Rapid Acute Coronary Syndrome Evaluation Over One Hour With High-Sensitivity Cardiac Troponin I: A United States-Based Stepped-Wedge, Randomized Trial.

STUDY OBJECTIVE: The real-world effectiveness and safety of a 0/1-hour accelerated protocol using high-sensitivity cardiac troponin (hs-cTn) to exclude myocardial infarction (MI) compared to routine care in the United States is uncertain. The objective was to compare a 0/1-hour accelerated protocol for evaluation of MI to a 0/3-hour standard care protocol. METHODS: The RACE-IT trial was a stepped-wedge, randomized trial across 9 emergency departments (EDs) that enrolled 32,609 patients evaluated for possible MI from July 2020 through April 2021. Patients undergoing high-sensitivity cardiac troponin I testing with concentrations less than or equal to 99th percentile were included. Patients who had MI excluded by the 0/1-hour protocol could be discharged from the ED. Patients in the standard care protocol had 0- and 3-hour troponin testing and application of a modified HEART score to be eligible for discharge. The primary endpoint was the proportion of patients discharged from the ED without 30-day death or MI. RESULTS: There were 13,505 and 19,104 patients evaluated in the standard care and accelerated protocol groups, respectively, of whom 19,152 (58.7%) were discharged directly from the ED. There was no significant difference in safe discharges between standard care and the accelerated protocol (59.5% vs 57.8%; adjusted odds ratio (aOR)=1.05, 95% confidence interval [CI] 0.95 to 1.16). At 30 days, there were 90 deaths or MIs with 38 (0.4%) in the standard care group and 52 (0.4%) in the accelerated protocol group (aOR=0.84, 95% CI 0.43 to 1.68). CONCLUSION: A 0/1-hour accelerated protocol using high-sensitivity cardiac troponin I did not lead to more safe ED discharges compared with standard care.

Endoscopic retrograde cholangiopancreatography outcomes in inflammatory bowel disease patients: a 12-year analysis of a national database.

BACKGROUND: Despite inflammatory bowel disease's (IBD) association with hepatobiliary disorders and the use of endoscopic retrograde cholangiopancreatography (ERCP) for both diagnostic and therapeutic evaluation of these diseases, it remains a poorly studied area within the literature. The purpose of this study is to examine the effect of IBD on the occurrence of adverse events (AE) pertaining to ERCP. METHODS: This project utilized the National Inpatient Sample (NIS) database, the largest inpatient database in the USA. All patients 18 years or older with and without IBD undergoing ERCP were identified from 2008 to 2019. Post-ERCP AEs were analyzed using multivariate logistic or linear regression controlling for age, race, and existing comorbidities using the Charlson comorbidity index (CCI). RESULTS: There was no difference in post-ERCP pancreatitis (PEP) or mortality. IBD patients were also found to have a lower risk of bleeding and decreased length of stay (LOS) despite adjustment for comorbidities. They also underwent less sphincterotomies when compared to the non-IBD cohort. Subgroup analysis between ulcerative colitis (UC) and Crohn's disease (CD) did not find any significant differences in outcomes. CONCLUSION: To our knowledge, this is the largest study to date evaluating ERCP outcomes in IBD patients. After adjustment of co-variates, there was no difference in the occurrence of PEP, infections, and perforation. IBD patients were less likely to experience post-ERCP bleeding and mortality and had shorter LOS which may be due to the decreased frequency of sphincterotomy in this population.

Cyclic-AMP signalling, MYC and hypoxia-inducible factor 1α intersect to regulate angiogenesis in B-cell lymphoma.

Angiogenesis and MYC expression associate with poor outcome in diffuse large B-cell lymphoma (DLBCL). MYC promotes neo-vasculature development but whether its deregulation in DLBCL contributes to angiogenesis is unclear. Examination of this relationship may uncover novel pathogenic regulatory circuitry as well as anti-angiogenic strategies in DLBCL. Here, we show that MYC expression positively correlates with vascular endothelial growth factor (VEGF) expression and angiogenesis in primary DLBCL biopsies, independently of dual expressor status or cell-of-origin classification. We found that MYC promotes VEGFA expression, a correlation that was validated in large datasets of mature B-cell tumours. Using DLBCL cell lines and patient-derived xenograft models, we identified the second messenger cyclic-AMP (cAMP) as a potent suppressor of MYC expression, VEGFA secretion and angiogenesis in DLBCL in normoxia. In hypoxia, cAMP switched targets and suppressed hypoxia-inducible factor 1α, a master regulator of VEGFA/angiogenesis in low oxygen environments. Lastly, we used the phosphodiesterase 4b (Pde4b) knockout mouse to demonstrate that the cAMP/PDE4 axis exercises additional anti-angiogenesis by directly targeting the lymphoma microenvironment. In conclusion, MYC could play a direct role in DLBCL angiogenesis, and modulation of cAMP levels, which can be achieved with clinical grade PDE4 inhibitors, has cell and non-cell autonomous anti-angiogenic activity in DLBCL.

Lesion size and shape in central vein sign assessment for multiple sclerosis diagnosis: An in vivo and postmortem MRI study.

BACKGROUND: The "central vein sign" (CVS), a linear hypointensity on T2*-weighted imaging corresponding to a central vein/venule, is associated with multiple sclerosis (MS) lesions. The effect of lesion-size exclusion criteria on MS diagnostic accuracy has not been extensively studied. OBJECTIVE: Investigate the optimal lesion-size exclusion criteria for CVS use in MS diagnosis. METHODS: Cross-sectional study of 163 MS and 51 non-MS, and radiological/histopathological correlation of 5 MS and 1 control autopsy cases. The effects of lesion-size exclusion on MS diagnosis using the CVS, and intralesional vein detection on histopathology were evaluated. RESULTS: CVS+ lesions were larger compared to CVS- lesions, with effect modification by MS diagnosis (mean difference +7.7 mm3, p = 0.004). CVS percentage-based criteria with no lesion-size exclusion showed the highest diagnostic accuracy in differentiating MS cases. However, a simple count of three or more CVS+ lesions greater than 3.5 mm is highly accurate and can be rapidly implemented (sensitivity 93%; specificity 88%). On magnetic resonance imaging (MRI)-histopathological correlation, the CVS had high specificity for identifying intralesional veins (0/7 false positives). CONCLUSION: Lesion-size measures add important information when using CVS+ lesion counts for MS diagnosis. The CVS is a specific biomarker corresponding to intralesional veins on histopathology.

Coarse-grained modelling of DNA plectoneme pinning in the presence of base-pair mismatches.

Damaged or mismatched DNA bases result in the formation of physical defects in double-stranded DNA. In vivo, defects in DNA must be rapidly and efficiently repaired to maintain cellular function and integrity. Defects can also alter the mechanical response of DNA to bending and twisting constraints, both of which are important in defining the mechanics of DNA supercoiling. Here, we use coarse-grained molecular dynamics (MD) simulation and supporting statistical-mechanical theory to study the effect of mismatched base pairs on DNA supercoiling. Our simulations show that plectoneme pinning at the mismatch site is deterministic under conditions of relatively high force (>2 pN) and high salt concentration (>0.5 M NaCl). Under physiologically relevant conditions of lower force (0.3 pN) and lower salt concentration (0.2 M NaCl), we find that plectoneme pinning becomes probabilistic and the pinning probability increases with the mismatch size. These findings are in line with experimental observations. The simulation framework, validated with experimental results and supported by the theoretical predictions, provides a way to study the effect of defects on DNA supercoiling and the dynamics of supercoiling in molecular detail.

Hemophagocytic Lymphohistiocytosis Hospitalizations in Adults and Its Association With Rheumatologic Diseases: Data From Nationwide Inpatient Sample.

OBJECTIVE: Hemophagocytic lymphohistiocytosis (HLH) is a rare potentially fatal multisystem inflammatory condition that is often triggered by an underlying medical condition. Epidemiologic data of HLH in adults with rheumatologic diseases are limited. The aim of our study was to characterize HLH hospitalizations in the US adult population with a special focus on patients with concomitant rheumatologic diseases. METHODS: We conducted a medical records review of hospitalizations in the United States during 2016 and 2017 with a diagnosis of HLH. Hospitalizations were selected from the National Inpatient Sample. International Classification of Diseases, Tenth Revision codes were used to identify rheumatologic diseases. A multivariate logistic regression analysis was used to calculate adjusted odds ratios (ORadj) for the association of HLH and rheumatologic diseases. RESULTS: Seven hundred fifty hospitalizations had a principal billing diagnosis of HLH. The median age of our study population was 47.5 years, and males made up 55% of the population. Overall mortality was 17%, and the median length of stay was 12 days. Twenty-five percent of the HLH cases had a concomitant rheumatologic diagnosis. Multivariate logistic regression analysis showed systemic lupus erythematosus (SLE) with nephritis (ORadj, 5.7), SLE without nephritis (ORadj, 9.2), adult-onset Still disease (ORadj, 338.9), and ankylosing spondylitis (ORadj, 10.7) were significantly associated with HLH. CONCLUSIONS: This analysis represents the largest sample to date to assess HLH hospitalizations. Our study showed that SLE, adult-onset Still disease, and ankylosing spondylitis were strongly associated with HLH.

Neurological Complications of Pulmonary Embolism: a Literature Review.

PURPOSE OF REVIEW: The present review discusses in-depth about neurological complications following acute venous thromboembolism (VTE). RECENT FINDINGS: Intracranial hemorrhage, acute ischemic cerebrovascular events, and VTE in brain tumors are described as central nervous system (CNS) complications of PE, while peripheral neuropathy and neuropathic pain are reported as peripheral nervous system (PNS) sequelae of PE. Syncope and seizure are illustrated as atypical neurological presentations of PE. Mounting evidence suggests higher risk of venous thromboembolism (VTE) in patients with neurological diseases, but data on reverse, i.e., neurological sequelae following VTE, is underexplored. The present review is an attempt to explore some of the latter issues categorized into CNS, PNS, and atypical complications following VTE.

Cerebrovascular Accident and SARS-CoV-19 (COVID-19): A Systematic Review.

BACKGROUND: While the most common neurologic symptoms reported in patients affected by SARS-CoV-2 are headache, dizziness, myalgia, mental fog, and anosmia, there is a growing basis of published peer-reviewed cases reporting stroke in the setting of SARS-CoV-2 infection. The peer-reviewed literature suggests an increased risk of cerebrovascular accident (CVA) in the setting of COVID-19 infection. METHODS: We searched 3 databases (PubMed, MEDLINE, and CINAHL) with search terms COVID-19, novel coronavirus, stroke, and cerebrovascular accident. Case series and case studies presenting patients positive for both COVID-19 and CVA published from January 1 through September 1, 2020, were included. Data collection and analysis was completed and risk of bias assessed. RESULTS: The search identified 28 studies across 7 counties comprising 73 patients. Amongst patients hospitalized for COVID-19 infection and CVA, the average age was 60; the most common preexisting conditions were hypertension and diabetes mellitus, and those without preexisting conditions were significantly younger with an average age of 47. Amongst hospitalized patients with COVID-19 and CVA, there was a bimodal association with COVID-19 infection severity with majority of patients classified with mild or critical COVID-19 infection. DISCUSSION: The data suggest SARS-CoV-2 is a risk factor for developing stroke, particularly in patients with hypertension and diabetes. Furthermore, the younger average age of stroke in patients with SARS-CoV-2, particularly those patients with zero identifiable preexisting conditions, creates high suspicion that SARS-CoV-2 is an independent risk factor for development of stroke; however, this cannot yet be proven without comparable control population. The data suggest the risk of developing CVA in the setting of COVID-19 infection is not dependent upon severity of illness. Continued studies must be done to understand the epidemiologic factors of COVID-19 infection and stroke and the pathophysiology of the COVID-associated hypercoagulable state.

Formation and Properties of a Self-Assembled Nanoparticle-Supported Lipid Bilayer Probed through Molecular Dynamics Simulations.

We have carried out coarse-grained molecular dynamics (MD) simulations to study the self-assembly procedure of a system of randomly placed lipid molecules, water beads, and a nanoparticle (NP). The self-assembly results in the formation of the nanoparticle-supported lipid bilayer (NPSLBL), with the self-assembly mechanism being driven by events such as the formation of small lipid clusters, merging of the lipid clusters in the vicinity of the NP to form NP-embedded vesicle with a pore, and collapsing of that pore to eventually form the equilibrated NPSLBL system overcoming a large free-energy barrier. Subsequently, we quantify the properties and the configurations of this NPSLBL system. We reveal that unlike our proposition of an equal number of lipid molecules occupying the inner and outer leaflets in a recent report studying the properties of a preassembled lipid bilayer, the equilibrated self-assembled NPSLBL system demonstrates a much larger number of lipid molecules occupying the outer leaflet as compared to the inner leaflet. Second, the thickness of the water layer entrapped between the NP and the inner leaflet shows similar values as predicted by experiments and our previous study. Finally, we reveal that, similar to our previous study, the diffusivity of the lipid molecules in the outer leaflet is larger than that in the inner leaflet but, due to higher temperature employed during our simulations, are even larger than that predicted by our previous study.

Nanovesicles Versus Nanoparticle-Supported Lipid Bilayers: Massive Differences in Bilayer Structures and in Diffusivities of Lipid Molecules and Nanoconfined Water.

We carry out molecular dynamics (MD) simulations to compare the equilibrium architecture and properties of nanoparticle-supported lipid bilayers (NPSLBLs) with the free vesicles of similar dimensions. Three key differences emerge. First, we witness that for a free vesicle, a much larger number of lipid molecules occupy the outer layer as compared to the inner layer; on the other hand, for the NPSLBL the number of lipid molecules occupying the inner and outer layers is identical. Second, we witness that the diffusivities of the lipid molecules occupying both the inner and the outer layers of the free vesicles are identical, whereas for the NPSLBLs the diffusivity of the lipid molecules in the outer layer is more than twice the diffusivity of the lipid molecules in the inner layer. Finally, the NPSLBLs entrap nanoscopic thin water film between the inner lipid layer and the NP and the diffusivity of this water film is nearly 1 order of magnitude smaller than the diffusivity of the bulk water; on the other hand, the water inside the free vesicles has a diffusivity that is only slightly lower than that of the bulk water. Our findings, possibly the first probing the atomistic details of the NPSLBLs, are anticipated to shed light on the properties of this important nanomaterial with applications in a large number of disciplines ranging from drug and gene delivery to characterizing curvature-sensitive molecules.

Ion at Air-Water Interface Enhances Capillary Wave Fluctuations: Energetics of Ion Adsorption.

Recent simulations provide the energetics of ion adsorption at the air-water (a/w) interface: The presence of the ion at the interface suppresses the fluctuations of the capillary waves (CWs) reducing the entropy and displaces the weakly interacting water molecules to the bulk causing a reduction in the enthalpy. Here, we provide atomistic simulation-based evidence that the inferences of the existing studies stem from considering a small simulation volume that pins the CWs. For an appropriate size of the simulation system, an ion at the a/w interface enhances the CW fluctuations. Furthermore, we discover that the characteristics of the waves governing these enhanced CW fluctuations ensure a significant decrease in the pressure-volume work causing the enthalpy decrease, while the same wave characteristics of the CWs become responsible for an entropy decrease. Overall, the paper revisits the free energy picture of this fundamental problem of ion adsorption at the a/w interface.

P53 expression correlates with poorer survival and augments the negative prognostic effect of MYC rearrangement, expression or concurrent MYC/BCL2 expression in diffuse large B-cell lymphoma.

In patients with diffuse large B-cell lymphoma, MYC rearrangement (MYC-R), MYC expression, or concurrent expression of MYC and BCL2 is associated with a poorer prognosis. P53 expression also has been shown to confer inferior survival in diffuse large B-cell lymphoma patients, but less is known about the role of P53 expression in those with MYC-R, MYC expression (MYC+), or MYC&BCL2 co-expression (MYC+/BCL2+). We studied P53 expression in 201 patients with untreated de novo diffuse large B-cell lymphoma. Sixty-seven (33%) cases were P53 positive, 56 (28%) had MYC-R (including 17 MYC/BCL2 double hit lymphoma), 86 (45%) were MYC+/BCL2+, and 47 (24%) were positive for both MYC and P53. Compared with patients with P53 negative lymphoma, the P53 positive group had a poorer overall survival (P=0.004). In patients with lymphoma harboring MYC-R, MYC expression or MYC+/BCL2+, P53 expression was associated with a significantly worse overall survival (P<0.0001, P=0.01, and P=0.035, respectively). Patients with lymphoma showing concurrent P53 expression and MYC-R had a worse prognosis compared with patients with either P53 expression or MYC-R alone (P<0.0001). Similarly, P53 enhanced the negative prognostic effect of MYC expression in DLBCL patients. In addition, among patients with lymphoma with concurrent MYC and P53 expression, MYC and BCL2 or BCL2 & P53 expression, those patients with tumors with MYC and P53 expression had the worst overall survival (P=0.005), regardless of BCL2 expression status. Multivariate analysis demonstrated that both MYC-R and P53 expression were independent prognostic factors in this patient cohort. In conclusion, our data suggest that P53 expression and MYC -R or MYC expression have an additive negative prognostic effect in diffuse large B-cell lymphoma patients. Assessment of P53 expression adds additional prognostic information in de novo diffuse large B-cell lymphoma patients, especially in subgroups with MYC-R, MYC expression and MYC and BCL2 double expression.

Increased MYC copy number is an independent prognostic factor in patients with diffuse large B-cell lymphoma.

Patients with double-hit or triple-hit lymphoma have a significantly worse prognosis compared to patients with diffuse large B-cell lymphoma without MYC rearrangement. However, the prognostic importance of extra copies of MYC, BCL2, or BCL6 has not been fully explored. We studied 663 patients with de novo diffuse large B-cell lymphoma in whom the status of MYC/8q24, BCL2/18q21, and BCL6/3q27 were assessed by fluorescence in situ hybridization. Cases of double or triple extra copy lymphoma were defined by the presence of increased MYC copies and increased BCL2 and/or BCL6 copies or rearrangement. In total, 76 patients with diffuse large B-cell lymphoma had MYC extra copies including 43 cases of double or triple extra copy lymphoma; 105 patients had diffuse large B-cell lymphoma with MYC-R including 56 double- or triple-hit lymphoma; and 482 diffuse large B-cell lymphoma patients had no MYC abnormality (MYC normal). Patients with MYC extra copies, similar to MYC-R, had a worse overall survival compared with MYC normal patients (both P<0.01). The prognosis between patients with MYC extra copies and MYC-R was not statistically significantly different (P=0.086). Cell-of-origin classification failed to correlate with survival in the MYC extra copies group, similar to the MYC-R patient group. Compared with patients with double- or triple-hit lymphoma, patients with double or triple extra copy lymphoma had a higher complete remission rate (P=0.02), but there was no significant statistical difference in overall survival (P=0.089). Intensive induction chemotherapy regimens improved the overall survival of patients with double or triple extra copy lymphoma, but there was no significant improvement of overall survival in patients with MYC-R tumors. Multivariate analysis showed that MYC extra copy in diffuse large B-cell lymphoma is an independent poor prognostic factor, similar to MYC rearrangement.

Prognostic impact of CD5 expression in diffuse large B-cell lymphoma in patients treated with rituximab-EPOCH.

OBJECTIVES: CD5-positive (CD5+) diffuse large B-cell lymphoma (DLBCL) represents 5%-10% of all DLBCL cases, which has been associated with a poorer prognosis in patients treated with R-CHOP. Prognostic impact of CD5 expression in patients with DLBCL treated with R-EPOCH has not been evaluated. METHODS: We studied 130 patients with de novo DLBCL who received frontline R-EPOCH therapy. The clinicopathologic features and overall survival (OS) were compared between patients with CD5+ and CD5- DLBCL. MYC, BCL2, and BCL6 rearrangements were examined by fluorescent in situ hybridization. RESULTS: Sixteen (12.3%) of 130 DLBCLs were CD5+. Most clinicopathologic features including cell of origin and frequency of MYC, BCL2, and BCL6 rearrangements were similar between CD5+ and CD5- groups. Patients with CD5+ DLBCL, however, showed higher rate of central nervous system relapse (33.3% vs 15.6%; P<.01) and a higher Ki67 proliferative index compared with CD5- patients. The median OS was significantly worse in CD5+ than CD5- patients (28.13 months vs not reached, P=.006). CD5 expression was an independent prognostic factor for OS in multivariate analysis. CONCLUSIONS: R-EPOCH therapy does not seem to impact the known poorer prognosis of patients with de novo CD5+ DLBCL, and CD5 expression was still an independent prognostic factor in R-EPOCH-treated patients with DLBCL.

Compression of polymer brushes in the weak interpenetration regime: scaling theory and molecular dynamics simulations.

We employ scaling theory and Molecular Dynamics (MD) simulations to probe the compression of the semi-dilute polymer brush bilayers (BBLs) in the weak interpenetration (IP) regime. Such a regime is characterized by two layers of interacting polymer brushes grafted on opposing planar surfaces having a separation dg, such that d0 < dg < 2d0, with d0 being the unperturbed brush height. Currently, scaling theories are known for polymer BBLs with a much larger degree of IP (i.e., dg < d0) - in such regimes, the brush height can be quantified by the corresponding IP length δ. On the other hand, we show that in the weak IP regime, the brush height is not solely dictated by δ. We develop new scaling theories to show that δ in this weak IP regime is different from that in the strong IP regime. Secondly, we establish that the compressed brush height in this weakly IP regime can be described as d ∼ Nχ with χ < 1 and varying monotonically with dg/d0. MD simulations are carried out to quantify δ and χ and the results match excellently with our new scaling theory predictions. Finally, we establish that our scaling theory can reasonably predict the experimentally witnessed variation of the interaction energy dictating the compressive force between the interpenetrating brushes in this weakly IP regime.

MYC/BCL6 double-hit lymphoma (DHL): a tumour associated with an aggressive clinical course and poor prognosis.

AIMS: Large B cell lymphomas with MYC and BCL6/3q27 rearrangements, designated MYC/BCL6 DHL, are uncommon. Our aim was to better characterize this group of tumours. METHODS AND RESULTS: We studied the clinicopathological features and outcome of 13 patients with MYC/BCL6 DHL and compared this group to a group of 83 MYC/BCL2 DHL patients. There were eight men and five women, with a median age of 63 years. Eleven tumours were classified as diffuse large B cell lymphomas (DLBCL) and two were B cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma (BCLU). Immunohistochemical analysis showed that these tumours were positive for BCL6 (100%), BCL2 (eight of 10; 80%) and CD10 (eight of 10; 80%). Nine of 12 (75%) cases had a germinal centre B cell (GCB) immunophenotype; in one case data were incomplete. All patients were treated with chemotherapy. The clinicopathological features of MYC/BCL6 DHL were similar to MYC/BCL2 DHL, except that MYC/BCL6 DHL had a GCB immunophenotype less often. Patients with MYC/BCL6 DHL had a poor overall survival, similar to patients with MYC/BCL2 DHL (P = 0.32). CONCLUSIONS: MYC/BCL6 DHL is an aggressive B cell lymphoma and patients often have an aggressive clinical course and poor prognosis, similar to patients with MYC/BCL2 DHL.

Side scatter versus CD45 flow cytometric plot can distinguish acute leukaemia subtypes.

BACKGROUND & OBJECTIVES: Flow cytometry is an important tool to diagnose acute leukaemia. Attempts are being made to find the minimal number of antibodies for correctly diagnosing acute leukaemia subtypes. The present study was designed to evaluate the analysis of side scatter (SSC) versus CD45 flow dot plot to distinguish acute myeloid leukaemia (AML) from acute lymphoblastic leukaemia (ALL), with minimal immunological markers. METHODS: One hundred consecutive cases of acute leukaemia were evaluated for blast cluster on SSC versus CD45 plots. The parameters studied included visual shape, CD45 and side scatter expression, continuity with residual granulocytes/lymphocytes/monocytes and ratio of maximum width to maximum height (w/h). The final diagnosis of ALL and AML and their subtypes was made by morphology, cytochemistry and immunophenotyping. Two sample Wilcoxon rank-sum (Mann Whitney) test and Kruskal-Wallis equality-of-populations rank tests were applied to elucidate the significance of the above ratios of blast cluster for diagnosis of ALL, AML and their subtypes. Receiver operating characteristic (ROC) curves were generated and the optimal cut-offs of the w/h ratio to distinguish between ALL and AML determined. RESULTS: Of the 100 cases, 57 of ALL and 43 cases of AML were diagnosed. The median w/h ratio of blast population was 3.8 for ALL and 1 for AML (P<0.001). ROC had area under curve of 0.9772.The optimal cut-off of the w/h ratio for distinction of ALL from AML was found to be 1.6. INTERPRETATION & CONCLUSIONS: Our findings suggest that if w/h ratio on SSC versus CD45 plot is less than 1.6, AML may be considered, and if it is more than 1.6, ALL may be diagnosed. Using morphometric analysis of the blast cluster on SSC versus CD45, it was possible to distinguish between ALL and AML, and their subtypes.

Comparative assessment of genetic diversity among Indian bamboo genotypes using RAPD and ISSR markers.

Bamboo is one of the important plant for pulp, paper and charcoal industries. After China, India is the second largest bamboo reserve in Asia. Around the globe, wide genetic diversity of bamboo is present which serves as the base for selection and improvement. DNA based molecular markers appears to be a striking substitute for systematic assessment of the genetic diversity in conservation and genetic improvement of plants. DNA based molecular markers such as RAPD and ISSR were used to assess the genetic diversity in 13 bamboo genotypes. Total 120 RAPD and 63 ISSR primers were tested, of which only 42 polymorphic primers (30 RAPD and 12 ISSR), gave reproducible amplification profile and were used in this study. 30 RAPD primers yielded total 645 amplified fragments, of which 623 were polymorphic, and 20.76 polymorphic bands per primer were observed across 13 genotypes. 12 ISSR primers produced 246 amplified fragments, of which 241 were polymorphic, and 20.08 polymorphic bands per primer was observed across 13 different genotypes. The Jaccard's coefficient of RAPD, ISSR and pooled RAPD and ISSR dendrograms ranged from 0.26 to 0.83, 0.23 to 0.86 and 0.26 to 0.84 respectively. The present study found the large genetic diversity present between different elite genotypes of bamboo. Such investigation can deliver a well understanding of the available genotypes, which might be further exploited for the paper industry.

Cellular and Exosomal MicroRNAs: Emerging Clinical Relevance as Targets for Breast Cancer Diagnosis and Prognosis.

Breast cancer accounts for the highest cancer cases globally, with 12% of occurrences progressing to metastatic breast cancer with a low survival rate and limited effective early intervention strategies augmented by late diagnosis. Moreover, a low concentration of prognostic and predictive markers hinders disease monitoring. Circulating and exosomal microRNAs (miRNAs) have recently shown a considerable interplay in breast cancer, standing out as effective diagnostic and prognostic markers. The primary functions are as gene regulatory agents at the genetic and epigenetic levels. An array of dysregulated miRNAs stimulates cancer-promoting mechanisms, activating oncogenes and controlling tumor-suppressing genes and mechanisms. Exosomes are vastly studied extracellular vesicles, carrying, and transporting cargo, including noncoding RNAs with premier roles in oncogenesis. Translocation of miRNAs from the circulation to exosomes, with RNA-binding proteins in stress-induced conditions, has shown significant cooperation in function to promote breast cancer. This review examines cellular and exosomal miRNA biogenesis and loading, the clinical implications of their dysregulation, their function in diagnosis, prognosis, and prediction of breast cancer, and in regulating cancer signaling pathways. The influence of cellular and exosomal miRNAs presents clinical significance on breast cancer diagnosis, subtyping, staging, prediction, and disease monitoring during treatment, hence a potent marker for breast cancer.