disorders like depression, insomnia, and anxiety due to disturbed sleep. It has also been observed as an adverse reaction of some drugs, like escitalopram, a selective serotonin reuptake inhibitor. Escitalopram is a widely prescribed, well-tolerated antidepressant and antianxiety drug that can induce a range of side effects, one of which is excessive yawning. Its excessive occurrence can be distressing for patients, affecting their socio-occupational functioning. Clinically, differentiating yawning induced by escitalopram treatment from that in depression can be a diagnostic hurdle. Awareness and recognition of this lesser known side effect can improve patient outcomes by allowing for timely adjustments and easing the discomfort., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. 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, Sinha et al.)

The origin of tinnitus remains a topic of discussion; however, numerous resting-state functional magnetic resonance imaging (rsfMRI) studies interpret it as a disruption in neural functional connectivity. Yet, there's notable inconsistency in the resting-state data across these studies. To shed light on this discrepancy, we conducted a meta-analysis of extant rsfMRI studies, aiming to identify potential regions that consistently signify core abnormalities in individuals with tinnitus., Methods: A systematic search on MEDLINE/PubMed, Google Scholar, and Scopus databases was performed to identify rsfMRI studies on tinnitus published up to October 2022. Coordinates related to the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) brain maps that showed significant differences between tinnitus patients and controls were extracted. Meta-analysis was performed using the activation likelihood estimation method. Data were included from 17 rsfMRI studies that reported a total of 63 distinct foci in ALFF and 46 foci in ReHo., Results: Our meta-analysis revealed several regions where tinnitus patients demonstrated increased ALFF and ReHO values, both individually and collectively, when compared to control subjects. These regions encompassed the insula, middle temporal gyrus, and inferior frontal gyrus on both sides. Additionally, increased activity was also noted in the cerebellum posterior lobe bilaterally and the right superior frontal gyrus., Conclusions: This meta-analysis demonstrates a unique pattern of resting-state brain abnormalities involving both the auditory and non-auditory brain regions as neuroimaging markers, which helps understand the neuro-pathophysiological mechanisms of tinnitus., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: This study aimed to evaluate and compare postoperative pain (PP) in single-visit nonsurgical endodontic retreatment (SV NSER) with 2% chlorhexidine (CHX), 0.1% octenidine (OCT) with or without ozone, and 5.25% sodium hypochlorite (NaOCl)., Materials and Methods: In this randomized, parallel, prospective, double-blind, clinical trial, 132 single-rooted, root-filled teeth with symptomatic apical periodontitis (AP) requiring NSER were allocated into six groups randomly (n = 22/group): 2% CHX with NaOCl (CHXH), 2% Ozonated CHX without NaOCl (OCHX), 2% Ozonated CHX with NaOCl (OCHXH), 0.1% OCT with NaOCl (OCTH), 0.1% Ozonated OCT without NaOCl (OOCT), and 0.1% Ozonated OCT with NaOCl (OOCTH). Standard NSER protocol was followed groups were irrigated with 15 ml of ozonated or nonozonated irrigant (CHX/OCT) for 3-5 min with ultrasonic agitation. PP at baseline, after 6, 12, 24, 48 h, and 7 days was recorded using the Visual Analog Scale (VAS). Logistic regression of predictor variables was compared using the Chi-square test. For group-wise and time-wise comparisons, a two-way analysis of variance followed by the post hoc Bonferroni test was carried out., Results: None of the patient-related variables in logistic regression obtained a statistically significant (P > 0.05) role in PP. The VAS score after 6 h was OCHX (4.72) > OOCT (4.42) > CHXH (4.23) > OCTH (3.95) > OCHXH (3.42) > OOCTH (3.21). OOCTH and OCHXH groups demonstrated statistically significant reductions in VAS scores at various time intervals (P < 0.05)., Conclusion: SV NSER with ozonated OCT, CHX irrigation, and NaOCl resulted in lesser PP at all time intervals, i.e., 6, 12, 24, 48 h, and 7 days in patients with symptomatic AP., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Conservative Dentistry and Endodontics.)