Correlation of Molecular Subtypes with Clinico-pathological Parameters in Breast Carcinoma

Background: To determine the correlation between clinic-pathological parameters, like age of the patient, size of the tumour, histologic type and grade with molecular subtype. Methods : This observational study included cases of breast cancer (n=50) . Histological grade was assessed according to Nottingham modification of Bloom-Richardson system. Representative sections with tumour and the adjacent normal tissue ( internal control) were processed for ER, PR and HER-2neu immune-histochemical staining. Thescoring of ER and PR was carried out using Allred scoring system. Molecular subtypes were defined as, triple negative/basal type(HER 2 -,ER- and PR-), hormone receptor(HR) +,HER2-/luminal A(HER2-, ER+ and PR+ or -), HR+,HER2+/luminal B(HER2 +,ER+ and PR+ or-), HR-,HER2+/HER2 enriched(HER2+, ER- and PR -). Results: Majority (96%) were infiltrating ductal carcinoma, one was invasive lobular carcinoma and one was colloid carcinoma. Three cases (6%) grade 1 carcinoma were recorded of which one case (2%) each was of luminal A, luminal B and HER2 enriched type. There were 23 (46%) grade 2 cases of which 8(16%) were luminal A, 7(14%) of luminal B, 7(14%) of HER2 enriched and one (2%) was basal like. There were 24(48%) grade 3 cases of which 6(12%) were luminal A, 9(18%) of luminal B, 6(12%) were HER2 enriched and 4(8%) were basal like. Conclusion: Along with other variables, molecular subtype is important in predicating prognosis of carcinoma breast .Luminal A cancers are more common in older age, while Luminal B are common in younger age group. Key Words: Carcinoma breast,Molecular Subtypes, Estrogen receptor, progesterone receptor, Human epidermal growth factor recepto

PRIMARY BILATERAL BREAST LYMPHOMA: A REVIEW OF LITERATURE AND REPORT OF FOUR CASES FROM A SINGLE CENTRE

Primary breast lymphoma is a rare entity and carries poor prognosis, bilateral breast lymphoma is even rarer and carries worst prognosis. Bilateral breast lymphoma is a rare disease and lacks treatment. Out of the 2766 cases of non- Hodgkin’s lymphoma registered at our institute from 1994 to 2013, 31 cases of breast lymphoma were found, of which four cases had bilateral involvement. In this review, we describe clinical presentation, histopathological subtypes, treatment administered and outcome of those four cases retrospectively. All patients were female with a median age of 31 years (range 24–64 years). Three patients were diagnosed with diffuse large B-cell lymphoma and mucosa associated lymphoid tissue lymphoma detected in one patient. Chemotherapy remained the main treatment modality and surgery (excision biopsy) was reserved for diagnostic purpose only, none of the patients received radiation therapy. Key words: Breast lymphoma, histopathological subtypes, palliation

Detection of BCR-ABL kinase domain mutations in CD34+ cells from newly diagnosed chronic phase CML patients and their association with imatinib resistance

BCR-ABL kinase domain (KD) mutations, the most common cause of imatinib resistance, are infrequently detected in newly diagnosed chronic-phase chronic myeloid leukemia (CP-CML) patients. Recent studies indicate pre-existing mutations (PEMs) can be detected in a higher percentage of CML patients using CD34+ stem/progenitor cells, and these mutations may correlate with imatinib resistance. We investigated KD mutations in CD34+ stem cells from 100 CP-CML patients by multiplex ASO-PCR and sequencing ASO-PCR products at the time of diagnosis. PEMs were detected in 32/100 patients and included F311L, M351T, and T315I. After a median follow-up of 30 months (range 8-48), all patients with PEMs exhibited imatinib resistance. Of 68 patients without PEMs, 24 developed imatinib resistance. Mutations were detected in 21 of these patients by ASO-PCR and KD sequencing. All 32 patients with PEMs had the same mutations. In imatinib-resistant patients without PEMs, we detected F311L, M351T, Y253F, and T315I mutations. All imatinib-resistant patients without T315I and Y253F mutations responded to imatinib dose escalation. In conclusion, BCR-ABL PEMs can be detected in a substantial number of CP-CML patients when investigated using CD34+ stem/progenitor cells. These mutations are associated with imatinib resistance, and mutation testing using CD34+ cells may facilitate improved, patient-tailored treatment

Jatropha curcas L. and Pongamia pinnata L. exhibited differential growth and bioaccumulation pattern irrigated with wastewater

Pakistan currently faces an acute shortage of water, which has increasingly been devastating for the past few decades. In order to mitigate water scarcity, agriculture sector of the country started using wastewater discharged from various industries. The present study aims to assess the impact of fertilizer industry effluent on Jatropha curcas L. and Pongamia pinnata L., which are popular biofuel tree species. Initially, one-year-old saplings were acclimatized in pots, then wastewater was applied in diluted concentrations of effluent using 20 and 40 mL L-1 to the treatment group while control plants were irrigated with tap water. The physico-chemical properties of the effluent showed high values 179 mg L-1 for biological oxygen demand (BOD), 257 mg L-1 for chemical oxygen demand (COD) and 1200 mg L-1 for total dissolved solid (TDS), respectively. Surprisingly, high concentrations of arsenic (15 µg L-1) and cadmium (0.78 mg L-1) were present but chromium (Cr) concentration was found within permissible limit to WHO. The levels applied caused a significant (p≤0.05) increase in plant growth and biomass. The extent of membrane damage assessed via malondialdehyde (MDA) production was also greater in the roots of P. pinnata while reverse was true for shoots of J. curcas. A more profound (p≤0.05) reduction in photosynthetic pigments and carotenoids was observed in P. pinnata at concentrated level of effluent. Overall, the study signifies a 2-folds potential of biofuel tree species for efficient reuse of wastewater, as well as for remediation of metals from wastewater and soil

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Plagiarism Detection Process using Data Mining Techniques

As the technology is growing very fast and usage of computer systems is increased  as compared to the old times, plagiarism is the phenomenon which is increasing day by day. Wrongful appropriation of someone else’s work is known as plagiarism. Manually detection of plagiarism is difficult so this process should be automated. There are various tools which can be used for plagiarism detection. Some works on intrinsic plagiarism while other work on extrinsic plagiarism. Data mining the field which can help in detecting the plagiarism as well as can help to improve the efficiency of the process. Different data mining techniques can be used to detect plagiarism. Text mining, clustering, bi-gram, tri-grams, n-grams are the techniques which can help in this process</strong

Bioprotection of Zea mays L. from aflatoxigenic Aspergillus flavus by Loigolactobacillus coryniformis BCH-4.

Fungal infection causes deterioration, discoloration, and loss of nutritional values of food products. The use of lactic acid bacteria has diverse applications in agriculture to combat pathogens and to improve the nutritional values of cereal grains. The current research evaluated the potential of Loigolactobacillus coryniformis BCH-4 against aflatoxins producing toxigenic Aspergillus flavus strain. The cell free supernatant (CFS) of Loig. coryniformis was used for the protection of Zea mays L. treated with A. flavus. No fungal growth was observed even after seven days. The FT-IR spectrum of untreated (T1: without any treatment) and treated maize grains (T2: MRS broth + A. flavus; T3: CFS + A. flavus) showed variations in peak intensities of functional group regions of lipids, proteins, and carbohydrates. Total phenolics, flavonoid contents, and antioxidant activity of T3 were significantly improved in comparison with T1 and T2. Aflatoxins were not found in T3 while observed in T2 (AFB1 and AFB2 = 487 and 16 ng/g each). HPLC analysis of CFS showed the presence of chlorogenic acid, p-coumaric acid, 4-hydroxybenzoic acid, caffeic acid, sinapic acid, salicylic acid, and benzoic acid. The presence of these acids in the CFS of Loig. coryniformis cumulatively increased the antioxidant contents and activity of T3 treated maize grains. Besides, CFS of Loig. coryniformis was passed through various treatments (heat, neutral pH, proteolytic enzymes and catalase), to observe its stability. It suggested that the inhibitory potential of CFS against A. flavus was due to the presence of organic acids, proteinaceous compounds and hydrogen peroxide. Conclusively, Loig. coryniformis BCH-4 could be used as a good bioprotecting agent for Zea mays L. by improving its nutritional and antioxidant contents

Pyrazolobenzothiazine-based carbothioamides as new structural leads for the inhibition of monoamine oxidases:design, synthesis, in vitro bioevaluation and molecular docking studies

Binding mode of potent inhibitor (green) &amp; cognate ligand (pink) in the active site of MAO-B.</p