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Introduction: Cytological examination of body fluids is a commonly performed investigation that provides information about inflammatory and malignant lesions, aiding in the diagnosis of effusion aetiology and potential differential diagnoses. The cell block technique, combined with cytospin study, offers an additional advantage in such cases. Aim: To compare the diagnostic utility of cell block method and cytospin method in detecting malignancy in body fluids. Materials and Methods: This cross-sectional observational study was conducted for a period of two years at Bharati Vidyapeeth (DTU) Medical College Hospital and Research Centre in Pune, Maharashtra, India. A total of 100 body fluid samples were analysed, including 73 pleural fluids, 24 ascitic fluids, and 3 pericardial fluids. Each fluid sample was divided into two equal parts: one processed for cytospin (CYTOTEK), and the other processed to create a cell block. Four Immunohistochemistry (IHC) markers (Thyroid Transcription Factor-1 (TTF-1), Cytokeratin 7 (CK7), Cytokeratin 20 (CK20), and Calretinin) were applied as needed. Data analysis was performed using the Statistical Package for Social Sciences (SPSS) version 25.0, and results were calculated using the Chi-square test. Results: Of the total 100 fluid samples, 65 were negative, 17 were positive, and 18 were suspicious for malignancy using the cytospin method. In comparison, the cell block method identified 63 samples as negative, 29 as positive, and 8 as suspicious for malignancy. The cell block method exhibited a higher sensitivity (100.00%) and specificity (94.03%) than the cytospin method (81.82% and 88.06%, respectively) in this study. Conclusion: Cell block method accurately diagnosed 10 cases as positive for malignancy that were initially deemed suspicious on cytospin smear. Therefore, the cell block method proved to be a superior diagnostic tool for malignancy compared to cytospin smear. Given that cell blocks allow for longer storage and additional analysis such as IHC and microarray, they should be adopted in addition to cytospin for effusion cytology

Background & Aims: Spontaneous portosystemic shunts (SPSS) develop frequently in cirrhosis. Changes over time and the effect of aetiological interventions on SPSS are unknown, so we aimed to explore the effect of these variables on SPSS evolution. Methods: Patients with cirrhosis from the Baveno VI-SPSS cohort were selected provided a follow-up abdominal CT or MRI scan was available. Clinical and laboratory data were collected at baseline and follow-up. Imaging tests were reviewed to evaluate changes in the presence and size of SPSS (large (L)-SPSS was ≥8 mm) over time. Regarding alcohol- or HCV-related cirrhosis, two populations were defined: cured patients (abstinent from alcohol or successful HCV therapy), and non-cured patients. Results: A total of 617 patients were included. At baseline SPSS distribution was 22% L-SPSS, 30% small (S)-SPSS, and 48% without (W)-SPSS. During follow-up (median follow-up of 63 months), SPSS distribution worsened: L-SPSS 26%, S-SPSS 32%, and W-SPSS 42% (p

Coronavirus disease 2019 (COVID-19) is the latest respiratory pandemic caused by severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). Although infection initiates in the proximal airways, severe and sometimes fatal symptoms of the disease are caused by infection of the alveolar type 2 (AT2) cells of the distal lung and associated inflammation. In this study, we develop primary human lung epithelial infection models to understand initial responses of proximal and distal lung epithelium to SARS-CoV-2 infection. Differentiated air-liquid interface (ALI) cultures of proximal airway epithelium and alveosphere cultures of distal lung AT2 cells are readily infected by SARS-CoV-2, leading to an epithelial cell-autonomous proinflammatory response with increased expression of interferon signaling genes. Studies to validate the efficacy of selected candidate COVID-19 drugs confirm that remdesivir strongly suppresses viral infection/replication. We provide a relevant platform for study of COVID-19 pathobiology and for rapid drug screening against SARS-CoV-2 and emergent respiratory pathogens.

Abstract Background Medulloblastoma (MB) is a malignant tumour of the cerebellum which can be classified into four major subgroups based on gene expression and genomic features. Single-cell transcriptome studies have defined the cellular states underlying each MB subgroup; however, the spatial organisation of these diverse cell states and how this impacts response to therapy remains to be determined. Methods Here, we used spatially resolved transcriptomics to define the cellular diversity within a sonic hedgehog (SHH) patient-derived model of MB and show that cells specific to a transcriptional state or spatial location are pivotal for CDK4/6 inhibitor, Palbociclib, treatment response. We integrated spatial gene expression with histological annotation and single-cell gene expression data from MB, developing an analysis strategy to spatially map cell type responses within the hybrid system of human and mouse cells and their interface within an intact brain tumour section. Results We distinguish neoplastic and non-neoplastic cells within tumours and from the surrounding cerebellar tissue, further refining pathological annotation. We identify a regional response to Palbociclib, with reduced proliferation and induced neuronal differentiation in both treated tumours. Additionally, we resolve at a cellular resolution a distinct tumour interface where the tumour contacts neighbouring mouse brain tissue consisting of abundant astrocytes and microglia and continues to proliferate despite Palbociclib treatment. Conclusions Our data highlight the power of using spatial transcriptomics to characterise the response of a tumour to a targeted therapy and provide further insights into the molecular and cellular basis underlying the response and resistance to CDK4/6 inhibitors in SHH MB.

The features of human speech signals and emotional states are used to estimate the blood pressure (BP) using a clustering-based model. The audio-emotion-dependent discriminative features are identified to distinguish individuals based on their speech to form emotional groups. We propose a bio-inspired Enhanced grey wolf spotted hyena optimization (EWHO) technique for emotion clustering, which adds significance to this research. The model derives the most informative and judicial features from the audio signal, along with the person's emotional states to estimate the BP using the multi-class support vector machine (SVM) classifier. The EWHO-based clustering method gives better accuracy (95.59%), precision (97.08%), recall (95.16%) and F1 measure (96.20%), as compared to other methods used for BP estimation. Additionally, the proposed EWHO algorithm gives superior results in terms of parameters such as the silhouette score, Davies-Bouldin score, homogeneity score, completeness score, Dunn index, and Jaccard similarity score.

BackgroundOne of the core features of autism spectrum disorder (ASD) is restricted, repetitive patterns of behavior, interests and activities (RRBs). RRBs are known to adversely affect cognition and adaptive functioning. We explored the relationship of RRBs with cognition and adaptive functioning in children with ASD in an Asian setting.MethodsThis cross-sectional study was conducted at a tertiary developmental pediatrics center in Singapore from September 2019 to October 2021. Parent-child dyads (parents and their children ≤7 years old diagnosed with ASD) were recruited. Parents completed the Repetitive Behavior Questionnaire-2 (RBQ-2), which reports total score and two subscales – Motor/Sensory Behaviors (RBQ-2 MS) and Rigidity/Routines/Preoccupation with Restricted Interests (RBQ-2 RRPRI). Standardized assessments included Mullen Scales of Early Learning (MSEL) and Vineland Adaptive Behavior Scales (VABS-II). Data analysis utilized descriptive statistics and Pearson’s correlation.ResultsParents of 113 children [75.2% male, mean (SD) age 5.0 (1.2) years] participated. Median (IQR) RBQ-2 score was 29.0 (11.0). Significant negative correlations (adjusted for age, gender and family history of ASD) were observed for total RBQ-2 scores with MSEL ELC scores (r = −0.248, n = 101, p = 0.014) and VABS-II ABC scores (r = −0.281, n = 88, p = 0.009). Specifically, these correlations of fair strength were seen only with the RBQ-2 MS subscale for both ELC (r = −0.321, n = 101, p = 0.001) and ABC (r = −0.3478, n = 88, p = 0.001).ConclusionIn children with ASD, severity of RRBs correlated with adverse cognition and adaptive functioning measures in our study, consistent with Western literature. While our study does not show causality, it adds to literature serving as a foundation for further research for both clinicians and researchers to target RRBs in improving outcomes with children in ASD.

Current smoking is associated with increased risk of severe COVID-19, but it is not clear how cigarette smoke (CS) exposure affects SARS-CoV-2 airway cell infection. We directly exposed air-liquid interface (ALI) cultures derived from primary human nonsmoker airway basal stem cells (ABSCs) to short term CS and then infected them with SARS-CoV-2. We found an increase in the number of infected airway cells after CS exposure with a lack of ABSC proliferation. Single-cell profiling of the cultures showed that the normal interferon response was reduced after CS exposure with infection. Treatment of CS-exposed ALI cultures with interferon β-1 abrogated the viral infection, suggesting one potential mechanism for more severe viral infection. Our data show that acute CS exposure allows for more severe airway epithelial disease from SARS-CoV-2 by reducing the innate immune response and ABSC proliferation and has implications for disease spread and severity in people exposed to CS.

Quantum computing is one of the most promising solutions for solving optimization problems in the healthcare world. Quantum computing development aims to light up the execution of a vast and complex set of algorithmic instructions. For its implementation, the machine learning models are continuously evolving. Hence, the new challenge is to improve the existing complex and critical machine learning training models. Therefore, the healthcare sector is shifting from a classical to a quantum domain to sustain patient-oriented attention to healthcare patrons. This paper presents a hybrid classical-quantum approach for training the unsupervised data models. In order to achieve good performance and optimization of the machine learning algorithms, a quantum k-means (QK-means) clustering problem was deployed on the IBM quantum simulators, i.e.,the IBM QASM simulator. In the first place, the approach was theoretically studied and then implemented to analyze the experimental results. The approach was further tested using small synthetics and cardiovascular datasets on a qsam simulator to obtain the clustering solution. The future direction connecting the dots is the incremental k-means algorithm with the quantum platform, which would open hitherto unimaginable technological doors.

This paper analyses the climate change mitigation strategies adopted by industries from the first commitment period of Kyoto Protocol (2008) till present day (2023). A systematic literature review was conducted using the AND operator to customise articles published in Scopus database of 15 years of first commitment period of Kyoto Protocol (2009–2023). Findings show that all the climate change mitigation strategies (CCMS) identified can broadly be classified into managerial and technological. These strategies span from carbon offsets to start-up (ex. renovation in construction industries) to hydrogen as an energy source. VOSviewer network analysis of research paper showed that large number of countries are working closely on CCMS with USA in the forefront. Keywords like climate change, sustainability, greenhouse gas (GHG) were found to be most common in the research articles. This study confirms the significance of adopting managerial and technological strategies in industries for sustainability management. In addition, finance for climate policy and mitigation in terms of cost effectiveness, trade-offs, pollution tax, investments seem to possess a considerable influence on the climate governance.

Aims: The aim of this study was to assess the angulation of the apical exit from radiographic apex of palatal root of maxillary first molar, to measure the distance between radiographic apex and apical exit of palatal root of maxillary first molar and to measure the distance of apical exit of palatal root of maxillary first molar from maxillary sinus floor. Materials and Methods: A total of 118 untreated, well-developed maxillary first molars were selected on cone-beam computed tomography scans. Data were collected and viewed by invivo5 software. Descriptive statistical analysis was given as mean value. Results: Radiographic apex and apical exit did not coincide in the large number of samples. The palatal root of maxillary first molar was found to be in direct contact with the floor of maxillary sinus in maximum samples. Conclusion: Apical exit does not coincide with the radiographic apex in all the cases. The distance between radiographic apex and apical foramina or apical exit ranges from 0 to 1.43 mm. The apical exit or apical foramina are in direct contact with maxillary sinus floor in 75% cases.

Abstract Pyridoxal-5′-phosphate (PLP) is a versatile cofactor that assists in different types of enzymatic reactions. PLP has also been reported to react with substrates and catalyze some of these reactions independent of enzymes. One such catalytic reaction is the breakdown of cysteine to produce hydrogen sulfide (H2S) in the presence of multivalent metal ions. However, the enzyme-independent catalytic activity of PLP in catabolizing cysteine in the absence of multivalent ions is unknown. In this study, we show that PLP reacts with cysteine to form a thiazolidine product, which is supported by quantum chemical calculations of the absorption spectrum. The reaction of PLP with cysteine is dependent on ionic strength and pH. The thiazolidine product slowly decomposes to produce H2S and the PLP regenerates to its active form with longer reaction times (> 24 h), suggesting that PLP can act as a catalyst. We propose an enzyme-independent plausible reaction mechanism for PLP catalyzed cysteine breakdown to produce H2S, which proceeds through the formation of thiazolidine ring intermediates that later hydrolyzes slowly to regenerate the PLP. This work demonstrates that PLP catalyzes cysteine breakdown in the absence of enzymes, base, and multivalent metal ions to produce H2S.

Abstract Hydroxyurea (HU) is found to be beneficial in sickle cell anaemia (SCA) patients, due to its ability to increase foetal haemoglobin (HbF), however, patients show a variable response. Differences in HbF levels are attributed to many factors; but, the role of miRNA in HbF regulation is sparsely investigated. In this study, we evaluated the effect of miRNA expression on HbF induction in relation to hydroxyurea therapy in 30 normal controls, 30 SCA patients at baseline, 20 patients after 3 and 6 months of hydroxyurea (HU) therapy. HbF levels were measured by HPLC. Total RNA and miRNA were extracted from CD71+ erythroid cells and the expression was determined using Taqman probes. The mean HbF level increased 7.54 ± 2.44 fold, after 3 months of HU therapy. After the HU therapy 8 miRNAs were significantly up-regulated while 2 were down-regulated. The increase in miR-210, miR16-1, and miR-29a expression and decrease in miR-96 expression were strongly associated with the HU mediated HbF induction. Post HU therapy, decreased miR-96 expression negatively correlate with HbF and γ-globin gene while increased expression of miR-210, miR-16-1 and miR-29a post HU therapy positively corelate with HbF and γ-globin gene. Thus, suggest that miR-210, miR-16-1 and miR-29a are positive regulator of γ-globin gene and miR-96 is negative regulator of γ-globin gene. The study suggests the role of miR-210, miR16-1, miR-29a, and miR-96 in γ-globin gene regulation leading to HbF induction. Identification of the relevant protein targets might be useful for understanding the HU mediated HbF induction.