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Blood is made up of three main components; erythrocytes, leukocytes and thrombocytes. Each of these blood components all have their own roles in the human body. Leukocytes, which can be divided into five types; Basophil, Neutrophil, Eosinophil, Lymphocytes and Monocytes are all part of the body’s defence mechanism to fight against pathogens that could harm the body. Identifying the presence of these blood cells is one of the fundamental ways to diagnose a disease. Hence, blood tests are always being run by physicians in clinical practice. Manually identifying leukocytes is a tedious and time-consuming process, and does not guarantee standardised results as it depends fully on the operator’s skills. Therefore, many works have been done to develop an automated method of leukocyte identification, which aims to reduce the processing time, cost-effective and is efficient in producing standardised results. The proposed method uses the technique of segmenting the nucleus and cytoplasm of leukocytes by extracting it from the Saturation level of the image.

Proteins of the bromodomain and extra-terminal (BET) domain family are epigenetic readers that bind acetylated histones through their bromodomains to regulate gene transcription. Dual-bromodomain BET inhibitors (DbBi) that bind with similar affinities to the first (BD1) and second (BD2) bromodomains of BRD2, BRD3, BRD4 and BRDt have displayed modest clinical activity in monotherapy cancer trials. A reduced number of thrombocytes in the blood (thrombocytopenia) as well as symptoms of gastrointestinal toxicity are dose-limiting adverse events for some types of DbBi 1 – 5 . Given that similar haematological and gastrointestinal defects were observed after genetic silencing of Brd4 in mice 6 , the platelet and gastrointestinal toxicities may represent on-target activities associated with BET inhibition. The two individual bromodomains in BET family proteins may have distinct functions 7 – 9 and different cellular phenotypes after pharmacological inhibition of one or both bromodomains have been reported 10 , 11 , suggesting that selectively targeting one of the bromodomains may result in a different efficacy and tolerability profile compared with DbBi. Available compounds that are selective to individual domains lack sufficient potency and the pharmacokinetics properties that are required for in vivo efficacy and tolerability assessment 10 – 13 . Here we carried out a medicinal chemistry campaign that led to the discovery of ABBV-744, a highly potent and selective inhibitor of the BD2 domain of BET family proteins with drug-like properties. In contrast to the broad range of cell growth inhibition induced by DbBi, the antiproliferative activity of ABBV-744 was largely, but not exclusively, restricted to cell lines of acute myeloid leukaemia and prostate cancer that expressed the full-length androgen receptor (AR). ABBV-744 retained robust activity in prostate cancer xenografts, and showed fewer platelet and gastrointestinal toxicities than the DbBi ABBV-075 14 . Analyses of RNA expression and chromatin immunoprecipitation followed by sequencing revealed that ABBV-744 displaced BRD4 from AR-containing super-enhancers and inhibited AR-dependent transcription, with less impact on global transcription compared with ABBV-075. These results underscore the potential value of selectively targeting the BD2 domain of BET family proteins for cancer therapy. ABBV-744, a selective inhibitor of the BD2 domains of BET family proteins, is effective against prostate cancer in mouse xenograft models, with lower toxicities than the dual-bromodomain BET inhibitor ABBV-075.

Allogeneic stem cell transplantation (alloSCT) is an effective immunotherapy in patients with hematological malignancies. Endothelial dysfunction was linked to major complications after alloSCT. We asked the question if the “Endothelial Activation and Stress Index” (EASIX; [(creatinine × LDH) ÷ thrombocytes]) can predict mortality after alloSCT. We performed a retrospective cohort analysis in five alloSCT centers in the USA and Germany. EASIX was assessed prior to conditioning (EASIX-pre) and correlated with mortality in 755 patients of a training cohort in multivariable models. The predictive model established in the training cohort was validated in 1267 adult allo-recipients. Increasing EASIX-pre predicted lower overall survival (OS) after alloSCT, and successful model validation was achieved for the validation cohort. We found that EASIX-pre predicts OS irrespective of established scores. Moreover, EASIX-pre was also a significant prognostic factor for transplant-associated microangiopathy. Finally, EASIX-pre correlated with biomarkers of endothelial homeostasis such as CXCL8, interleukin-18, and insulin-like-growth-factor-1 serum levels. This study establishes EASIX-pre based on a standard laboratory biomarker panel as a predictor of individual risk of mortality after alloSCT independently from established clinical criteria.

Appendicitis is an inflammation of the vermiform appendix. In 2019, worldwide there were estimated to be more than seventeen million cases of acute appendicitis. The difference in lifetime risk and incidence of appendicitis from various studies around the world raises a new possibility that there are differences in the characteristics of appendicitis in each population. This study aims to determine the main characteristics of appendicitis patients. This is an analytic-research with a cross sectional approach using total sampling technique with a total of 211 patients at PKU Muhammadiyah Bantul Hospital 2022. Appendicitis patients were predominantly female; in the age range of 20-44 years; the most common type was uncomplicated appendicitis; the average length of stay was 5 days; the average leukocyte was 10,616/ µL; the average thrombocytes count was 323,825/µL; and the most common complaint was abdominal pain. The characteristics of appendicitis patients are different in each population. Doctors are required to understand the disease and conduct a comprehensive examination so that patients can be treated properly.

The Eastern spot-billed duck ( Anas zonorhyncha ) is a common migratory waterfowl widely distributed throughout East Asia. However, the lack of species-specific reference intervals, defined as the normal range of values derived from a healthy population for clinical interpretation, hampers accurate health assessment and clinical diagnostics in this species. This is further complicated by hematologic characteristics of avian blood, such as nucleated red blood cells and thrombocytes, which pose challenges to conventional automated measurement systems optimized for mammals. This study aimed to establish hematological and biochemical reference intervals for juvenile Eastern spot-billed ducks and to evaluate the accuracy of an automated hematology analyzer (XN-1000V, Sysmex, Japan), which newly supports avian blood analysis, compared to traditional manual counting methods. Blood samples were collected from 55 clinically healthy juvenile ducks. The established reference intervals were largely consistent with those reported in related Anas species, though Eastern spot-billed ducks exhibited a heterophil-predominant leukogram. No significant differences were observed between sexes. Comparison between manual and automated methods revealed statistically significant differences in most hematological parameters; however, most of these differences were not clinically relevant, except for thrombocyte counts. Moderate correlations were found for key parameters, including WBC, RBC, hemoglobin, PCV, and MCV, suggesting potential clinical applicability of the automated analyzer with some limitations. This study provides the first species-specific hematologic and biochemical reference intervals for juvenile Eastern spot-billed ducks under semi-captive conditions, offering valuable baseline data for clinical assessments in this subset of the population. Additionally, it highlights the need for further optimization of XN-1000V analyzers for reliable and precise application in avian diagnostics.

Purpose [ 177 Lu]Lu-DOTATATE is an established somatostatin receptor (SSTR) agonist for the treatment of metastasized neuroendocrine neoplasms, while the SSTR antagonist [ 177 Lu]Lu-DOTA-LM3 has only scarcely been employed in clinics. Impressive preclinical data obtained with [ 161 Tb]Tb-DOTA-LM3 in tumor-bearing mice indicated the potential of terbium-161 as an alternative to lutetium-177. The aim of the present study was to compare the tolerability of 161 Tb- and 177 Lu-based DOTA-LM3 and DOTATATE in immunocompetent mice. Methods Dosimetry calculations were performed based on biodistribution data of the radiopeptides in immunocompetent mice. Treatment-related effects on blood cell counts were assessed on Days 10, 28 and 56 after application of [ 161 Tb]Tb-DOTA-LM3 or [ 161 Tb]Tb-DOTATATE at 20 MBq per mouse. These radiopeptides were also applied at 100 MBq per mouse and the effects compared to those observed after application of the 177 Lu-labeled counterparts. Bone marrow smears, blood plasma parameters and organ histology were assessed at the end of the study. Results The absorbed organ dose was commonly higher for the SSTR antagonist than for the SSTR agonist and for terbium-161 over lutetium-177. Application of a therapeutic activity level of 20 MBq [ 161 Tb]Tb-DOTA-LM3 or [ 161 Tb]Tb-DOTATATE was well tolerated without major hematological changes. The injection of 100 MBq of the 161 Tb- and 177 Lu-based somatostatin analogues affected the blood cell counts, however. The lymphocytes were 40–50% lower in treated mice compared to the untreated controls on Day 10 irrespective of the radionuclide employed. At the same timepoint, thrombocyte and erythrocyte counts were 30–50% and 6–12% lower, respectively, after administration of the SSTR antagonist ( p  < 0.05) while changes were less pronounced in mice injected with the SSTR agonist. All blood cell counts were in the normal range on Day 56. Histological analyses revealed minimal abnormalities in the kidneys, liver and spleen of treated mice. No correlation was observed between the organ dose and frequency of the occurrence of abnormalities. Conclusion Hematologic changes were more pronounced in mice treated with the SSTR antagonist than in those treated with the SSTR agonist. Despite the increased absorbed dose delivered by terbium-161 over lutetium-177, [ 161 Tb]Tb-DOTA-LM3 and [ 161 Tb]Tb-DOTATATE should be safe at activity levels that are recommended for their respective 177 Lu-based analogues. Graphical Abstract

Food and feeds contaminated with mycotoxins have been a threat to the rearing industry by causing some of the most fatal toxic reactions not only in the farm animals but also in humans who consume them. Toxicity to juvenile goats was induced by feed contamination with T-2 toxin (at 10 and 20 ppm dosage; group I and II, respectively). The toxicity impact was assessed on days 15 and 30 post treatment with respect to growth performance, oxidative stress, apoptotic studies and detailed pathomorphology. The study revealed that apart from the obvious clinical toxicosis (weakness, lethargy, and retardation in growth), the toxin fed groups also exhibited significant haematological (reduced hemoglobin, total leukocyte and thrombocyte counts) and biochemical changes (increased levels of oxidative stress markers with concomitant decrease in levels of serum and tissue catalase and superoxide dismutase). The pathomorphological and histological alterations suggested that the liver and intestine were the most affected organs. Ultra-structurally, varying degrees of degeneration, cytoplasmic vacuolations and pleomorphic mitochondria were observed in the hepatocytes and the enterocytes of the intestine. Kidney also revealed extensive degeneration of the cytoplasmic organelles with similar condensation of the heterochromatin whereas the neuronal degeneration was characterized by circular, whirling structures. In addition, the central vein and portal triad of the hepatocytes, cryptic epithelial cells of the intestine, MLNs in the lymphoid follicles, PCT and DCT of the nephronal tissues and the white pulp of the spleen exhibited extensive apoptosis. In this study, it was also observed that the expression of HSPs, pro-apoptotic proteins and pro-inflammatory cytokines were significantly upregulated in response to the toxin treatment. These results suggest that the pathogenesis of T-2 toxicosis in goats employs oxidative, apoptotic and inflammatory mechanisms.

Inflammation plays a pivotal role in atherothrombosis. Colchicine is an anti-inflammatory drug that may attenuate this process. Cardiovascular protective effects of anti-inflammatory drugs, however, seem to be limited to patients with a biochemical response. We therefore investigated whether short-term exposure to colchicine reduced inflammatory markers and whether additional laboratory changes occur in patients with chronic coronary artery disease. In 138 consecutive patients with chronic coronary artery disease and a high sensitivity C-reactive Protein (hs-CRP) [greater than or equal to] 2 mg/L, inflammatory markers, lipids, haematologic parameters and renal function were measured at baseline and after 30 days exposure to colchicine 0.5mg once daily. Hs-CRP decreased from baseline 4.40 mg/L (interquartile range [IQR] 2.83-6.99 mg/L) to 2.33 mg/L (IQR 1.41-4.17, median of the differences -1.66 mg/L, 95% confidence interval [CI] -2.17 - -1.22 mg/L, p-value <0.01), corresponding to a median change from baseline of -40%. Interleukin-6 decreased from 2.51 ng/L (IQR 1.59-4.32 ng/L) to 2.22 ng/L (median of the differences -0.36 ng/L, 95%CI -0.70 - -0.01 ng/L, p-value 0.04), corresponding to a median change from baseline of -16%. No clinically relevant changes in lipid fractions were observed. Both leukocyte and thrombocyte count decreased (median change from baseline -7% and -4% respectively). Estimated glomerular filtration rate decreased with a mean change from baseline of -2%. In patients with chronic coronary artery disease and elevated hs-CRP, one-month exposure to colchicine 0.5 mg once daily was associated with a reduction of inflammatory markers. A small effect was seen on white blood cell count and platelet count, as well as a small decrease in estimated glomerular filtration rate.

PurposeTo determine prognostic factors and overall survival (OS) in therapy-related myeloid neoplasm (t-MN) of patients after receiving peptide receptor radionuclide therapy (PRRT).MethodsAll patients treated from February 1999 until September 2019 at our center who had bone marrow biopsy-proven t-MN after PRRT were included. Patient characteristics, laboratory results, and all tumor-directed therapies before t-MN diagnosis were collected. Cox regression analysis was performed to identify parameters associated with OS. Receiver operating characteristic (ROC) curve analysis was used to define cutoff values as well as sensitivity and specificity of the parameters.ResultsOut of 1631 patients treated with PRRT, 30 patients developed t-MN comprising myelodysplastic syndrome (MDS) in 23 patients (77%) and acute myeloid leukemia (AML) in 7 patients (23%). The median OS of t-MN patients was 13 months (range 9.1–16.9 months): 6 months for AML and 15 months for the MDS subgroup, respectively. Higher platelet level was a significant prognostic parameter for longer OS (hazard ratio (HR): 0.99, P < 0.05). Using ROC analysis, the best cutoff value for thrombocyte count was 183.5 Gpt/L, resulting in a sensitivity of 92.3% and a specificity of 50%. Other factors, such as hemoglobin level, did not show a significant correlation with OS.ConclusionEven rarely occurred, the OS is gravely compromised in t-MN patients after PRRT, and even less in the AML subgroup (6 months). Higher platelet value was a significant prognostic parameter for longer OS in t-MN patients.