EEG based functional connectivity in resting and emotional states may identify major depressive disorder using machine learning.

OBJECTIVE: Disrupted brain network connectivity underlies major depressive disorder (MDD). Altered EEG based Functional connectivity (FC) with Emotional stimuli in major depressive disorder (MDD) in addition to resting state FC may help in improving the diagnostic accuracy of machine learning classification models. We explored the potential of EEG-based FC during resting state and emotional processing, for diagnosing MDD using machine learning approach. METHODS: EEG was recorded during resting state and while watching emotionally contagious happy and sad videos in 24 drug-naïve MDD patients and 25 healthy controls. FC was quantified using the Phase Lag Index. Three Random Forest classifier models were constructed to classify MDD patients and healthy controls, Model-I incorporating FC features from the resting state and Model-II and Model-III incorporating FC features while watching happy and sad videos respectively. RESULTS: Important features distinguishing MDD and healthy controls were from all frequency bands and represent functional connectivity between fronto-temporal, fronto-parietal and fronto occipital regions. The cross-validation accuracies for Model-I, Model-II and Model-III were 92.3%, 94.9% and 89.7% and test accuracies were 60%, 80% and 70% respectively. Incorporating emotionally contagious videos improved the classification accuracies. CONCLUSION: Findings support EEG FC patterns during resting state and emotional processing along with machine learning can be used to diagnose MDD. Future research should focus on replicating and validating these results. SIGNIFICANCE: EEG FC pattern combined with machine learning may be used for assisting in diagnosing MDD.

Bioproduction of yeast single cell oil with acute oral toxicity study intended for edible oil application.

Human nutrition and health rely on edible oils. Global demand for edible oils is expanding, necessitating the discovery of new natural oil sources subjected to adequate quality and safety evaluation. However, in contrast to other agricultural products, India's edible oil supply is surprisingly dependent on imports. The microbial oil is generated by fermentation of oleaginous yeast Rhodotorula mucilaginosa IIPL32 MTCC 25056 using biodiesel plant byproduct crude glycerol as a fermentable carbon source. Enriched with monounsaturated fatty acid, nutritional indices mapping based on the fatty acid composition of the yeast SCO, suggested its plausible use as an edible oil blend. In the present study, acute toxicity evaluation of the yeast SCO in C57BL/6 mice has been performed by randomly dividing the animals into 5 groups with 50, 300, 2000, and 5000 mg/Kg yeast SCO dosage, respectively, and predicted the median lethal dose (LD50). Detailed blood biochemistry and kidney and liver histopathology analyses were also reported. The functions of the liver enzymes were also evaluated to check and confirm the anticipated toxicity. To determine cell viability and in vitro biocompatibility, the 3T3-L1 cell line and haemolysis tests were performed. The results suggested the plausible use of yeast SCO as an edible oil blend due to its non-toxic nature in mice models.

A Study of Ki-67 Immunostaining in Prostate Carcinomas and Its Correlation with Gleason's Score and Prognosis: An Experience at a Tertiary Centre in the Himalayan Foothills.

Prostate cancer is a significant cause of cancer-related mortality among men worldwide, necessitating the exploration of prognostic biomarkers to aid in accurate risk assessment and treatment decision-making. This cross-sectional study aimed to comprehensively evaluate the role of Ki-67 as a prognostic marker in prostate cancer by examining its association with clinicopathological parameters. A total of 102 archived cases of prostate core biopsy specimens, histopathologically reported as prostate carcinoma, were included in this study. Histopathological grading was conducted using Gleason's scoring and grading system based on morphology. The statistical software "R" was utilized for data analysis. Kruskal-Wallis test and Fisher's exact test were employed to analyze the association between Ki-67 expression and clinicopathological parameters. The study revealed significant correlations between Ki-67 expression and various clinicopathological parameters in prostate cancer cases. High Ki-67 expression levels were associated with higher Gleason scores, increased incidence of perineural invasion, advanced T stages, lymph node metastasis, presence of distant metastasis, and higher prognostic stage groups. The findings of this cross-sectional study support the potential of Ki-67 as a prognostic marker in prostate cancer. The significant associations observed between Ki-67 expression and clinicopathological parameters indicate its usefulness in risk stratification and treatment decision-making. The incorporation of histopathological grading, including Gleason scoring, and analysis of perineural invasion strengthens the validity of the study. Ki-67, in combination with morphological assessments, provides valuable prognostic information for prostate cancer patients.

Beware it's benign: A unique case of concomitant benign breast pathologies.

Complex sclerosing lesion (CSL)/radial scar of breast is a benign entity that can pose a diagnostic challenge due to resemblance to breast carcinoma on imaging. Hamartoma are uncommon benign tumors, composed of disorganized mixture of glandular, fibrous, and adipose tissues, which can exhibit classical imaging characteristics. Here we describe a case of concomitant CSL and hamartoma in left beast, of which CSL presented as suspicious mass on imaging but was ultimately confirmed to be benign on histopathology with 4 years of documented stability.

Systematic Review of Sleep Duration and Development of Myopia.

There is a knowledge gap in the relationship between sleep duration and myopia. Since sleep duration is a modifiable risk factor, its association with the development and progression of myopia has implications for public health. This review was conducted in accordance with the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The bibliographic databases of PubMed and Scopus were searched for published studies on the association between sleep duration and myopia. These databases were searched in December 2023 with no date or study design limits. The relevant literature was extracted and met the priori determined population (children, adolescents, and adults suffering from myopia with or without corrective glasses), intervention/exposure (sleep), and the outcome (various indicators of sleep especially sleep duration/bedtime/wake time and sleep quality). Data were gathered by gender, age, and refraction technique and standardized to the definition of myopia as refractive error ≥0.50 diopter. The relevant literature was extracted from these electronic databases using the keywords "sleep," "sleep duration," "bedtime," and "myopia." English language articles related to the topic were included. Articles that have discussed the role of risk factors for myopia but did not mention any relation to sleep were excluded. Sixteen studies were included after reviewing the relevant literature, and only six studies have shown a significant relationship between shorter duration of sleep and the development of myopia. This review suggests that apart from other environmental factors, sleep duration may have a role in developing myopia. Thus, increasing awareness about optimum sleep duration has a potential utility to reduce the development and progression of myopia.

The Relationship of Grade, Stage and Tobacco Usage in Head and Neck Squamous Cell Carcinoma With p53, PIK3CA and MicroRNA Profiles.

BACKGROUND:  Head and neck squamous cell carcinoma (HNSCC) has multiple epigenetic modifications including post-transcriptional regulation by microRNAs (miRNAs) as well as alterations in molecular pathways due to mutations. Examining these miRNAs and location-specific molecular alterations is essential to understanding the intricacies of HNSCC and directing focused diagnoses and treatments. AIM:  To investigate tobacco-related changes in the expression of miRNAs and proteins with clinicopathological parameters of HNSCC and disease-modifying personal habits like tobacco and alcohol use. METHODOLOGY:  The study concentrated on oropharyngeal cancers using immunohistochemistry and reverse transcription-polymerase chain reaction. Expression of microRNAs mir15a, mir20b, mir21, mir31, mir33b, mir146a, mir155, mir218, mir363 and mir497 and immunohistochemical expression of P53 and PIK3CA were correlated with grade, stage and personal habits like tobacco and alcohol intake. RESULTS:  mir21 and mir15a are under-expressed in higher grades with a trend towards statistical significance (P-value of 0.094 and 0.056 by one-way analysis of variance (ANOVA) on ΔCT values). mir155 and mir146a are overexpressed in stage IV tumours while mir 31 is under-expressed in stage IV tumours but statistical significance was not reached. mir497 showed overexpression in tobacco users, but these results were limited by many tumours not showing any amplification for the miRNA and statistical significance was not reached. There was no statistically significant association found between immunohistochemical expression of p53 and PIK3CA with grade, stage or personal habits. CONCLUSION:  Through the deciphering of complex miRNA patterns and their relationships with clinicopathology, this study attempted to increase our understanding of HNSCC. Some candidate miRNAs showing probable association with grade, stage and personal habits were identified, but larger studies are needed to confirm or refute the importance of these miRNAs.

Comparison of Patient's Procedural Tolerance of EBUS-TBNA Performed Through Nasal Versus Oral Route: The NO-EBUS Randomized Clinical Trial.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a commonly performed procedure by the bronchoscopist for the evaluation of mediastinal lesions. However, evidence directly comparing the nasal and oral routes to guide the choice of an optimal insertion approach is scanty. METHODS: In this prospective, parallel-group, open-label randomized clinical trial, adults posted for a linear EBUS-TBNA examination under conscious sedation were randomized to undergo the procedure via the nasal or oral route. The primary objective was to assess the equivalence of subject-rated tolerance of EBUS-TBNA procedure in the 2 groups. Key secondary objectives were to assess the equivalence of subject-rated overall experience, willingness for a repeat procedure, operator-rated subject's tolerance, and operator-rated ease of performing the procedure. RESULTS: One hundred and eighty subjects were randomized in a 1:1 ratio to the nasal (n=98) or oral (n=82) group. Outcome measures were assessed by both per-protocol (PP) and intention-to-treat (ITT) analysis. Subject-rated procedural tolerance, overall satisfaction and operator's ease of performing the procedure were found to be equivalent in the 2 groups ( P <0.05 in all cases for PP and ITT analysis). The operator-rated subject's tolerance was, however, nonequivalent ( P =0.0596, 0.1286 for PP and ITT, respectively). Subject's willingness to undergo a repeat procedure was similar in both groups [90% CI of difference in proportions: (-0.023, 0.121) in PP and (-0.028, 0.115) in ITT analysis]. CONCLUSION: Nasal route for EBUS-TBNA could be considered where it is feasible and preferable for the patient as well as the operator.

Leukemia-associated aberrant immunophenotype: A flow cytometry-based experience of 110 cases from a tertiary care center in Northern India.

Background: Leukemic cells express a characteristic set of "cluster of differentiation" (CD) markers, which forms the basis of the current WHO classification. Leukemia-associated aberrant immunophenotype (LAIP) refers to expression of unusual CD markers by leukemic cells, which are not normally expressed by their respective lineage. The incidence of LAIP varies considerably, and its clinical implications, prognostic relevance, and sensitivity to therapy are still debatable. This study was conducted to identify the immunophenotypic aberrancies in newly diagnosed leukemias in our Institute. Method: This was an observational study, which included newly diagnosed leukemias on flow cytometry. Aberrant immunophenotypic expressions were recorded whenever present and were correlated with prognostic factors like age, gender, and total leucocyte count (TLC). Results: The study included 110 newly diagnosed cases of leukemias (85 acute and 25 chronic) over 1.5 years. Immunophenotypic aberrancies were detected in 40.4% of the cases. The highest incidence of aberrations was detected in acute myeloid leukemia (60.7%). LAIPs were detected in 50% of T-acute lymphoblastic leukemia and 25% cases of in B-cell acute lymphoblastic leukemia (B-ALL). Aberrant CD33 and CD56 expression in B-ALL correlated with poor prognostic factors like higher age and higher TLC, respectively. Immunophenotypic aberrancies were present in 28% cases of chronic lymphocytic leukemia. Conclusion: The results of this study have generated valuable baseline data on the incidence of LAIPs in this region. This information is vital because establishing LAIPs at the time of diagnosis is crucial for disease monitoring. Some LAIPs are associated with underlying cytogenetic abnormalities and hence impact the management and prognosis.

Detecting Human Epidermal Growth Factor Receptor 2 (HER2) Amplification: Proof of Concept of an Alternative Approach.

BACKGROUND: There are multiple genes that are co-amplified along with human epidermal growth factor receptor 2 (HER2) in chromosome 17. GRB7 and PGAP3 are two such genes. We hypothesize that the protein products of these genes may serve as immunohistochemistry (IHC) markers for detecting HER2 amplification in breast cancer. METHODS: Tissue sections from one hundred and thirty-five primary breast carcinoma cases were subjected to immunohistochemical staining for antibodies against HER2, GRB7, and PGAP3 and graded on a scale of 1 to 3. Both membranous staining and cytoplasmic staining were assessed for GRB7 and PGAP3. For equivocal HER2 IHC positivity, fluorescent in situ hybridization was performed to get the final HER2 status. RESULTS: IHC staining for GRB7 and PGAP 3 was a moderate to strong predictor for HER2 status (area under the curve (AUC) of 0.768, 0.868,0.754, and 0.790 for GRB7 membranous staining, GRB7 cytoplasmic staining, PGAP3 membranous staining, and PGAP3 cytoplasmic staining respectively). A combination of GRB7 cytoplasmic and PGAP3 membranous staining resulted in an AUC of 0.905 (95% CI 0.855-0.954), while a combination of GRB7 and PGAP3 cytoplasmic staining resulted in an AUC of 0.902 (95% CI 0.851-0.953). CONCLUSION: The point estimates for the AUC of GRB7 and combined GRB7 and PGAP3 in predicting the AUC suggest a strong predictive ability of these markers to predict HER2. With further refinement in technique, cytoplasmic staining and membranous IHC staining for GRB7 and PGAP3 have potential to serve as surrogate markers for HER2 status. The strategy of using protein products of co-amplified genes of HER2 is likely to be successful in technical validation.

Thalassemia and Hemoglobinopathy Screening in Women Attending Antenatal Clinic at a Tertiary Care Center in Uttarakhand, India: A Re-look at the Laboratory Parameters Mandating High-Performance Liquid Chromatography Workup.

INTRODUCTION: Thalassemia and hemoglobinopathies are the most common inherited hematological disorders. Of these, ß thalassemia is the commonest disorder reported in India, followed by certain hemoglobinopathies encountered in different regions of the country. The data pertaining to the incidence of these disorders in the Uttarakhand region of India are sparse. AIM AND OBJECTIVES: To ascertain the prevalence and spectrum of thalassemia/hemoglobinopathies amongst antenatal women in Uttarakhand. The study also aimed to analyze the ability of red cell indices in differentiating beta thalassemia trait (BTT) from mild iron deficiency anemia (IDA). MATERIAL AND METHODS: A total of 460 pregnant women in the first trimester of pregnancy were screened by cation exchange high-performance liquid chromatography. Retention time and proportions of normal/abnormal hemoglobin peaks were documented in all cases. Hemoglobin A2 (HbA2) values of ≥4% were taken as a cut-off for diagnosing BTT. Blood samples were also collected for complete blood counts, reticulocyte counts, and serum ferritin. The ability of the various discriminatory indices to differentiate between IDA and BTT was also assessed. RESULTS: The prevalence of BTT and hemoglobin D-Punjab trait amongst pregnant women was found to be 2.6% and 0.2%, respectively. RBC count, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) were found to be moderately strong predictors of BTT, with an area under the curve of 0.860, 0.857, and 0.842, respectively, which were comparable to the discriminatory indices found to be most useful in this study. CONCLUSION: In view of the 2.6% prevalence of BTT in antenatal women in this region of Uttarakhand, a routine screening will be helpful in detecting carriers early in the antenatal period. Careful interpretation of red cell indices is crucial to the distinction between BTT and IDA. Discriminatory indices are reasonably accurate in differentiating BTT from mild iron deficiency, but for practical purposes, MCV and MCH provide equivalent information to identify cases that require further workup.

Cytomorphologic visualization of circulating tumor cells in urinary bladder cancer patients using ScreenCell™ technology: Potential as a simple cytology test.

Circulating tumor cells (CTC) are a recent technique which is a potentially important prognostic factor in many solid tumors. There are many techniques of detecting CTCs, but they usually implement costly techniques like EpCAM targeted detection, fluorescence-based diagnosis, or magnetic bead based positive or negative selection. The diagnostic utility of simple cytomorphological diagnosis after routine staining of CTCs have been rarely studied. We aimed to detect CTCs in 24 patients clinically suspected to have Urinary Bladder Cancer using a simple but efficient patented filtration technology (ScreenCell™), followed by optical microscopic visualization after routine May-Grunwald-Giemsa (MGG) staining. The detected CTCs were then tested for association with the histologic type, lamina propria invasion, deep muscle invasion and the T-stage. Out of the 24 patients tested, one was found to have papilloma, nine had low grade urothelial carcinoma, 13 had high grade urothelial carcinoma and one had poorly differentiated adenocarcinoma. Of these, two LGUC, eight HGUC and one adenocarcinoma had detectable CTC. Presence of CTCs had a statistically significant association with Lamina propria invasion (P = .006) and T-stage (P = .02), and a trend toward significance for differentiating LGUC from HGUC (P = .10). These results suggest that cytomorphological detection of CTC is likely to be clinically useful in diagnosis and prognostication of urinary blader cancers. These findings need to be confirmed on studies with larger sample sizes.

Insights into the perceptual moment theory: Experimental evidence from simultaneity judgment.

The perception appears to flow in a continuous pattern but evidence suggest that perception may involve discrete temporal sampling of peripheral cues. Stroud's perceptual moment theory proposes that perception occurs in discrete moments; however, more experimental evidence is required to support this theory. The present study characterized the decision function for asynchrony detection using variable stimulus-onset asynchronies (SOAs). Fourteen healthy volunteers (twelve males and two females), ages 21.5 ± 3.8 years (mean ± SD) participated in the study. A microcontroller was used to randomly present 280 events of paired stimuli (two red LEDs) with varying SOAs from -65 to 65 ms in steps of 5 ms. Participants were asked to press the "L" or "R" response key based on whether the left or right LED lit up first and to press the "S" key if they could not perceive the order. Asynchrony detection does not exhibit a fixed threshold value; instead, its decision function shows a monotonic increase with increasing SOAs. The asynchrony detection was 50% at an SOA of 27.8 ± 1.7 ms (mean ± SE). The curve plateaued off near 100% at SOA of 57.2 ms, which may correspond to the duration of one perceptual moment for visual perception. Data from a separate group of ten volunteers was used to validate the results. Results indicate that perception is temporally discretized rather than continuous, and the estimated duration of one perceptual moment is around 57.2 ms. This simple experiment gives objective evidence for Stroud's perceptual moment theory.

Malignant pleural effusion from a case of squamous-cell carcinoma of the oral cavity: Cytological detection of a rare outcome.

Distant metastases from carcinomas of the oral cavity are rare. Detection of these metastasis are essential for staging and management of the patient. These tumours may metastasize to lung, liver, brain and bone; but pleural involvement by squamous-cell carcinoma is distinctly rare. We present a case of bilateral pleural effusion arising from distant metastasis of squamous-cell carcinoma detected on cytology.

Systematic Review and Meta-Analysis of the Diagnostic Accuracy of the International Academy of Cytology Yokohama System for Reporting Breast Fine-Needle Aspiration Biopsy in Diagnosing Breast Cancer.

OBJECTIVES: The primary objective is to determine the accuracy of fine-needle aspiration biopsy (FNAB) in breast lesions reported according to the International Academy of Cytology (IAC) Yokohama system for reporting breast FNAB. The participants include any patient presenting with any breast lesion found suitable for FNAB. The target condition was breast cancer. The secondary objective was to study the proportion of inadequate FNAB in the selected studies. METHODS: PubMed/MEDLINE and Embase were searched for studies having all the following key search terms: Breast AND FNAB AND Diagnostic Accuracy published in the time frame of 2017 to May 16, 2022. The Cochrane and PROSPERO databases, citations of selected articles and articles citing the selected articles were also searched. Studies assessing the diagnostic accuracy of breast FNAB in diagnosing breast cancer, which had at least 75 subjects (and at least 20 subjects each in the benign and malignant FNAB groups), were selected. The reference standard was histopathology (or adequate clinical follow-up for benign disease). Studies were screened independently by two researchers, with a consensus reached among the authors in cases of conflict. The risk of bias and applicability were assessed using the QUADAS-2 tool. Sensitivity and specificity at each diagnostic cut-off were assessed by bivariate generalized linear mixed-model meta-analysis. The area under the receiver operating characteristics curve (AUC) and inadequacy rate were assessed by random-effects meta-analysis. The confidence intervals of sensitivity, specificity, and AUC were examined against a value of 0.95. RESULTS: Twenty-two studies, all of which were cross-sectional single-gate studies, were selected with a total of 10,886 subjects with a primary breast lesion having concurrent FNAB and reference standard reports. Sensitivity and specificity, with 95% confidence intervals, were 0.978 [0.968, 0.985] and 0.832 [0.76, 0.886] for the diagnostic cut-off of "Atypical considered positive for malignancy," 0.916 [0.892, 0.935] and 0.983 [0.97, 0.99] for the cut-off of "Suspicious of Malignancy considered positive," and 0.763 [0.706, 0.812] and 0.999 [0.994, 1] for the cut-off of "Malignant considered positive." The overall AUC was 0.975 [0.962, 0.984]. FNAB sampling without imaging guidance was associated with lower inadequacy. DISCUSSION: There is strong evidence that the overall accuracy, sensitivity for "Atypical category considered positive" and specificity when "Suspicious or Malignant categories are considered positive" of FNAB are high when using the categories of the IAC Yokohama Reporting System, demonstrating the usefulness of FNAB in diagnosing breast cancer.

Flow Cytometric Expression of CD49d in Newly Diagnosed Chronic Lymphocytic Leukemia and Its Correlation with Established Prognostic Markers.

Introduction Chronic lymphocytic leukemia (CLL) is the commonest hematological malignancy in the West but is relatively uncommon in India. The prognosis of CLL is determined by well-established prognostic markers. CD49d has been emerging as a promising prognostic marker in CLL. CD49d expression in CLL has been found to have an aggressive clinical course, shorter time to first treatment, and poorer prognosis. The aim of this study was to analyze the flow cytometric expression of CD49d in newly diagnosed CLL and to correlate its expression with clinico-hematological parameters. Materials and Methods Twenty-five consecutive patients of CLL, diagnosed on flow cytometry, were included in the study. Patients on treatment or those with relapse were excluded. The panel for flow cytometry included the routine markers used for CLL diagnosis along with CD49d. The expression of CD49d was correlated with clinico-hematological parameters in all patients. "R" software was used for the statistical analysis. Fisher's exact test and Wilcox test were used to assess the correlation of CD49d to categorical and continuous data, respectively. Results The mean age of the patients was 62.6 ± 12.5 years, and 80% were symptomatic at diagnosis. CD49d expression was found in 44% cases, with a higher proportion being male patients. CD49d and prolymphocyte percentage showed a statistically significant correlation ( p = 0.0007). We found a statistically significant correlation between CD49d expression and lymphadenopathy and splenomegaly with p -values of 0.033 and 0.0472, respectively. CD49d positivity correlated significantly with a higher Rai stage ( p = 0.0196) and intermediate and high-risk cases according to Binet staging ( p = 0.033). Conclusion CD49d expression in the present study correlated with a higher prolymphocyte percentage, lymphadenopathy, splenomegaly, and higher Rai and Binet stages. CD49d expression on flow cytometry was reproducible and easy to interpret.

Relationship of Tubule Formation, Indian File Pattern and Apocrine Change With Estrogen and Progesterone Receptors and HER2 Immunostaining.

OBJECTIVES: In breast carcinomas, histomorphological features like low-grade and lobular differentiation are associated with estrogen receptor (ER) and progesterone receptor (PR) expression. Apocrine carcinoma is associated with human epidermal growth factor receptor 2 (HER2) positivity. Studies have not emphasized the association between other histological features like tubule formation, Indian file pattern and apocrine change (which may be found in all grades of tumors or as a part of a mixed pattern of no special type) and immunohistochemistry (IHC). The study was designed to find the association between these morphological factors and ER, PR and HER2 status. MATERIALS AND METHODS: The presence or absence of tubule formation, Indian file pattern and apocrine change was correlated with ER, PR and HER2 expression in core biopsies of 102 invasive breast carcinomas. STATISTICAL ANALYSIS: Fisher exact test with median unbiased odds ratio was used. RESULTS: Tubule formation and/or Indian file pattern were significantly associated with ER in all tumors (P-value <0.001), as well as separately for grade II, grade III, HER2-negative and HER2-positive tumors. Comparable results were obtained for their association with PR. Apocrine change was significantly associated with HER2 in all tumors (P-value <0.001), as well as separately for grade III, ER-positive and ER-negative tumors. CONCLUSION: These histomorphological patterns are modest predictors of IHC status in breast carcinomas, even in tumors of higher grade. Knowledge of these morphological correlates of ER, PR and HER2 in breast cancer may serve as an aid in the quality management of breast carcinoma reporting.

Expression of Programmed Cell Death-1 (PD-1) and Its Ligand (PD-L1) in Breast Cancers and Its Association with Clinicopathological Parameters.

Introduction Cancer immunotherapy targeting the programmed cell death ligand 1 (PD-L1) and programmed cell death-1 (PD-1) axis has revolutionized cancer therapy. PD-L1 also serves as a predictive marker for such therapy. To assess the potential of such therapy in any cancer, the positivity of PD-1 and PD-L1 in such cancers needs to be assessed. However, such studies for breast cancer are lacking in South Asia. We aimed to estimate the positivity of PD-L1 and PD-1 receptors in breast cancer and its various clinicopathological groups in our patient population. Materials and Methods We studied the immunoexpression of PD-1 and PD-L1 in 103 histologically proven invasive carcinoma breast cases from October 2018 to April 2019. The percent positivity of PD-1 and PD-L1 with 95% confidence intervals (CI) was estimated for all the cases as well as groups defined by stage, grade, molecular subtype, hormone receptor status, K i -67, and age. Results PD-1 positivity was seen in 72 (69.9%) cases (95% CI: 60.1-78.6). PD-L1 immunoexpression was seen in 61 (59.2%) cases (95% CI: 49.1-68.8) in immune cells and in 39 (37.9%) cases (95% CI: 28.5-50.0) in tumor cells. No significant association was found between PD-1, PD-L1 and age, overall clinical stage, grade, size, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and K i -67. Moderate-to-high PD-1 and PD-L1 immunopositivity was seen in all subtypes of breast cancer. Conclusion PD-1 and PD-L1 is expressed in all subgroups of breast carcinoma. Patients in all such groups are amenable to immunotherapy, provided they are found suitable otherwise.

Immunoexpression of Programmed Death-1 Receptor (PD-1) and Programmed Death-Ligand 1 (PD-L1) in Non-Small-Cell Lung Carcinoma and Its Correlation With Other Clinicopathological Parameters: A Cross-Sectional Study From North India.

Aim To study the prevalence of programmed death-1 receptor (PD-1) and programmed death-ligand 1 (PD-L1) positive cases in non-small-cell lung carcinoma (NSCLC) and their association with other clinicopathological parameters in a tertiary care setting in North India. Material and methods One hundred histologically proven NSCLC cases having sufficient tumor material from July 2016 to July 2018 were examined, and the prevalence of PD-1 and PD-L1 positivity in NSCLC was studied. In addition, H&E-stained sections were reviewed, and 100 consecutive cases meeting study criteria were identified as study cases. Histopathological categorization was done using a panel of immunohistochemical markers. Statistical analysis and results The PD-1 positivity in lymphocytes was 29% (95% CI: 20.4%-38.9%). Membranous positivity for PD-L1 in tumor cells was 27% (95% CI: 18.6%-36.8%) and in tumor-infiltrating lymphocytes was 22% (95% CI: 14.3%-31.4%). There was no statistically significant association between PD-1 or PD-L1 status with age, gender, smoking, pleural effusion, clinical stage, histological type, or lymphocyte infiltration. Conclusion The moderately high prevalence may justify routine testing for PD-1 or PD-L1 in NSCLC, which should preferably be carried out in all cases rather than any selected subsets. However, there was no significant correlation between PD-1 and PD-L1 with the clinical parameters studied.

Clinical and Biochemical Correlation With Cytomorphological Findings of Lymphocytic Thyroiditis: An Experience at a Tertiary Centre in the Himalayan Foothills.

Introduction Lymphocytic thyroiditis is an autoimmune disorder and one of the major causes of hypothyroidism. On cytomorphology, it is characterized by follicular destruction by lymphocytes with elevated biochemical markers, including a panel of autoantibodies against thyroid antigens. This study aimed to determine the prevalence of various cytological features of lymphocytic thyroiditis and their correlation with clinical presentation and biochemical parameters. Materials and methods We conducted a hospital-based cross-sectional study of 105 patients diagnosed with lymphocytic thyroiditis on cytology at our tertiary care center in the Himalayan foothills from December 2018 to December 2019. We recorded and analyzed baseline demographic characteristics, clinical features, and biochemical parameters to assess correlations between cytological findings and grades. Results The study included 105 patients with lymphocytic thyroiditis (90 females, 15 males). The study population age ranged from 11 years to 80 years, with the disease most common in patients aged 21 to 40 years. Grade II was the most common cytological presentation (n=65, 62%). Thyroid-stimulating hormone levels were elevated in 33.3% of cases, and anti-thyroid peroxidase levels were elevated in all 25 cases for whom data were available (p>0.05). Conclusion Cytological diagnosis of lymphocytic thyroiditis was compatible in all cases in the study. However, cytological grading did not correlate with the clinical presentation and biochemical parameters. The diagnosis of lymphocytic thyroiditis could be missed if clinicians use clinical findings and biochemical parameters alone.

Intermittent hypoxia and sleep disruption in obstructive sleep apnea increase serum tau and amyloid-beta levels.

Obstructive sleep apnea is characterized by intermittent hypoxia and sleep disruption, leading to accelerated neurodegenerative changes and cognitive decline. Serum amyloid-beta and tau proteins, which are markers for Alzheimer's disease, have been reported to increase in patients with obstructive sleep apnea. This study compared the serum levels of amyloid-beta proteins and tau proteins in 46 cognitively normal obstructive sleep apnea patients and 30 healthy controls. Sleep parameters and severity of obstructive sleep apnea were determined using overnight polysomnography. Serum levels of Aß40, Aß42, total tau and phosphorylated-tau were determined by enzyme-linked immunosorbent assay. Patients with obstructive sleep apnea had significantly higher median serum levels of Aß40 (121.0 versus 78.3 pg ml-1 ), Aß42 (105.6 versus 18.6 pg ml-1 ) and total tau (168.5 versus 10.9 pg ml-1 ) than controls. Serum levels of phosphorylated-tau did not differ significantly between the two groups. Serum levels of amyloid and tau proteins correlated with parameters of nocturnal oxygen saturation. Rapid eye movement sleep was negatively correlated with total amyloid-beta proteins. We conclude that serum levels of amyloid-beta and total tau are higher in patients with obstructive sleep apnea and hypoxia as well as changes in sleep architecture associated with their increased levels. Patients with obstructive sleep apnea should be closely monitored for the signs of cognitive impairment. Obstructive sleep apnea is a modifiable risk factor, and its treatment may reverse neurodegenerative changes and prevent cognitive impairment.