FDA-Approved Chimeric Antigen Receptor (CAR)-T Cell Therapy for Different Cancers-A Recent Perspective.

Cancer is one of the most prevalent diseases in the world, and their rate of occurence has been increased in recent decades. Current review article, summarizes the novel treatment options Chimeric Antigen Receptor-T (CAR-T) cell therapy for various cancers constitute a major health and development challenge, impacting every aspect of sustainable development quoted by goal 3 good health and well-being of UN sustainable goals. WHO estimates that 70% of cancer deaths occur in low- and middle- income countries (LMICs) by 2030, LMICs are expected to bear the brunt of the expected 24.1 million new cancer cases per year. This current review article focuses and discussed about CAR-T cell therapy for various cancers against most prevalent non-communicable disease cancer disease stipulated by WHO and UN sustainable goals. Three literature databases Google scholar, Science Direct, PubMed was utilized to search and collect CAR-T cell treatment options for different cancers published articles sources in between January 2000 and December 2023. There were a total of 18,700 papers found, with 48 of them being found to be eligible focusing various cancer treatment by CAR-T cells utilized for the study. Based on the information gathered, CAR-T cell therapy treating different cancers and their merit and its advantages in heal and improve certain cancers was also discussed in this review article with their detailed molecular mechanisms. This article also gives an insight to utilize CAR-T cell treatment protocols for rejuvenating cancer patient from such ruthless cancer disease condition thereby improving life span of cancer patients and eradication of disease in some cases.

Evolutionary Computing for the Radiative-Convective Heat Transfer of a Wetted Wavy Fin Using a Genetic Algorithm-Based Neural Network.

Evolutionary algorithms are a large class of optimization techniques inspired by the ideas of natural selection, and can be employed to address challenging problems. These algorithms iteratively evolve populations using crossover, which combines genetic information from two parent solutions, and mutation, which adds random changes. This iterative process tends to produce effective solutions. Inspired by this, the current study presents the results of thermal variation on the surface of a wetted wavy fin using a genetic algorithm in the context of parameter estimation for artificial neural network models. The physical features of convective and radiative heat transfer during wet surface conditions are also considered to develop the model. The highly nonlinear governing ordinary differential equation of the proposed fin problem is transmuted into a dimensionless equation. The graphical outcomes of the aspects of the thermal profile are demonstrated for specific non-dimensional variables. The primary observation of the current study is a decrease in temperature profile with a rise in wet parameters and convective-conductive parameters. The implemented genetic algorithm offers a powerful optimization technique that can effectively tune the parameters of the artificial neural network, leading to an enhanced predictive accuracy and convergence with the numerically obtained solution.

Seroprevalence of COVID-19 antibody among children aged 5-17 years in an urban and rural area of Ernakulam District, Kerala.

Background: The age group of 5-17 years belongs to the vulnerable segment of the population for COVID-19 infection in India. Seroprevalence in this population can therefore allow inferences to be made about the extent of infection. Objectives: The objective of this study was to assess the seroprevalence and to determine the factors associated with COVID-19 antibody among children aged 5-17 years in an urban and rural area of Kochi, Kerala. Methods: A community-based cross-sectional study was undertaken in the urban and rural field practice areas of the community medicine department in a medical college, Kochi. A semi-structured questionnaire was used to collect information about sociodemographic data, history related to COVID-19, and the severe acute respiratory syndrome coronavirus 2 antibody test result. Blood samples were collected and tested for the presence of COVID-19 antibodies using the Wantai test kit after attaining informed assent from the parent/guardian. Results: The seroprevalence of the COVID-19 antibody was 48.3% among participants. The seroprevalence of COVID-19 antibody was higher among children of mothers with skilled/unskilled occupation, residents of rural area, above poverty line category, those with a history of COVID-19, and those who had a history of contact with COVID-19-positive patients. Conclusion: Half of the study population were COVID antibody positive, and the rest were at risk of infection. Therefore, adherence to COVID-19 guidelines is essential to control further spread of infection among children.

Pilot of a questionnaire study regarding perception of undergraduate medical students towards online classes: Process and perspectives.

BACKGROUND: The COVID-19 pandemic situation has forced a shift in medical education from physical classroom to virtual online teaching. However, students and teachers perceive this differently. It is important to study these perceptions to improve the teaching-learning process, and thus to validate the role of online learning in the country. OBJECTIVE: To document the process of a pilot for a questionnaire-based study regarding perception of undergraduate medical students towards on-going online classes. METHODS: Medical Education Department of a teaching hospital developed a new questionnaire with the primary objective of studying the satisfaction and usefulness of the online classes (e-Learning). Content validity was done. For the pilot work, 10% of the total student strength was targeted. Random purposive sampling from each phase of the undergraduate course was done to choose the participants. The questionnaire was administered via Google Classroom. It was an external, undeclared type of pilot. All the responses were documented and analysed for both changes in the questions as well as for statistical sample size derivation for the main study. RESULTS: Responses from 30 students were analysed for the pilot study. Based on the proportion of the level of satisfaction (23.3%) and usefulness (23.3%) of the on-going online classes observed, and with 20% relative precision and 95% confidence, the minimum sample size for the main study was calculated. The responses revealed the need for minor changes in the questionnaire tool for overall feasibility and achievement of the objectives of the main study. CONCLUSIONS: A pilot study is a necessary component for a research project, especially when it involves the use of a new tool. This paper shows the relevance of the same. The authors intend to convey the importance of documenting the processes of conduct of a pilot study, the issues involved therein, and the steps taken to resolve the same.

Clinical Implication of Immunohaematological Tests in ABO haemolytic disease of newborn: Revisiting an old disease.

OBJECTIVE: We aimed to assess the frequency distribution of of ABO haemolytic disease of newborn (ABO-HDN) and to know the predictive value of immunohaematological tests in identifying at risk neonates. BACKGROUND: ABO incompatibility, although a common cause of haemolytic disease of newborn, has several unaddressed issues related to it. MATERIAL AND METHODS: A prospective study over 20 months was carried out in a tertiary care centre in South India. Blood grouping, Direct Antiglobulin test (DAT) and elution studies were performed on neonatal samples, whereas blood grouping, antibody screening and antibody titration were performed on maternal samples. In suspected cases, ABO-HDN was diagnosed after excluding other possible causes for haemolysis. The laboratory results were correlated with the clinical details to assess the predictive value of the tests. RESULTS: Of the total 2856 pregnancies, 34% had ABO incompatibility. On testing with columnagglutination test (CAT), the overall DAT positivity and that among ABO-incompatible cases were 3.8% and 11.2%, respectively,) whereas by conventinal tube technique (CTT) it was 0.6% and 2.4% respectively. CAT was found to have higher sensitivity, and the predictive value was higher for CTT. Maternal IgG titre showed a positive linear relationship with the DAT strength and the rise in indirect bilirubin levels. The positive predictive value of combination of tests such as DAT, elution and titation was 94.12%, which was much higher than that of the individual tests. CONCLUSION: DAT positivity is a predictor of early rise in serum bilirubin level, and a combination of tests has a better predictive value than individual tests towards development of clinically significant hyperbilirubinemia in ABO-HDN.

Measuring liquidity in Indian stock market: A dimensional perspective.

Market liquidity ensures the marketability of security and is an indispensable feature of stock markets. Previous studies have emphasized the role of stock market liquidity in empirical finance. However, they have inadequately explored its multidimensional nature. This study eliminates the ambiguities related to market liquidity by precisely measuring it by using popular and proven liquidity measures. As such, the present study aims to evaluate market liquidity in terms of depth, breadth, tightness, and immediacy in the Indian equity market and also identifies crucial interdependencies between liquidity dimensions. The study selects 500 stocks constituting the NIFTY 500 index of the National Stock Exchange, India, as of 26th May 2019. The data on trading volume, bid price, ask price, the number of shares outstanding, closing share prices were retrieved for the period from 1st April 2009 to 31st March 2019. The study employs Share Turnover, Amihud Illiquidity Ratio, Relative Quoted Spreads, and Coefficient of Elasticity of Trading for liquidity measurement. The Vector Auto-Regressive (VAR) model is used to establish the simultaneous relationships between liquidity dimensions. The analysis is conducted at the aggregate market level as well as across turnover based stock groups divided based on their rankings in terms of stock specific share turnover. The empirical results evidenced the presence of consistent depth, strong breadth, and immediacy but lower tightness in the Indian equity market. The market depth and tightness appear to be relevant in determining dimensional interdependencies. Also, less frequently traded stocks exhibit higher illiquidity in the wake of lower tightness. The findings of this study will assist the investors to wisely understand the multifaceted nature of market liquidity and base their trading decisions accordingly. Moreover, the regulators of the stock exchange can devise liquidity enhancing policies based on the directional movements among liquidity dimensions.

Frequency and clinical significance of red cell antibodies in pregnancy - A prospective study from India.

BACKGROUND: For appropriate management of hemolytic disease of the fetus and newborn (HDFN), it is important to detect irregular red cell antibody in the antenatal period. Though it is a simple one-step method, it is not part of routine antenatal screening in many developing countries. To reiterate the importance of antenatal antibody screening, we have assessed the frequency and clinical significance of irregular red cell antibodies in our patient population. MATERIALS AND METHODS: A prospective study was carried out from October 2013 to May 2015 at a tertiary care center from south India. All antenatal samples received by the laboratory for red cell antibody screening were screened using a commercial three-cell screening panel. Antibody identification along with further Immunohematological techniques as required were performed for cases with positive screening results. Neonates of the alloimmunized cases were followed up to determine the clinical significance of the antibody. RESULTS: A total of 2336 antenatal mothers were screened for red cell antibodies. The overall rate of alloimmunization in the study group was 2.27%. Alloimmunization rate among RhD-negative pregnancies was 6.9%. Other than anti-D (49%), we identified anti-D + anti-C (5%), anti-G (5%), anti-c (5%), anti-E (2%), anti-e (2%), anti-H (Bombay phenotype) (7%), anti-M (2%), anti-Lea (2%), anti-Leb (12%), and autoantibodies (9%) in the maternal serum. Anti-D, anti-D + anti-C, anti-G, anti-c, and anti-H were found to be clinically significant in this study. CONCLUSION: This study showed that 1 in 125 RhD-positive pregnancies can develop red cell alloantibodies. Hence, implementing routine antenatal antibody screening irrespective of RhD status is essential.

Severe haemolytic disease of a newborn with variant D mimicking blocked-D phenomenon.

Anti-D is still the most common antibody causing severe haemolytic disease of the fetus and newborn (HDFN). In a mother with a very high titer of anti-D, antibodies can coat and block the D antigens on the red blood cells of the newborn. This blocking phenomenon prevents agglutination of the D-positive red cells with the IgM anti-D typing reagent, giving false negative results. Here, we report the case of a newborn with variant D phenotype and severe HDFN, which mimicked the blocked-D phenomenon, which, at the first instance, confused both the treating clinicians and the transfusion service personnel.

Red cell storage lesion and the effect of buffy-coat reduction on the biochemical parameters.

BACKGROUND: Biochemical and metabolic changes in stored RBC may influence the clinical outcome. We aimed to study the temporal changes in the biochemical parameters and the effect of buffy-coat reduction on RBC storage lesions. MATERIALS AND METHODS: A prospective observational study was conducted on fifteen RBC units five each of buffy coat reduced CPD/SAGM (quadruple bags), non-buffycoat reduced CPD/SAGM (triple bags) and non-buffycoat reduced CPDA (double bags). Biochemical parameters such as K+, LDH, pH plasma hemoglobin and percentage hemolysis were measured sequentially on day 7,14, 21, 28, 35 and 42. The data was analyzed using SPSS version 20. RESULTS: Extracellular K+ and LDH increased rapidly starting from the first week of storage. And the all the parameters including percentage hemolysis were significantly higher in RBC stored in CPDA (double bags) compared to that stored in SAGM (triple and quadruple). The difference observed in buffy-coat reduced units in comparison to the non-leukocyte reduced units were statistically not significant. CONCLUSION: The quality of red cells stored in SAGM was superior to that suspended in CPDA measured in terms of percent hemolysis, plasma hemoglobin, potassium and LDH. There was no effect of buffy-coat leukocyte reduction on the red cell storage lesion.

Effect of plasma component transfusion on conventional coagulation screening tests.

BACKGROUND: Conventional coagulation screening tests such as Prothrombin time, International normalized ratio (INR) and activated partial thromboplastin time are often used to predict bleeding in various clinical situations. We aimed to observe the effect of Fresh-frozen plasma (FFP) on these parameters. METHODS: Patients' demographics, pre- and post-transfusion coagulation parameters were noted to assess the level of correction. The magnitude of improvement in INR was determined using the formula given by Holland and Brooks. Data was analyzed using IBM SPSS Statistics 20. RESULTS: Among 2082 episodes, 4991 units of FFP were transfused at an average of 5 units per patient. Median dose of FFP administered per episode was 10 mL/kg (5.8-13.4). The mean change in INR following transfusion was 8.9% of the pre-transfusion INR and thus considered to be statistically significant. CONCLUSION: FFP transfusions as a prophylactic measure especially in patients with mildly deranged conventional coagulation screening tests without any empirical evidence of clinical bleeding needs further scrutiny. Reduction in INR following FFP transfusions was better in cohort having higher pre-transfusion INR value (> 3.0).

Synthesis and biological evaluation of Schizandrin derivatives as potential anti-cancer agents.

A new series of Schizandrin (1) derivatives were synthesized utilizing the C-9 position of the Schizandrin core and evaluated for their cytotoxic activities against HeLa (cervical cancer), A549 (lung cancer), MCF-7 (breast cancer) and DU-145 (prostate cancer) cell lines. Among the synthesized series, 4e, 4f, 4g and 5 showed potent activities against tested cell lines. More significantly, compound 5 exhibited most potent cytotoxic activity against DU-145 with an IC50 value of 1.38 µM which is comparable to the standard agent, doxorubicin. Further, flow cytometry analysis indicated that 5 arrested cells in G2/M phase and consequently leading to apoptosis. Molecular docking analysis showed that 5 occupied the colchicine binding pocket of tubulin. Overall, the present study demonstrates that 5, as a mitotic-agent.

Novel Gomisin B analogues as potential cytotoxic agents: Design, synthesis, biological evaluation and docking studies.

As part of pharmacological-phytochemical integrated studies on medicinal flora, Gomisin B (1) was isolated as major phytochemical lead from schisandra grandiflora, a plant traditionally used in different Asian systems of medicine. A series of 1,2,3-triazoles derivatives were synthesized at the C-7' position of the gomisin B core through diastereoselective Michael addition followed by regioselective Huisgen 1,3-dipolar cycloaddition reactions. All these triazolyl derivatives (5a-5q) were well characterized using modern spectroscopic techniques and evaluated for their anti-cancer activity against a panel of five human cancerous cell-lines. Among them, compound 5b exhibited the best cytotoxicity against SIHA cell (IC50 0.24 µM) which was more than the standard drug doxorubicin, while the other derivatives were exhibited moderate to low activities in tested cell lines. The cell cycle analysis indicated that compound 5b stalled HeLa cells at G2/M phase. 5b promoted tubulin polymerization and this was supported by the docking studies, wherein 5b showed significant binding affinity at the colchicine binding pocket of tubulin. Overall, we identified a novel small molecule that demonstrated anticancer activity by promoting in vitro tubulin assembly.

Advanced glycation end-products inhibitors isolated from Schisandra grandiflora.

Free radicals scavenging and advanced glycation end-products (AGEs) inhibitory potentials in crude chloroform extract of Schisandra grandiflora were evaluated. Bioassay-guided isolation of the chloroform extract led to the identification of 24 compounds. Among the isolates, ( ± ) gomisin M1, arisantetralone C and D, macelignan, saurulignan B and SZ-MO displayed potent-free radical scavenging as well as AGEs inhibitory potentials. This is the first report identifying the presence of AGEs inhibitory activity and assigning AGEs inhibitory activity to these compounds. Therefore, our research finds new application of traditional medicinal plant S. grandiflora having capacity to reduce formation and accumulation of AGEs in diabetes.

New free radical scavenging neolignans from fruits of Piper attenuatum.

OBJECTIVE: The aim was to study and identify free radicals scavenging and antihyperglycemic principles in fruit of Piper attenuatum. MATERIALS AND METHODS: Bioassay guided identification of extracts possessing potent free radical scavenging activity, and isolation of compounds was done. Chloroform extract of P. attenuatum possessing potent radical scavenging activity was also evaluated for antihyperglycemic activity following oral glucose tolerance test in rats. RESULTS: Nine neolignans namely, denudatin B (1), iso-4', 5'-dimethoxy-3, 4-methylenedioxy-2'-oxo-Δ(3',5',8')-8.1'-lignan (2), lancifolin D (3), denudatin A (4), wallichinin (5), piperenone (6), lancifolin C (7), 2-oxo-piperol B (8), piperkadsin A (9) and a crotepoxide (10) was identified in Chloroform extract of P. attenuatum. Neolignans (1-9) displayed potent 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) radical and piperkadsin A (9) also displayed 1, 1-diphenyl-2-picrylhydrazyl radical scavenging activity. Analysis of structure-activity relationship revealed that presence of furan ring and methoxy groups is an important criterion to influence 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) radical scavenging potentials. Chloroform extract of P. attenuatum fruit could not display antihyperglycemic activity following oral glucose tolerance test in rats. CONCLUSION: Neolignans present in P. attenuatum fruits are potent free radical scavengers and this is the first report identifying these compounds and activities in this fruit.

Novel sesquiterpenes from Schisandra grandiflora: isolation, cytotoxic activity and synthesis of their triazole derivatives using "click" reaction.

Phytochemical investigation of hexane extract from the fruits of Schisandra grandiflora afforded three novel sesquiterpenes (1-3) along with the three known compounds (4-6). The structures of these isolates were determined by extensive analysis of spectroscopic data (1D, 2D NMR). Further, a series of triazole analogues of 3 and 4 were prepared using "Click" reaction protocol. The reaction scheme involving one-carbon homologation of 3 and 4 using the Bestmann-Ohira reagent followed by regioselective Huisgen 1,3-dipolar cycloaddition reaction of various azides leading to the formation of triazole analogues (20a-20k &21a-21c) which is being reported for the first time. All the triazole products were characterized using spectral data analysis. The anti-proliferative activity of the isolates and the synthetic analogues were studied against Hela (Cervical cancer), A549 (Lung cancer), DU-145 (Prostate cancer), MCF-7 (Breast cancer) and B-16 (Mouse melanoma) cancer cell lines.

Phytochemical investigation of sesquiterpenes from the fruits of Schisandra chinensis and their cytotoxic activity.

Phytochemical investigation of ethanolic extract from the fruits of Schisandra chinensis led to the isolation of four new sesquiterpenes (1-4); their structures were determined by a combination of NMR (1D and 2D) and MS spectroscopic techniques. In addition, all these isolates were screened for their cytotoxic activities against MCF-7, Caco-2, Hela, Lncap, Hep G2 and MDA-MB231 cancer cell lines. Results indicated that compounds 2 and 3 displayed potent cytotoxic activity against Caco2 cell lines with IC50 values of 17.10 µg/mM and 16.46 µg/mM, respectively.

Methyl angolensate and mexicanolide-type limonoids from the seeds of Cipadessa baccifera.

Six new methyl angolensate type (1-6) and three new mexicanolide-type (7-9) limonoids, along with six known limonoids (10-15), were isolated from the seeds of Cipadessa baccifera. The structures of all these compounds were established by extensive 1D, 2D NMR, and HRESIMS experiments, and structures of 11 and 13 were further confirmed by a single crystal X-ray diffraction analysis, which are reported for the first time. The cytotoxic activities of these isolates were also studied against A549, MCF7, ME-180, HT-29, B-16, ACHN cancer cell lines using MTT assay, and results indicated that compounds 4, 10, and 14 displayed potent cytotoxic activity against B-16, ACHN cell lines with an IC50 values of 8.51 and 7.0 µg/mL, respectively.

Evaluation of obstetric admissions to intensive care unit of a tertiary referral center in coastal India.

BACKGROUND AND AIM: To evaluate the occurrence, indications, course, interventions, and outcome of obstetric patients admitted to the intensive care unit (ICU). DESIGN: Retrospective study. SETTING: ICU of a Medical College Hospital. MATERIALS AND METHODS: The data collected were age, parity, obstetric status, primary diagnosis, interventions, and outcome of obstetric patients admitted to the ICU from Jan 2005 to June 2011. RESULTS: Total deliveries were 16,804 in 6.5 years. Obstetric admissions to the ICU were (n = 65) which constitutes 0.39% of deliveries. Majority of the admissions were in the postpartum period (n = 46, 70.8%). The two common indications for admission were obstetric hemorrhage (n = 18, 27.7%) and pregnancy related hypertension with its complications (n = 17, 26.2%). The most common intervention was artificial ventilation (n = 41, 63%). The mortality among obstetric admissions in the ICU was (33.8% (22/65)). The patients appropriate for High Dependency Unit (HDU) care was (32.3% (21/65)). The statistical analysis was done by fractional percentage and Chi-square test. CONCLUSIONS: Hemorrhage and pregnancy-related hypertension with its complications are the two common indications for ICU admissions. The need for a HDU should be considered.

Synthesis, anticancer, and antibacterial activities of piplartine derivatives on cell cycle regulation and growth inhibition.

A series of piplartine derivatives were synthesized via Baylis-Hillman reaction and evaluated for anticancer and antibacterial activities. The cytotoxicity of these compounds was examined in two different human tumor cell lines, IMR-32 and HeLa. The antibacterial activity was examined in Staphylococcus aureus and Pseudomonas aeruginosa. The results showed that compounds 2b, 2e, and 2j were found to be the most active compounds, which displayed line no cytotoxicity, but G2-M cell cycle arrest in tumor cells, and showed cytostatic effects in bacteria.