An Omicron-specific, self-amplifying mRNA booster vaccine for COVID-19: a phase 2/3 randomized trial.

Here we conducted a multicenter open-label, randomized phase 2 and 3 study to assess the safety and immunogenicity of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron-specific (BA.1/B.1.1.529), monovalent, thermostable, self-amplifying mRNA vaccine, GEMCOVAC-OM, when administered intradermally as a booster in healthy adults who had received two doses of BBV152 or ChAdOx1 nCoV-19. GEMCOVAC-OM was well tolerated with no related serious adverse events in both phase 2 and phase 3. In phase 2, the safety and immunogenicity of GEMCOVAC-OM was compared with our prototype mRNA vaccine GEMCOVAC-19 (D614G variant-specific) in 140 participants. At day 29 after vaccination, there was a significant rise in anti-spike (BA.1) IgG antibodies with GEMCOVAC-OM (P < 0.0001) and GEMCOVAC-19 (P < 0.0001). However, the IgG titers (primary endpoint) and seroconversion were higher with GEMCOVAC-OM (P < 0.0001). In phase 3, GEMCOVAC-OM was compared with ChAdOx1 nCoV-19 in 3,140 participants (safety cohort), which included an immunogenicity cohort of 420 participants. At day 29, neutralizing antibody titers against the BA.1 variant of SARS-CoV-2 were significantly higher than baseline in the GEMCOVAC-OM arm (P < 0.0001), but not in the ChAdOx1 nCoV-19 arm (P = 0.1490). GEMCOVAC-OM was noninferior (primary endpoint) and superior to ChAdOx1 nCoV-19 in terms of neutralizing antibody titers and seroconversion rate (lower bound 95% confidence interval of least square geometric mean ratio >1 and difference in seroconversion >0% for superiority). At day 29, anti-spike IgG antibodies and seroconversion (secondary endpoints) were significantly higher with GEMCOVAC-OM (P < 0.0001). These results demonstrate that GEMCOVAC-OM is safe and boosts immune responses against the B.1.1.529 variant. Clinical Trial Registry India identifier: CTRI/2022/10/046475 .

Squamous Cell Carcinoma Arising in a Zenker's Diverticulum.

Squamous cell carcinoma (SCC) developing in a Zenker's diverticulum (ZD) is an uncommon condition. The preferred treatment for SCC in the pharyngeal pouch is complete diverticulum resection. Only histopathological evaluation of the pouch can rule out SCC. Here, we present a case of a 62-year-old male patient, who was evaluated for repeated episodes of aspiration and dysphagia, and diagnosed to have a large ZD, the patient underwent Zenker's diverticulectomy with cricopharyngeal myotomy with wide margins due to clinically suspicious specimen. Histopathological examination revealed well-differentiated SCC arising within ZD, involving the whole thickness of the wall and almost touching the serosa (1 mm). The patient developed metastatic lung nodule on PET-CT, so metastatic lung nodule was excised with video-assisted thoracoscopic surgery (VATS), and chemotherapy and immunotherapy were given. On follow-up imaging patient is tumor-free to date, two years after the surgery. The occurrence of synchronous or metachronous lung cancer makes it one of the rarest cases.

Designing a novel fractional order mathematical model for COVID-19 incorporating lockdown measures.

This research focuses on the design of a novel fractional model for simulating the ongoing spread of the coronavirus (COVID-19). The model is composed of multiple categories named susceptible [Formula: see text], infected [Formula: see text], treated [Formula: see text], and recovered [Formula: see text] with the susceptible category further divided into two subcategories [Formula: see text] and [Formula: see text]. In light of the need for restrictive measures such as mandatory masks and social distancing to control the virus, the study of the dynamics and spread of the virus is an important topic. In addition, we investigate the positivity of the solution and its boundedness to ensure positive results. Furthermore, equilibrium points for the system are determined, and a stability analysis is conducted. Additionally, this study employs the analytical technique of the Laplace Adomian decomposition method (LADM) to simulate the different compartments of the model, taking into account various scenarios. The Laplace transform is used to convert the nonlinear resulting equations into an equivalent linear form, and the Adomian polynomials are utilized to treat the nonlinear terms. Solving this set of equations yields the solution for the state variables. To further assess the dynamics of the model, numerical simulations are conducted and compared with the results from LADM. Additionally, a comparison with real data from Italy is demonstrated, which shows a perfect agreement between the obtained data using the numerical and Laplace Adomian techniques. The graphical simulation is employed to investigate the effect of fractional-order terms, and an analysis of parameters is done to observe how quickly stabilization can be achieved with or without confinement rules. It is demonstrated that if no confinement rules are applied, it will take longer for stabilization after more people have been affected; however, if strict measures and a low contact rate are implemented, stabilization can be reached sooner.

A study on fractional tumor-immune interaction model related to lung cancer via generalized Laguerre polynomials.

BACKGROUND: Cancer, a complex and deadly health concern today, is characterized by forming potentially malignant tumors or cancer cells. The dynamic interaction between these cells and their environment is crucial to the disease. Mathematical models can enhance our understanding of these interactions, helping us predict disease progression and treatment strategies. METHODS: In this study, we develop a fractional tumor-immune interaction model specifically for lung cancer (FTIIM-LC). We present some definitions and significant results related to the Caputo operator. We employ the generalized Laguerre polynomials (GLPs) method to find the optimal solution for the FTIIM-LC model. We then conduct a numerical simulation and compare the results of our method with other techniques and real-world data. RESULTS: We propose a FTIIM-LC model in this paper. The approximate solution for the proposed model is derived using a series of expansions in a new set of polynomials, the GLPs. To streamline the process, we integrate Lagrange multipliers, GLPs, and operational matrices of fractional and ordinary derivatives. We conduct a numerical simulation to study the effects of varying fractional orders and achieve the expected theoretical results. CONCLUSION: The findings of this study demonstrate that the optimization methods used can effectively predict and analyze complex phenomena. This innovative approach can also be applied to other nonlinear differential equations, such as the fractional Klein-Gordon equation, fractional diffusion-wave equation, breast cancer model, and fractional optimal control problems.

Cowden Syndrome With Gall Bladder Polyps and Incidental Gall Bladder Carcinoma.

Cowden syndrome is an uncommon autosomal dominant disorder characterized by multiple hamartomas in various tissues. It is associated with germline mutation in the phosphatase and tensin homolog (PTEN) gene. It has an increased risk of malignancies of various organs (commonly breast, thyroid, and endometrium) and benign overgrowth of tissues like skin, colon, and thyroid. Here, we present a case of Cowden syndrome in a middle-aged female who presented with acute cholecystitis with gall bladder polyps along with intestinal polyps. She underwent total proctocolectomy with ileal pouch-anal anastomosis (IPAA) with diversion ileostomy and cholecystectomy, which was further proceeded to completion of radical cholecystectomy based on the final histopathology report as incidental gall bladder carcinoma. To the best of our knowledge, this association is seen for the first time in the literature. In Cowden syndrome, patients should be counseled for regular follow-up and instructed to be aware of the signs and symptoms of different types of cancers with higher incidence.

A fractional-order mathematical model for analyzing the pandemic trend of COVID-19.

Many countries worldwide have been affected by the outbreak of the novel coronavirus (COVID-19) that was first reported in China. To understand and forecast the transmission dynamics of this disease, fractional-order derivative-based modeling can be beneficial. We propose in this paper a fractional-order mathematical model to examine the COVID-19 disease outbreak. This model outlines the multiple mechanisms of transmission within the dynamics of infection. The basic reproduction number and the equilibrium points are calculated from the model to assess the transmissibility of the COVID-19. Sensitivity analysis is discussed to explain the significance of the epidemic parameters. The existence and uniqueness of the solution to the proposed model have been proven using the fixed-point theorem and by helping the Arzela-Ascoli theorem. Using the predictor-corrector algorithm, we approximated the solution of the proposed model. The results obtained are represented by using figures that illustrate the behavior of the predicted model classes. Finally, the study of the stability of the numerical method is carried out using some results and primary lemmas.

Optimal Solution of a Fractional HIV/AIDS Epidemic Mathematical Model.

This article presents a fractional mathematical model of the human immunodeficiency virus (HIV)/AIDS spread with a fractional derivative of the Caputo type. The model includes five compartments corresponding to the variables describing the susceptible patients, HIV-infected patients, people with AIDS but not receiving antiretroviral treatment, patients being treated, and individuals who are immune to HIV infection by sexual contact. Moreover, it is assumed that the total population is constant. We construct an optimization technique supported by a class of basis functions, consisting of the generalized shifted Jacobi polynomials (GSJPs). The solution of the fractional HIV/AIDS epidemic model is approximated by means of GSJPs with coefficients and parameters in the matrix form. After calculating and combining the operational matrices with the Lagrange multipliers, we obtain the optimization method. The theorems on the existence, unique, and convergence results of the method are proved. Several illustrative examples show the performance of the proposed method. Mathematics Subject Classification: 97M60; 41A58; 92C42.

Modeling the SARS-CoV-2 parallel transmission dynamics: Asymptomatic and symptomatic pathways.

Asymptomatic transmission of the coronavirus disease and the infected individual prediction has become very important in the COVID-19 outbreak study. The asymptomatic and symptomatic transmission studies are still ongoing to assess their impacts on disease monitoring and burden. However, there has been limited research on how asymptomatic and symptomatic transmissions together can affect the coronavirus disease outbreak. A mathematical model is therefore needed to be developed in order to assess the effect of these transmissions on the coronavirus disease dynamics. This paper develops a mathematical model concerning asymptomatic and symptomatic disease transmission processes in the COVID-19 outbreak. The model sensitivity has been analysed in terms of the variance of each parameter, and the local stability at two equilibrium points have been discussed in terms of the basic reproduction number (R0). It is found that the disease-free equilibrium gets stable for R0 < 1 whereas the endemic equilibrium becomes stable for R0 > 1 and unstable otherwise. The proportion of the effect of asymptomatic and symptomatic transmission rates on R0 is calculated to be approximately between 1 and 3. The results demonstrate that asymptomatic transmission has a significant impact compared to symptomatic transmission in the disease outbreak. Outcomes of this study will contribute to setting an effective control strategy for the COVID-19 outbreak.

Series Representations for Uncertain Fractional IVPs in the Fuzzy Conformable Fractional Sense.

Fuzzy differential equations provide a crucial tool for modeling numerous phenomena and uncertainties that potentially arise in various applications across physics, applied sciences and engineering. Reliable and effective analytical methods are necessary to obtain the required solutions, as it is very difficult to obtain accurate solutions for certain fuzzy differential equations. In this paper, certain fuzzy approximate solutions are constructed and analyzed by means of a residual power series (RPS) technique involving some class of fuzzy fractional differential equations. The considered methodology for finding the fuzzy solutions relies on converting the target equations into two fractional crisp systems in terms of ρ-cut representations. The residual power series therefore gives solutions for the converted systems by combining fractional residual functions and fractional Taylor expansions to obtain values of the coefficients of the fractional power series. To validate the efficiency and the applicability of our proposed approach we derive solutions of the fuzzy fractional initial value problem by testing two attractive applications. The compatibility of the behavior of the solutions is determined via some graphical and numerical analysis of the proposed results. Moreover, the comparative results point out that the proposed method is more accurate compared to the other existing methods. Finally, the results attained in this article emphasize that the residual power series technique is easy, efficient, and fast for predicting solutions of the uncertain models arising in real physical phenomena.

New Parameterized Inequalities for η-Quasiconvex Functions via (p, q)-Calculus.

In this work, first, we consider novel parameterized identities for the left and right part of the (p,q)-analogue of Hermite-Hadamard inequality. Second, using these new parameterized identities, we give new parameterized (p,q)-trapezoid and parameterized (p,q)-midpoint type integral inequalities via η-quasiconvex function. By changing values of parameter µ∈[0,1], some new special cases from the main results are obtained and some known results are recaptured as well. Finally, at the end, an application to special means is given as well. This new research has the potential to establish new boundaries in comparative literature and some well-known implications. From an application perspective, the proposed research on the η-quasiconvex function has interesting results that illustrate the applicability and superiority of the results obtained.

Extension of Operational Matrix Technique for the Solution of Nonlinear System of Caputo Fractional Differential Equations Subjected to Integral Type Boundary Constrains.

We extend the operational matrices technique to design a spectral solution of nonlinear fractional differential equations (FDEs). The derivative is considered in the Caputo sense. The coupled system of two FDEs is considered, subjected to more generalized integral type conditions. The basis of our approach is the most simple orthogonal polynomials. Several new matrices are derived that have strong applications in the development of computational scheme. The scheme presented in this article is able to convert nonlinear coupled system of FDEs to an equivalent S-lvester type algebraic equation. The solution of the algebraic structure is constructed by converting the system into a complex Schur form. After conversion, the solution of the resultant triangular system is obtained and transformed back to construct the solution of algebraic structure. The solution of the matrix equation is used to construct the solution of the related nonlinear system of FDEs. The convergence of the proposed method is investigated analytically and verified experimentally through a wide variety of test problems.

Some New Hermite-Hadamard and Related Inequalities for Convex Functions via (p,q)-Integral.

In this investigation, for convex functions, some new (p,q)-Hermite-Hadamard-type inequalities using the notions of (p,q)π2 derivative and (p,q)π2 integral are obtained. Furthermore, for (p,q)π2-differentiable convex functions, some new (p,q) estimates for midpoint and trapezoidal-type inequalities using the notions of (p,q)π2 integral are offered. It is also shown that the newly proved results for p=1 and q→1- can be converted into some existing results. Finally, we discuss how the special means can be used to address newly discovered inequalities.

India's need for long-term solutions to COVID-19-like pandemics: A policy paper by Organized Medicine Academic Guild.

The entire world seems to have responded to COVID-19 pandemic in a knee-jerk manner with a short mindset without building on the existing strengths of public health infrastructure. National governments cannot be blamed for this as we are dealing with a crisis that comes once in a lifetime. Realising this, the Organized Medicine Academic Guild (OMAG) an association of major health associations in this country has suggested measures for long-term solutions to COVID-19-like pandemics in the form of a policy paper by OMAG.

Ambispective study of clinical picture, management practices and outcome of snake bite patients at tertiary care centre in Northern India.

BACKGROUND: Snakebite is a common but neglected public health problem of tropical & subtropical regions worldwide. This study was conducted to look into profile, first aid measures, management strategy and outcomes of snake bite patients. METHODS: This was an ambispective study conducted in the Department of Medicine & Emergency Medicine at AIIMS, New Delhi from June 2011 to May 2017 and enrolled 54 patients. In retrospective part 33 case records of snake bite patients were retrieved and in prospective part 21 patients were recruited. All relevant information including demographic parameters, first aid measures, clinical and laboratory profile and outcomes were recorded in pre made proformas. All data were analysed using IBM Stata version 13 and Microsoft Excel 2011. RESULTS: Majority of patients were male, and the mean age was 27.6 years. Maximum numbers of bites 34 (63%) happened in the rainy season and Krait was the most common culprit species. Neurological manifestations were most common (70.4%) followed by haematological. Most common complication was ventilatory failure (78.6%), and median dose of ASV was 20 vials. Forty-nine (90.7%) patients were discharged successfully. There was significant association of sepsis and shock with non survivors of snake bite with respective P values of 0.02 and 0.007. CONCLUSION: Neurotoxic snake bite (70.4%) was the most common type of envenomation. Most common complication was ventilatory failure and majority of patient (90.7%) successfully discharged. Sepsis and shock were significantly associated with non survivors of snake bite.

Modeling, analysis and prediction of new variants of covid-19 and dengue co-infection on complex network.

Recently, four new strains of SARS-COV-2 were reported in different countries which are mutants and considered as 70 % more dangerous than the existing covid-19 virus. In this paper, hybrid mathematical models of new strains and co-infection in Caputo, Caputo-Fabrizio, and Atangana-Baleanu are presented. The idea behind this co-infection modeling is that, as per medical reports, both dengue and covid-19 have similar symptoms at the early stages. Our aim is to evaluate and predict the transmission dynamics of both deadly viruses. The qualitative study via stability analysis is discussed at equilibria and reproduction number R 0 is computed. For the numerical purpose, Adams-Bashforth-Moulton and Newton methods are employed to obtain the approximate solutions of the proposed model. Sensitivity analysis is carried out to assessed the effects of various biological parameters and rates of transmission on the dynamics of both viruses. We also compared our results with some reported data against infected, recovered, and death cases.

Unsatisfactory quality of E. coli asparaginase biogenerics in India: Implications for clinical outcomes in acute lymphoblastic leukaemia.

BACKGROUND: The biotherapeutic asparaginase is a cornerstone of therapy in acute lymphoblastic leukaemia (ALL). With limited access to the original native Escherichia coli-derived asparaginase (EcASNase), a variety of EcASNase biogenerics are used in low-middle-income countries (LMICs). The variable quality of these biogenerics potentially influences clinical outcomes. PROCEDURE: Seven biogeneric EcASNases (P1-P7) marketed widely in India were evaluated, with P2 as an exemplar for in vivo monitoring. Therapeutic activity of P2 (10,000 IU/m2 /dose, intramuscular, every 72 hours) was monitored during induction therapy, and drug-related toxicities recorded. Molecular identity, purity and in vitro drug activity of seven biogenerics were characterised using multimodal analyses, and findings compared with reference EcASNase (R). RESULTS: In patients (N = 62) receiving P2, subtherapeutic asparaginase activity (<100 U/L) was observed in 66% (46/70) of trough timepoints (72 hours postdose) during induction. Twelve patients (19%), 11 with high-risk ALL, developed hypersensitivity. Isoforms of EcASNase were identified in all seven biogenerics. All generic products contained impurities with batch-to-batch variability. These included high levels of protein aggregates and host cell protein contamination. In vitro assays of EcASNase activity and leukaemia cell line cytotoxicity were not discriminatory. CONCLUSIONS: Our findings confirm widespread concerns over the unsatisfactory quality and therapeutic activity of native EcASNase biogenerics marketed in LMICs. Appropriate use of these products requires monitored studies to identify clinical suitability and determine appropriate dosing and schedule. For large parts of the world, assured access to high-quality asparaginases remains an unmet therapeutic need.

Parathyroid adenoma presenting as genu valgum in a child: A rare case report.

INTRODUCTION: Parathyroid adenoma is the most common cause of primary hyperparathyroidism (PHPT). Patients typically present with elevated serum calcium levels and elevated serum parathyroid hormone levels. The incidence and prevalence is higher in adults but is rare in pediatric age group. CASE PRESENTATION: A 12-year-old, pre-pubertal female presented with pain in bilateral knee joints and gait abnormality since one year. Her past medical history and family history were insignificant. On general examination, no other congenital bony deformities were observed besides genu valgum. Laboratory tests showed hypocalcemia and elevated serum levels of intact parathyroid hormone. Radiograph of bilateral both knee joints was suggestive of genu valgum. Ultra sonogram of neck revealed enlarged parathyroid gland and a Technetium (99mTc) sestamibi scan was suggestive of right inferior parathyroid adenoma. Surgical resection was performed and post-operative hypocalcemia was seen. After necessary treatment was given and the patient was discharged when asymptomatic. DISCUSSION AND CONCLUSION: Parathyroid adenoma causing primary hyperparathyroidism is a rare disease in children. They typically present with nonspecific symptoms involving gastrointestinal, musculoskeletal, renal and neurological symptoms due to hypercalcemia. Moreover, Genu valgum is a rare presentation in children with parathyroid adenoma.

Compliance with 6 h-Sepsis Resuscitation Bundle of Surviving Sepsis Campaign before and after Resident Physicians' Training: A Quality Improvement Interventional Study among Indian Patients.

BACKGROUND: Surviving sepsis campaign (SSC) recommends 6 h-sepsis resuscitation bundle for severe sepsis (now termed "sepsis" after the Sepsis-3 definition) or septic shock. The study was done to assess the guideline compliance in Indian patients before and after the resident physicians' training and their impact on the survival. SUBJECTS AND METHODS: Prospective interventional study (time series design) was conducted. Resident physicians, who were regularly managing the patients of severe sepsis/septic shock, were trained by providing the education and feedback on the guideline compliance at 6-month intervals for three quality improvement (QI) phases. Case details of preintervention and QI phases' patients were reviewed as per the quality indicators, defined by SSC guideline, and compared. RESULTS: The baseline compliance of composite six components of 6 h-sepsis resuscitation bundle was low and significantly increased on postintervention (baseline 0% to 18% at QI 3 (P for trend = 0.01). The compliance of individual components was improved too: serum lactate measurement (26%, P = 0.002), obtaining blood culture (28%, P = 0.003), antibiotic administration (2%, P = 0.56), provision of fluid bolus (60%, P = 0.02), attainment of target central venous pressure (50%, P = 0.03), and optimization of central venous oxygen saturation (20%, P = 0.21). The hospital mortality showed a decreasing trend (18%, P = 0.06). Patients compliant to composite bundle got the mortality benefit (odds ratios = 0.25, 95% [confidence interval, 0.07-0.9]). The study, however, did not show any benefits of mean hospital/Intensive Care Unit (ICU) length of stay. CONCLUSIONS: The study establishes lack of acceptance to the prevailing guideline; however, it has shown a significant improvement in adaptation and mortality benefit without reducing mean hospital/ICU length of stay after physicians' repeated educational programs. The barriers to implementation of the prevalent guideline should be searched out in further trials.

Noninstantaneous impulsive inequalities via conformable fractional calculus.

We establish some new noninstantaneous impulsive inequalities using the conformable fractional calculus.

An Interventional Quality Improvement Study to Assess the Compliance to Cardiopulmonary Resuscitation Documentation in an Indian Teaching Hospital.

BACKGROUND: Cardiopulmonary resuscitation (CPR) should be performed as per the international guidelines; however, compliance to these guidelines is difficult to assess. This study was conducted to determine the compliance to American Heart Association (2010) guideline on CPR documentation by among resident physicians before and after resident training (two arms). METHODS: This pre-postinterventional quality improvement study was conducted in a referral center, North India. Data of hospitalized in-hospital CPR patients were collected in the form of quality indicators (checklists) as defined by the guideline and compared between two arms of before-after resident training. Residents were given appropriate training in CPR technique as per the guideline. The compliance of CPR documentation was assessed pre- and post-intervention. RESULTS: The baseline arm compliance of various components of CPR documentation was low. The postintervention arm compliances of all components significantly increased (baseline, 2.5% to postintervention, 15.11%, P = 0.03). Individual components assessed were documentation of assessment of responsiveness (65% to 77.9%, P = 0.19), assessment of breathing (37.5% to 58.1%, P = 0.03), assessment of carotid pulse (62.5% to 79%, P = 0.05), rate of chest compressions (20% to 39.5%, P = 0.04), airway management (62.5% to 82.5%, P = 0.02), and compressions to breaths ratio (12.5% to 31.4%, P = 0.02). Documentation of chest compression rate compared to nondocumentation (12 of 42 vs. 11 of 84, P = 0.04) was independently associated with a higher rate of return of spontaneous circulation. The study however did not show any survival benefits. CONCLUSIONS: This study establishes that the compliance to CPR documentation is poor as assessed by CPR documentation content and quality, which improves after physician training, but not up to the mark level (100%) that may be due to busy Indian hospital settings and human behavioral factors. Due to ethical constraints of live CPR assessment, this document checklist approach may be considered as an internal quality assessment method for CPR compliance. Furthermore, correct instruction in CPR technique along with proper documentation of the procedure is required, followed up with periodic re-education during the residency period and beyond.