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Background: Asthma is one of the most common chronic diseases globally. It is characterized by airflow obstruction that varies markedly, regardless of treatment. It is a type of airway inflammation due to bronchial hyperresponsiveness to a wide range of allergens, leading to excessive, usually reversible, airway narrowing. Asthma occurs more frequently in obese people, and it may be linked to pro-inflammatory adipokines. Apelin, a bioactive peptide belonging to the adipokines group, is identified as an endogenous ligand of an orphan G-protein coupled receptor named Apelin receptor (AR or APJ). Apelin is demonstrated in mature adipocytes and is highly expressed in pulmonary tissue, including bronchial and alveolar epithelial cells and small pulmonary blood vessels. Aim: The aim of this study was to evaluate the level of serum apelin in adult nonobese patients diagnosed with bronchial asthma cases and compare with healthy volunteers. We also aimed to correlate serum apelin levels with the severity of bronchial asthma. Materials and Methods: Twenty-two nonobese clinically diagnosed cases of bronchial asthma were included as cases and 66 age, sex, and socio-economic status-matched healthy volunteers as controls. Body mass index of cases and control subjects was calculated by weight (kg) per height (m2). Pulmonary function tests of the cases were done using spirometry. Serum apelin levels were estimated using Abbkine human ELISA-based kit. Statistical analysis was done using Pearson’s correlation test and analysis of variance. Results: We recruited 22 nonobese bronchial asthma cases (mean age = 38.2 ± 10.5 years) and 66 matched controls (mean age = 39.5 ± 12.0 years. Majority of the sample were females (n = 19 cases [86.3%], 54 controls [81.8%]). The mean serum apelin levels in cases and controls were 1355.3 ± 781.0 ng/L and 725.9 ± 375.6 ng/L, respectively; this difference was statistically significant (t = 5.053, df = 86, p = 0.001). The mean serum apelin levels in mild and moderate cases of bronchial asthma were 1121.5 ± 535.9 ng/L and 2150.2 ± 1019.1 ng/L, respectively. This difference was also statistically significant (t = 3.06, df = 20, p = 0.01). Conclusion: Serum apelin levels differ significantly between adult patients with bronchial asthma and population controls. Further, serum apelin levels differed with illness severity. These findings have important implications for disease management.

Abstract 3D brain atlases are key resources to understand the brain’s spatial organization and promote interoperability across different studies. However, unlike the adult mouse brain, the lack of developing mouse brain 3D reference atlases hinders advancements in understanding brain development. Here, we present a 3D developmental common coordinate framework (DevCCF) spanning embryonic day (E)11.5, E13.5, E15.5, E18.5, and postnatal day (P)4, P14, and P56, featuring undistorted morphologically averaged atlas templates created from magnetic resonance imaging and co-registered high-resolution light sheet fluorescence microscopy templates. The DevCCF with 3D anatomical segmentations can be downloaded or explored via an interactive 3D web-visualizer. As a use case, we utilize the DevCCF to unveil GABAergic neuron emergence in embryonic brains. Moreover, we map the Allen CCFv3 and spatial transcriptome cell-type data to our stereotaxic P56 atlas. In summary, the DevCCF is an openly accessible resource for multi-study data integration to advance our understanding of brain development.

The conventional closed and open jet tunnels suffer from various adverse blockage effects that alter the flow conditions generating erroneous results when larger than allowable blockage models are tested. The maximum acceptable blockage is limited to 25 % for an open jet tunnel. The physics behind the inferior blockage capacity and their redressal is investigated. Hitherto, numerical models are developed to rectify the blockage troubles that introduce an additional complex case-based mathematical modeling to reckoning the results. In the current paper novel approach to redesigning the tunnel to solve blockage troubles is investigated that facilitates evading of mathematical techniques and securing accurate results straightforwardly. A hypothetical design incorporating the remedies is proposed, capable of conditioning the flow in a manner that debilitates the adverse effects of solid blockage, wake blockage, jet expansion, etc. The hypothesis is theoretically expounded by the boundary layer and jet flow phenomenon. The modified blower-type open jet wind tunnel constitutes a centrifugal blower, long inlet duct, plenum chamber around the test section, and collector. The modified wind tunnel is tested through experiments executed on four different-sized Savonius rotors creating 10 %, 30 %, 50 %, and 60 % blockage. The static pressure along the contours of the blades of rotors is obtained. The experimental results are juxtaposed with CFD results carried out at free-wind boundary conditions and standard classic experimental results performed in conventional wind tunnel at 11 % blockage. A blockage enhancement of 25 % is achieved by the approach of modification in the design of a conventional open jet wind tunnel.

Abstract BackgroundGenetic testing can determine familial and personal risks for heritable thoracic aortic aneurysms and dissections (TAD). The 2022 American College of Cardiology/American Heart Association guidelines for TAD recommend management decisions based on the specific gene mutation. However, many clinicians lack sufficient comfort or insight to integrate genetic information into clinical practice. ObjectiveWe therefore developed the Genomic Medicine Guidance (GMG) application, an interactive point-of-care tool to inform clinicians and patients about TAD diagnosis, treatment, and surveillance. GMG is a REDCap-based application that combines publicly available genetic data and clinical recommendations based on the TAD guidelines into one translational education tool. MethodsTAD genetic information in GMG was sourced from the Montalcino Aortic Consortium, a worldwide collaboration of TAD centers of excellence, and the National Institutes of Health genetic repositories ClinVar and ClinGen. ResultsThe application streamlines data on the 13 most frequently mutated TAD genes with 2286 unique pathogenic mutations that cause TAD so that users receive comprehensive recommendations for diagnostic testing, imaging, surveillance, medical therapy, and preventative surgical repair, as well as guidance for exercise safety and management during pregnancy. The application output can be displayed in a clinician view or exported as an informative pamphlet in a patient-friendly format. ConclusionsThe overall goal of the GMG application is to make genomic medicine more accessible to clinicians and patients while serving as a unifying platform for research. We anticipate that these features will be catalysts for collaborative projects aiming to understand the spectrum of genetic variants contributing to TAD.

A recyclability perspective is essential in the sustainable development of energy storage devices, such as lithium-ion batteries (LIBs), but the development of LIBs prioritizes battery capacity and energy density over recyclability, and hence, the recycling methods are complex and the recycling rate is low compared to other technologies. To improve this situation, the underlying battery design must be changed and the material choices need to be made with a sustainable mindset. A suitable and effective approach is to utilize bio-materials, such as paper and electrode composites made from graphite and cellulose, and adopt already existing recycling methods connected to the paper industry. To address this, we have developed a concept for fabricating fully disposable and resource-efficient paper-based electrodes with a large-scale roll-to-roll coating operation in which the conductive material is a nanographite and microcrystalline cellulose mixture coated on a paper separator. The overall best result was achieved with coated roll 08 with a coat weight of 12.83(22) g/m2 and after calendering, the highest density of 1.117(97) g/cm3, as well as the highest electrical conductivity with a resistivity of 0.1293(17) mΩ·m. We also verified the use of this concept as an anode in LIB half-cell coin cells, showing a specific capacity of 147 mAh/g, i.e., 40% of graphite’s theoretical performance, and a good long-term stability of battery capacity over extended cycling. This concept highlights the potential of using paper as a separator and strengthens the outlook of a new design concept wherein paper can both act as a separator and a substrate for coating the anode material.

Abstract The ionizable lipidoid is a key component of lipid nanoparticles (LNPs). Degradable lipidoids containing extended alkyl branches have received tremendous attention, yet their optimization and investigation are underappreciated. Here, we devise an in situ construction method for the combinatorial synthesis of degradable branched (DB) lipidoids. We find that appending branch tails to inefficacious lipidoids via degradable linkers boosts mRNA delivery efficiency up to three orders of magnitude. Combinatorial screening and systematic investigation of two libraries of DB-lipidoids reveal important structural criteria that govern their in vivo potency. The lead DB-LNP demonstrates robust delivery of mRNA therapeutics and gene editors into the liver. In a diet-induced obese mouse model, we show that repeated administration of DB-LNP encapsulating mRNA encoding human fibroblast growth factor 21 alleviates obesity and fatty liver. Together, we offer a construction strategy for high-throughput and cost-efficient synthesis of DB-lipidoids. This study provides insights into branched lipidoids for efficient mRNA delivery.

Background: 'Time is brain' goes the adage. Rapid and precise management of stroke is of the utmost essence. The modified National Institutes of Health Stroke Scale (mNIHSS) and the modified Rankin Scale (mRS) predict stroke severity and functional disability outcomes. However, the mRS can be administered more rapidly than the mNIHSS and therefore might be better to assess patient outcomes. Hence, the aim of this study was to assess the correlation of stroke severity on admission and functional disability outcomes on the day of discharge or on the 8th day of hospitalization. Materials and Methods: This was an observational, cross-sectional study with a sample size of 61 participants. The mNIHSS score was calculated on admission for patients with clinical features suggestive of stroke and mRS was calculated on the 8th day of hospitalization or on discharge. Evaluation of the association between continuous variables was done using Spearman's correlation analysis. Results: Correlation between mNIHSS and mRS was positive and statistically significant (rho = 0.866, 95% CI [0.751, 0.925]. For each point increase in the mNIHSS, the odds of having higher mRS scores are 153% more than the odds of having lower mRS scores (aOR = 2.534, 95% CI [1.904, 3.560]). Conclusion: Our study concluded that mRS can be reliably used to predict the functional outcomes for patients with stroke in circumstances where the mNIHSS may prove to be lengthy. Thus, where 'time is brain', the mRS can be used with a similar power to predict the outcome.

Abstract Background Training law enforcement officers (LEOs) to administer naloxone is a recommended strategy to reduce overdose deaths in the United States. To achieve this, an evidence-based and scalable naloxone training curriculum that is easy to use and readily scalable is needed. Convenient web-based training is a flexible method for delivering educational interventions particularly for LEOs who have irregular or shifting schedules. This study examined the effectiveness of a comprehensive web-based naloxone training that was created in partnership with LEOs on their knowledge, confidence, and attitudes regarding naloxone. Methods From May 2019 to September 2020, five law enforcement departments from Michigan participated in web-based naloxone training. A total of 182 LEOs (77% male) were in the final sample based on matching pre-and post-test surveys. LEOs were assessed on knowledge, confidence, and attitudes towards naloxone. Negative binomial and Poisson regression was conducted to assess associations between knowledge, confidence, and attitudes towards naloxone before and after training. Results Significant improvements in overdose knowledge and confidence were revealed across all departments with median (IQR) total composite scores for knowledge increasing from 35 (32, 37) to 40 (39, 42) (p

Splicing is the stepwise molecular process by which introns are removed from pre-mRNA and exons are joined together to form mature mRNA sequences. The ordering and spatial distribution of these steps remain controversial, with opposing models suggesting splicing occurs either during or after transcription. We used single-molecule RNA FISH, expansion microscopy, and live-cell imaging to reveal the spatiotemporal distribution of nascent transcripts in mammalian cells. At super-resolution levels, we found that pre-mRNA formed clouds around the transcription site. These clouds indicate the existence of a transcription-site-proximal zone through which RNA move more slowly than in the nucleoplasm. Full-length pre-mRNA undergo continuous splicing as they move through this zone following transcription, suggesting a model in which splicing can occur post-transcriptionally but still within the proximity of the transcription site, thus seeming co-transcriptional by most assays. These results may unify conflicting reports of co-transcriptional versus post-transcriptional splicing.

Abstract Background Though the incidence of atrial fibrillation (AF) is increased in patients with cancer, the effectiveness of catheter ablation (CA) for AF in patients with cancer is not well studied. Methods We conducted a retrospective cohort study of patients who underwent CA for AF. Patients with a history of cancer within 5-years prior to, or those with an exposure to anthracyclines and/or thoracic radiation at any time prior to the index ablation were compared to patients without a history of cancer who underwent AF ablation. The primary outcome was freedom from AF [with or without anti-arrhythmic drugs (AADs), or need for repeat CA at 12-months post-ablation]. Secondary endpoints included freedom from AF at 12 months post-ablation with AADs and without AADs. Safety endpoints included bleeding, pulmonary vein stenosis, stroke, and cardiac tamponade. Multivariable regression analysis was performed to identify independent risk predictors of the primary outcome. Results Among 502 patients included in the study, 251 (50%) had a history of cancer. Freedom from AF at 12 months did not differ between patients with and without cancer (83.3% vs 72.5%, p 0.28). The need for repeat ablation was also similar between groups (20.7% vs 27.5%, p 0.29). Multivariable regression analysis did not identify a history of cancer or cancer-related therapy as independent predictors of recurrent AF after ablation. There was no difference in safety endpoints between groups. Conclusion CA is a safe and effective treatment for AF in patients with a history of cancer and those with exposure to potentially cardiotoxic therapy.

Distal renal tubular acidosis (dRTA), also known as Type 1 renal tubular acidosis, is a rare disorder. It primarily occurs through the inability to secrete H+ ions. The causes of dRTA can be divided into primary and secondary. The most common secondary cause of dRTA is Sjögren syndrome. dRTA typically presents as hypokalemia with non-anion gap metabolic acidosis. Here, we present a patient where Sjögren's syndrome causing dRTA was masked by the presence of hypernatremia causing metabolic acidosis with a high anion gap.

Abstract Background Medullary thyroid cancer (MTC) accounts for approximately 1.6% of new cases of thyroid cancer. The objective of this study was to describe patient characteristics, biomarker testing, treatment patterns, and clinical outcomes among patients with advanced/metastatic MTC in a real-world setting in the United States and to identify potential gaps in the care of these patients. Methods Selected oncologists retrospectively reviewed medical records of patients aged ≥ 12 years diagnosed with advanced MTC. Patients must have initiated ≥ 1 line of systemic treatment for advanced/metastatic MTC between January 2013–December 2018 to be eligible. Patient characteristics, biomarker testing, and treatment patterns were summarized descriptively; progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Results The 203 patients included in this study had a mean (SD) age of 52.2 (10.4) years; mean (SD) duration of follow-up from start of first-line treatment was 24.5 (16.0) months. Most patients (82.8%) were initially diagnosed with stage IVA, IVB, or IVC disease. Among all patients, 121 (59.6%) had testing for RET mutations, of whom 37.2% had RET-mutant MTC. The RET-mutation type was reported for 28 patients; the most common mutations reported were M918T (64.3%) and C634R (32.1%). Of the 203 patients, 75.9% received only one line of systemic treatment for advanced disease, and 36% were still undergoing first-line therapy at the time of data extraction. Cabozantinib (30.0%), vandetanib (30.0%), sorafenib (17.2%), and lenvatinib (4.9%) were the most common first-line treatments. Among 49 patients who received second-line treatment, most received cabozantinib (22.4%), vandetanib (20.4%), lenvatinib (12.2%), or sunitinib (12.2%). Median PFS (95% confidence interval [CI]) from start of first- and second-line treatments was 26.6 months (20.8–60.8) and 15.3 months (6.6-not estimable [NE]), respectively. Median OS from initiation of first- and second-line treatment was 63.8 months (46.3-NE) and 22.4 months (12.4-NE), respectively. Conclusions For the treatment of advanced/metastatic MTC, no specific preference of sequencing systemic agents was observed in the first- and second-line settings. Considering the recent approval of selective RET inhibitors for patients with RET-mutant MTC, future research should investigate how treatment patterns evolve for these patients.

Abstract The COVID-19 pandemic has revealed the power of internet disinformation in influencing global health. The deluge of information travels faster than the epidemic itself and is a threat to the health of millions across the globe. Health apps need to leverage machine learning for delivering the right information while constantly learning misinformation trends and deliver these effectively in vernacular languages in order to combat the infodemic at the grassroot levels in the general public. Our application, WashKaro, is a multi-pronged intervention that uses conversational Artificial Intelligence (AI), machine translation, and natural language processing to combat misinformation (NLP). WashKaro uses AI to provide accurate information matched against WHO recommendations and delivered in an understandable format in local languages. The primary aim of this study was to assess the use of neural models for text summarization and machine learning for delivering WHO matched COVID-19 information to mitigate the misinfodemic. The secondary aim of this study was to develop a symptom assessment tool and segmentation insights for improving the delivery of information. A total of 5026 people downloaded the app during the study window; among those, 1545 were actively engaged users. Our study shows that 3.4 times more females engaged with the App in Hindi as compared to males, the relevance of AI-filtered news content doubled within 45 days of continuous machine learning, and the prudence of integrated AI chatbot “Satya” increased thus proving the usefulness of a mHealth platform to mitigate health misinformation. We conclude that a machine learning application delivering bite-sized vernacular audios and conversational AI is a practical approach to mitigate health misinformation.

Abstract Currently, there is a huge production in the automotive industries and energy consumption resulted into spike in the cost and emissions of greenhouse gases. Hence, an efficient energy utilisation mechanism has become a prime most important factor. Energy and its conservation problem also have raised and become one of the prominent critical factors needed to address. Therefore, the development of smart grid infrastructure is one of the solutions to address the above issue.This article discusses different methods and mechanisms require to manage energy efficiently within the smart grid network using communication technologies and protocols and proposed an integration method of electric vehicles and smart grid using communication networks for charging or discharging electricity and exchanging relevant information. In addition, this paper discusses different integration strategies and multi‐agent system implementation in the smart grid network. The proposed multi‐agent system shows the efficient method for monitoring power flow and maintaining the stability of the grid. The paper also presents the optimal scheduling of charging of electric vehicles in the smart grid network. Finally, the authors investigated and presented many standard communication protocols and their comparisons with respect to different scenarios. This paper discuss different methods and concepts which would require to manage energy efficiently by using recent communication technologies, communication protocols, and sensor technologies.

Background: Surgical therapy has been a long-standing option for valvular heart disease, in patients with history of cancer, it carries an increased risk of complications. Objectives: Transcatheter edge-to-edge repair (TEER) for mitral regurgitation, represents a less invasive option. However, patients with history of cancer have generally been excluded from trials. Methods: A retrospective cohort analysis was performed on de-identified, aggregate patient data from the TriNetX research network. Patients 18 ≥ years of age, who had undergone TEER between January 1, 2013 and May 19, 2021, were identified using the CPT codes and divided into two cohorts based on a history of cancer. Subgroup analysis was performed based on history of systemic antineoplastic therapy. Odds ratio and log-rank test were used to compare the outcomes over 1 and 12-months. Results: In matched cohorts (503 patients in each, mean age 77.7 years, men 55 vs 58 %, white 84 vs 87 % in non-cancer and cancer cohorts respectively), the risk of heart failure exacerbation, all-cause mortality and all-cause hospitalizations were similar at 1 and 12 months among patients undergoing TEER. Risk of major complications (ischemic stroke, blood product transfusion and cardiac tamponade) were also similar. In the cancer cohort, hematologic/lymphoid malignancies were the most common (28.0 %) and 12.5 % patients had a history of metastatic cancer. There was no significant difference in heart failure exacerbation or all-cause mortality based on history of systemic antineoplastic therapy. Conclusions: Overall outcomes following TEER are similar in patients with a history of cancer and should be considered in selected patients in this population.

Frailty is an emerging concept in clinical practice used to predict outcomes and dictate treatment algorithms. Frail patients, especially older adults, are at higher risk for adverse outcomes. Aneurysmal subarachnoid hemorrhage (aSAH) is a neurosurgical emergency associated with high morbidity and mortality rates that have previously been shown to correlate with frailty. However, the relationship between treatment selection and post-treatment outcomes in frail aSAH patients is not established. We conducted a meta-analysis of the relevant literature in accordance with PRISMA guidelines. We searched PubMed, Embase, Web of Science, and Google Scholar using “Subarachnoid hemorrhage AND frailty” and “subarachnoid hemorrhage AND frail” as search terms. Data on cohort age, frailty measurements, clinical grading systems, and post-treatment outcomes were extracted. Of 74 studies identified, four studies were included, with a total of 64,668 patients. Percent frailty was 30.4% under a random-effects model in all aSAH patients (p < 0.001). Overall mortality rate of aSAH patients was 11.7% when using a random-effects model (p < 0.001). There was no significant difference in mortality rate between frail and non-frail aSAH patients, but this analysis only included two studies and should be interpreted cautiously. Age and clinical grading, rather than frailty, independently predicted outcomes and mortality in aSAH patients.

Introduction Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality.Methods Prospective cohort study in 109 institutions in 41 countries. Inclusion criteria: children

Abstract Background The dense social contact networks and high mobility in congested urban areas facilitate the rapid transmission of infectious diseases. Typical mechanistic epidemiological models are either based on uniform mixing with ad-hoc contact processes or need real-time or archived population mobility data to simulate the social networks. However, the rapid and global transmission of the novel coronavirus (SARS-CoV-2) has led to unprecedented lockdowns at global and regional scales, leaving the archived datasets to limited use. Findings While it is often hypothesized that population density is a significant driver in disease propagation, the disparate disease trajectories and infection rates exhibited by the different cities with comparable densities require a high-resolution description of the disease and its drivers. In this study, we explore the impact of creation of containment zones on travel patterns within the city. Further, we use a dynamical network-based infectious disease model to understand the key drivers of disease spread at sub-kilometer scales demonstrated in the city of Ahmedabad, India, which has been classified as a SARS-CoV-2 hotspot. We find that in addition to the contact network and population density, road connectivity patterns and ease of transit are strongly correlated with the rate of transmission of the disease. Given the limited access to real-time traffic data during lockdowns, we generate road connectivity networks using open-source imageries and travel patterns from open-source surveys and government reports. Within the proposed framework, we then analyze the relative merits of social distancing, enforced lockdowns, and enhanced testing and quarantining mitigating the disease spread. Scope Our results suggest that the declaration of micro-containment zones within the city with high road network density combined with enhanced testing can help in containing the outbreaks until clinical interventions become available.

Background: Globally, 425 million individuals were living with diabetes in 2017, and the numbers are expected to rise to 693 million by 2045. India, with more than 72 million people with type 2 diabetes mellitus (T2DM) in 2017, was reported to have the second largest population of individuals living with T2DM (https://www.diabetesatlas.org/upload/resources/previous/files/8/IDF_DA_8e-EN-final.pdf). The traditional Indian diet is heavily dependent on carbohydrates, and this acts as an obstacle for diabetes control. Carbohydrate restriction is associated with improvements in glycemic control and a reduction in the risk of the worsening of the disease and its complications. Objective: We investigate the real-world effectiveness of personalized carbohydrate reduction by using seed-based flour (sunflower seeds, pumpkin seeds, watermelon seeds, soya, and flaxseeds) with high-carbohydrate grain-based flour in the food along with remote health coach support for patients on the high glycated hemoglobin (HbA1c) levels and weight loss of patients. Materials and Methods: This study is a nonrandomized outpatient intervention focusing on adults with T2DM. With their consent, patients were enrolled from four clinics across Gujarat, Ahmedabad. The key inclusion criteria focused on patients with Hba1c between 7 and 10 with a body mass index more than 25 kg/m2 from 21 to 60 years of age. The key exclusion criteria were patients with advanced renal, cardiac, or liver dysfunction, pregnancy or planned pregnancy, historical ketoacidosis problems, and patients on SGLT2 inhibitors or pre-mix insulin. The intervention was personalized carbohydrate restriction. Patients were advised to avoid high-carbohydrate food categories such as grains, sugars, and high-carbohydrate fruits. They were advised to take seeds and nuts-based flour, nonstarchy vegetables, sprouts, and berries family fruits. Patients were also provided with recipes and options for all meals of the day. No restriction was made on the intake on nonstarchy vegetables. Patients were also provided with Diahappy Health’s Health coach to constantly provide remote support to resolve queries and doubts through phones. Duration of Study: For each participant, the study was carried out for 12 weeks at a stretch. Benefits: The study demonstrates an average 2.34% drop in HbA1c levels in participants who completed the program. There was also an average weight drop of 9 kg achieved in the participants.

Oocyte cryopreservation is a boon for women undergoing assisted reproductive technology. With the evolution in the technique of cryopreservation over the last three decades, there has been an exponential rise in the number of oocyte cryopreservation cycles for diverse indications. Apart from cancer patients, it has also been promoted as a mode of fertility insurance to overcome the age-related decline in fertility as well as post-surgical decline following endometriosis surgery. The objective of the review is to evaluate its clinical applications, ideal age at freezing, optimal oocyte number, freezing method of choice, efficacy, safety and recent advances. In the last decade, vitrification has surpassed slow freezing for oocyte cryopreservation. Although closed system of vitrification provides the aseptic environment, open vitrification is commonly followed in practice. Early to mid-thirties is a reasonable age group for planned oocyte cryopreservation, although it might be recommended at a younger age, in patients with diminished ovarian reserve. The patients should be motivated to preserve around 14–20 mature oocytes for successful live birth. Various studies have shown comparable fertilisation and pregnancy rates between Intracytoplasmic sperm injection with fresh and frozen-thawed oocytes. The available evidence has shown no increase in the incidence of congenital abnormalities in babies born through vitrified oocytes. In the future, image analysis using artificial intelligence, and spindle visualisation using poloscope may further enhance the outcome of oocyte cryopreservation.

Abstract Background Cancer cachexia is a life‐threatening metabolic syndrome that causes significant loss of skeletal muscle mass and significantly increases mortality in cancer patients. Currently, there is an urgent need for better understanding of the molecular pathophysiology of this disease so that effective therapies can be developed. The majority of pre‐clinical studies evaluating skeletal muscle's response to cancer have focused on one or two pre‐clinical models, and almost all have focused specifically on limb muscles. In the current study, we reveal key differences in the histology and transcriptomic signatures of a limb muscle and a respiratory muscle in orthotopic pancreatic cancer patient‐derived xenograft (PDX) mice. Methods To create four cohorts of PDX mice evaluated in this study, tumours resected from four pancreatic ductal adenocarcinoma patients were portioned and attached to the pancreas of immunodeficient NSG mice. Results Body weight, muscle mass, and fat mass were significantly decreased in each PDX line. Histological assessment of cryosections taken from the tibialis anterior (TA) and diaphragm (DIA) revealed differential effects of tumour burden on their morphology. Subsequent genome‐wide microarray analysis on TA and DIA also revealed key differences between their transcriptomes in response to cancer. Genes up‐regulated in the DIA were enriched for extracellular matrix protein‐encoding genes and genes related to the inflammatory response, while down‐regulated genes were enriched for mitochondria related protein‐encoding genes. Conversely, the TA showed up‐regulation of canonical atrophy‐associated pathways such as ubiquitin‐mediated protein degradation and apoptosis, and down‐regulation of genes encoding extracellular matrix proteins. Conclusions These data suggest that distinct biological processes may account for wasting in different skeletal muscles in response to the same tumour burden. Further investigation into these differences will be critical for the future development of effective clinical strategies to counter cancer cachexia.

The past decade has seen an increasing number of applications of deep learning (DL) techniques to biomedical fields, especially in neuroimaging-based analysis. Such DL-based methods are generally data-intensive and require a large number of training instances, which might be infeasible to acquire from a single acquisition site, especially for data, such as fMRI scans, due to the time and costs that they demand. We can attempt to address this issue by combining fMRI data from various sites, thereby creating a bigger heterogeneous dataset. Unfortunately, the inherent differences in the combined data, known as batch effects, often hamper learning a model. To mitigate this issue, techniques such as multi-source domain adaptation [Multi-source Domain Adversarial Networks (MSDA)] aim at learning an effective classification function that uses (learned) domain-invariant latent features. This article analyzes and compares the performance of various popular MSDA methods [MDAN, Domain AggRegation Networks (DARN), Multi-Domain Matching Networks (MDMN), and Moment Matching for MSDA (M3SDA)] at predicting different labels (illness, age, and sex) of images from two public rs-fMRI datasets: ABIDE 1and ADHD-200. It also evaluates the impact of various conditions such as class imbalance, the number of sites along with a comparison of the degree of adaptation of each of the methods, thereby presenting the effectiveness of MSDA models in neuroimaging-based applications.

Objectives Paediatric cancer is a leading cause of death for children. Children in low-income and middle-income countries (LMICs) were four times more likely to die than children in high-income countries (HICs). This study aimed to test the hypothesis that the COVID-19 pandemic had affected the delivery of healthcare services worldwide, and exacerbated the disparity in paediatric cancer outcomes between LMICs and HICs.Design A multicentre, international, collaborative cohort study.Setting 91 hospitals and cancer centres in 39 countries providing cancer treatment to paediatric patients between March and December 2020.Participants Patients were included if they were under the age of 18 years, and newly diagnosed with or undergoing active cancer treatment for Acute lymphoblastic leukaemia, non-Hodgkin’s lymphoma, Hodgkin lymphoma, Wilms’ tumour, sarcoma, retinoblastoma, gliomas, medulloblastomas or neuroblastomas, in keeping with the WHO Global Initiative for Childhood Cancer.Main outcome measure All-cause mortality at 30 days and 90 days.Results 1660 patients were recruited. 219 children had changes to their treatment due to the pandemic. Patients in LMICs were primarily affected (n=182/219, 83.1%). Relative to patients with paediatric cancer in HICs, patients with paediatric cancer in LMICs had 12.1 (95% CI 2.93 to 50.3) and 7.9 (95% CI 3.2 to 19.7) times the odds of death at 30 days and 90 days, respectively, after presentation during the COVID-19 pandemic (p

Background: Damaged cardiac tissues could potentially be regenerated by transplanting bioengineered cardiac patches to the heart surface. To be fully paradigm-shifting, such patches may need to be transplanted using minimally invasive robotic cardiac surgery (not only traditional open surgery). Here, we present novel robotic designs, initial prototyping and a new surgical operation for instruments to transplant patches via robotic minimally invasive heart surgery.Methods: Robotic surgical instruments and automated control systems were designed, tested with simulation software and prototyped. Surgical proof-of-concept testing was performed on a pig cadaver.Results: Three robotic instrument designs were developed. The first (called “Claw” for the claw-like patch holder at the tip) operates on a rack and pinion mechanism. The second design (“Shell-Beak”) uses adjustable folding plates and rods with a bevel gear mechanism. The third (“HeartStamp”) utilizes a stamp platform protruding through an adjustable ring. For the HeartStamp, rods run through a cylindrical structure designed to fit a uniportal Video-Assisted Thorascopic Surgery (VATS) surgical port. Designed to work with or without a sterile sheath, the patch is pushed out by the stamp platform as it protrudes. Two instrument robotic control systems were designed, simulated in silico and one of these underwent early ‘sizing and learning’ prototyping as a proof-of-concept. To reflect real surgical conditions, surgery was run “live” and reported exactly (as-it-happened). We successfully picked up, transferred and released a patch onto the heart using the HeartStamp in a pig cadaver model.Conclusion: These world-first designs, early prototypes and a novel surgical operation pave the way for robotic instruments for automated keyhole patch transplantation to the heart. Our novel approach is presented for others to build upon free from restrictions or cost—potentially a significant moment in myocardial regeneration surgery which may open a therapeutic avenue for patients unfit for traditional open surgery.

BackgroundThe adoption of nonpharmaceutical interventions and their surveillance are critical for detecting and stopping possible transmission routes of COVID-19. A study of the effects of these interventions can help shape public health decisions. The efficacy of nonpharmaceutical interventions can be affected by public behaviors in events, such as protests. We examined mask use and mask fit in the United States, from social media images, especially during the Black Lives Matter (BLM) protests, representing the first large-scale public gatherings in the pandemic. ObjectiveThis study assessed the use and fit of face masks and social distancing in the United States and events of large physical gatherings through public social media images from 6 cities and BLM protests. MethodsWe collected and analyzed 2.04 million public social media images from New York City, Dallas, Seattle, New Orleans, Boston, and Minneapolis between February 1, 2020, and May 31, 2020. We evaluated correlations between online mask usage trends and COVID-19 cases. We looked for significant changes in mask use patterns and group posting around important policy decisions. For BLM protests, we analyzed 195,452 posts from New York and Minneapolis from May 25, 2020, to July 15, 2020. We looked at differences in adopting the preventive measures in the BLM protests through the mask fit score. ResultsThe average percentage of group pictures dropped from 8.05% to 4.65% after the lockdown week. New York City, Dallas, Seattle, New Orleans, Boston, and Minneapolis observed increases of 5.0%, 7.4%, 7.4%, 6.5%, 5.6%, and 7.1%, respectively, in mask use between February 2020 and May 2020. Boston and Minneapolis observed significant increases of 3.0% and 7.4%, respectively, in mask use after the mask mandates. Differences of 6.2% and 8.3% were found in group pictures between BLM posts and non-BLM posts for New York City and Minneapolis, respectively. In contrast, the differences in the percentage of masked faces in group pictures between BLM and non-BLM posts were 29.0% and 20.1% for New York City and Minneapolis, respectively. Across protests, 35% of individuals wore a mask with a fit score greater than 80%. ConclusionsThe study found a significant drop in group posting when the stay-at-home laws were applied and a significant increase in mask use for 2 of 3 cities where masks were mandated. Although a positive trend toward mask use and social distancing was observed, a high percentage of posts showed disregard for the guidelines. BLM-related posts captured the lack of seriousness to safety measures, with a high percentage of group pictures and low mask fit scores. Thus, the methodology provides a directional indication of how government policies can be indirectly monitored through social media.

We present the survey design, implementation, and outlook for COSMOS-Web, a 255 hr treasury program conducted by the James Webb Space Telescope in its first cycle of observations. COSMOS-Web is a contiguous 0.54 deg ^2 NIRCam imaging survey in four filters (F115W, F150W, F277W, and F444W) that will reach 5 σ point-source depths ranging ∼27.5–28.2 mag. In parallel, we will obtain 0.19 deg ^2 of MIRI imaging in one filter (F770W) reaching 5 σ point-source depths of ∼25.3–26.0 mag. COSMOS-Web will build on the rich heritage of multiwavelength observations and data products available in the COSMOS field. The design of COSMOS-Web is motivated by three primary science goals: (1) to discover thousands of galaxies in the Epoch of Reionization (6 ≲ z ≲ 11) and map reionization’s spatial distribution, environments, and drivers on scales sufficiently large to mitigate cosmic variance, (2) to identify hundreds of rare quiescent galaxies at z > 4 and place constraints on the formation of the universe’s most-massive galaxies ( M _⋆ > 10 ^10 M _⊙ ), and (3) directly measure the evolution of the stellar-mass-to-halo-mass relation using weak gravitational lensing out to z ∼ 2.5 and measure its variance with galaxies’ star formation histories and morphologies. In addition, we anticipate COSMOS-Web’s legacy value to reach far beyond these scientific goals, touching many other areas of astrophysics, such as the identification of the first direct collapse black hole candidates, ultracool subdwarf stars in the Galactic halo, and possibly the identification of z > 10 pair-instability supernovae. In this paper we provide an overview of the survey’s key measurements, specifications, goals, and prospects for new discovery.

Nowadays the position of natural fibers in the world fiber is stable, growing in the area of their application, not only in textiles but also in more eco-friendly composites. This work is focused on study of the effect of SiC as filler material on the banana peduncle/Carbon fibers reinforced hybrid composites. Four different laminates are fabricated by varying the matrix composition (BP, BP+SiC, carbon+BP, Carbon+BP+SiC ). The alkaline treatment with 6% NaoH of the BP fibers improves the specific strength and binding properties. The filler added composites laminates shows higher mechanical properties. From the results, it is seen that mechanical properties like Tensile, Flexural, ILSS, Impact and hardness are improved by 89, 75, 99, 68 and 64% by the addition of the SiC to the banana peduncle/Carbon fiber composite laminate.

Introduction Childhood cancers are a leading cause of non-communicable disease deaths for children around the world. The COVID-19 pandemic may have impacted on global children’s cancer services, which can have consequences for childhood cancer outcomes. The Global Health Research Group on Children’s Non-Communicable Diseases is currently undertaking the first international cohort study to determine the variation in paediatric cancer management during the COVID-19 pandemic, and the short-term to medium-term impacts on childhood cancer outcomes.Methods and analysis This is a multicentre, international cohort study that will use routinely collected hospital data in a deidentified and anonymised form. Patients will be recruited consecutively into the study, with a 12-month follow-up period. Patients will be included if they are below the age of 18 years and undergoing anticancer treatment for the following cancers: acute lymphoblastic leukaemia, Burkitt lymphoma, Hodgkin lymphoma, Wilms tumour, sarcoma, retinoblastoma, gliomas, medulloblastomas and neuroblastomas. Patients must be newly presented or must be undergoing active anticancer treatment from 12 March 2020 to 12 December 2020. The primary objective of the study was to determine all-cause mortality rates of 30 days, 90 days and 12 months. This study will examine the factors that influenced these outcomes. χ2 analysis will be used to compare mortality between low-income and middle-income countries and high-income countries. Multilevel, multivariable logistic regression analysis will be undertaken to identify patient-level and hospital-level factors affecting outcomes with adjustment for confounding factors.Ethics and dissemination At the host centre, this study was deemed to be exempt from ethical committee approval due to the use of anonymised registry data. At other centres, participating collaborators have gained local approvals in accordance with their institutional ethical regulations. Collaborators will be encouraged to present the results locally, nationally and internationally. The results will be submitted for publication in a peer-reviewed journal.

Abstract. Desirable outcomes including rejection- and infection-free kidney transplantation are not guaranteed despite current strategies for immunosuppression and using prophylactic antimicrobial medications. Graft survival depends on factors beyond human leukocyte antigen matching such as the level of immunosuppression, infections, and management of other comorbidities. Risk stratification of transplant patients based on predisposing genetic modifiers and applying precision pharmacotherapy may help improving the transplant outcomes. Unlike certain fields such as oncology in which consistent attempts are being carried out to move away from the “error and trial approach,” transplant medicine is lagging behind in implementing personalized immunosuppressive therapy. The need for maintaining a precarious balance between underimmunosuppression and overimmunosuppression coupled with adverse effects of medications calls for a gene-based guidance for precision pharmacotherapy in transplantation. Technologic advances in molecular genetics have led to increased accessibility of genetic tests at a reduced cost and have set the stage for widespread use of gene-based therapies in clinical care. Evidence-based guidelines available for precision pharmacotherapy have been proposed, including guidelines from Clinical Pharmacogenetics Implementation Consortium, the Pharmacogenomics Knowledge Base National Institute of General Medical Sciences of the National Institutes of Health, and the US Food and Drug Administration. In this review, we discuss the implications of pharmacogenetics and potential role for genetic variants-based risk stratification in kidney transplantation. A single score that provides overall genetic risk, a polygenic risk score, can be achieved by combining of allograft rejection/loss-associated variants carried by an individual and integrated into practice after clinical validation.

Herb-induced liver injury (HILI) is often an underreported sequela for many herbal remedies due to the lack of safety measurements involving these supplements. Cimicifuga racemosa and Thuja occidentalis are two herbal medications commonly used by women for fertility purposes. Many herbal preparations of these two supplements do not specify the risks behind their individual usage. We present a case of a 40-year-old woman who developed acute liver injury after concomitant use of these two products assessed for causality using the updated RUCAM. Upon a detailed investigation, the patient did not have evidence of underlying liver disease or any other risk factors to explain her presentation. After discontinuation of both herbal supplements, the patient had complete resolution of her symptoms and a significant improvement of transaminitis. This report highlights the importance of potential risk of hepatotoxicity induced by concomitant use of Cimicifuga racemosa and Thuja occidentalis.

Abstract Introduction A learning health system (LHS) must improve care in ways that are meaningful to patients, integrating patient‐centered outcomes (PCOs) into core infrastructure. PCOs are common following cancer treatment, such as urinary incontinence (UI) following prostatectomy. However, PCOs are not systematically recorded because they can only be described by the patient, are subjective and captured as unstructured text in the electronic health record (EHR). Therefore, PCOs pose significant challenges for phenotyping patients. Here, we present a natural language processing (NLP) approach for phenotyping patients with UI to classify their disease into severity subtypes, which can increase opportunities to provide precision‐based therapy and promote a value‐based delivery system. Methods Patients undergoing prostate cancer treatment from 2008 to 2018 were identified at an academic medical center. Using a hybrid NLP pipeline that combines rule‐based and deep learning methodologies, we classified positive UI cases as mild, moderate, and severe by mining clinical notes. Results The rule‐based model accurately classified UI into disease severity categories (accuracy: 0.86), which outperformed the deep learning model (accuracy: 0.73). In the deep learning model, the recall rates for mild and moderate group were higher than the precision rate (0.78 and 0.79, respectively). A hybrid model that combined both methods did not improve the accuracy of the rule‐based model but did outperform the deep learning model (accuracy: 0.75). Conclusion Phenotyping patients based on indication and severity of PCOs is essential to advance a patient centered LHS. EHRs contain valuable information on PCOs and by using NLP methods, it is feasible to accurately and efficiently phenotype PCO severity. Phenotyping must extend beyond the identification of disease to provide classification of disease severity that can be used to guide treatment and inform shared decision‐making. Our methods demonstrate a path to a patient centered LHS that could advance precision medicine.

Introduction: Kites were first introduced by the Chinese more than three thousand years ago, but in places like India, Pakistan and Afghanistan, Kite flying is celebrated in unique way. People enjoy cutting down others kites and there is an instinct to catch the threads of the “Cut-Kite” and rejoice the gain. In this study conducted at a tertiary care emergency medicine department to understand demographic profile and injuries related in such a festive celebration, occurring in one urban area, to spread awareness and reduce such incidence. Methodology: This cross-sectional descriptive study was conducted using preformatted form in consecutive two year. Results: Among 83 cases we studied, 81% were male. 65% were in the age group of 11-40. 70% incidences took place in noon and evening hours. 68.67 % presented in 108 ambulance services, 43% presented with fall from height (terraces), 34 % had road traffic accidents because of strings and festival related excitement. Maximum had fall from 1 storey buildings. 56% received Out Patient based treatment. Among the admitted patients 15% had head injury, 2 cut throat, 9.7% had fractures and 1 had to undergo laparotomy, 2 died eventually during the hospital stay because of grievous injuries. Conclusion: This study re-emphasizes the importance of spreading awareness and increasing the care, particularly of children during such an enjoyable festival.

Regulation of plant root angle is critical for obtaining nutrients and water and is an important trait for plant breeding. A plant’s final, long-term root angle is the net result of a complex series of decisions made by a root tip in response to changes in nutrient availability, impediments, the gravity vector and other stimuli. When a root tip is displaced from the gravity vector, the short-term process of gravitropism results in rapid reorientation of the root toward the vertical. Here, we explore both short- and long-term regulation of root growth angle, using natural variation in tomato to identify shared and separate genetic features of the two responses. Mapping of expression quantitative trait loci mapping and leveraging natural variation between and within species including Arabidopsis suggest a role for PURPLE ACID PHOSPHATASE 27 and CELL DIVISION CYCLE 73 in determining root angle.

Two-component systems are a major family of signal transduction pathways and a rich source of sensors for biotechnology. Here, the authors develop a general method for rationally tuning two-component system input detection thresholds via specific point mutations in sensor histidine kinase proteins.

This study demonstrates the utility of an updated mass balance model for predicting the distribution of organic chemicals in in vitro test systems (IV-MBM EQP v2.0) and evaluates its performance with empirical data. The IV-MBM EQP v2.0 tool was parameterized and applied to four independent data sets with measured ratios of bulk medium or freely-dissolved to initial nominal concentrations (e.g., C24/C0 where C24 is the measured concentration after 24 h of exposure and C0 is the initial nominal concentration). Model performance varied depending on the data set, chemical properties (e.g., “volatiles” vs. “non-volatiles”, neutral vs. ionizable organics), and model assumptions but overall is deemed acceptable. For example, the r2 was greater than 0.8 and the mean absolute error (MAE) in the predictions was less than a factor of two for most neutral organics included. Model performance was not as good for the ionizable organic chemicals included but the r2 was still greater than 0.7 and the MAE less than a factor of three. The IV-MBM EQP v2.0 model was subsequently applied to several hundred chemicals on Canada’s Domestic Substances List (DSL) with nominal effects data (AC50s) reported for two in vitro assays. We report the frequency of chemicals with AC50s corresponding to predicted cell membrane concentrations in the baseline toxicity range (i.e., >20–60 mM) and tabulate the number of chemicals with “volatility issues” (majority of chemical in headspace) and “solubility issues” (freely-dissolved concentration greater than water solubility after distribution). In addition, the predicted “equivalent EQP blood concentrations” (i.e., blood concentration at equilibrium with predicted cellular concentration) were compared to the AC50s as a function of hydrophobicity (log octanol-water partition or distribution ratio). The predicted equivalent EQP blood concentrations exceed the AC50 by up to a factor of 100 depending on hydrophobicity and assay conditions. The implications of using AC50s as direct surrogates for human blood concentrations when estimating the oral equivalent doses using a toxicokinetic model (i.e., reverse dosimetry) are then briefly discussed.

In this research, a piezoelectric film was utilized to develop a low-cost biomedical device for diagnosis and management of breathing disorders. First, it was shown that when a commercial polyvinylidene fluoride (PVDF) film was subjected to airflow generated from human breath, the voltage generated increased with decreasing film thickness. Then, a device was fabricated that records a patient's breathing pattern and sends this data to a remote email address via the Raspberry Pi, an inexpensive computer. It was shown that the breathing patterns could be recorded in a reproducible manner with this device. Next, the efficacy of the device to detect breathing disorders was tested. A restrictive ventilatory abnormality was simulated by tying a crepe bandage around the chest. It was shown that this device could successfully distinguish between breathing in a normal patient and the breathing of a patient with a restrictive ventilatory abnormality. It is possible to fabricate this device for less than $100, thereby making it accessible to a large number of patients with chronic lung diseases.

Receptor tyrosine kinases, such as the epidermal growth factor (EGF) receptor (EGFR) and Met lead to activation of intracellular signals including Akt, a critical regulator of cell survival, metabolism and proliferation. Upon binding their respective ligands, each of these receptors is recruited into clathrin coated pits (CCPs) eventually leading to endocytosis. We have recently shown that phosphorylation of Gab1 and Akt following EGFR activation requires clathrin, but does not require receptor endocytosis. We examined whether clathrin regulates Akt signaling downstream of Met, as it does for EGFR signaling. Stimulation with the Met ligand Hepatocyte Growth Factor (HGF) leads to enrichment of phosphorylated Gab1 (pGab1) within CCPs in ARPE-19 cells. Perturbation of clathrin using the inhibitor pitstop2 decreases HGF-stimulated Akt phosphorylation. These results indicate that clathrin may regulate Met signaling leading to Akt phosphorylation similarly as it does for EGFR signaling.

Introduction. Stroke remains a global leading cause of death and disability. Traditional description of plasma biology in the aftermath of acute ischaemic stroke favours development of hypercoagulability, resulting from complex interplay between plasma and endothelial factors. However, no single assay measures the overall global coagulation process. We postulate that thrombin generation would assist in identifying coagulation abnormalities after acute stroke. Aim. To investigate the coagulation abnormalities after acute ischaemic stroke using thrombin generation. Methods. We evaluated thrombin generation, measured with calibrated automated thrombography in stroke of different aetiological types (n=170) within 48 hours of symptoms onset (baseline) and in the second week (time 2) and in normal healthy volunteers (n=71). Results. Two-point thrombin generation assays showed prolonged lag time and time to peak at baseline (3.3 (2.9, 4.0) versus 3.6 (3.2, 4.7); p=0.005) and (3.3 (2.9, 4.0) versus 3.6 (3.2, 4.7); p=0.002), respectively, and at time 2 (3.5 (2.9, 4.2) versus 4.0 (3.1, 4.9); p=0.004) and (5.9 (5.3, 6.6) versus 6.8 (5.8, 7.7) p=0.05), respectively, in cardioembolic stroke (n=39), when compared to noncardioembolic stroke (n=117). The result was reproduced in multiple comparisons between acute ischaemic stroke subgroups and normal healthy volunteers. Endogenous thrombin potential and peak thrombin did not indicate hypercoagulability after acute ischaemic stroke, and thrombolytic therapy did not affect thrombin generation assays. Conclusion. Our findings suggest that thrombin generation in platelet poor plasma is not useful in defining hypercoagulability in acute ischaemic stroke. This is similar to observed trend in coronary artery disease and contrary to other hypercoagulable states.

Background: Medical education across the globe is perceived as being inherently stressful. Studies on psychological problems such as stress, depression and anxiety among medical students have found that these disorders are under diagnosed and under treated. In this background the present study was undertaken with the objectives to assess the magnitude of depression and its association with stress among medical students. Methods: A Cross sectional study was undertaken among 235 medical students in a private medical college, Pondicherry. Tools similar to General Health Questionaire (GHQ-12) and Beck depression Inventory (BDI) was used to screen psychological stress and depression respectively. Results: The prevalence of depression was 71% among medical students. Psychological stress was associated with depression. Conclusion: Emphasize should be laid on the importance of screening for depression of medical students on a regular basis for early detection and rendering appropriate intervention like group counseling, stress management training etc. to protect the future professionals.

Myeloid sarcoma is a rare extramedullary tumour consisting of immature myeloid cells. It can arise at any anatomical location and often develops in the bowel. This report describes a case of severe acute disseminated intravascular coagulation (DIC) with multi-organ failure occurring in a 57-year-old man with chronic myelomonocytic leukaemia during bowel resection for newly diagnosed adenocarcinoma of the sigmoid colon. Histopa thology however revealed a differentiating myeloid sarcoma encompassing a well-differentiated adenocarcinoma. This is the first documented case of acute DIC to be triggered following surgical manipulation of myeloid sarcoma.

Weak intermolecular interactions such as hydrogen bonding and hydrophobic interactions are key players in stabilizing energetically-favored ligands, in an open conformational environment of protein structures. However, it is still poorly understood how the binding parameters associated with these interactions facilitate a drug-lead to recognize a specific target and improve drugs efficacy. To understand this, comprehensive analysis of hydrophobic interactions, hydrogen bonding and binding affinity have been analyzed at the interface of c-Src and c-Abl kinases and 4-amino substituted 1H-pyrazolo [3, 4-d] pyrimidine compounds.In-silico docking studies were performed, using Discovery Studio software modules LigandFit, CDOCKER and ZDOCK, to investigate the role of ligand binding affinity at the hydrophobic pocket of c-Src and c-Abl kinase. Hydrophobic and hydrogen bonding interactions of docked molecules were compared using LigPlot program. Furthermore, 3D-QSAR and MFA calculations were scrutinized to quantify the role of weak interactions in binding affinity and drug efficacy.The in-silico method has enabled us to reveal that a multi-targeted small molecule binds with low affinity to its respective targets. But its binding affinity can be altered by integrating the conformationally favored functional groups at the active site of the ligand-target interface. Docking studies of 4-amino-substituted molecules at the bioactive cascade of the c-Src and c-Abl have concluded that 3D structural folding at the protein-ligand groove is also a hallmark for molecular recognition of multi-targeted compounds and for predicting their biological activity. The results presented here demonstrate that hydrogen bonding and optimized hydrophobic interactions both stabilize the ligands at the target site, and help alter binding affinity and drug efficacy.

ABSTRACT Objectives To primarily evaluate the functional outcomes of PCNL for bilateral renal calculi/calculi in solitary functioning kidney with Chronic Kidney Disease(CKD). To identify factors affecting the renal replacement therapy following PCNL. Materials and Methods Patients with bilateral renal calculi/calculi in solitary kidney and CKD (eGFR2) and Good Performance Status [Eastern Cooperative Oncology Group (ECOG): 0–2] were included in the study. Results A total of 60 patients with CKD who had bilateral renal calculi/calculi in solitary functioning kidney underwent PCNL. At 6 months, eGFR improved or stabilized in 45 (75%) patients, while in 15 (25%) patients eGFR deteriorated. A total of 5 (14.28%) and 2 (25%) patients of CKD stage 4 and 5 respectively had improvement in eGFR as well as CKD stage. Fourteen (82.35%), 21 (60%), 3 (37.5%) patients of CKD stage 3, 4, 5 had improvement in eGFR but not significant enough to cause stage migration. Again 3 (17.65%) , 9 ( 40%) and 3 (37.5%) patients of CKD stage 3, 4, 5 had reduction in eGFR but not significant enough to cause stage migration. None of the patients had worsening of CKD stage. Preoperative CKD stage and eGFR were compared with measurements made at the final follow up visit (6 months). Conclusion Our results indicate that most patients of renal calculi with CKD show improvement or stabilization of renal function with aggressive stone removal. Improvement is more in patients who have mild to moderate CKD. Aggressive management of comorbidities, peri-operative UTI and complications may delay or avoid progression of CKD status in such patients.

Hypoxia increases inspiratory muscle work and consequently contributes to a reduction in exercise performance. We evaluate the effects of inspiratory muscle warm-up (IMW) on a 10 km cycling time trial in normoxia (NOR) and hypoxia (HYP). Eight cyclists performed four time trial sessions, two in HYP (FiO 2 : 0.145) and two in NOR (FiO 2 : 0.209), of which one was with IMW (set at 40% of maximal inspiratory pressure-MIP) and the other was with the placebo effect (PLA: set at 15% MIP). Time trials were unchanged by IMW (NOR IMW : 893.8 ± 31.5 vs. NOR PLA : 925.5 ± 51.0 s; HYP IMW : 976.8 ± 34.2 vs. HYP PLA : 1008.3 ± 56.0 s; p > 0.05), while ventilation was higher in HYP IMW (107.7 ± 18.3) than HYP PLA (100.1 ± 18.9 L.min -1 ; p ≤ 0.05), and SpO 2 was lower (HYP IMW : 73 ± 6 vs. HYP PLA : 76 ± 6%; p ≤ 0.05). A post-exercise-induced reduction in inspiratory strength was correlated with exercise elapsed time during IMW sessions (HYP IMW : r = -0.79; p ≤ 0.05; NOR IMW : r = -0.70; p ≤ 0.05). IMW did not improve the 10 km time trial performance under normoxia and hypoxia.