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Atopic Dermatitis [AD] is a chronic relapsing inflammatory dermatological disease characterized by itch, dry skin, localized or disseminated eczematous lesions and hyperpigmentation of skin. There are several exogeneous and endogenous risk factors for development of AD. The endogenous factors include genetic factors, atopy, skin hyperreactivity and exogeneous factors such as food, dust, pollen, epidermal, fungal, bacterial, and vaccine-associated factors. The management of AD includes topical treatments such as topical corticosteroids, topical capsaicin, topical calcineurin inhibitors and phosphodiesterase inhibitors. Systemic therapies such as corticosteroids, immunosuppressants, biologicals, gabapentinoids and antidepressants are provided to patients with inadequate systemic therapies have wide range of side effects limiting their use in many patients. Therefore, there is a need for innovative treatment options. This led to development of Janus kinase inhibitors. First generation JAK inhibitors includes Tofacitinib, Baricitinib, Ruxolitinib, Oclacitinib. Second generation drugs such as Upadacitinib and Abrocitinib are more specific towards the JAK isoforms. This review addresses the importance of Abrocitinb for the treatment of Atopic Dermatitis. Abrocitinib an oral once daily treatment for moderate to severe atopic dermatitis developed by Pfizer. Studies shows that Abrocitinib is better alternative in non- responders to Dupilumab therapy or patients with contraindications to the Dupilumab. The patient’s adherence to medication will also be better with oral route rather than injections. Abrocitinib will be widely accepted because of its clinical benefits such as reduction in itching and more convenient oral route of administration.

The TECH-STAT-VIEW is a cutting-edge online intranet program with significant implications for universities and academic institutions. This system allows departments or the whole university to track and monitor student attendance in real time. It also provides a platform for viewing and searching college-related information, as well as receiving updates on grades, leaves and staff attendance. Staff employees have the ability to easily upload and download information to the database. Users must first register and be allowed access based on their identification as a student to the specific staff member in order to fully utilize the system's capabilities to view or modify information. The intranet-based TSV platform's ultimate goal is to provide easy access to information at all levels of organizational management, acting as a complete knowledge and information management system. Using the Django framework, developers may create a strong and scalable web application with a user-friendly interface that is simple to maintain. The Python programming language, with its many libraries and tools, provides the resources required to create sophisticated and feature-rich programs. The Python programming language and the Django framework work well together to create a college administration system that satisfies the demands of current educational institutions.

Carboxymethyl cellulose (CMC) extraction from Musa paradisiaca (MP) pseudo stem by alkaline treatment and their properties were examined in the current research work. One of the most well-known types of lignin biomass waste that is readily available globally is MP. In many nations, including Taiwan, Sri Lanka, the Philippines, India, and the Philippines, these plants have been used for traditional reasons. Whole plant parts have been used as food, including the pseudo-stem, flower buds, trunk, fruits, and leaves. Sequestration of cellulose was attained by alkaline treatment and bleaching from raw fibers. Cellulose fiber is a biodegradable, naturally occurring, and renewable polymer that is used in a variety of industries, including the food, paper, cosmetic, and pharmaceutical sectors. The cellulose obtained from forest and agricultural residue has numerous advantages such as being environmentally safe, recyclable, and economically feasible respectively. The main process of cellulose extraction from MP pseudo stem are digesting process using a digester, bleaching, and neutralization which shows a zero-waste process. The alkali treatment takes less time to get a final product whereas enzyme treatment, and steam explosion treatment takes high energy and more cost. Hence, cellulose extract from alkaline treatment is economically feasible and environmentally friendly.

Benzoxazole is one of the most prominent heterocyclic structures and is found in an extensive range of biologically active compounds. It is one of the often occurring heterocyclic nitrogen-containing moieties that perform as the primary active elements of pharmaceutical compounds. It can be viewed as isosteres of the naturally occurring guanine and adenine nucleic bases since they interact effectively with the polymeric components of biological systems. A wide range of biological features, including analgesic, antibacterial, anti-inflammatory, anti-hyperglycemic, anticancer, antiviral, antifungal, antileishmanial, and antitubercular activities, they are significantly influenced by heterocyclic compounds with a benzoxazole nucleus. Keywords: Benzoxazole, anticancer, antihyperglycemic, antibacterial, Caboxamycin, Pseudopteroxazole

The term school discipline includes student self-management, classroom management, behaviour management, and school exclusion practices. This article is based on the perspectives of rangatahi on disciplinary practices from two different high schools. Ten Years 9–11 students from one school who had experienced exclusion, and 10 fully engaged Year 13 students in another school reflected on their strategic navigation of the culture of classroom and school discipline. Students were aware of how to exercise agency within their school’s disciplinary regime and called for more democratic and equitable processes and dialogical relationships with their teachers.

Tetrahydro-β-carboline, a derivative of β-carboline alkaloid, is found in a variety of plants, animals, insects, mammals, and human tissues and body fluids. It is found abundantly in nature and includes both natural and synthetic forms. Tetrahydro-β-carboline and their derivatives have been proven to exhibit important biological features, which makes it easier to build novel synthetic techniques for the alteration of Tetrahydro-β-carboline core to create high potential medications. Tetrahydro-β-carboline was proven to exhibit various pharmacological activities such as antiviral, antileishmanial, anticancer, antifungal, HDAC inhibitor, antithrombotic, antimalarial, analgesic, and anti-AD inhibitor action. The characterization, chemistry, structure activity relationship, and Antimicrobial activities of tetrahydro-β-carboline derivatives are highlighted in this review along with recent research and developments in these areas. Keywords: Tetrahydro-β-carboline, Tetrahydro-pyrido[3,4-b]-indole, Heterocycle, Alkaloid, Structure, Activity, Derivative, Antimicrobial activity, Occurrence.

Organometallic compound ferrocene formation was a serendipity and due to its "barrel-shape" which grants 3D geometry of the organometallic compound it has an optimal spatial design for better fitting and connection inside the pockets of the dynamic site in natural targets and receptors. The benzimidazole motif has developed to be a significant privileged heterocyclic platform. Ferrocenyl benzimidazole is a complex organic compound having ferrocene an organometallic compound attached to the 2-position of benzimidazole an aromatic heterocyclic compound. Ferrocene benzimidazole derivatives have attracted lots of attention for the construction of new compounds due to their wide applications. By combining ferrocene and benzimidazole produce a vast range of pharmacological actions. Synthetic method and pharmacological effects of various ferrocenyl benzimidazole derivatives were examined. This review gives the medicinal activities of 2- ferrocenyl benzimidazole derivatives like cytotoxic activity, anti-malarial, anti-microbial, anti-fungal etc. were furnished. Keywords: ferrocene, benzimidazole, cyclopentadiene, 2-ferrocenyl benzimidazole, cytotoxic, anti-malarial.

Heterocyclic compounds represent an important class of organic compounds having vivid biological and pharmacological properties. These heterocyclic moieties, either individually or in fused form, are continuously used by researchers for the creation of new drugs due to their extensive biological profile. Isatin (1 H - indole-2,3-dione), also known as (2,3- dioxoindoline, indole quinine and indenedione), exhibits a broad range of biological activity and is therefore regarded as a bio-active heterocyclic moiety. Isatin derivatives are synthesized by using two common methods such as Sandmeyer’s and Stolle process. The isatin moiety also shows important chemical reactions such as oxidation, ring expansion, Friedel–Crafts reaction and aldol condensation. The advances in the use of isatins for organic synthesis during the last twenty-five years, as well as a survey of its biological and pharmacological properties are reported in this review. Keywords: 2,3-dioxoindoline, Spectral characterization, Novel 2,3dioxoindoline, Tautomerization, SARS-CoV-2

Coumarins are heterocyclic compound with a benzopyrone structure. Coumarins are a large group of organic compounds found in several plants even in bacteria and fungi. The biological activities of coumarins and its derivatives includes anticoagulant, anticancer, antiulcer, antifungal, anti-HIV, antimicrobial, antiosteoporosis, antioxidant and anti- inflammatory activity. Hydrazide-hydrazone derivatives act as structural sub units in many pharmacologically active compounds including coumarins to give biological activities like antimicrobial, anticancer, antifungal, anti-inflammatory, antiviral, anti-tubercular, and antiprotozoal activity. The interest in the synthesis of coumarin derivatives has been gaining importance over the last decades, reflecting the importance of such compounds in both medical and chemical research. In this review hydrazide-hydrazone derivatives of coumarins are taken into consideration and emphasised on the anticancer, antitubercular, antimicrobial, antioxidant and antidiabetic activity of these derivatives. Keywords: Coumarin, hydrazide, heterocyclic, benzopyran, antitumor, antimicrobial, antioxidant

Vaccines are a critical new tool in the battle against COVID-19. Development of safe and effective vaccines are necessary to combat the pandemic. The aim of the study is to provide public awareness to improve vaccination rate and prevent vaccination hesitancy by studying the knowledge, attitude and perception about COVID-19 vaccines, the occurrence of side effects after the administration of COVID-19 vaccine and its management. The participants who fulfilled the inclusion criteria were provided the previously structured and approved data collection form. The knowledge, attitude and perception towards COVID-19 vaccination was then determined by allocating a score for each response. The collected data was statistically interpreted using SPSS software and R software. The incidence of side effects following administration of 2 doses of COVID-19 vaccine and its management was analyzed. The knowledge regarding COVID-19 vaccinations was low among more than half of the total study population. Female gender showed a higher knowledge score compared to males. Nearly half of the study population (42.5%) was found to have a high attitude score. Age as a variable was found to be of significant association with attitude. It was concluded from our study that the majority of the participants were aware about the COVID-19 vaccines available in India. This study also points out that a majority of the participants experienced fear and hesitancy prior to getting vaccinated. Only a minority of the respondents were of the belief that vaccination would prevent the spread of COVID -19 infection.

For this 2022 first edition, Vijaya Dharan reimagines an education system for autistic learners.

The aim of this Project is to develop a system for the “LOAN APPROVAL PREDICTION version” At instances when any financial organization lends the cash to the man or woman, it is usually been a excessive hazard. Today information is increasing with the fast pace in the banks, therefore the bankers want to evaluate the individual’s records before giving the mortgage. It can be a huge headache to evaluate the facts. This trouble is solved through studying and education the facts through the use of one of the device mastering algorithms. For this, we have generated a model for the prediction that the man or woman will get the loan or not. The primary objective of this paper is to check whether the individual can get the loan or not by evaluating the facts with the help of selection tree classifiers that can offers the accurate end result for the prediction.

Aim: To assess the repertoire of antibody after complete vaccination of covishield concerning SARS-CoV-2. Study Design: Observational Study. Place And Duration of Study: The study was conducted in community area in Kerala for a duration of six months from January 2022 to June 2022. Methodology: The study was conducted in community area using 30 samples. The participants who fulfill inclusion criteria were selected and samples were collected by convenience sampling from the community and analyzed by the DDRC (Doctor’s Diagnostic and Research Centre) by using Electrochemiluminescence immunoassay. The collected data was statistically interpreted using SPSS software version 26.0 and the development of antibody after complete dose of vaccination was analyzed. Results: In this study blood samples were collected from 30 subjects fulfilling the inclusion criteria. Out of 30 subjects, 12 were females and 18 were males. The mean interval between the doses were 91.63. All the 30 samples produced antibodies greater than 250 U/ml. The study helps to provide qualitative evidence that the vaccine produces antibody response. Conclusion: Covid-19 vaccines are being available into public for human use after limited testing and trials. Many efforts are being directed towards development of vaccines against SARS-CoV-2. The information made available from this study can be utilized to prove that covishield vaccine is effective for producing antibodies. Most of the people took vaccines since it was mandatory rather than concerning its benefits. By providing evidence of antibody development after complete vaccination can improve the public attitude towards the vaccination.

Tubulin nucleation is a highly frequent event in microtubule (MT) dynamics but is poorly understood. In this work, we characterized the structural changes during the initial nucleation phase of dynamic tubulin. Using size-exclusion chromatography-eluted tubulin dimers in an assembly buffer solution free of glycerol and tubulin aggregates enabled us to start from a well-defined initial thermodynamic ensemble of isolated dynamic tubulin dimers and short oligomers. Following a temperature increase, time-resolved X-ray scattering and cryo-transmission electron microscopy during the initial nucleation phase revealed an isodesmic assembly mechanism of one-dimensional (1D) tubulin oligomers (where dimers were added and/or removed one at a time), leading to sufficiently stable two-dimensional (2D) dynamic nanostructures, required for MT assembly. A substantial amount of tubulin octamers accumulated before two-dimensional lattices appeared. Under subcritical assembly conditions, we observed a slower isodesmic assembly mechanism, but the concentration of 1D oligomers was insufficient to form the multistranded 2D nucleus required for MT formation.

A double-outlet left ventricle (DOLV) is a congenital cardiac anomaly that rarely is encountered. This case report demonstrates the echocardiographic features of DOLV in the form of the pulmonary artery arising completely from the left ventricle with D-looped ventricles, especially when evaluated by intraoperative transesophageal echocardiography (TEE), along with the correlation of characteristic features with cardiac computerized tomography. The features pertinent to the differentiation of DOLV from double-outlet right ventricle and congenitally corrected transposition of the great arteries by echocardiography have been described. To the authors' knowledge, this was the first report of intraoperative TEE in the case of DOLV. In addition, the use of intraoperative echocardiography to rule out coronary compression as a cause for post-repair ventricular tachycardia, by use of TEE to rule out ventricular dysfunction and regional wall motion abnormalities, as well as epicardial echocardiography to demonstrate normal coronary blood flow, has been reported.

Introduction: Antibiotics are anti-microbial agents used for the treatment of various bacterial infections. Excessive use, inappropriate prescription pattern conduct to antibiotic resistance (AR). Antibiotic resistance leads to an increase in the cost of medical care. Our study assess the economic burden due to antibiotic resistance based on antimicrobial susceptibility testing in different infections. Methods: The data for the study was collected prospectively and recorded in a data collection form specially designed for the study based on inclusion and exclusion criteria obtained from the Department of General Medicine, NIMS Hospital, Neyyattinkara, Thiruvananthapuram of patients with infectious diseases during the period of 6 months from April 2021 to September 2021. Results: 128 patients were studied, 53.1% (n=68) were males and 46.9% (n=60) were females and the most frequent age range was between 46-60 years of age (35%, n=45).The most common infection seen in patients was urinary tract infection (20.3%, n=26). The socioeconomic status, (50%, n=64) belonged to lower- middle class. Antibiotic sensitivity test was done in (52.3%, n=67) and the patients with resistance (Rs.26530.81) had more mean cost than those without resistance (Rs.18412.01) showing highly significant difference (p=0.001). The resistant patients without antibiotic sensitivity testing had (Rs.30193.14). Conclusion: Our study demonstrated that the resistant patients without antibiotic sensitivity testing had a significantly higher financial burden. Therefore, we strongly recommend to perform antibiotic sensitivity testing (AST) in patients with infectious diseases. Also, patient should be well-informed about the details and the results of antibiotic sensitivity testing to ensure medication adherence and to avoid self- medication.

The transportation sector is moving towards environmentally sustainable energy sources that are dependable, regulatory, and sustainable as the world battles with the negative impacts of conventional vehicles in conjunction with the shortage of fossil resources. Electric cars (EVs) are the Solution to the problem, However, the battery of an electric vehicle is crucial to its operation and the motor with all its operations use a sizable portion of an EV's battery which results in limited battery life. Therefore, preserving battery life in electric vehicles is a challenge that needs to be overcome by regulating the consumption of battery energy efficiently. The proposed work is focused on creating a Battery Management System(BMS) that limits the charging process using an eco-charging software function. The battery's state of charge (SoC) is monitored through a microcontroller, working in tandem with a software function to cease charging at 80%. The battery management system promises to increase battery life while also enhancing the convenience of charging and lowering the cost of EV ownership in the long run, {"references":["Abas, N., Kalair, A., & Khan, N. (2015). Review of fossil fuels and future energy technologies. Futures, 69, 31-49.","Ali, M. B., & Boukettaya, G. (2022, May). A Review of Factors Influencing the Adoption of Electric Vehicles in the World. In 2022 19th International Multi-Conference on Systems, Signals & Devices (SSD) (pp. 2139-2144). IEEE.","Sholichah, A. I., Hisjam, M., & Sutopo, W. (2020, October). The Selection of Lithium Battery raw Materials by Environmental, Economic, and Social Sustainable. In IOP Conference Series: Materials Science and Engineering (Vol. 943, No. 1, p. 012047). IOP Publishing.","Kaunda, R. B. (2020). Potential environmental impacts of lithium mining. Journal of energy & natural resources law, 38(3), 237-244.","Kostopoulos, E. D., Spyropoulos, G. C., & Kaldellis, J. K. (2020). Real-world study for the optimal charging of electric vehicles. Energy Rep 6: 418–426.","Ahmed, S. T., Kumar, V. V., Singh, K. K., Singh, A., Muthukumaran, V., & Gupta, D. (2022). 6G enabled federated learning for secure IoMT resource recommendation and propagation analysis. Computers and Electrical Engineering, 102, 108210.","Ma, S., Jiang, M., Tao, P., Song, C., Wu, J., Wang, J., ... & Shang, W. (2018). Temperature effect and thermal impact in lithium-ion batteries: A review. Progress in Natural Science: Materials International, 28(6), 653-666.","Liu, Y. C. (2010). Battery management systems for improving battery efficiency in electric vehicles. World Electric vehicle journal, 4(2), 351-357.","Ahmed, S. T., Sreedhar Kumar, S., Anusha, B., Bhumika, P., Gunashree, M., & Ishwarya, B. (2020). A generalized study on data mining and clustering algorithms. New Trends in Computational Vision and Bio-inspired Computing: Selected works presented at the ICCVBIC 2018, Coimbatore, India, 1121-1129.","Collin, R., Miao, Y., Yokochi, A., Enjeti, P., & Von Jouanne, A. (2019). Advanced electric vehicle fast-charging technologies. Energies, 12(10), 1839.","Ahmed, S. T., & Basha, S. M. (2022). Analog Electronic Circuits: Principles and Fundamentals. MileStone Research Publications.","Collin, R., Miao, Y., Yokochi, A., Enjeti, P., & Von Jouanne, A. (2019). Advanced electric vehicle fast-charging technologies. Energies, 12(10), 1839."]}

The major area in which the automotive manufacturers are working is to produce high-performance vehicles with lighter weight, higher fuel economy and lower emissions. In this regard, hollow camshafts are widely used in modern diesel and gasoline engines due to their inherent advantages of less rotational inertia, less friction, less weight and better design flexibility. However, the dynamic loads of chain system, valve train and fuel injection pump (if applicable) makes it challenging to design over-head hollow camshafts with the required factor of safety (FOS).In the present work, high-fidelity FE model of a hollow camshaft assembly is simulated to evaluate the structural performance for assembly loads, valve train operating loads, fuel injection pump loads and chain system loads. The investigation is carried out in a high power-density (70 kW/lit) 4-cylinder in-line diesel engine. The camshaft is used for operating the intake valves which induce varying stresses in-line with the engine firing order. Moreover, the camshaft is also used to drive the high-pressure fuel injection pump (FIP) at the rear-end which can add significant torsional stresses. Furthermore, the stresses induced by the hub-loads of timing chain is found to be having a significant effect on the bending behavior of the front-end of the camshaft. In addition to these operating stresses, the camshaft is subjected to different kinds of mean stresses induced by the bolt (used to fasten the drive-sprocket) and interference fit of the camshaft child parts (cam and front plug). Hence, the authors propose a robust and reliable evaluation methodology to evaluate the structural performance and factor of safety (FOS). The dynamic bending behavior of the camshaft under press-fit loads of cam lobes and front plug is discussed. The present work also covers the load-path and multi axial stress state induced on the hollow camshaft under varying load conditions apart from estimating the fatigue life. Moreover, the investigation includes the assessment of different parameters influencing the stress multi-axiality on the camshaft to arrive at potential improvements in the camshaft design. Overall, the results arrived using this methodology is found to be having a good correlation with the parts used for durability testing. Thus, the proposed methodology can be used for evaluating hollow camshafts of modern engines subjected to complex and highly dynamic loads.

The fuel economy of the internal combustion engine becomes progressively critical, especially with the stringent standards set by the government. To meet the government norms such as CAFE (Corporate Fuel Average Economy), different technologies are being explored and implemented in internal combustion engines. Several technologies such as variable oil pump, map controlled PCJ (Piston Cooling Jet), variable or switchable water pump & ball bearing turbocharger etc. This study investigates the effectiveness of implementing map-controlled PCJ implemented for a 1.5-litre 3-cylinder diesel engine.PCJ’s are major consumers of oil flow and map-controlled PCJ is used by many OEM’s e.g., Ford EcoSport to reduce the oil pump flow. In map-controlled PCJ, the oil to the PCJ is controlled using a solenoid valve. The solenoid valve can be completely variable or ON/OFF type. In our application, the ON/OFF type solenoid value is used to regulate the oil flow to PCJ. Conventionally, the oil to the PCJ is supplied at all operating conditions of the engine, even when the piston temperature is within the material acceptable limit. This adds to the parasitic loss of the internal combustion engine, due to the high friction power consumed by the oil pump to meet the oil flow rate requirement. Using the solenoid-controlled PCJ along with Variable Displacement Oil Pump (VDOP), the flow to the PCJ can be shut down at certain operating conditions such as high speed, and low load conditions. Using the VDOP, the total oil flow rate can be reduced whenever there is no flow to the PCJ, this will help to reduce engine friction load & improve the overall fuel economy.The objective of the paper is to show the systemic approach, design modifications & challenges involved in the implementation of the map controlled PCJ. The final engine with the map-controlled PCJ along with VDOP is evaluated in the NEDC (New European Driving Cycle) drive cycle to understand the benefits & an overall fuel economy of 1 – 2 % was observed. Results are discussed in detail, which have enabled to take required decision on implementation of Map Controlled PCJ in the specific engine application.

The Introduction of Corporate Average Fuel Economy (henceforth will be addressed as CAFE) regulations demand suitable technological upgrades to meet the significant increase in targets of vehicle fleet fuel economy. Engine Downsizing and Friction Reduction measures help in getting one step closer to the target. In a Conventional Oil Pump, the pump discharge flow and pressure are a direct function of operating speed. There is no control over lubricant flow which results in increased power and fuel consumption due to its unnecessary pumping characteristics irrespective of the actual engine demand. This paper discusses the introduction of a variable displacement oil pump (henceforth will be addressed as VDOP) that was adapted to a 1.5-liter 3 Cylinder Diesel Engine. This approach helps the system to reduce parasitic losses as the oil flow is regulated based on the mechanical needs of the engine. The flow is regulated with help of a solenoid valve which receives input from the ECU. The engine Oil Pump has a major role in enabling the transfer of lubricant to all moving engine components. The demand majorly depends on engine performance characteristics, bearing clearances, operating temperatures, and wear behavior of engine components. The paper explains the boundary conditions for VDOP design packaging, challenges in system adaptation, impact on engine lubrication circuit, performance, and friction reduction benefit.

The global automotive industry is growing rapidly in recent years and the market competition has increased drastically. There is a high demand for passenger car segment vehicles with high torque delivery and fuel economy for a pleasant drivability experience. Also, to meet the more stringent emission requirements, automakers are trying very hard to reduce the overall vehicle gross weight. In lowering both fuel consumption and CO2 generation, serious efforts have been made to reduce the overall engine weight. An engine cylinder block is generally considered to be the heaviest part within a complete engine and block alone accounts for 3-4% of the total weight of the average vehicle, thus playing a key role in weight reduction consideration. Aluminum casting alloys as a substitute for the traditional cast iron can mean a reduction in engine block weight between 40 and 55% [9], even if the lower strength of aluminum compared to grey cast iron is considered. Thus, designers of aluminum engine blocks are constantly striving to design better and lighter blocks in order to improve and enhance the efficiency of automobile engines.This work is a part of design and development of 2.2 L, 4-cylinder turbocharged intercooler (TCIC) diesel engine for a complete new monocoque vehicle platform, focused on automotive passenger car application with high operating in cylinder combustion pressures around 190 bar. The paper portrays the effective system approach essential for selecting aluminum as the choice of material, selection of alloy composition, casting process, heat treatment and key design criteria. The ongoing substitution of cast iron in engine blocks by aluminum casting alloys also requires the design and development of a new “tribological” system. Selection of cost-effective cylinder liner system and the drawbacks of this heterogeneous concept such as the lack of metallic bonding with the surrounding cast aluminum alloy and higher bore distortion are addressed during design and development. Statistical database, quality tools like design failure mode and effect analysis (DFMEA), design for manufacture and assembly (DFMA) etc., classical design methods, finite element analysis (FEA), advanced computer-aided engineering (CAE) and computational fluid dynamics (CFD) simulation tools have helped in materializing this concept into production. Experimental validation of the design is carried out as a part of design verification and validation. And results are elaborated to show the effectiveness of integrated approach used for the development program.

In the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS), inhibition of the IL1β inflammatory pathway by canakinumab has been shown to significantly reduce lung cancer incidence and mortality. Here we performed molecular characterization of CANTOS patients who developed lung cancer during the study, including circulating tumor DNA (ctDNA) and soluble inflammatory biomarker analysis. Catalogue of Somatic Mutations in Cancer (COSMIC) database ctDNA mutations were detected in 65% (46/71) of the CANTOS patients with lung cancer, with 51% (36/71) having detectable ctDNA at the time point closest to lung cancer diagnosis and 43% (29/67) having detectable ctDNA at trial randomization. Mutations commonly found in lung cancer were observed with no evidence of enrichment in any mutation following canakinumab treatment. Median time to lung cancer diagnosis in patients with (n = 29) versus without (n = 38) detectable COSMIC ctDNA mutations at baseline was 407 days versus 837 days (P = 0.011). For serum inflammatory biomarker analysis, circulating levels of C-reactive protein (CRP), IL6, IL18, IL1 receptor antagonist, TNFα, leptin, adiponectin, fibrinogen, and plasminogen activator inhibitor-1 were determined. Patients with the highest level of baseline CRP or IL6, both downstream of IL1β signaling, trended toward a shorter time to lung cancer diagnosis. Other inflammation markers outside of the IL1β pathway at baseline did not trend with time to lung cancer diagnosis. These results provide further evidence for the importance of IL1β-mediated protumor inflammation in lung cancer and suggest canakinumab's effect may be mediated in part by delaying disease progression of diverse molecular subtypes of lung cancer.Significance:These findings suggest that targeting the IL1β inflammatory pathway might be critical in reducing tumor-promoting inflammation and lung cancer incidence.

Supplementary Data

Purpose: Brain metastases develop in one third of patients with advanced HER2+ breast cancer. Effective therapy for patients with central nervous system (CNS) progression after cranial radiation is extremely limited and represents a major clinical challenge. Lapatinib, an epidermal growth factor receptor/HER2 inhibitor, was associated with regressions of CNS lesions in a small phase 2 trial. The current study was done to further evaluate the CNS activity of lapatinib. The study was later amended to allow patients who progressed on lapatinib the option of receiving lapatinib plus capecitabine.Experimental Design: Eligible patients had HER2+ breast cancer, progressive brain metastases, prior trastuzumab, and cranial radiotherapy. The primary end point was CNS objective response, defined as ≥50% volumetric reduction of CNS lesion(s) in the absence of increasing steroid use, progressive neurologic signs and symptoms, or progressive extra-CNS disease.Results: Two-hundred and forty-two patients entered the study. CNS objective responses to lapatinib were observed in 6% of patients. In an exploratory analysis, 21% of patients experienced a ≥20% volumetric reduction in their CNS lesions. An association was observed between volumetric reduction and improvement in progression-free survival and neurologic signs and symptoms. Of the 50 evaluable patients who entered the lapatinib plus capecitabine extension, 20% experienced a CNS objective response and 40% experienced a ≥20% volumetric reduction in their CNS lesions.Conclusions: This study confirms the modest CNS antitumor activity of lapatinib. Additional responses were observed with the combination of lapatinib and capecitabine. Further studies of lapatinib-based regimens for CNS metastases from HER2+ breast cancer are warranted.

Supplementary Data from Multicenter Phase II Study of Lapatinib in Patients with Brain Metastases from HER2-Positive Breast Cancer

Introduction: Propolis is a compound produced by bee’s which exerts antibacterial action against oral microorganisms especially streptococcus mutans. Propolis has different concentrations which exhibit different properties like antibacterial, antifungal, antiviral, antiparasitic, anti-inflammatory, antiproliferative and antioxidant. Materials and Methods: Antimicrobial activity of propolis was first demonstrated through disk diffusion method and broth dilution method. In the disk diffusion method, 5 grams of propolis was diluted with 50ml of ethanol in an eppendorf tube. Different concentrations of propolis (ie) 50mm, 40mm, 30mm were added to sterile discs using a micropipette and were exposed to the bacteria and the results were observed. In the broth dilution method, different concentrations of propolis 1g, 1.25g, 1.5g were taken and dissolved in ethanol. Then 5ml of sterile distilled water was added to the propolis solution. The above solution was autoclaved for 1 and half hours. It was then exposed to the bacteria for half an hour and results were observed. Results: This study was conducted to assess the antimicrobial activity of propolis against Streptococcus mutans in comparison with 0.2% chlorhexidine. When microorganisms were exposed to propolis for 24 hours, it affected the bacterial viability. There was a complete elimination of bacteria with propolis. Antimicrobial activity of chlorhexidine was evaluated and a similar result was obtained. Thus when we compare the antimicrobial activity of propolis and chlorhexidine there was no significant difference with a p value of 0.01 which is statistically significant. Conclusion: This study showed a positive inhibitory influence of propolis with respect to the Streptococcus mutans.

Background Overseas-born people who are ineligible for government-subsidised health care experience barriers to accessing HIV pre-exposure prophylaxis (PrEP) in Australia. This study aimed to assess a program providing free PrEP to overseas-born adults at risk of acquiring HIV. Methods Medicare-Ineligible Expanded Implementation in Communities (MI-EPIC) was a single-arm, open-label trial of daily tenofovir disoproxil fumarate/emtricitabine as PrEP. Six clinics recruited Medicare-ineligible adults who met HIV risk criteria in New South Wales, Australia. We recorded data on HIV and sexually transmitted infection (STI) diagnoses, and PrEP dispensing from July 2019 to June 2020. PrEP adherence as a medication possession ratio (MPR) was calculated as pills dispensed divided by days. We administered an optional survey on behaviours and attitudes to PrEP and sexual health. Results The 221 participants (206 men; 93.2%) had a median age of 29 years (IQR 26–34). Participants were mostly born in Asia (53.4%), Latin America or the Caribbean (25.3%), or Europe (10.9%). Adherence was high; 190 participants (86.0%) had an MPR of >60%. Of 121 survey participants, 42 (34.7%) completed the survey in a language other than English. Of participants who had not used PrEP in the 6 months before enrolment (n = 45, 37.2%), the most common reasons were cost (n = 22, 48.9%), and lack of knowledge about accessing PrEP (n = 20, 44.4%). Conclusions Medicare-ineligible people at risk of HIV demonstrate high adherence when given access to free PrEP and translated information. Increasing PrEP awareness and reducing barriers to accessing PrEP in this high-risk population should be priorities in HIV prevention.

Migrasomes are newly discovered cell organelles forming by local swelling of retraction fibers. The migrasome formation critically depends on tetraspanin proteins present in the retraction fiber membranes and is modulated by the membrane tension and bending rigidity. It remained unknown how and in which time sequence these factors are involved in migrasome nucleation, growth, and stabilization, and what are the possible intermediate stages of migrasome biogenesis. Here using live cell imaging and a biomimetic system for migrasomes and retraction fibers, we reveal that migrasome formation is a two-stage process. At the first stage, which in biomimetic system is mediated by membrane tension, local swellings largely devoid of tetraspanin 4 form on the retraction fibers. At the second stage, tetraspanin 4 molecules migrate toward and onto these swellings, which grow up to several microns in size and transform into migrasomes. This tetraspanin 4 recruitment to the swellings is essential for migrasome growth and stabilization. Based on these findings we propose that the major role of tetraspanin proteins is in stabilizing the migrasome structure, while the migrasome nucleation and initial growth stages can be driven by membrane mechanical stresses.

The amount of particles and organic matter in wash-waters and effluent from the processing of fruits and vegetables determines whether they need to be treated to fulfil regulatory standards for their intended use. This research proposes a novel technique in photovoltaic cell-based renewable energy in saline water analysis using the oxidation process and deep learning techniques. Here, the saline water oxidation is carried out based on photovoltaic cell-based renewable and saline water analysis is carried out using Markov fuzzy-based Q-radial function neural networks (MFQRFNN). The plan is entirely web-oriented to enable better control and effective monitoring of water consumption. This monitoring makes use of a communication system that collects data in the form of irregularly spaced time series. Experimental analysis has been carried out based on water salinity data in terms of accuracy, precision, recall, specificity, computational cost, and kappa coefficient.

This paper presents the design and performance of a low-cost, low-power remote condition monitoring (CM) solution for large-scale solar photovoltaic (PV) systems. The developed CM solution utilises ESP-NOW and Long Range Wide Area Network (LoRaWAN) wireless communication protocols for data exchanges. The developed solution operates in selfpower mode, with each IoT node capable of monitoring up to 16 channels of voltage, current, and temperature of the PV panels. The 2.4GHz ESP-NOW wireless communication protocol is used for data transfer between the IoT nodes in a many-to one configuration. The transceiver node stores messages from all IoT nodes and broadcasts them via the LoRaWAN network to the server. The developed hardware and software solutions were tested to measure the accuracy and reliability of the CM system. As a result, a fully-functioning low-cost solar PV CM system is developed, with an overall sensor measurement error of less than 3%, with an average Received Signal Strength Indicator (RSSI) of -105dBm in non-line-of-sight conditions.

Despite seminal advances towards understanding the infection mechanism of SARS-CoV-2, it continues to cause significant morbidity and mortality worldwide. Though mass immunization programs have been implemented in several countries, the viral transmission cycle has shown a continuous progression in the form of multiple waves. A constant change in the frequencies of dominant viral lineages, arising from the accumulation of nucleotide variations (NVs) through favourable selection, is understandably expected to be a major determinant of disease severity and possible vaccine escape. Indeed, worldwide efforts have been initiated to identify specific virus lineage(s) and/or NVs that may cause a severe clinical presentation or facilitate vaccination breakthrough. Since host genetics is expected to play a major role in shaping virus evolution, it is imperative to study role of genome-wide SARS-CoV-2 NVs across various populations. In the current study, we analysed the whole genome sequence of 3543 SARS-CoV-2 infected samples obtained from the state of Telangana, India (including 210 from our previous study), collected over an extended period from April, 2020 to October, 2021. We present a unique perspective on the evolution of prevalent virus lineages and NVs during this time period. We also highlight presence of specific NVs likely to be associated favourably with samples classified as vaccination breakthroughs. Finally, we report genome-wide intra-host variations (iSNVs) at novel genomic positions. The results presented here provide critical insights into virus evolution over an extended time period and pave the way to rigorously investigate the role of specific NVs in vaccination breakthroughs.

Cor pulmonale is a condition in which an alteration in the function and structure of the right ventricle of heart occurs, primarily as a result of respiratory disease which leads to increased blood flow resistance in the pulmonary circulation. Pulmonary hypertension is considered to be the most common link between lungs and heart dysfunction. Chronic obstructive airway disease is a common risk factor for the development of Pulmonary artery hypertension. The management requires focus on the underlying disease condition and treatment of the complications associated with Cor Pulmonale. Here the patient was a 55 year old female patient, presented with symptoms of Cor Pulmonale with a history of COPD and a recent case of severe pulmonary artery hypertension. She had anasarca and elevated BNP which indicated the right ventricle failure of heart associated with Cor pulmonale. The treatment included Loop diuretics, PDE 5 Inhibitors, Anticoagulants, Bronchodilators, Oxygen therapy and Antibiotics. The condition of the patient improved and hence was discharged.

Tubulin self-association is a critical process in microtubule dynamics. The early intermediate structures, energetics, and their regulation by fluxes of chemical energy, associated with guanosine triphosphate (GTP) hydrolysis, are poorly understood. We reconstituted an in vitro minimal model system, mimicking the key elements of the nontemplated tubulin assembly. To resolve the distribution of GTP- and guanosine diphosphate (GDP)-tubulin structures, at low temperatures (∼10 °C) and below the critical concentration for the microtubule assembly, we analyzed in-line size-exclusion chromatography-small-angle X-ray scattering (SEC-SAXS) chromatograms of GTP- and GDP-tubulin solutions. Both solutions rapidly attained steady state. The SEC-SAXS data were consistent with an isodesmic thermodynamic model of longitudinal tubulin self-association into 1D oligomers, terminated by the formation of tubulin single rings. The analysis showed that free dimers coexisted with tetramers and hexamers. Tubulin monomers and lateral association between dimers were not detected. The dimer-dimer longitudinal self-association standard Helmholtz free energies were -14.2 ± 0.4 kBT (-8.0 ± 0.2 kcal mol-1) and -13.1 ± 0.5 kBT (-7.4 ± 0.3 kcal mol-1) for GDP- and GTP-tubulin, respectively. We then determined the mass fractions of dimers, tetramers, and hexamers as a function of the total tubulin concentration. A small fraction of stable tubulin single rings, with a radius of 19.2 ± 0.2 nm, was detected in the GDP-tubulin solution. In the GTP-tubulin solution, this fraction was significantly lower. Cryo-TEM images and SEC-multiangle light-scattering analysis corroborated these findings. Our analyses provide an accurate structure-stability description of cold tubulin solutions.

This paper presents a Linear Quadratic Regulator (LQR) control strategy for a non-linear 3-DOF helicopter system. The optimal tracking approach yields robustness to both structured (parameter variation) and unstructured (disturbance) uncertainties. First, the 3-DOF helicopter system is linearized around an operating point and its state-space model is derived. Then, the LQR controller is designed. Numerical results show the controller’s robustness and high performance under uncertainties. In comparison with other existing control strategies, the control approach proposed in this paper is a lot more simple, hence its comparison with the PID controller, an equally simple control strategy. To better evaluate the execution and the performance of the LQR control strategy, two quantitative tracking performance metrics are presented; (i) the integral of the tracking errors, and (ii) the integral of the control signals of the system. Comparative results show the prevalence of the proposed strategy, as it achieves the highest tracking accuracy with the lowest control exertion.