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Abstract Background Precancerous and malignant tumours arise within the oral cavity from a predisposed “field” of epithelial cells upon exposure to carcinogenic stimulus. This phenomenon is known as “Field Cancerization”. The molecular genomic and transcriptomic alterations that lead to field cancerization and tumour progression is unknown in Indian Oral squamous cell carcinoma (OSCC) patients. Methods We have performed whole exome sequencing, copy-number variation array and whole transcriptome sequencing from five tumours and dysplastic lesions (sampled from distinct anatomical subsites - one each from buccal anterior and posterior alveolus, dorsum of tongue–mucosal melanoma, lip and left buccal mucosa) and blood from a rare OSCC patient with field cancerization. Results A missense CASP8 gene mutation (p.S375F) was observed to be the initiating event in oral tumour field development. APOBEC mutation signatures, arm-level copy number alterations, depletion of CD8 + T cells and activated NK cells and enrichment of pro-inflammatory mast cells were features of early-originating tumours. Pharmacological inhibition of CASP8 protein in a CASP8-wild type OSCC cell line showed enhanced levels of cellular migration and viability. Conclusion CASP8 alterations are the earliest driving events in oral field carcinogenesis, whereas additional somatic mutational, copy number and transcriptomic alterations ultimately lead to OSCC tumour formation and progression.

Abstract Human papillomavirus (HPV) drives cervical cancer (CaCx) pathogenesis and viral oncoproteins jeopardize global gene expression in such cancers. In this study, our aim was to identify differentially expressed coding (DEcGs) and long noncoding RNA genes (DElncGs) specifically sense intronic and Natural Antisense Transcripts as they are located in the genic regions and may have a direct influence on the expression pattern of their neighbouring coding genes. We compared HPV16-positive CaCx patients (N = 44) with HPV-negative normal individuals (N = 34) by employing strand-specific RNA-seq and determined the relationships between DEcGs and DElncGs and their clinical implications. By performing Gene set enrichment and protein–protein interaction (PPI) analyses of DEcGs, we identified enrichment of processes crucial for abortive virus life cycle and cancer progression. The DEcGs formed 16 gene clusters which we identified through Molecular Complex Detection (MCODE) plugin of Cytoscape. All the gene clusters portrayed cancer-related functions. We recorded significantly correlated expression levels of 79 DElncGs with DEcGs at proximal genomic loci based on Pearson’s Correlation coefficients. Of these gene pairs, 24 pairs portrayed significantly altered correlation coefficients among patients, compared to normal individuals. Of these, 6 DEcGs of 6 such gene pairs, belonged to 5 of the identified gene clusters, one of which was survival-associated. Out of the 24 correlated DEcG: DElncG pairs, we identified 3 pairs, where expression of both members was significantly associated with patient overall survival. The findings justify the cooperative roles of these gene pairs, in patient prognostication, thereby bearing immense potential for translation. Thus, elucidation of correlative strengths between paired DElncGs and DEcGs in patient and normal samples, could serve as a foundation for identification of therapeutic and prognostic targets of HPV16-positive CaCx. Graphical abstract

Background: Critically ill patients on Non- invasive Ventilation (NIV) or Continuous Positive Airway Pressure (CPAP) tend to desaturate off ventilatory support. Hence, they are unable to meet their nutritional needs, leading to increase in hospital stay. It was evident during the COVID 19 pandemic. The failure rates of NIV were unusually high, from 30-45%. Despite the overall success of the treatment modality, NIV failure rates still range between 18% and 40% in the acute setting. It was seen that the patients on NIV get only 650 Kcal/ day which is far lower than the required energy requirement. There is a need to have an affordable and sustainable solution to deliver adequate nutrition to critically ill patients on NIV and CPAP, which is able to maintain a NG/ OG tube without frequent disconnections from the ventilator. With this fact in mind a NIV mask with inbuilt feeding port (NIV-IFP) was designed. Aims and Objectives: The aim of this case series was to compare the modified NIV-IFP mask with the conventional mask in terms of both effectiveness of ventilation as well as caloric replacement in critically ill patients. For the purpose of this study, we enlisted three patients who were critically ill and required NIV. Results: With the use of NIV-IFP mask we were able to substitute adequate amount of nutrition (2000Kcal to 2500 Kcal) without any discontinuation of NIV application and with minimal leak in the mask. Conclusion: When compared to other available technologies in this field, the NIV mask with the inbuilt feeding port is very economical and can be a boon in third world countries. The placement of this unique mechanism in the mask was instrumental in weaning off patients from NIV and avoided Invasive ventilation. It was proved beyond doubt that addition of this gland nut assembly was extremely effective in delivering adequate nutrition to our patients without compromising on the ventilation.

Environmental fluctuations, solar irradiance, and ambient temperature significantly affect photovoltaic (PV) system output. PV systems should be efficient at the Maximum Power Point in various weather climates to maximize their potential power output. The Maximum Power Point Tracking (MPPT) technique is employed to plan a specific location that yields the maximum amount of power. Operating dispersed alternative energy sources connected to the grid in this situation makes energy control an unavoidable task. This research article suggests designing a power electronics converter topology that links sustainable resources and electric vehicles to the power grid. There are four modes of operation for this proposed converter topology: grid-to-vehicle, vehicle-to-grid, renewable-to-vehicle, and renewable-to-grid discussed. The three power electronic converters and their uses are discussed, and their controllers are also designed to maintain the energy balance and stability in all cases. The battery characteristics indicate the operating mode. The work primarily focuses on the converter’s Triple Port Integrated Topology (TPIT) power flow and voltage control. Here, three power converters integrate the TPIT with three systems-the electric grid, renewable energy, and electric vehicles-into one system. The source battery and solar photovoltaic (PV) array cells are integrated using unidirectional and bidirectional DC-DC converters. The future scope of the work is to investigate the potential of adding additional ports for integrating other energy resources, such as hydrogen fuel cells or additional renewable sources, to create a more versatile and robust energy management system for EV charging stations.

Abstract Background MAL (T-lymphocyte maturation-associated protein) is highly downregulated in most cancers, including cervical cancer (CaCx), attributable to promoter hypermethylation. Long noncoding RNA genes (lncGs) play pivotal roles in CaCx pathogenesis, by interacting with human papillomavirus (HPV)-encoded oncoproteins, and epigenetically regulating coding gene expression. Hence, we attempted to decipher the impact and underlying mechanisms of MAL downregulation in HPV16-related CaCx pathogenesis, by interrogating the interactive roles of MAL antisense lncRNA AC103563.8, E7 oncoprotein and PRC2 complex protein, EZH2. Results Employing strand-specific RNA-sequencing, we confirmed the downregulated expression of MAL in association with poor overall survival of CaCx patients bearing HPV16, along with its antisense long noncoding RNA (lncRNA) AC103563.8. The strength of positive correlation between MAL and AC103563.8 was significantly high among patients compared to normal individuals. While downregulated expression of MAL was significantly associated with poor overall survival of CaCx patients bearing HPV16, AC103563.8 did not reveal any such association. We confirmed the enrichment of chromatin suppressive mark, H3K27me3 at MAL promoter, using ChIP-qPCR in HPV16-positive SiHa cells. Subsequent E7 knockdown in such cells significantly increased MAL expression, concomitant with decreased EZH2 expression and H3K27me3 marks at MAL promoter. In silico analysis revealed that both E7 and EZH2 bear the potential of interacting with AC103563.8, at the same binding domain. RNA immunoprecipitation with anti-EZH2 and anti-E7 antibodies, respectively, and subsequent quantitative PCR analysis in E7-silenced and unperturbed SiHa cells confirmed the interaction of AC103563.8 with EZH2 and E7, respectively. Apparently, AC103563.8 seems to preclude EZH2 and bind with E7, failing to block EZH2 function in patients. Thereby, enhanced EZH2 expression in the presence of E7 could potentially inactivate the MAL promoter through H3K27me3 marks, corroborating our previous results of MAL expression downregulation in patients. Conclusion AC103563.8-E7-EZH2 axis, therefore, appears to crucially regulate the expression of MAL, through chromatin inactivation in HPV16-CaCx pathogenesis, warranting therapeutic strategy development.

Hypoxia is a crucial factor in tumor biology, affecting various solid tumors to different extents. Its influence spans both early and advanced stages of cancer, altering cellular functions and promoting resistance to therapy. Hypoxia reduces the effectiveness of radiotherapy, chemotherapy, and immunotherapy, making it a target for improving therapeutic outcomes. Despite extensive research, gaps persist, necessitating the exploration of new chemical and pharmacological interventions to modulate hypoxia-related pathways. This review discusses the complex pathways involved in hypoxia and the associated pharmacotherapies, highlighting the limitations of current treatments. It emphasizes the potential of nanoparticle-based platforms for delivering anti-hypoxic agents, particularly oxygen (O2), to the tumor microenvironment. Combining anti-hypoxic drugs with conventional cancer therapies shows promise in enhancing remission rates. The intricate relationship between hypoxia and tumor progression necessitates novel therapeutic strategies. Nanoparticle-based delivery systems can significantly improve cancer treatment efficacy by targeting hypoxia-associated pathways. The synergistic effects of combined therapies underscore the importance of multimodal approaches in overcoming hypoxia-mediated resistance. Continued research and innovation in this area hold great potential for advancing cancer therapy and improving patient outcomes.

This article extensively analyses PI, Type-2, and Type-3 controllers in interfacing converters, specifically focusing on boost and interleaved-boost converters. The primary objective is to enhance regulation within a standalone microgrid system integrated with photovoltaic (PV) sources. The analysis encompasses various aspects of regulation, including line and load regulation, reference tracking, and parametric sensitivity analysis. The initial phase of the study involves examining interfacing converters, specifically the boost and interleaved-boost converters, using small-signal modelling in the continuous conduction mode (CCM). Subsequently, we propose and implement PI, Type-2, and Type-3 controllers for the closed-loop operation of these converters to achieve improved dynamic efficiency and reliability. The implemented control strategy integrates maximum power point tracking (MPPT) with these controllers (PI, Type-2, Type-3) and compares boost and interleaved-boost converters comprehensively. This comparison is supported by theoretical, numerical, and graphical analyses of various transient parameters such as rise time, settling time, and maximum overshoot. The results of our study demonstrate that the interleaved-boost converter (IBC) coupled with a Type-3 controller exhibits the most favourable transient performance across all aspects of regulation, including line and load regulation, reference tracking, and parametric sensitivity analysis. To validate the proposed methodology, we conducted experimental work with an input voltage of 10 V, using the parameters of the Exide 225-watt polycrystalline solar panel as a reference.

Abstract Background For various cancers, differences in response to treatment and subsequent survival period have been reported to be associated with variation in immune contextures. Aim We sought to identify whether such association exists in respect of gingivobuccal oral cancer. Materials and methods We performed deep immune profiling of tumor and margin tissues collected from 46 treatment naïve, Human Papillomavirus (HPV) negative, patients. Each patient was followed for 24 months and prognosis (recurrence/death) noted. Key findings were validated by comparing with TCGA‐HNSC cohort data. Results About 28% of patients showed poor post‐treatment prognosis. These patients exhibited a high probability of recurrence even within 1 year and death within 2 years. There was restricted immune cell infiltration in tumor, but not in margin, among these patients. Reduced expression of eight immune‐related genes (IRGs) (NT5E, THRA, RBP1, TLR4, ITGA6, BMPR1B, ITGAV, SSTR1) in tumor strongly predicted better quality of prognosis, both in our patient cohort and in TCGA‐HNSC cohort. Tumors of patients with better prognosis were associated with (a) lower CD73+ cells with concomitant lower expression level of NT5E/CD73, (b) higher proportions of CD4+ and CD8+ T cells, B cells, NK cells, M1 macrophages, (c) higher %Granzyme+ cells, (d) higher TCR and BCR repertoire diversities. CD73 expression in tumor was associated with low CD8+ and CD4+ T cells, low immune repertoire diversity, and advanced cancer stage. Discussion and conclusion High infiltration of anti‐tumor immune cells in both tumors and margins results in good prognosis, while in patients with minimal infiltration in tumors in spite of high infiltration in margins results in poor prognosis. Targeted CD73 immune‐checkpoint inhibition may improve clinical outcome.

Abstract The proposed topology is used to connect a single-phase and a three-phase renewable energy resources to the grid. The single-phase source is coupled to a single-phase PFC boost converter, which enhances the input PF utilizing two feedback loops: outer voltage loop control and inner current loop control. The basic hightlight is to study the PFC converter in microgrid application where renewables are integrated with the systems. The basic aim is to observe the overall performance of the converters with various disturbances such as load variations, etc. Here, the single-phase and three-phase stand-alone inverter is used to get the the output of the PFC boost converters. A symmetrical sinusoidal output voltage waveform should be produced and maintained by the inverter. The three-phase source is also coupled to a PFC buck converter, which enhances the input PF utilizing two feedback loops: outer voltage loop control and inner current loop control. The single-phase stand-alone inverter receives the output of the PFC buck converter. The transformer receives the outputs of both the inverters as it is a multi-winding high-frequency transformer and offers isolation between the grid and the source. The pulses for the switches in the single-phase inverter coupled stand-alone system were generated using a sinusoidal pulse width modulation approach. Both the PI controllers are implemented to maintain the regulations. The simulation results are achieved by varying the load, maintaining a constant voltage, and observing whether the current varies as the load changes. It also provides the efficacy of the study.

Real-time RT-PCR is used as a gold standard method for the diagnosis of COVID-19. Since real-time RT PCR is nucleic acid-based, it is a highly sensitive and specific test. However, this test takes 4–8 h to generate results and, in emergency settings, this delay may prove fatal for certain patients. The frequent surge in COVID cases increases patient load in emergency settings. Thus, a nucleic acid-based rapid POC test is required that can generate results quickly as well as being comparable to real-time RT-PCR. In this study, comparison of real-time RT-PCR was carried out using the rapid nucleic acid-based LAMP method. Nasopharyngeal swabs were taken in duplicate from patients visiting the kiosk and were analyzed for the presence of the SARS-CoV-2 virus by both real-time RT-PCR and LAMP techniques ID NOW(bbott). Out of 14 positive and 31 negative samples tested by real-time RT-PCR, 13 samples were identified as positive and 31 were observed as negative with the LAMP-based test. Hence, the sensitivity and specificity of this method were found to be 92.9% and 93.5%, respectively. Therefore, LAMP-based point-of-care testing has the potential to be used in hospital emergency settings for quick diagnosis of critically ill patients, and the information generated here will further draw the attention of policymakers toward such nucleic acid-based rapid tests.

Abstract Objective: We aimed to assess risk of COVID-19 infection & seroprotection status in healthcare workers (HCWs) in both hospital and community settings following an intensive vaccination drive in India. Setting: Tertiary Care Hospital Methods: We surveyed COVID-19 exposure risk, personal protective equipment (PPE) compliance, vaccination status, mental health & COVID-19 infection rate across different HCW cadres. Elecsys® test for COVID-19 spike (Anti-SARS-CoV-2S; ACOVs) and nucleocapsid (Anti-SARS-CoV-2; ACOV) responses following vaccination and/or COVID-19 infection were measured in a stratified sample of 386 HCW. Results: We enrolled 945 HCWs (60.6% male, age 35.9 ± 9.8 years, 352 nurses, 211 doctors, 248 paramedics & 134 support staff). Hospital PPE compliance was 90.8%. Vaccination coverage was 891/945 (94.3%). ACOVs neutralizing antibody was reactive in 381/386 (98.7%). ACOVs titer (U/ml) was higher in the post-COVID-19 infection group (N =269; 242.1 ± 35.7 U/ml) than in the post-vaccine or never infected subgroup (N = 115, 204.1 ± 81.3 U/ml). RT PCR + COVID-19 infections were documented in 224/945 (23.7%) and 6 HCWs had disease of moderate severity, with no deaths. However, 232/386 (60.1%) of HCWs tested positive for nucleocapsid ACOV antibody, suggesting undocumented or subclinical COVID-19 infection. On multivariate logistic regression, only female gender [aOR 1.79, 95% CI 1.07–3.0, P = .025] and COVID-19 family contact [aOR 5.1, 95% CI 3.84–9.5, P < .001] were predictors of risk of developing COVID-19 infection, independent of association with patient-related exposure. Conclusion: Our HCWs were PPE compliant and vaccine motivated, with immunization coverage of 94.3% and seroprotection rate of 98.7%. There was no relationship between HCW COVID-19 infection to exposure characteristics in the hospital. Vaccination reduced disease severity and prevented death in HCW.

Therapeutic options for managing Pancreatic ductal adenocarcinoma (PDAC), one of the deadliest types of aggressive malignancies, are limited and disappointing. Therefore, despite suboptimal clinical effects, gemcitabine (GEM) remains the first-line chemotherapeutic drug in the clinic for PDAC treatment. The therapeutic limitations of GEM are primarily due to poor bioavailability and the development of chemoresistance resulting from the addiction of mutant-K-RAS/AKT/ERK signaling-mediated desmoplastic barriers with a hypoxic microenvironment. Several new therapeutic approaches, including nanoparticle-assisted drug delivery, are being investigated by us and others. This study used pH-responsive nanoparticles encapsulated ERK inhibitor (SCH772984) and surface functionalized with tumor-penetrating peptide, iRGD, to target PDAC tumors. We used a small molecule, SCH772984, to target ERK1 and ERK2 in PDAC and other cancer cells. This nanocarrier efficiently released ERKi in hypoxic and low-pH environments. We also found that the free-GEM, which is functionally weak when combined with nanoencapsulated ERKi, led to significant synergistic treatment outcomes in vitro and in vivo. In particular, the combination approaches significantly enhanced the GEM effect in PDAC growth inhibition and prolonged survival of the animals in a genetically engineered KPC (LSL-KrasG12D/+/LSL-Trp53R172H/+/Pdx-1-Cre) pancreatic cancer mouse model, which is not observed in a single therapy. Mechanistically, we anticipate that the GEM efficacy was increased as ERKi blocks desmoplasia by impairing the production of desmoplastic regulatory factors in PDAC cells and KPC mouse tumors. Therefore, 2nd generation ERKi (SCH 772984)-iRGD-pHNPs are vital for the cellular response to GEM and denote a promising therapeutic target in PDAC with mutant K-RAS.

الملخص: أهداف البحث: هدفت هذه الدراسة إلى إيجاد القياس النسيجي للصفيحة القشرية المخيخية والنواة المسننة لمخيخ الجنين البشري وأيضا دراسة عدد الخلايا العصبية وشكلها، وعمر الحمل لظهور الورقات المخيخية، والمادة البيضاء، وشجرة الحياة المخيخية. طريقة البحث: تمت دراسة المقاطع المجهرية من مخيخ الجنين البشري المصبوغة بالهيماتوكسيلين والأيوزين وبصبغة بيلشوفسكي. النتائج: تباينت سماكة الصفيحة القشرية لمخيخ الجنين البشري بين الطبقة الحبيبية الخارجية- 36.06 ± 9.36 إلى 50.05 ± 34.06 ميكرومتر ، الطبقة الجزيئية- 32.76 ± 17.16 إلى 52 ± 28.6 ميكرومتر، طبقة خلايا بوركيني 9.36 ± 6.8 إلى 15.6 ± 4.68 ميكرومتر وطبقة حبيبية داخلية- 66.65 ± 24.42 إلى 146.63 ± 47.79 ميكرومتر في أسابيع الحمل المختلفة. وبالمثل، فإن عدد الخلايا العصبية لكل مجال رؤية عند قوة 1000 من المجهر المركب يختلف بين الطبقة الحبيبية الخارجية- 89.92 ± 42 إلى 142.84 ± 50 ، الطبقة الجزيئية- 15 ± 12.5 إلى 25 ± 8.25 ، طبقة خلايا بوركيني 3.5 ± 1 إلى 5 ± 2.5 وطبقة حبيبية داخلية- 98.5 ± 69.75 إلى 224 ± 47 في أسابيع الحمل المختلفة. كانت المادة البيضاء في مخيخ الجنين موجودة بالفعل في عمر الأسبوع الثاني عشر من الحمل بينما ظهرت الورقات المخيخية في الأسبوع 16–20 من الحمل. أصبحت شجرة الحياة المخيخية والنواة المسننة واضحة بعد الأسبوع العشرين من الحمل. كانت الخلايا العصبية الجنينية مستديرة باستثناء خلية بوركيني. الاستنتاجات: تختلف سماكة وتعداد الخلايا العصبية للطبقات القشرية المخيخية للجنين البشري وقياسات النواة المسننة جنبًا إلى جنب مع السمات النسيجية الأخرى مع تقدم عمر الحمل من الأسبوع الثاني عشر من الحمل حتى الولادة. Abstract: Objectives: This study was aimed at determining the histomorphometry of the cerebellar cortical laminae and the dentate nucleus of the human fetal cerebellum; the number and shape of the neurons; and the gestational age of appearance of the cerebellar folia, white matter and arbor vitae cerebelli. Methods: Microscopic sections of the human fetal cerebellum stained with hematoxylin and eosin and Bielschowsky silver stain were studied. Results: The thickness of the cortical laminae of the human fetal cerebellum varied among gestational weeks as follows: external granular layer: 36.06 ± 9.36–50.05 ± 34.06 μm, molecular layer: 32.76 ± 17.16–52 ± 28.6 μm, Purkinje cell layer: 9.36 ± 6.8–15.6 ± 4.68 μm and internal granular layer: 66.65 ± 24.42–146.63 ± 47.79 μm. Similarly, the number of neurons per field of view at 1000X under a compound microscope varied among gestational weeks as follows: external granular layer: 89.92 ± 42–142.84 ± 50, molecular layer: 15 ± 12.5–25 ± 8.25, Purkinje cell layer: 3.5 ± 1–5 ± 2.5 and internal granular layer: 98.5 ± 69.75–224 ± 47.White matter in the fetal cerebellum was already present at the age of 12th gestational week, whereas cerebellar folia appeared at 16–20 gestational weeks. Arbor vitae cerebelli and the dentate nucleus became conspicuous after the 20th gestational week. Fetal neurons were round except for Purkinje cells. Conclusions: The thickness and neuronal counts of the human fetal cerebellar cortical layers and the measurements of the dentate nucleus along with other histomorphological features varied with gestational age from the 12th week of gestation until birth.

Gynecological and obstetric infectious diseases are crucial to women’s health. There is growing evidence that links the presence of Fusobacterium nucleatum (F. nucleatum), an anaerobic oral commensal and potential periodontal pathogen, to the development and progression of various human diseases, including cancers. While the role of this opportunistic oral pathogen has been extensively studied in colorectal cancer in recent years, research on its epidemiological evidence and mechanistic link to gynecological diseases (GDs) is still ongoing. Thus, the present review, which is the first of its kind, aims to undertake a comprehensive and critical reappraisal of F. nucleatum, including the genetics and mechanistic role in promoting adverse pregnancy outcomes (APOs) and various GDs, including cancers. Additionally, this review discusses new conceptual advances that link the immunomodulatory role of F. nucleatum to the development and progression of breast, ovarian, endometrial, and cervical carcinomas through the activation of various direct and indirect signaling pathways. However, further studies are needed to explore and elucidate the highly dynamic process of host–F. nucleatum interactions and discover new pathways, which will pave the way for the development of better preventive and therapeutic strategies against this pathobiont.

Currently, intelligent, responsive biomaterials have been widely explored, considering the fact that responsive biomaterials provide controlled and predictable results in various biomedical systems. Responsive nanostructures undergo reversible or irreversible changes in the presence of a stimulus, and that stimuli can be temperature, a magnetic field, ultrasound, pH, humidity, pressure, light, electric field, etc. Different types of stimuli being used in drug delivery shall be explained here. Recent research progress in the design, development and applications of biomaterials comprising responsive nanostructures is also described here. More emphasis will be given on the various nanostructures explored for the smart stimuli responsive drug delivery at the target site such as wound healing, cancer therapy, inflammation, and pain management in order to achieve the improved efficacy and sustainability with the lowest side effects. However, it is still a big challenge to develop well-defined responsive nanostructures with ordered output; thus, challenges faced during the design and development of these nanostructures shall also be included in this article. Clinical perspectives and applicability of the responsive nanostructures in the targeted drug delivery shall be discussed here.

Abstract The efficacy of Hydroxychloroquine (HCQ) as post-exposure prophylaxis (PEP) for the prevention of COVID-19 was contentious. In this randomized control double-blind clinical trial, asymptomatic individuals with direct contact with laboratory-confirmed COVID-19 cases were randomized into PEP/HCQ (N = 574) and control/placebo (N = 594) group. The PEP/HCQ group received tablet HCQ 400 mg q 12 hourly on day one followed by 400 mg once weekly for 3 weeks, and the control/Placebo group received matching Placebo. The incidence of COVID-19 was similar (p = 0.761) in PEP [N = 24 out of 574, (4.2%)] and control [N = 27 out of 594, (4.5%)] groups. Total absolute risk reduction for the incidence of new-onset COVID-19 was -0.3% points with an overall relative risk of 0.91 (95% confidence interval, 0.52 to 1.60) and the number needed to treat (NNT) was 333 to prevent the incident of one case of COVID-19. The study found that, PEP with HCQ was not advantageous for the prevention of COVID-19 in asymptomatic individuals with high risk for SARS-CoV-2 infection. Though HCQ is a safer drug, the practice of irrational and indiscriminate use of HCQ for COVID-19 should be restrained with better pharmacovigilance.

Hemoglobin (Hb) present in the lung epithelium is of unknown significance. However Hb being an nitric oxide (NO) scavenger can bind to NO and reduce its deleterious effects. Hence we postulated an NO scavenging role for this lung Hb. Doing transwell co-culture with bronchial epithelial cells, A549/16-HBE (apical) and human airway smooth muscle cells (HASMCs as basal), we found that Hb can protect the smooth muscle soluble guanylyl cyclase (sGC) from excess NO. Inducing the apical A549/16-HBE cells with cytokines to trigger iNOS expression and NO generation caused a time dependent increase in SNO-sGC and this was accompanied with a concomitant drop in sGC-α1β1 heterodimerization. Silencing Hbαβ in the apical cells further increased the SNO on sGC with a faster drop in the sGC heterodimer and these effects were additive along with further silencing of thioredoxin 1 (Trx1). Since heme of Hb is critical for NO scavenging we determined the Hb heme in a mouse model of allergic asthma (OVA) and found that Hb in the inflammed OVA lungs was low in heme or heme-free relative to those of naïve lungs. Further we established a direct correlation between the status of the sGC heterodimer and the Hb heme from lung samples of human asthma, iPAH, COPD and cystic fibrosis. These findings present a new mechanism of protection of lung sGC by the epithelial Hb, and suggests that this protection maybe lost in asthma or COPD where lung Hb is unable to scavenge the NO due to it being heme-deprived.

Background: We have recently provided the evidence of interconvertible cellular states, driving non-genetic heterogeneity among stem-like oral cancer cells (oral-SLCCs). Here, NOTCH pathway-activity status is explored as one of the possible mechanisms behind this stochastic plasticity. Methods: Oral-SLCCs were enriched in 3D-spheroids. Constitutively-active and inactive status of NOTCH pathway was achieved by genetic or pharmacological approaches. RNA sequencing and real-time PCR was performed for gene expression studies. in vitro cytotoxicity assessments were performed by AlamarBlue assay and in vivo effects were studied by xenograft growth in zebrafish embryo. Results: We have observed stochastic plasticity in oral-SLCCs, spontaneously maintaining both NOTCH-active and inactive states. While cisplatin refraction was associated with post-treatment adaptation to the active-state of NOTCH pathway, oral-SLCCs with inactive NOTCH pathway status showed aggressive tumor growth and poor prognosis. RNAseq analysis clearly suggested the upregulation of JAK-STAT pathway in NOTCH pathway-inactive subset. The 3D-spheroids with lower NOTCH-activity status displayed significantly higher sensitivity to JAK-selective drugs, Ruxolitinib or Tofacitinib or siRNA mediated downregulation of tested partners STAT3/4. Oral-SLCCs were programmed to adapt the inactive status of NOTCH pathway by exposing to γ-secretase inhibitors, LY411575 or RO4929097, followed by targeting with JAK-inhibitors, Ruxolitinib or Tofacitinib. This approach resulted in a very significant inhibition in viability of 3D-spheroids as well as xenograft initiation in Zebrafish embryos. Conclusion: Study revealed for the first time that NOTCH pathway-inactive state exhibit activation of JAK-STAT pathways, as synthetic lethal pair. Therefore, co-inhibition of these pathway may serve as novel therapeutic strategy against aggressive oral cancer.

الملخص: أهداف البحث: تُظهر المؤلفات عددًا قليلاً جدًا من الدراسات التي تشرح مورفولوجيا الخلايا العصبية المعوية والعقد في البشر. هدفت هذه الدراسة إلى تحديد النسيج المورفولوجي للخلايا العصبية المعوية والعقد في القولون الجنيني البشري. طرق البحث: تم تلوين المقاطع النسيجية لقولون الجنين البشري بالهيماتوكسيلين ويوزين، فضية بيلشوفسكي وبقع ماسون ثلاثية الألوان لدراسة التشكل النسيجي للأمعاء الخلايا العصبية والعقد. النتائج: الخلايا العصبية المعوية تكون مبعثرة في الأسابيع الأولى من التطور وتتكون العقد مع تقدم عمر الجنين. كانت هجرة الخلايا العصبية المعوية أقل وفي شكل متباعد خلال الأسابيع الأولى ومع تقدم العمر كانت أكثر وفي شكل عقدي. كانت الخلايا العصبية المعوية مستديرة وبيضاوية وهرمية ومسطحة في جميع طبقات القولون. كانت العقد المعوية في المصل بيضاوية في الأسابيع الأولى واستطالت في أواخر الأسابيع بينما كانت قليلة وبيضاوية وغير منتظمة وممدودة بين طبقات العضلات وتحت المخاطية. زادت المسافة بين العقد المعوية في الطبقة المصلية، ولكن تقلبت في الطبقات المتبقية مع تقدم عمر الحمل. عدد الخلايا العصبية المعوية والعقد كانت أكثر في الطبقة المصلية وأقل في الطبقات الأخرى خلال الأسابيع الأولى وكلما تقدم عمر الجنين انخفضت في الطبقة المصلية ولكن زادت في الطبقات الأخرى. الاستنتاجات: هناك أشكال وأعداد مختلفة من الخلايا العصبية المعوية والعقد والمسافات بين العقد في الطبقات المختلفة من القولون الجنيني. Abstract: Objective: Literature shows very few studies explaining morphology of enteric neurons and ganglia in humans. This study was aimed at determining the morpho-histology of enteric neurons and ganglia in human fetal colon. Methods: Histological sections of human fetal colon were stained with hematoxylin and eosin, Bielschowsky's silver and Masson's trichrome stains to study the morpho-histology of enteric neurons and ganglia. Results: Enteric neurons scattered in the early weeks of development and ganglionated as the fetal age progresses. Migration of enteric neurons was less and in scattered form during early weeks and as the age progresses it was more and in ganglionated form. Enteric neurons were round, oval, pyramidal and flat in all layers of colon. Enteric ganglia in serosa were oval in early weeks, oval and elongated in late weeks whereas in between the muscle layers and submucosa they were few and oval, irregular and elongated. Distance between the enteric ganglia increased in serosa but fluctuated in the remaining layers as the gestational age progressed. Number of enteric neurons and ganglia was more in serosa and less in other layers during early weeks and as the fetal age progressed they decreased in serosa but increased in other layers. Conclusion: There are various shapes and numbers of enteric neurons and ganglia and distances between the ganglia in different layers of fetal colon.

Abstract Objectives The aim of this study was to validate an active matrix metalloproteinase (MMP‐8) point‐of‐care diagnostic tool in COVID‐19 patients with periodontal disease. Subjects, Materials, and Methods Seventy‐two COVID‐19‐positive and 30 COVID‐19‐negative subjects were enrolled in the study. Demographic data were recorded, periodontal examination carried out, and chairside tests run for evaluating the expression of active MMP‐8 (aMMP‐8) in the site with maximum periodontal breakdown via gingival crevicular fluid sampling as well as via a mouth rinse‐based kit for general disease activity. In COVID‐19‐positive patients, the kits were run again once the patients turned COVID‐19 negative. Results The overall (n = 102) sensitivity/specificity of the mouthrinse‐based kits to detect periodontal disease was 79.41%/36.76% and that of site‐specific kits was 64.71%/55.88% while adjusting for age, gender, and smoking status increased the sensitivity and specificity (82.35%/76.47% and 73.53%/88.24, respectively). Receiver operating characteristic (ROC) analysis for the adjusted model revealed very good area under the ROC curve 0.746–0.869 (p

Abstract Partly because of advances in power electronic converters, the share of renewable energy in power generation is steadily increasing. The main medium of interface for integrating renewable energy sources to the utility grid is the power electronic inverter. Virtual oscillator control (VOC) is a time-domain approach for controlling parallel inverters in a standalone microgrid (MG). The concept is to simulate nonlinear deadzone oscillator dynamics in a system of inverters to ensure a stable AC MG in the absence of communication. VOC is a time-domain and self-synchronizing controller that simply requires the measurement of filter current, whereas traditional droop control and the virtual synchronous machine (VSM) require low pass filters for active and reactive power calculations. In this work, a particle swarm optimization (PSO)-based VOC method (VOC-PSO) is proposed, in which the parameters of the VOC are designed using the PSO algorithm. The system performance using droop, VSM, VOC, and VOC-PSO controllers are investigated using MATLAB and Opal-RT real-time digital simulator platforms. The results show that the proposed VOC-PSO gives improved performance over other control strategies. The efficacy of the proposed VOC-PSO control method is also demonstrated by the experimental results.

With the wider availability of healthcare data such as Electronic Health Records (EHR), more and more data-driven based approaches have been proposed to improve the quality-of-care delivery. Predictive modeling, which aims at building computational models for predicting clinical risk, is a popular research topic in healthcare analytics. However, concerns about privacy of healthcare data may hinder the development of effective predictive models that are generalizable because this often requires rich diverse data from multiple clinical institutions. Recently, federated learning (FL) has demonstrated promise in addressing this concern. However, data heterogeneity from different local participating sites may affect prediction performance of federated models. Due to acute kidney injury (AKI) and sepsis' high prevalence among patients admitted to intensive care units (ICU), the early prediction of these conditions based on AI is an important topic in critical care medicine. In this study, we take AKI and sepsis onset risk prediction in ICU as two examples to explore the impact of data heterogeneity in the FL framework as well as compare performances across frameworks. We built predictive models based on local, pooled, and FL frameworks using EHR data across multiple hospitals. The local framework only used data from each site itself. The pooled framework combined data from all sites. In the FL framework, each local site did not have access to other sites' data. A model was updated locally, and its parameters were shared to a central aggregator, which was used to update the federated model's parameters and then subsequently, shared with each site. We found models built within a FL framework outperformed local counterparts. Then, we analyzed variable importance discrepancies across sites and frameworks. Finally, we explored potential sources of the heterogeneity within the EHR data. The different distributions of demographic profiles, medication use, and site information contributed to data heterogeneity.

Abstract Background Morphological organization, folial pattern formation and establishment of the neural circuitry within the cerebellum are the important events taking place during the development of the cerebellum. Expression of engrailed homeobox 2 (EN2) gene plays an essential role in taking place of these events in the developing cerebellum. Main body A search was performed by following the PRISMA guidelines to review the role of the EN2 gene in the development of the cerebellum. Human and animal in vivo and in vitro studies showed that expression of the EN2 gene maintains the normal development of the cerebellum, morphological organization, cerebellar foliation, fissure formation, establishment of the afferent topography, molecular pattern formation and patterned gene expression in the developing cerebellum. Altered expression of the EN2 gene changes the morphology and folial pattern of the cerebellum, whereas its activation rescues these defects. EN2 gene polymorphism is reported as a susceptible cause for autism spectrum disorder (ASD). Ectopic expression of EN2 gene may result cancer and it also may play anti-oncogenic role depending on the organ of its expression. Conclusion Expression of the EN2 gene is essential for the normal development of the cerebellum. Its altered expression results deformed cerebellum, polymorphysm is associated with autism and ectopic expression may results cancer.

Abstract Recently published clinical data from COVID-19 patients indicated that statin therapy is associated with a better clinical outcome and a significant reduction in the risk of mortality. In this study by computational analysis, we have aimed to predict the possible mechanism of the statin group of drugs by which they can inhibit SARS-CoV-2 pathogenesis. Blind docking of the critical structural and functional proteins of SARS-CoV-2 like RNA-dependent RNA polymerase, M-protease of 3-CL-Pro, Helicase, and the Spike proteins ( wild type and mutants from different VOCs) were performed using the Schrodinger docking tool. We observed that fluvastatin and pitavastatin showed fair, binding affinities to RNA polymerase and 3-CL-Pro, whereas fluvastatin showed the strongest binding affinity to the helicase. Fluvastatin also showed the highest affinity for the Spike Delta and a fair docking score for other spike variants. Additionally, molecular dynamics simulation confirmed the formation of a stable drug-protein complex between Fluvastatin and target proteins. Thus our study shows that of all the statins, fluvastatin can bind to multiple target proteins of SARS-CoV-2, including the spike-mutant proteins. This property might contribute to the potent antiviral efficacy of this drug.

Enteric neurons and ganglia are derived from vagal and sacral neural crest cells, which undergo migration from the neural tube to the gut wall. In the gut wall, they first undergo rostrocaudal migration followed by migration from the superficial to deep layers. After migration, they proliferate and differentiate into the enteric plexus. Expression of the Rearranged During Transfection (RET) gene and its protein RET plays a crucial role in the formation of enteric neurons. This review describes the molecular mechanism by which the RET gene and the RET protein influence the development of enteric neurons. Vagal neural crest cells give rise to enteric neurons and glia of the foregut and midgut while sacral neural crest cells give rise to neurons of the hindgut. Interaction of RET protein with its ligands (glial cell derived neurotrophic factor (GDNF), neurturin (NRTN), and artemin (ARTN)) and its co-receptors (GDNF receptor alpha proteins (GFRα1-4)) activates the Phosphoinositide-3-kinase-protein kinase B (PI3K-PKB/AKT), RAS mitogen-activated protein kinase (RAS/MAPK) and phospholipase Cγ (PLCγ) signaling pathways, which control the survival, migration, proliferation, differentiation, and maturation of the vagal and sacral neural crest cells into enteric neurons. Abnormalities of the RET gene result in Hirschsprung's disease.

Background: Data on outcomes of coronavirus disease 2019 (COVID-19) in pregnancy are scarce, although they represent a unique physiological state affecting both the mother and child. We present collated data from a tertiary care center in North India, encompassing the outcome, clinical characteristics, and management of these patients. Materials and Methods: Parturients ≥ 18 years old, with COVID-19 reverse transcriptase polymerase chain reaction positive for severe acute respiratory syndrome coronavirus 2, requiring intensive care unit (ICU) admission at a tertiary care hospital were included. Data were retrospectively collected from April 2020 to November 2021. Results: In all, 26 parturients were admitted to ICU with COVID-19. Five patients were admitted during the first wave, and all were asymptomatic. Twenty-one patients presented during the second wave (March 2021 onward), among which four were asymptomatic and 17 symptomatic (all with severe pneumonia). Three patients presented in the second trimester, all with critical disease, out of which one did not survive. Two patients had twin gestation, and others were singleton pregnancies. Seven patients (27%) were primigravida, and five patients (19.2%) had more than third pregnancy. Twenty critically ill women (77%) delivered during the hospital stay. Six patients died during the second wave, and four deaths (66.7%) were because of COVID-19 acute respiratory distress syndrome (ARDS). Conclusions: The number of admissions and mortality related to COVID-19 ARDS was higher in the second wave than in the first. We report the safe use of remdesivir and tocilizumab in our patients.

The penetration of renewable energy sources (RESs) in the distribution system becomes a challenge for the reliable and safe operation of the existing power system. The sporadic characteristics of sustainable energy sources along with the random load variations greatly affect the power quality and stability of the system. Hence, it requires storage Systems with both high energy and high power handling capacity to coexist in microgrids. An efficient energy management structure is designed in this paper for a grid-connected PV system combined with hybrid storage of supercapacitor and battery. The combined supercapacitor and battery storage system grips the average and transient power changes, which provides a quick control for the DC-link voltage, i. e., it stabilizes the system and helps achieve the PV power smoothing. The average power distribution between the power grid and battery is done by checking the state of charge (SOC) of a battery, and an effective and efficient energy management scheme is proposed. Additionally, the use of a supercapacitor lessens the current stress on the battery system during unexpected disparity in the generated power and load requirement. The performance and efficacy of the proposed energy management scheme are justified by simulation studies.

Summary: Background: Cauda equina syndrome (CES) results from nerve root compression in the lumbosacral spine, usually due to a prolapsed intervertebral disc. Evidence for management of CES is limited by its infrequent occurrence and lack of standardised clinical definitions and outcome measures. Methods: This is a prospective multi-centre observational cohort study of adults with CES in the UK. We assessed presentation, investigation, management, and all Core Outcome Set domains up to one year post-operatively using clinician and participant reporting. Univariable and multivariable associations with the Oswestry Disability Index (ODI) and urinary outcomes were investigated. Findings: In 621 participants with CES, catheterisation for urinary retention was required pre-operatively in 31% (191/615). At discharge, only 13% (78/616) required a catheter. Median time to surgery from symptom onset was 3 days (IQR:1–8) with 32% (175/545) undergoing surgery within 48 h. Earlier surgery was associated with catheterisation (OR:2.2, 95%CI:1.5–3.3) but not with admission ODI or radiological compression. In multivariable analyses catheter requirement at discharge was associated with pre-operative catheterisation (OR:10.6, 95%CI:5.8–20.4) and one-year ODI was associated with presentation ODI (r = 0.3, 95%CI:0.2–0.4), but neither outcome was associated with time to surgery or radiological compression. Additional healthcare services were required by 65% (320/490) during one year follow up. Interpretation: Post-operative functional improvement occurred even in those presenting with urinary retention. There was no association between outcomes and time to surgery in this observational study. Significant healthcare needs remained post-operatively. Funding: DCN Endowment Fund funded study administration. Castor EDC provided database use. No other study funding was received.

Physicians establish diagnosis by assessing a patient's signs, symptoms, age, sex, laboratory test findings and the disease history. All this must be done in limited time and against the backdrop of an increasing overall workload. In the era of evidence-based medicine it is utmost important for a clinician to be abreast of the latest guidelines and treatment protocols which are changing rapidly. In resource limited settings, the updated knowledge often does not reach the point-of-care. This paper presents an artificial intelligence (AI)-based approach for integrating comprehensive disease knowledge, to support physicians and healthcare workers in arriving at accurate diagnoses at the point-of-care. We integrated different disease-related knowledge bodies to construct a comprehensive, machine interpretable diseasomics knowledge-graph that includes the Disease Ontology, disease symptoms, SNOMED CT, DisGeNET, and PharmGKB data. The resulting disease-symptom network comprises knowledge from the Symptom Ontology, electronic health records (EHR), human symptom disease network, Disease Ontology, Wikipedia, PubMed, textbooks, and symptomology knowledge sources with 84.56% accuracy. We also integrated spatial and temporal comorbidity knowledge obtained from EHR for two population data sets from Spain and Sweden respectively. The knowledge graph is stored in a graph database as a digital twin of the disease knowledge. We use node2vec (node embedding) as digital triplet for link prediction in disease-symptom networks to identify missing associations. This diseasomics knowledge graph is expected to democratize the medical knowledge and empower non-specialist health workers to make evidence based informed decisions and help achieve the goal of universal health coverage (UHC). The machine interpretable knowledge graphs presented in this paper are associations between various entities and do not imply causation. Our differential diagnostic tool focusses on signs and symptoms and does not include a complete assessment of patient's lifestyle and health history which would typically be necessary to rule out conditions and to arrive at a final diagnosis. The predicted diseases are ordered according to the specific disease burden in South Asia. The knowledge graphs and the tools presented here can be used as a guide.

Nitric oxide (NO) is a signal molecule and plays a critical role in the regulation of vascular tone, displays anti-platelet and anti-inflammatory properties. While our earlier and current studies found that low NO doses trigger a rapid heme insertion into immature heme-free soluble guanylyl cyclase β subunit (apo-sGCβ), resulting in a mature sGC-αβ heterodimer, more recent evidence suggests that low NO doses can also trigger heme-maturation of hemoglobin and myoglobin. This low NO phenomena was not only limited to sGC and the globins, but was also found to occur in all three nitric oxide synthases (iNOS, nNOS and eNOS) and Myeloperoxidase (MPO). Interestingly high NO doses were inhibitory to heme-insertion for these hemeproteins, suggesting that NO has a dose-dependent dual effect as it can act both ways to induce or inhibit heme-maturation of key hemeproteins. While low NO stimulated heme-insertion of globins required the presence of the NO-sGC-cGMP signal pathway, iNOS heme-maturation also required the presence of an active sGC. These effects of low NO were significantly diminished in the tissues of double (n/eNOS−/−) and triple (n/i/eNOS−/−) NOS knock out mice where lung sGC was found be heme-free and the myoglobin or hemoglobin from the heart/lungs were found be low in heme, suggesting that loss of endogenous NO globally impacts the whole animal and that this impact of low NO is both essential and physiologically relevant for hemeprotein maturation. Effects of low NO were also found to be protective against ischemia reperfusion injury on an ex vivo lung perfusion (EVLP) system prior to lung transplant, which further suggests that low NO levels are also therapeutic.

In addition to playing a major role in tumor cell biology, p53 generates a microenvironment that promotes antitumor immune surveillance via tumor-associated macrophages. We examined whether increasing p53 signaling in the tumor microenvironment influences antitumor T cell immunity. Our findings indicate that increased p53 signaling induced either pharmacologically with APR-246 (eprenetapopt) or in p53-overexpressing transgenic mice can disinhibit antitumor T cell immunity and augment the efficacy of immune checkpoint blockade. We demonstrated that increased p53 expression in tumor-associated macrophages induces canonical p53-associated functions such as senescence and activation of a p53-dependent senescence-associated secretory phenotype. This was linked with decreased expression of proteins associated with M2 polarization by tumor-associated macrophages. Our preclinical data led to the development of a clinical trial in patients with solid tumors combining APR-246 with pembrolizumab. Biospecimens from select patients participating in this ongoing trial showed that there was a suppression of M2-polarized myeloid cells and increase in T cell proliferation with therapy in those who responded to the therapy. Our findings, based on both genetic and a small molecule–based pharmacological approach, suggest that increasing p53 expression in tumor-associated macrophages reprograms the tumor microenvironment to augment the response to immune checkpoint blockade.

Inflammation is the defense mechanism of the immune system against harmful stimuli such as pathogens, toxic compounds, damaged cells, radiation, etc., and is characterized by tissue redness, swelling, heat generation, pain, and loss of tissue functions. Inflammation is essential in the recruitment of immune cells at the site of infection, which not only aids in the elimination of the cause, but also initiates the healing process. However, prolonged inflammation often brings about several chronic inflammatory disorders; hence, a balance between the pro- and anti-inflammatory responses is essential in order to eliminate the cause while producing the least damage to the host. A growing body of evidence indicates that extracellular vesicles (EVs) play a major role in cell–cell communication via the transfer of bioactive molecules in the form of proteins, lipids, DNA, RNAs, miRNAs, etc., between the cells. The present review provides a brief classification of the EVs followed by a detailed description of how EVs contribute to the pathogenesis of various inflammation-associated diseases and their implications as a therapeutic measure. The latter part of the review also highlights how EVs act as a bridging entity in blood coagulation disorders and associated inflammation. The findings illustrated in the present review may open a new therapeutic window to target EV-associated inflammatory responses, thereby minimizing the negative outcomes.

Four-valve involvement (mitral, aortic, tricuspid, and pulmonary) in rheumatic heart disease (RHD) is an exceedingly rare entity. We report the case of a 24-year-old male, a known case of RHD, who presented with dyspnea and presyncope for 2 months. On examination, the patient had severe mitral stenosis, moderate mitral regurgitation, severe aortic stenosis, severe aortic regurgitation, and severe tricuspid regurgitation. Echocardiography revealed severe tricuspid stenosis with moderate pulmonary stenosis in addition to other clinically detectable valve lesions. The patient underwent aortic and mitral valve replacement, tricuspid valve repair with pulmonary valvotomy successfully.

Single diverticulum of the right atrium is a rare congenital malformation. We describe echocardiographic and computed tomography scan findings of a congenital right atrial diverticulum and its successful surgical resection in a 5-year-old boy. A review of available literature is also done discussing the possible etiology and management of this disease entity.

Background: Medications studied for therapeutic benefits in coronavirus disease 2019 (COVID-19) have produced inconclusive efficacy results except for steroids. Objective: A prospective randomized open-label, parallel-arm Phase I/II clinical trial was planned to compare essential oil (EO) blend versus placebo nebulization in mild COVID-19. Methods: A Phase I safety evaluation was carried out in a single ascending and multiple ascending dose study designs. We assessed Phase II therapeutic efficacy on COVID-19 and general respiratory symptoms on days 0, 3, 5, 7, 10, and 14 on the predesigned case record form. Viremia was evaluated on day 0, day 5, and day 10. Results: Dose-limiting toxicities were not reached with the doses, frequencies, and duration studied, thus confirming the formulation's preliminary safety. General respiratory symptoms (p

In this work, we report the restoration of a polluted urban stream by employing the multistage vortex aerator (MVA), an in-line mixer device that improves the dissolved oxygen concentration of polluted streams and accelerates the water purification rate. It was observed during the field experiment that the dissolved oxygen was enhanced up to 7.05 mg/L and the water quality was improved to a good grade. As a result, the complex odor was successfully eliminated and reduced by up to 71.9%, while the water quality grade was also improved by more than two grades on average. Stream water quality indicators monitored for twelve months revealed high removal rates of total phosphorous (56.4%) and suspended solids (61%). The study demonstrated MVA as a promising eco-friendly technology for significant improvement in urban stream water quality. Moreover, the MVA process creates no secondary pollution and is believed to be a sustainable treatment option for odorous water bodies. Overall, the MVA process is technically feasible for implementation, and this study provides a specific reference as a basis for the treatment of polluted water bodies in urban settings.

Background: Hysterectomy, removal of the uterus, is one of the most frequently performed gynecological surgeries, with approximately six hundred thousand women undergoing this procedure annually in the United States. Indications of hysterectomy vary from benign conditions to malignancies of the genital tract. Hysterectomy is also associated with intraoperative and postoperative complications. Aims and Objectives: The aim of the current study was to analyze indications, complications, duration of hospital stay, blood loss during surgery and correlation of preoperative diagnosis with final histopathology report of all abdominal hysterectomies performed at a teaching hospital. Materials and Methods: This study involved all patients who underwent abdominal hysterectomy at Manipal Teaching Hospital, Pokhara, Nepal over a span of 18 months (from 1st January, 2018 to 31st June, 2019). It was a retrospective study. All the patients undergoing abdominal hysterectomy during the study period were taken without any exclusion criteria. Results: There were 101 cases of abdominal hysterectomies performed during the study period. Majority of the patients were from urban areas than rural areas (67.3% vs 32.7%). Mean age of patients undergoing abdominal hysterectomy was 45.48 years with 2 standard deviation (SD) of 8.75. The youngest patient aged 26 years and the eldest aged 67 years. Mean parity was 2.50 with 2 SD of 1.197. Majority of the patients presented with pain abdomen (49.5%) and menstrual disorders (38.6%). The most common indication for hysterectomy was uterine fibroids (51.5%) followed by ovarian pathology (16.8%). The histopathology report of the patients showed that majority of the patients had fibroid uterus (51.4%) and ovarian pathology (16.8%). Mean intraoperative blood loss was 239.60 ml with 2 SD of 197.144. Mean hospital stay was: 7.29 days with 2SD of 3.144. The maximum hospital stay was 18 days in two patients and most patients had hospital stay between 5 to 8 days. The commonest complication was surgical site infection (9.9%) needing resuturing followed by urinary tract infection (7.9%). Conclusion: Wide spectrums of lesions were encountered during the surgery. The preoperative diagnosis, duration of hospital stay, average blood loss, surgical complications and histopathological reports correlated with various others studies.

Abstract Cap-independent translation initiation plays crucial roles in fine-tuning gene expression under global translation shutdown conditions. Translation of uncapped or de-capped transcripts can be stimulated by Cap-independent translation enhancer (CITE) elements, but the mechanisms of CITE-mediated translation initiation remain understudied. Here, we characterized a short 5ʹ-UTR RNA sequence from black beetle virus, BBV-seq. Mutational analysis indicates that the entire BBV-seq is required for efficient translation initiation, but this sequence does not operate as an IRES-type module. In yeast cell-free translation extracts, BBV-seq promoted efficient initiation on cap-free mRNA using a scanning mechanism. Moreover, BBV-seq can increase translation efficiency resulting from conventional cap-dependent translation initiation. Using genetic approaches, we found that BBV-seq exploits RNA-binding properties of eIF4G1 to promote initiation. Thus, BBV-seq constitutes a previously uncharacterized short, linear CITE that influences eIF4G1 to initiate 5′ end-dependent, cap-independent translation. These findings bring new insights into CITE-mediated translational control of gene expression.