COVID 19: Prevention and treatment through the Indian perspective.

The most destructive period the world has experienced seems to be behind us. Not a single nation was spared by this disease, and many continue to struggle today. Even after recovering from COVID, patient may continue to experience some post-COVID effects, such as heart irregularities or a decline in lung vitality. In the past three years (2019-2022), the world has witnessed the power of a small entity, a single peculiar virus. Science initially appeared to be helpless in this regard, but due to the emergence of disease, pharmaceutics (the development of anti-covid drugs), immunology (the rapid antigen test), microbiology (the isolation of viruses from infected people), biotechnology (the development of recombinant vaccines), biochemistry (the blood profile, the D-dimer test), and biochemistry (blood profile, D-dimer test), biophysics (PCR, RT-PCR, CT Scan, MRI) had worked together to fight the disease. The results of these efforts are the development of new diagnostic techniques, possible treatment and finally the availability of vaccines against COVID-19. However, it is not proven that the treatment through the traditional medical system is directly active on SARS-CoV-2 but is instead indirectly acting on SARS-CoV-2 effects by improving symptoms derived from the viral disease. In India, the traditional system of medicine and tradition knowledge together worked in the pandemic and proved effective strategies in prevention and treatment of SARS-CoV-2. The use of effective masks, PPE kits, plasma therapy, yoga, lockdowns and social seclusion, use of modern antiviral drugs, monoclonal antibodies, herbal remedies, homoeopathy, hygienic practice, as well as the willpower of people, are all contributing to the fight against COVID. Which methods or practices will be effective against COVID nobody is aware since medical professionals who wear PPE kits do not live longer, and some people in India who remained unprotected and roamed freely were not susceptible to infection. The focus of this review is on the mode of transmission, diagnosis, preventive measures, vaccines currently under development, modern medicine developed against SARS-CoV-2, ayurvedic medicine used during pandemic, homoeopathic medicine used during pandemic, and specific yoga poses that can be used to lessen COVID-related symptoms.

Bisphenol A-induced oxidative stress increases the production of ovarian cancer stem cells in mice.

Bisphenol A (BPA) belongs to the endocrine disruptor chemicals (EDCs) causing various reproductive disorders in females. We analysed the toxic effects of BPA in the uterus and ovaries. The BPA was administered orally with the repeated low dose (LD, 1 mg/kg) and high dose (HD, 5 mg/kg) of body weight on alternate days for 4 months via oral gavage to Swiss mice. BPA administration decreases body weight, ovarian weight and size at LD, but increases ovarian weight and size at HD. The uterus weight, length, and diameter were increased in both the treated groups. The histopathological data show decreased ovarian follicle size, epithelial hyperplasia, and lymphocytic infiltration in the ovary. The BPA-treated uterus shows increased vascularization, atrophied endometrium and myometrium, and endometrial hyperplasia (EH) with aberrant glandular growth. The cancer stem cells (CSCs) in the ovaries were identified based on staining with anti-mouse CD44 and anti-mouse CD133 antibodies and analysed by flow cytometry. Three different populations of ovarian CSCs: CD44+CD133-, CD44+CD133+, and CD44-CD133+, can be recognised based on the intensity of these receptors. CD44+CD133- and CD44+CD133+ cell percentages were increased in BPA-treated groups. CD44-CD133+ were increased in LD but decreased in HD. The BPA administration also induces ROS production, which decreases the expression of antioxidant genes Superoxide dismutase 1 (SOD1), Superoxide dismutase 2 (SOD2), Catalase (CAT), Glutathione peroxidase 1 (GPX1), and Forkhead box O3 (FOXO3) in ovarian cells. In conclusion, BPA exposure induced an inflammatory response, increased CSC proportions, induced ROS, and decreased antioxidant responses in the ovaries.

Inter-organ differences in redox imbalance and apoptosis depict metabolic resilience in migratory redheaded buntings.

Migration, a bird's metabolic apex, depends primarily on the liver and muscle for fuel mobilization and endurance flight. In migratory redheaded buntings, adaptive increase in mitochondrial membrane (MM) proton gradient to drive ATP synthesis, measured by MM potential (MMP+) and reactive oxygen species (ROS) response, have been well characterized in the blood but not in the muscle or liver. We assessed MMP+, ROS, and apoptosis in the liver and pectoralis muscle of photosensitive nonmigratory (nMig.) male redheaded buntings photoinduced to migratory (Mig.) states. Relative expression levels of genes associated with energy (ACADM, PEPCK, GOT2, GLUT1, and CS), ROS modulation (SIRT1), mitochondrial free-radical scavengers (SOD1, PRX4, NOS2, GPX1, and GPX4), anti-apoptotic genes (NF-κß), apoptotic (CASP7), and tissue damage using histology, during migration were assessed. The MMP+ decreased and the ROS concentration increased, due to the metabolic load on liver and pectoralis muscle tissues during Mig. However, percentage of apoptotic cells increased in liver but decreased in muscle, which is of functional significance to migratory passerines. During Mig., in muscle, SIRT1 increased, while an increase in anti-apoptotic NF-κß aided immune pathway-mediated antioxidant activity and guarded against muscle oxidative damage during migration. Inter-organ differences in metabolism add to our current understanding of metabolic flexibility that supports successful migration in buntings.

Prototyping a wearable and stretchable graphene-on-PDMS sensor for strain detection on human body physiological and joint movements.

In the era of wearable electronic devices, which are quite popular nowadays, our research is focused on flexible as well as stretchable strain sensors, which are gaining humongous popularity because of recent advances in nanocomposites and their microstructures. Sensors that are stretchable and flexible based on graphene can be a prospective 'gateway' over the considerable biomedical speciality. The scientific community still faces a great problem in developing versatile and user-friendly graphene-based wearable strain sensors that satisfy the prerequisites of susceptible, ample range of sensing, and recoverable structural deformations. In this paper, we report the fabrication, development, detailed experimental analysis and electronic interfacing of a robust but simple PDMS/graphene/PDMS (PGP) multilayer strain sensor by drop casting conductive graphene ink as the sensing material onto a PDMS substrate. Electrochemical exfoliation of graphite leads to the production of abundant, fast and economical graphene. The PGP sensor selective to strain has a broad strain range of ⁓60%, with a maximum gauge factor of 850, detection of human physiological motion and personalized health monitoring, and the versatility to detect stretching with great sensitivity, recovery and repeatability. Additionally, recoverable structural deformation is demonstrated by the PGP strain sensors, and the sensor response is quite rapid for various ranges of frequency disturbances. The structural designation of graphene's overlap and crack structure is responsible for the resistance variations that give rise to the remarkable strain detection properties of this sensor. The comprehensive detection of resistance change resulting from different human body joints and physiological movements demonstrates that the PGP strain sensor is an effective choice for advanced biomedical and therapeutic electronic device utility.

Impact of sphingolipid synthesis inhibition on the drug susceptibility patterns of Trichophyton species.

The well known dermatophyte infections caused by Trichophyton species are an ambiguous problem to treat using the present arsenal of antifungals. This study expounds on the effect of inhibition of sphingolipid pathway on Trichophyton growth. Findings from the drug susceptibility assays suggest sphingolipid inhibition severely restricts the growth of T. interdigitale and T. tonsurans. The observed synergistic effects of combinations of sphingolipid inhibitor and conventional drugs provide a promising treatment strategy against Trichophyton infection.

Selective elimination of younger erythrocytes in blood circulation and associated molecular changes in benzo (a) pyrene induced mouse model of lung cancer.

Background: Anemia is a common feature in cancer patients. The present research was conducted to explore the mechanisms of induction of anemia in a mouse model of lung cancer. Methods: The lung cancer was induced by treating orally with BaP (50 mg/kg body weight, twice a week for four weeks). The erythrocyte kinetics were studied using a double in vivo biotinylation (DIB) technique. ROS production and apoptosis analysis were done by staining with the CMH2DCFDA stain and anti-mouse Annexin V antibody, followed by flow cytometry. The expression of antioxidant, apoptotic, anti-apoptotic and inflammatory genes was analyzed by quantitative PCR (RT-qPCR). Results: BaP-induced tumour reduced body weight and induced persistent haemolytic anaemia. The kinetics data suggest that, though reticulocyte production was enhanced, the proportion of young erythrocytes did not increase in the same proportion. The young aged erythrocytes were selectively eliminated from blood circulation, but intermediate and old aged erythrocytes persisted for a longer duration. The tumour progression leads to a significant increase in ROS production and apoptosis in the erythrocytes. The molecular data suggests that the expression levels of antioxidants (SOD1, catalase, and GPX1) and erythropoietin (Epo) were significantly increased. The anti-inflammatory genes Interleukin-6 (IL-6), Interleukin-10 (IL-10) were significantly decreased.Apoptotic genes Bax, and caspase 3 were significantly decreased while Bcl 2 was significantly increased in the blood of tumour-bearing mice. Conclusions: The overall data suggest that erythrocyte turnover is severely modulated with the progression of tumor. The apoptosis, ROS levels, antioxidant, anti-apoptotic, and Epo gene expressions were increased, but proapoptotic and anti-inflammatory gene expression were suppressed.

Evaluation of programmed cell death ligand 1 expression in a contemporary cohort of penile squamous cell carcinoma and its correlation with clinicopathologic and survival parameters: A study of 134 patients.

OBJECTIVES: Penile squamous cell carcinomas (PCs) are rare malignancies with a dismal prognosis in a metastatic setting; therefore, novel immunotherapeutic modalities are an unmet need. One such modality is the immune checkpoint molecule programmed cell death ligand 1 (PD-L1). We sought to analyze PD-L1 expression and its correlation with various clinicopathologic parameters in a contemporary cohort of 134 patients with PC. METHODS: A cohort of 134 patients with PC was studied for PD-L1 immunohistochemistry. The PD-L1 expression was evaluated using a combined proportion score with a cutoff of 1 or higher to define positivity. The results were correlated with various clinicopathologic parameters. RESULTS: Overall, 77 (57%) patients had positive PD-L1 expression. Significantly high PD-L1 expression was observed in high-grade tumors (P = .006). We found that 37% of human papillomavirus (HPV)-associated subtypes and 73% of other histotype tumors expressed PD-L1, while 63% of HPV-associated tumors and 27% of other histotype tumors did not (odds ratio, 1.35; P = .002 when compared for HPV-associated groups vs all others). Similarly, PD-L1-positive tumors had a 3.61-times higher chance of being node positive than PD-L1-negative tumors (P = .0009). In addition, PD-L1 high-positive tumors had a 5-times higher chance of being p16ink4a negative than PD-L1 low-positive tumors (P = .004). The PD-L1-positive tumors had a lower overall survival and cancer-specific survival than PD-L1-negative tumors. CONCLUSIONS: Overall, PD-L1 expression is associated with high-grade and metastatic tumors. Lower PD-L1 expression is observed more frequently in HPV-associated (warty or basaloid) subtypes than in other, predominantly HPV-independent types. As a result, PD-L1 positivity, including higher expression, portends lower overall and cancer-specific survival. These data provide a rational for further investigating PD-L1-based immunotherapeutics in PC.

Multifaceted Spindle Cell/Sclerosing Rhabdomyosarcoma With Role of Immunohistochemistry in Avoiding Misdiagnosis: A Multi-Institutional Study of 45 Distinct Tumors.

Background. Spindle cell/sclerosing rhabdomyosarcoma is a rare neoplasm and has an aggressive clinical course. Because of its rarity, we performed a multi-institutional collaboration to comprehend the overarching clinical, histopathological, and immunohistochemical characteristics of a cohort of spindle cell/sclerosing rhabdomyosarcoma. Materials and Methods. Forty-five patients with spindle cell/sclerosing rhabdomyosarcoma were identified. Demographics, clinical, histopathological, and immunohistochemistry data were reviewed and recorded. Results. The patients' age ranged from 1 to 85 years with a male to female ratio of 1.2:1. There were 15 children/adolescents and 30 adults. Eighteen (40%) tumors were located in the head and neck region. Twenty-four (53%) tumors displayed a bimorphic cellular arrangement with hypercellular areas having short, long, and sweeping fascicular and herringbone pattern, and hypocellular areas with stromal sclerosis and associated hyalinized and/or chondromyxoid matrix. Histomorphological differentials considered were leiomyosarcoma, malignant peripheral nerve sheath tumor, fibrosarcoma, nodular fasciitis, liposarcoma, synovial sarcoma, sarcomatoid carcinoma, solitary fibrous tumor, dermatofibrosarcoma protuberans, and schwannoma. Six tumors exhibited marked stromal sclerosis. The myogenic nature was confirmed by immunohistochemistry. Positivity for at least one skeletal muscle-associated marker (MyoD1 and/or myogenin) was observed. Conclusion. Spindle cell/sclerosing rhabdomyosarcoma diagnosis can be challenging as a number of malignant spindle cell neoplasm mimic this entity. Thus a correct diagnosis requires immunohistochemical work up with a broad panel of antibodies. In view of rarity of this neoplasm, further studies on a large cohort of patients with clinical follow-up data are needed for a better understanding of this tumor.

Aflatoxin B1 administration causes inflammation and apoptosis in the lungs and spleen.

Aflatoxin is a naturally occurring mycotoxin that has numerous toxic effects. The main aim of the present study was to evaluate the toxic effects of aflatoxin B1 (AFB1) on the lungs and spleen. Mice were repeatedly exposed to AFB1 (0.3 mg/kg body weight) on alternate days for four weeks via oral route. The histopathological data in AFB1-treated mice show alveolar epithelial hyperplasia with inflammation and the presence of numerous alveolar macrophages with minimal hemorrhage. There was an increase in vascular neutrophils and interstitial inflammation. The branching of vessels was plugged with neutrophils. AFB1 administration also causes splenomegaly. The AFB1-treated spleen shows the tingible body macrophages (TBM) scattered within the splenic white pulp. Apoptosis may lead to atrophy in a selected region of the white pulp area. There is a decrease in cellularity within the periarteriolar lymphatic sheath (PALS). The inflammation causes the congestion of red pulp with the increase in nuclear debris, and vacuoles are also visible. The flow cytometry data further suggests enhanced apoptosis in lung and spleen cells.

Beyond membrane components: uncovering the intriguing world of fungal sphingolipid synthesis and regulation.

Sphingolipids (SLs) are essential to fungal survival and represent a major class of structural and signaling lipids. Unique SL structures and their biosynthetic enzymes in filamentous fungi make them an ideal drug target. Several studies have contributed towards the functional characterization of specific SL metabolism genes, which have been complemented by advanced lipidomics methods which allow accurate identification and quantification of lipid structures and pathway mapping. These studies have provided a better understanding of SL biosynthesis, degradation and regulation networks in filamentous fungi, which are discussed and elaborated here.

Altered dynamics of mitochondria and reactive oxygen species in the erythrocytes of migrating red-headed buntings.

Background: Blood antioxidants provide propensity to mitigate reactive oxygen species (ROS) apart from other oxidative challenges during a high-energy state of migration in night migratory songbirds. The study investigated the modulation of erythrocytes, mitochondrial abundance, hematocrit changes, and relative expression of fat transport-related genes during migration in red-headed buntings (Emberiza bruniceps). We hypothesized an increase in antioxidants along with the mitigation of mitochondria-related reactive oxygen species elevation and consequential apoptosis occurring during migration. Methods: Male red-headed buntings (n = 6) were placed under short days (8 h of light and 16 h of dark, 8L:16D)/long days (14L:10D) and photo induced to simulated non-migratory, nMig; pre-migratory, pMig; and migratory, Mig, states. Erythrocyte shape, reactive oxygen species production, mitochondrial membrane potential (MMP), reticulocyte proportion, and apoptosis were analyzed using flow cytometry and relative expression of fat metabolizing and antioxidant genes was measured by using qPCR. Results: There was a significant increase in hematocrit, erythrocyte area, and mitochondrial membrane potential. Reactive oxygen species and apoptotic erythrocyte proportion declined in the Mig state. The changes in antioxidant genes (SOD1 and NOS2), fatty acid translocase (CD36), and metabolic (FABP3, DGAT2, GOT2, and ATGL) genes showed a significant increment during the Mig state. Conclusion: These results suggested that adaptive changes occur in mitochondrial behavior and apoptosis of erythrocytes. The transition in erythrocytes, antioxidant genes, and fatty acid metabolism gene expressions suggested differences in regulatory strategies at the cellular/transcriptional level during different states of simulated migration in birds.

Aflatoxin B1 administration induces reactive oxygen species production and apoptosis of erythrocytes in mice.

Aflatoxin is a naturally occurring mycotoxin that has various toxic effects to humans and various other animals. In the current study, we have investigated the toxic effects of Aflatoxin B1 (AFB1) on erythrocytes in the blood circulation of mice. Mice were administered orally with repeated doses of AFB1 (0.3 mg/kg of body weight three times a week for four weeks). AFB1 administration resulted in sustained anemia and a significant reduction in blood erythrocyte number as well as hemoglobin level was seen at different time schedules. Body weight, erythrocyte count, and Hb were significantly decreased on days 30 and 45 post-AFB1 administration. The reticulocytes proportion in circulation was analyzed by staining the cells with anti-mouse CD71 monoclonal antibody and flow cytometric analysis. The ROS level and apoptotic cell proportion were determined by staining with CM-H2DCFDA and Annexin V antibody. AFB1 treatment leads to an increment in reticulocytes production. A significant increase in reactive oxygen species (ROS) and apoptotic cells were also observed in erythrocytes.

Multi-species occupancy modeling suggests interspecific interaction among the three ungulate species.

Species with sympatric distribution influence ecosystem dynamics and are impacted by the presence of other co-existing species. Assessing the coexistence and the role of interspecific interactions with the landscape variables is necessary to know the species co-occurrence in space. In the Indian Himalayan region, such studies are completely lacking due to limited efforts being made, mainly because of complex terrains and inaccessible landscape features. We used camera trapping and sign survey in a multi-species occupancy framework to understand the influence of environmental variables on occupancy and detection probability of species-specific and pair-wise interaction of the three ungulates in Uttarkashi. Our results concluded that individual species' occupancy probabilities were related both to the environmental variables and the presence or absence of other interacting species. Our top model showed evidence of interspecific interaction among species pairs, and the occupancy probability of species one varied in the presence or absence of another species. The overall activity patterns were similar among all the three species and were found active throughout the day. The activity overlap between sambar-barking deer (Dhat1 value = 0.85) was considerably higher than barking deer-goral (Dhat1 value = 0.78). The findings of the present study will be useful for the conservation and management of ungulates in the Indian Himalayan and adjoining regions.

Analytical Validation of a Deep Neural Network Algorithm for the Detection of Ovarian Cancer.

PURPOSE: Early detection of ovarian cancer, the deadliest gynecologic cancer, is crucial for reducing mortality. Current noninvasive risk assessment measures include protein biomarkers in combination with other clinical factors, which vary in their accuracy. Machine learning can be applied to optimizing the combination of these features, leading to more accurate assessment of malignancy. However, the low prevalence of the disease can make rigorous validation of these tests challenging and can result in unbalanced performance. METHODS: MIA3G is a deep feedforward neural network for ovarian cancer risk assessment, using seven protein biomarkers along with age and menopausal status as input features. The algorithm was developed on a heterogenous data set of 1,067 serum specimens from women with adnexal masses (prevalence = 31.8%). It was subsequently validated on a cohort almost twice that size (N = 2,000). RESULTS: In the analytical validation data set (prevalence = 4.9%), MIA3G demonstrated a sensitivity of 89.8% and a specificity of 84.02%. The positive predictive value was 22.45%, and the negative predictive value was 99.38%. When stratified by cancer type and stage, MIA3G achieved sensitivities of 94.94% for epithelial ovarian cancer, 76.92% for early-stage cancer, and 98.04% for late-stage cancer. CONCLUSION: The balanced performance of MIA3G leads to a high sensitivity and high specificity, a combination that may be clinically useful for providers in evaluating the appropriate management strategy for their patients. Limitations of this work include the largely retrospective nature of the data set and the unequal, albeit random, assignment of histologic subtypes between the training and validation data sets. Future directions may include the addition of new biomarkers or other modalities to strengthen the performance of the algorithm.

Cyclic constrained immunoreactive peptides from crucial P. falciparum proteins: potential implications in malaria diagnostics.

Malaria is still a global challenge with significant morbidity and mortality, especially in the African, South-East Asian, and Latin American regions. Malaria diagnosis is a crucial pillar in the control and elimination efforts, often accomplished by the administration of mass-scale Rapid diagnostic tests (RDTs). The inherent limitations of RDTs- insensitivity in scenarios of low transmission settings and deletion of one of the target proteins- Histidine rich protein 2/3 (HRP-2/3) are evident from multiple reports, thus necessitating the need to explore novel diagnostic tools/targets. The present study used peptide microarray to screen potential epitopes from 13 antigenic proteins (CSP, EXP1, LSA1, TRAP, AARP, AMA1, GLURP, MSP1, MSP2, MSP3, MSP4, P48/45, HAP2) of P. falciparum. Three cyclic constrained immunoreactive peptides- C6 (EXP1), A8 (MSP2), B7 (GLURP) were identified from 5458 cyclic constrained peptides (in duplicate) against P. falciparum-infected sera. Peptides (C6, A8, B7- cyclic constrained) and (G11, DSQ, NQN- corresponding linear peptides) were fairly immunoreactive towards P. falciparum-infected sera in dot-blot assay. Using direct ELISA, cyclic constrained peptides (C6 and B7) were found to be specific to P. falciparum-infected sera. A substantial number of samples were tested and the peptides successfully differentiated the P. falciparum positive and negative samples with high confidence. In conclusion, the study identified 3 cyclic constrained immunoreactive peptides (C6, B7, and A8) from P. falciparum secretory/surface proteins and further validated for diagnostic potential of 2 peptides (C6 and B7) with field-collected P. falciparum-infected sera samples.

Pfhrp2/3 gene deletion and genetic variation in PfHRP2-based RDTs with P. falciparum positive samples from India and its implication on malaria control.

BACKGROUND: Recent studies have documented Pfhrp2/3 gene deletion globally as one of the biological threats in the fight against malaria. For malaria diagnosis, PfHRP2 based RDTs are most widely used in India, and performance of these RDTs are affected by deleted Pfhrp2/3 gene in Plasmodium falciparum. This study was planned to confirm Pfhrp2/3 gene deletion incidences and genetic variation in PfHRP2-based RDT positive with P.falciparum malaria cases from India. METHODOLOGY: Confirmed positive samples by PfHRP2-based RDTs as P. falciparum (n = 240) from six different endemic regions of India were validated by PCR to assure the actual infection. Two hundred forty samples qualified for DNA intactness by single-copy genes were subjected to amplification for the Pfhrp2/3 gene and its neighbouring gene (downstream and upstream) by PCR genotyping. Genetic variation in samples was analysed post-sequencing using Mega X software. Statistical analysis was performed to validate the genetic variation using Mann-Whitney Test. RESULTS: RDT target region of Pfhrp2 gene (exon2) was found deleted in a single sample with presence of the Pfhrp3 exon2. Complete gene deletion of 4.2% was observed in the Pfhrp3 gene. Partial gene deletion was recorded for both pfhrp2 gene (exon2-0.4%, upstream 25.8% and downstream -9.1%) and Pfhrp3 gene (exon2-18.75%, upstream - 22.08% and downstream 13.3%). Eleven new unique types of amino acid repeat sequence and earlier reported amino acid repeat type was found in the Pfhrp2 gene, prompting high genetic variation. CONCLUSIONS: This study suggests that parasites lacking Pfhrp2/3 gene and its neighbouring gene (downstream and upstream) are present in malaria endemic areas of India, resulting in false positive results by RDT. Systematic countrywide monitoring for malaria control and elimination of malaria is warranted in this regard.

The integrative bioinformatics approaches to predict the xanthohumol as anti-breast cancer molecule: Targeting cancer cells signaling PI3K and AKT kinase pathway.

Background: Breast cancer is the most common type of cancer in women, and vast research is being conducted throughout the world for the treatment of this malignancy by natural products using various computational approaches. Xanthohumol, a prenylated flavonoid, is known for its anticancer activity; however, the mechanism behind its action is still in the preliminary stage. Methods: The current study aimed to analyze the efficacy of xanthohumol compared to the currently available anticancer drugs targeting phosphoinositide-3-kinase (PI3K), serine/threonine kinase (AKT) receptors, and human epidermal growth factor receptor 2 (HER2) for breast cancer treatment through in silico analysis. Results: The result revealed that the target compound showed significant binding affinity to targets within the PI3K, AKT, and HER2 signaling pathways with a binding energy of -7.5, -7.9, and -7.9 kcal/mol, respectively. Further prediction studies were then made concerning this compound's absorption, distribution, metabolism, and excretion (ADME) as well as drug-likeness properties, resulting in its oral bioavailability with only a single violation of Lipinski's rule of five. Conclusions: The finding revealed the ability of xanthohumol to bind with multiple cancer cell signaling molecules including PI3K, AKT kinase, and HER2. The current novel study opened the door to advancing research into the management and treatment of breast cancer.

COVID-19 associated mucormycosis: Staging and management recommendations (Report of a multi-disciplinary expert committee).

Even before the onslaught of COVID-19 pandemic could settle, the unprecedented rise in cases with COVID-19 associated mucormycosis pushed the medical health to the fringe. Hyperglycaemia and corticosteroids appear to be the most consistent associations leading to the commonest manifestation of mucormycosis, Rhino-Orbito-Cerebral Mucormycosis. To address challenges right from categorisation and staging of the disease to the management of relentless progression, a multi-disciplinary expert committee was formed to handle the task in an evidence-based format to enforce best practices. The report of the committee on one hand attempts to succinctly present the currently available evidence while at the other also attempts to bridge the evidence-deficient gaps with the specialty-specific virtuosity of experts.

p53 and p16ink4a As Predictive and Prognostic Biomarkers for Nodal metastasis and Survival in A Contemporary Cohort of Penile Squamous Cell Carcinoma.

BACKGROUND: Human papilloma virus (HPV) infection is implicated in a proportion of invasive squamous cell carcinoma of the penis (PC). A subset of PC involves dysregulation of the p53 pathway. HPV in situ hybridization (ISH) and p16ink4a positivity are surrogate markers for HPV infection, and p53 immunohistochemistry (IHC) denotes abnormality in the p53 pathway. There remains an ambiguity with regard to the contribution of both the pathways in the prognosis of PC. We sought to analyze the clinicopathologic characteristics of a cohort of Indian PC patients with respect to p16 ink4a and p53 expression. PATIENTS AND METHODS: A cohort of 123 PC patients was studied for p16ink4aand p53IHC and HPVISH. The results of these biomarkers were correlated with various clinicopathologic parameters. RESULTS: p16ink4a and HPV ISH were positive in 47% and 53% of the tumors, respectively. The proportion of warty, basaloid, or mixed warty-basaloid tumor subtypes showed significant p16ink4apositivity (P < .0001) compared to other subtypes. Twenty-eight patients were dual negative (p53- /p16ink4a-), 32 were dual positive (p53+/p16ink4a+), 38 were p53+/p16ink4a-, and 25 were p53-/p16ink4a +. In patients where p16ink4a was negative, a p53-positive phenotype had a higher propensity for lymph node metastases (OR, 5.42; 95% CI, 1.75-16.80; P = .003). Similarly, p53 positivity dictates nodal involvement in the p16ink4a-positive subset of tumors (OR, 5.00; 95% CI, 1.23-20.17; P = .024). On multivariate analyses, pathologic subtypes (warty, warty-basaloid, and basaloid) (P < .0001), p16ink4aexpression (P < .0001), and absence of nodal metastasis (P < .0001) were significant predictors of improved overall (OS) and cancer specific survival (CSS). In Kaplan-Meier analysis, the OS was significantly longer in patients with p16ink4a + tumors (P < .0001), as was the CSS (P < .0001). Patients with dual positive tumors had a significantly higher OS (P < .001) and CSS (P = .012), in the entire cohort. In the node positive patients, dual positivity was associated with significantly higher OS (P < .0001); however, the median CSS for p53+/p16ink4a+tumors were not significantly different compared to p53- /p16ink4a- tumors (P = .064), although there was a trend towards improved CSS. CONCLUSIONS: There is a strong concordance between p16ink4aIHC and HPV ISH results. p16ink4a status is an independent predictor of survival (OS and CSS) in our cohort of PCs. p53 is a predictor of nodal metastasis irrespective of p16 status. Dual positive tumors have a significantly better outcome in comparison to dual negative tumors.

PD-L1 expression and its clinicopathologic and genomic correlation in the non-small cell lung carcinoma patients: An Indian perspective.

BACKGROUND: Immunotherapy with checkpoint inhibitor programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) antibodies targeting the cellular immune checkpoints is the present area of interest showing promising results in patients with advanced non-small cell lung cancer (NSCLC). As there is paucity of PD-L1 expression data from the Indian perspective, we studied the correlation of clinicopathologic profile and oncogenic driver mutations in these patients. MATERIALS AND METHODS: Samples from 252 advanced NSCLCs patients were studied for PD-L1 expression through immunohistochemistry using rabbit anti-human PD-L1 monoclonal antibody (clone SP263) on Ventana BenchMark ULTRA autostainer. Simultaneously, genetic mutations were studied by next generation sequencing (for EGFR, ALK, ROS, MET, and BRAF). PD-L1 expression was analyzed for association with clinicopathologic features and various mutations. RESULTS: PD-L1 positivity was seen in 134 patients (53.2 %). It was twice more prevalent in males than females. No significant correlation was observed between PD-L1 expression with age, gender, site of testing (primary vs. metastatic tumors), smoking status, tumor laterality, stage, or histologic type; however, there was significant difference among solid and acinar types of adenocarcinoma combined together vs. other adenocarcinoma subtypes (p = 0.013), and well and moderately differentiated vs. poorly differentiated tumors (p = 0.022). When types/extent of PD-L1 positivity (≥25 %) were compared with demographics, clinical, and pathologic variables, significant differences were observed across the tumor grades (high-grade vs. low-grade) (p = 0.009) and stages (p = 0.039). The PD-L1 expression failed to demonstrate any statistical significance with oncogenic drivers. High PD-L1 expression (TPS ≥ 50) was observed in 27.6 % patients, and it was more prevalent in female patients (32.4 %), aged ≥60 years (33.8 %), smokers (27.3 %), poorly differentiated (36.8 %) and stage IV tumors (28.2 %). Exon 19 deletion was more prevalent in PD-L1 negative tumors whereas exon 21 substitution (L858R) was seen more in PD-L1 positive tumors. CONCLUSIONS: This is the largest Indian study demonstrating PD-L1 expression in NSCLC patients comparing with clinicopathologic and genomic parameters. PD-L1 expression was significantly associated with high-grade, solid, and acinar types of adenocarcinoma and advanced tumors. High PD-L1 expression was more prevalent in female patients, aged ≥60 years, smokers, and poorly differentiated and stage IV tumors (28.2 %). Exon 19 deletion was more in PD-L1 negative tumors whereas exon 21 substitution (L858R) was more in PD-L1 positive tumors. PD-L1 is a potential predictive marker stratifying patients who benefit from PD-1 pathway-targeted therapy.