Hasil untuk "Diseases of the blood and blood-forming organs"

P. Palmiero, Pierpaolo Caretto, M. M. Ciccone et al.

Pre-eclampsia is a severe pregnancy complication affecting 5–8% of pregnancies worldwide, marked by high blood pressure and organ damage typically occurring after 20 weeks of gestation. It is a leading cause of maternal and fetal morbidity and mortality. Though its exact cause is unknown, it involves placental abnormalities and improper blood vessel development. Risk factors include a history of pre-eclampsia, chronic hypertension, diabetes, obesity, and autoimmune disorders. Symptoms include high blood pressure, proteinuria, headaches, vision changes, and abdominal pain. Untreated, it can lead to seizures, stroke, preterm birth, or death. Delivery is the definitive treatment, with management strategies such as monitoring and blood pressure control. Pre-eclampsia significantly increases long-term cardiovascular disease (CVD) risks, including hypertension, ischemic heart disease, and stroke, linked to shared mechanisms like endothelial dysfunction and inflammation. Women with severe or recurrent pre-eclampsia have heightened risks, often developing chronic hypertension within a decade postpartum. It also impacts offspring, with daughters at elevated risk for pre-eclampsia and CVD. Hypertensive disorders of pregnancy, including pre-eclampsia, induce changes like left ventricular hypertrophy and diastolic dysfunction, raising risks for heart failure with preserved ejection fraction and coronary atherosclerosis. Overlapping with peripartum cardiomyopathy, pre-eclampsia underscores a spectrum of pregnancy-related cardiovascular disorders. Long-term monitoring and lifestyle interventions are crucial for managing risks, with research into genetic and biological mechanisms offering the potential for targeted prevention.

Tomohisa Ohmura, Yoshinaga Kajimoto, Masahiro Kameda et al.

Cerebral autoregulation is a robust regulatory mechanism that stabilizes cerebral blood flow in response to reduced blood pressure, thereby preventing cerebral ischaemia. Scientists have long believed that cerebral autoregulation also stabilizes cerebral blood flow against increases in intracranial pressure, which is another component that determines cerebral perfusion pressure. However, this idea was inconsistent with the complex pathogenesis of normal pressure hydrocephalus, which includes components of chronic cerebral ischaemia due to mild increases in intracranial pressure. Twenty-one patients who underwent ventriculoperitoneal shunt surgery for normal pressure hydrocephalus were included in this study. To determine the pressure setting of the Codman-Hakim programmable valve, intracranial pressure was measured after shunt surgery by puncturing the Ommaya reservoir, which formed a closed circuit with the needle and the syringe. Then, intracranial pressure was continuously measured with intermittent infusion of cerebrospinal fluid from the same closed circuit. We also continuously measured oximetry data, such as regional cerebral oxygen saturation derived from near-infrared spectroscopy monitoring. These data were digitized, recorded, and used for calculating intracranial compliance and the relationship between cerebrospinal fluid volume loading and intracranial pressure. This study demonstrates that in patients with normal pressure hydrocephalus, cerebral venous vascular bed compression induces mild cerebral ischaemia when intracranial pressure is slightly higher than physiological venous pressure. Cerebral venous compression impairs cerebral blood flow by quadratically increasing circulatory resistance according to Poiseuille’s law. Furthermore, chronic cerebral ischaemia occurred even at low or normal intracranial pressures when deep and subcortical white matter hyperintensities (DSWMHs) were severe. The fact that cerebral blood flow impairment begins at very low intracranial pressures indicates that cerebral autoregulation to compensate for reduced venous blood flow is not functioning adequately in NPH. These processes provide a link between impaired cerebrospinal fluid circulation, cerebral autoregulation, and neurological dysfunction, which has been missing in patients with NPH involving small vessel arteriosclerosis. These findings may provide insight into similar conditions, such as normal-tension glaucoma and chronic kidney disease, in which a mild increase in local compartment pressure leads to chronic ischemia in organs protected by autoregulatory mechanisms.

Omid Seidizadeh, Luciano Baronciani, Flora Peyvandi

von Willebrand disease (VWD) is the most common inherited bleeding disorder characterized by defects in the quantity or function of the von Willebrand factor (VWF). The diagnosis of VWD is complex, requiring a battery of tests to evaluate the amount, functions, and multimeric structure of the VWF glycoprotein. The diagnosis can also be accomplished or confirmed by sequencing the VWF gene (VWF). Genetic testing of VWF has been around for 4 decades following the cloning of VWF, and nowadays, it has been integrated into the diagnostic panel of VWD. With the introduction of next-generation sequencing, genetic analysis of the VWF has become more practical than it was in the past, when Sanger sequencing was used. A number of laboratories have applied or started to use genetic testing with next-generation sequencing for VWD diagnosis. Considering the increasing application of genetic testing in VWD and the wide availability and decreasing cost of gene sequencing, we sought to discuss the challenges and considerations involved in applying genetic testing to VWD.

Marta Rosado-Fernández, Elisenda Climent, Mercè Fernández-Miró et al.

Purpose: It has been previously described that some women with type 1 diabetes (T1D) may experience changes in glucose levels in relation to their menstrual cycle. However, whether an advanced hybrid closed-loop system (AHCL) can mitigate these cycle-dependent changes is yet to be determined. Methods: This study is a prospective analysis of a cohort of premenopausal women with T1D with spontaneous menstrual cycles who are users of an AHCL system 780G Medtronic^®. Three consecutive cycles were analyzed for each patient, and each cycle was divided into three phases (menstrual, luteal, and rest of cycle phase). Results: Fifteen subjects were included. Mean age was 38 ± 7.6 years, HbA1c was 7.12 ± 0.7%, and diabetes duration was 21 ± 13.7 years. Mean glucose was higher in the luteal phase compared to the menstrual period (<i>p</i> = 0.029 luteal vs. menstrual) and the rest of the cycle (<i>p</i> = 0.018 luteal vs. rest of cycle). The time in range (TIR) was lower in the luteal phase compared to the rest of cycle phase (<i>p</i> = 0.015 luteal vs. rest of cycle). The time below range (TBR) was significantly higher in the menstrual compared to the luteal phase (<i>p</i> = 0.007 luteal vs. menstrual). Daily insulin requirements were higher in luteal phase compared to rest of cycle (<i>p</i> = 0.017 luteal vs. rest of cycle). Conclusions: A higher mean glucose and lower TIR, despite a higher total insulin dose, was observed in the luteal phase. A higher TBR was observed in the menstrual phase. However, AHCL with 780G Medtronic^® achieves a TIR of almost 70% in all cycle phases.

LI Baixun, LIU Tianxu, HUANG Liqin et al.

Hepatitis E is an acute and self-limiting viral hepatitis caused by the hepatitis E virus (HEV). It has a higher mortality rate among immunosuppressed patients and pregnant women infected with HEV. Although HEV infections in humans are mostly caused by contaminated water or food worldwide, the incidence of transfusion-transmitted hepatitis E is continuously rising. Additionally, the prevalence of serum anti-HEV IgG in the blood donors in China is at a relatively high level, making it worth considering screening blood donors for HEV. This article briefly reviews the globally reported cases of transfusion-transmitted hepatitis E and the HEV screening strategies for blood donations.

D. Kasmi, I. Carmosino, M.L. Bisegna et al.

Background: the low-intensity regimen of venetoclax (VEN) and azacitidine (AZA) demonstrates favorable efficacy and tolerable safety profile in previously untreated elderly pts with acute myeloid leukemia (AML) unfit for intensive chemotherapy. Nonetheless, these benefits are accompanied by significant cytopenias and infectious complications. Methods: in this retrospective study, 65 treatment-naïve elderly pts diagnosed with AML and treated at our institution between 2017 and 2024 were analyzed. Of these, 35 pts received VEN+AZA as first-line treatment (frontline group) and 30 after progression on prior AZA treatment (R/R group). Overall, 58.5% of pts received antimicrobial prophylaxis. Regarding cycle 1 (C1), 41.5% were treated as inpts, while 58.5% as outpts. Results: the most common infections during C1 were FUO (16.9%), pulmonary infections (15.4%) and sepsis (7.7%). Median OS was 17.2 months (range, 8.8-25.6) in pts who received antimicrobial prophylaxis vs. 14.7 (range, 4.7-24.7) in those who did not (p=.97). OS of pts who developed infections was 12 months (range, 8.6-15.5) vs. 46.4 in those who did not (range, 9.8-83.0; p=0.011). Univariate analysis (UVA) showed that acquired infections significantly impacted OS [HR=2.491, p=0.014, (95%CI, 1.3–4.4)], which was confirmed in multivariate analysis (MVA) for OS [HR=2.5, p=.014, (95%CI 1.2–5.2)] and EFS [HR=1.9, p=.053, (95%CI 0.99-3.7)]. Treatment setting was a crucial predictive factor for infection development during C1 of AZA+VEN in both UVA [HR=.257, p=.016, (95%CI 0.08-0.7)] and MVA [HR=.256, p=.035, (95%CI 0.07-0.9)]. In R/R group, 1-year OS was 71% in pts without infections (95%CI, 71-99) vs. 63% (95%CI, 43-91) in those with (p= 0.027). 1-year EFS was 71% (95%CI, 51-99) vs. 50% (95%CI, 31-82), respectively (p=0.045). 3-month cumulative incidence of infection in frontline group was 79% (95%CI, 51-92) in inpts vs. 50% (95%CI, 23-72) in outpts (p=.043). In R/R group was 75% (95%CI, 36-92) in unfit pts vs. 28% (95%CI, 9.7-50) in those fit (p=.002). In pts <75 years old was 63% (95%CI, 37-81) vs. 75% (95%CI, 2.5-46) in those ≥75 years (p=.0021). Pts with a PLT count at C1d28 ≥100x109/L developed fewer infections compared to those with lower counts [23%, (95%CI, 5.1-49) vs. 65%, (95%CI, 36-83), p=.023]. Conclusions: performing C1 in an inpatient setting is associated with higher risk of infections and poorer survival outcomes. PLT recovery at day 28 plays a protective role, particularly in R/R group.

Shivanand Hemant Kumatagi, J. Akash, Vinu Rajendran et al.

AIM: The aim of this study was to find out the incidence of seizure recurrence among blood donors who developed vasovagal reaction (VVR). SETTINGS AND DESIGN: A prospective survey-based study conducted at the department of transfusion medicine of a tertiary care referral hospital in southern India. SUBJECTS AND METHODS: All donors who were diagnosed with VVR and loss of consciousness with or without convulsions during 3½ years study period were telephonically contacted to a maximum of 3 times. Whether they experienced a repeat episode of convulsions during 6-month follow-up period irrespective of blood donation was enquired. RESULTS: Out of 66 donors who were included in the study, 45 (68%) donors could be successfully contacted. One donor out of 45 (2.22%) had developed a repeat episode of seizure 5 months postdonation. However, she also had a previous history of seizures which was not revealed during the medical examination. CONCLUSIONS: Our study shows that the VVR with convulsions during blood donation can trigger a secondary episode if the donor had convulsions in their past before donation. We did not find any donor who developed a new seizure episode without a past history of seizure. However, more studies are needed to confirm the same.

Joanne E Davis, Mandy Ludford-Menting, Y. Yang et al.

Blinatumomab is an anti-CD19 bispecific T cell engager designed to bring together CD3+ T cells with CD19+ malignant B cell targets to enable synapse formation and disease eradication of B-ALL. We hypothesised that the proportion of T cells and their ability to bind to their targets may may be a biomarker of response. In this study, we assessed the effect of blinatumomab co-administered with reduced intensity chemotherapy in newly diagnosed B-ALL patients. Furthermore, we developed a method to detect T and B cell conjugates, as measured by conventional flow cytometry, and confirmed using imaging flow cytometry. The research is a cooperative trial group study lead by Australasian Leukemia and Lymphoma Group (ALLG), as ALLG ALL08. Patients with untreated Ph-ve B-ALL aged 40-65 years were enrolled on the ALLG sponsored ALL08 study (ACTRN12617000084381) and treated with alternating cycles of blinatumomab and methotrexate/cytarabine. Peripheral blood mononuclear cells (PBMC) were collected from patients (n=30) at baseline and after C1D28, and healthy age matched donors (n=5). Immune phenotyping of PBMC was performed using spectral cytometry (31-plex, Cytek Aurora). Live video microscopy of purified T cells co-incubated with CD19+ Raji target cells +/- blinatumomab (10 ng/ml, Leica microscope), and whole PBMC synapse assays +/- blinatumomab (BD Fortessa and Cytek Amnis ImageStream flow cytometer) were performed. T:B cell synapse formation was determined by co-expression of T and tumour cell markers. Analysis was conducted using FlowJo, IMARIS, IDEAS and PRISM software. After 1 cycle of blinatumomab treatment, CD19+ B cells decreased and naïve CD8+TIM3+ T cells significantly increased in the blood of B-ALL patients. Live video microscopy demonstrated the number of synapses formed after C1D28 halved compared to the screening sample. Furthermore, patients with a complete response had significantly higher synapse formation at screening, compared to patients with relapsed disease. Subsequent analysis using the whole PBMC synapse assay indicated fewer T cell multimers bound to endogenous B cells when the tumour burden exceeded 20% of circulating PBMC. After blinatumomab engagement multiple T cells were bound to each B cell in complexes comprising of CD4+CD8-, CD4+CD8+ and CD4-CD8+ T cells. Imaging flow cytometry confirmed that the number and size of multimers increased significantly in the presence of bispecific antibodies. Blinatumomab-driven synapse formation was reduced in patients with high B-ALL burden and resulted in increased naive CD8+ T cell frequency in the blood following one cycle of therapy. Decreased synapse formation by T cells collected prior to blinatumomab therapy was associated with clinical relapse, indicating impaired blinatumomab-mediated T cell function. Despite evident ongoing T cell-B cell synapse formation there was a failure of clearance of residual B cells. Optimal blinatumomab therapeutic efficacy may require modifications of dosing schedule based on disease burden and demonstration of effective T cell engagement. Our novel whole PBMC synapse assay identified T cell multimers bound to target cells with different frequencies depending on the percentage of endogenous B cells present in the blood, which may be used as a biomarker to provide a real-world assessment of bispecific antibody efficacy. No conflict of interest to disclose. Drug and funding support was provided by Amgen for the conduct of this study, however they had no role in the study design, conduct, analysis or interpretation of results 12617000084381

Bolin Liu, Alexander Fulton, Hector Zenil

Understanding disease relationships through blood biomarkers offers a pathway toward data driven taxonomy and precision medicine. We constructed a digital blood twin from 103 disease signatures comprising longitudinal hematological and biochemical analytes. Profiles were standardized into a unified disease analyte matrix, and pairwise Pearson correlations were computed to assess similarity. Hierarchical clustering revealed robust grouping of hematopoietic disorders, while metabolic, endocrine, and respiratory diseases were more heterogeneous, reflecting weaker cohesion. To evaluate structure, the tree was cut at a stringent threshold, yielding 16 groups. Enrichment of the largest heterogeneous cluster (Cluster 9) showed convergence on cytokine-signaling pathways, indicating shared immunological and inflammatory mechanisms across clinical boundaries. Dimensionality reduction with PCA and UMAP corroborated these results, consistently separating hematological diseases. Random Forest feature selection identified neutrophils, mean corpuscular volume, red blood cell count, and platelets as the most discriminative analytes, reinforcing hematopoietic markers as key drivers. Collectively, these findings show that blood-derived digital signatures can recover clinically meaningful clusters while revealing mechanistic overlaps across categories. The coherence of hematological diseases contrasts with the dispersion of systemic and metabolic disorders, underscoring both the promise and limits of blood-based classification. This framework highlights the potential of integrating routine laboratory data with computational methods to refine disease ontology, map comorbidities, and advance precision diagnostics.

Akio Suzuki, Hiroyuki Tomita, Hideshi Okada

Three types of capillaries, namely continuous, fenestrated, and sinusoidal, form the microvascular system; each type has a specialized structure and function to respond to the demands of the organs they supply. The endothelial glycocalyx, a gel-like layer of glycoproteins that covers the luminal surface of the capillary endothelium, is also thought to maintain organ and vascular homeostasis by exhibiting different morphologies based on the functions of the organs and capillaries in which it is found. Recent advances in analytical technology have enabled more detailed observations of the endothelial glycocalyx, revealing that it indeed differs in structure across various organs. Furthermore, differences in the lectin staining patterns suggest the presence of different endothelial glycocalyx components across various organs. Interestingly, injury to the endothelial glycocalyx due to various pathological and physiological stimuli causes the release of these components into the blood. Thus, circulating glycocalyx components may be useful biomarkers of organ dysfunction and disease severity. Moreover, a recent study suggested that chronic injury to the glycocalyx reduces the production of these glycocalyx components and changes their structure, leading it to become more vulnerable to external stimuli. In this review, we have summarized the various endothelial glycocalyx structures and their functions.

Jisun Lee, Seung-Kee Min

Adventitial cystic disease (ACD), a rare vascular disease characterized by mucus accumulation in the adventitia of blood vessels, typically affects the popliteal artery. We present the case of a 61-year-old female diagnosed with ACD in 2018 who was initially treated with endovascular stenting and percutaneous aspiration of the cyst. The patient, who had been asymptomatic for 5 years, developed a stent fracture and pseudoaneurysm requiring surgical intervention. Despite initial successful treatment, complications such as stent fracture and recurrence can occur; therefore, surgical treatment is recommended to optimize outcomes in patients with ACD. Endovascular treatment and cyst aspiration should only be considered in cases with high surgical risk. After treatment, long-term follow-up and individualized management strategies are important to monitor ACD recurrence.

GAF Maia, JLR Cunha-Júnior, A Erbetta et al.

Introdução: A infecção por Dengue é transmitida pelo mosquito Aedes aegypti e constitui um grande problema de saúde pública, principalmente em regiões tropicais, onde o meio ambiente favorece sua proliferação e apresenta significativa morbidade. As epidemias de Dengue têm apresentado um problema recorrente no setor de saúde pública, caracterizado por surtos intermitentes de casos e uma extensão das regiões afetadas. As manifestações da Dengue são muito complexas, com quadro febril e de evolução benigna na sua forma clássica, mas agressiva na sua forma grave, sendo uma das mais importantes arboviroses que afeta o homem. Os achados laboratoriais no hemograma são importantes para a caracterização fisiopatológica da gravidade, através de valores crescentes do hematócrito com a hemoconcentração e diminuição das plaquetas nas manifestações hemorrágicas. Na Dengue Clássica, a leucopenia é achado usual (embora possa ocorrer leucocitose), pode estar presente linfocitose com reatividade linfocitária e a trombocitopenia é observada ocasionalmente. Na Dengue Grave a contagem de leucócitos é variável, podendo ocorrer desde a leucopenia até a leucocitose leve, e a linfocitose com reatividade linfocitária é um achado comum. Destacam-se a concentração de hematócrito e a trombocitopenia, com contagem de plaquetas abaixo de 100.000/mm3. Objetivos: Analisar o perfil de hemogramas realizados no período de 12/01/2024 a 26/02/2024 de casos positivos para Dengue. Métodos: Este estudo contou com amostras de sangue positivas para Dengue, coletadas no período de 12/01/2024 a 26/02/2024, enviadas para análise de rotina com o pedido de hemograma para o Laboratório de Hematologia do Hospital de Clínicas da UNICAMP (Campinas-SP). As amostras (n = 59) foram incluídas no estudo, independentemente da idade, que variou de 20 anos a 75 anos. As amostras foram processadas no analisador automatizado (Sysmex XN-9000). Para todas as amostras de sangue foram confeccionados os esfregaços, os quais foram avaliados por microscopia pelos profissionais do laboratório. As análises estatísticas utilizadas foram descritiva e correlação de Pearson. Resultados/Discussão: Das amostras analisadas, 39% (23) foram do sexo feminino e 61% (36) do sexo masculino. 1,69% (1 amostra) apresentou contagem de leucócitos acima de 10 × 103/mm3, 37,3% (22 amostras) apresentaram leucócitos abaixo de 4 × 103/mm3 e 61% (36 amostras) estavam dentro dos valores de referência. Plaquetopenia foi observada em 10,2% das amostras (6 amostras), que cursaram com presença expressiva de linfócitos reativos. Não houve correlação entre o número total de leucócitos e o número de plaquetas com um r = -0.0408. Quando comparamos número de plaquetas e presença de linfócitos reativos obtivemos uma correlação moderada negativa de r = -0.5008. 66,7% das amostras (4 amostras) com plaquetopenia também cursaram com leucopenia. Entre as amostras analisadas, 89,83% (53 amostras) apresentaram plaquetas acima de 100 x 103/mm3, sendo 33,97% (18 amostras) com leucopenia. Conclusão: O perfil dos resultados obtidos no Hemograma em pacientes positivos para Dengue são compatíveis com a dados da literatura. O agravamento desta arbovirose apresentou ao hemograma resultados de plaquetopenia, presença de linfócitos reativos e em alguns casos a leucopenia. Na Dengue clássica também obtivemos dados que corroboram com achados da literatura.

I. M. O. Intervention Lissa Sabrina, I. P. PCI Sidharta Salim Adnyana, Amalia Nurjanah Pradnyandari et al.

Coronary artery bypass grafting (CABG) is the most ideal and frequently performed procedure for multi-vascular coronary artery stenosis, but its long-term prognosis is unfavorable. A 64-year-old male with a history of coronary artery graft surgery seven years ago complained of recurrent chest pain radiating to the jaw, relieved by isosorbide dinitrate. Physical examination, electrocardiography, and echocardiography test results were within normal limits. Laboratory results showed critical blood urea nitrogen (BUN) values requiring hemodialysis, on angiographic examination showed stenosis in all grafted and native coronary arteries. The diagnoses were grade III coronary artery disease and renal failure. Percutaneous coronary intervention using a drug-eluting stent (DES) in the saphenous vein graft conduit of the right coronary artery was performed, along with dual antiplatelet agents, b-blockers, nitrates, and statins.

Amelia Puspita Suhendro Revascularization dengan Laki-Lak Patients, Ketut Sumada with Lsl Induced by Chronic, Ni Ketut Post-Traumatic Unexplained et al.

Background: Chorea hyperglycemia basal ganglia (C-H-BG) syndrome is an uncommon manifestation of diabetes mellitus seen in patients with poor glycemic control. Case: A 74-year-old poorly controlled diabetic women with acute onset of movement disorder in the form of uncontrolled choreiform movements of her left upper and lower extremity. Her initial glucose level was 289 mg/dL and HbA1C was 9.5%. Discussion: Most C-H-BG patients are older Asian female. Female predisposition is probably related to the estrogen decline during menopause, resulting in gamma-aminobutyric acid (GABA) depletion or dopamine receptors hypersensitivity and enhancement of dopaminergic system. Its pathophysiology has not been entirely defined. Conclusion: C-H-BG is a rare manifestation of poorly controlled diabetes. Early recognition and treatment of elevated blood glucose levels appear to lead to total resolution.

Albert J. Miao, Shan Lin, Jingpei Lu et al.

Hemorrhaging occurs in surgeries of all types, forcing surgeons to quickly adapt to the visual interference that results from blood rapidly filling the surgical field. Introducing automation into the crucial surgical task of hemostasis management would offload mental and physical tasks from the surgeon and surgical assistants while simultaneously increasing the efficiency and safety of the operation. The first step in automation of hemostasis management is detection of blood in the surgical field. To propel the development of blood detection algorithms in surgeries, we present HemoSet, the first blood segmentation dataset based on bleeding during a live animal robotic surgery. Our dataset features vessel hemorrhage scenarios where turbulent flow leads to abnormal pooling geometries in surgical fields. These pools are formed in conditions endemic to surgical procedures -- uneven heterogeneous tissue, under glossy lighting conditions and rapid tool movement. We benchmark several state-of-the-art segmentation models and provide insight into the difficulties specific to blood detection. We intend for HemoSet to spur development of autonomous blood suction tools by providing a platform for training and refining blood segmentation models, addressing the precision needed for such robotics.

Md Taimur Ahad, Israt Jahan Payel, Bo Song et al.

Blood cancer can only be diagnosed properly if it is detected early. Each year, more than 1.24 million new cases of blood cancer are reported worldwide. There are about 6,000 cancers worldwide due to this disease. The importance of cancer detection and classification has prompted researchers to evaluate Deep Convolutional Neural Networks for the purpose of classifying blood cancers. The objective of this research is to conduct an in-depth investigation of the efficacy and suitability of modern Convolutional Neural Network (CNN) architectures for the detection and classification of blood malignancies. The study focuses on investigating the potential of Deep Convolutional Neural Networks (D-CNNs), comprising not only the foundational CNN models but also those improved through transfer learning methods and incorporated into ensemble strategies, to detect diverse forms of blood cancer with a high degree of accuracy. This paper provides a comprehensive investigation into five deep learning architectures derived from CNNs. These models, namely VGG19, ResNet152v2, SEresNet152, ResNet101, and DenseNet201, integrate ensemble learning techniques with transfer learning strategies. A comparison of DenseNet201 (98.08%), VGG19 (96.94%), and SEresNet152 (90.93%) shows that DVS outperforms CNN. With transfer learning, DenseNet201 had 95.00% accuracy, VGG19 had 72.29%, and SEresNet152 had 94.16%. In the study, the ensemble DVS model achieved 98.76% accuracy. Based on our study, the ensemble DVS model is the best for detecting and classifying blood cancers.

A. Chauhan, C. Sasmal

This study employs extensive three-dimensional direct numerical simulations (DNS) to investigate the influence of blood non-Newtonian behaviors on the hemodynamics around a bileaflet mechanical heart valve under both steady inflow and physiologically realistic pulsatile flow conditions. Under steady inflow conditions, the study reveals that blood rheology impacts velocity and pressure field variations, as well as the values of clinically important surface and time-averaged parameters like wall shear stress (WSS) and pressure recovery. Notably, this influence is most pronounced at low Reynolds numbers, gradually diminishing as the Reynolds number increases. For instance, surface-averaged WSS values obtained with the non-Newtonian shear-thinning power-law model exceed those obtained with the Newtonian model. At $Re = 750$, this difference reaches around 67\%, reducing to less than 1\% at $Re = 5000$. Correspondingly, pressure recovery downstream of the valve leaflets is lower for the shear-thinning blood than the constant viscosity one, with the difference decreasing as the Reynolds number increases. On the other hand, in pulsatile flow conditions, jets formed between the leaflets and the valve housing wall are shorter than steady inflow conditions. Additionally, surface-averaged wall shear stress and blood damage (BD) parameter values are higher (with differences more than 13\% and 47\%, respectively) during the peak stage of the cardiac cycle, especially for blood exhibiting non-Newtonian yield stress characteristics compared to the shear-thinning or constant viscosity characteristics. Therefore, blood non-Newtonian behaviors, including shear-thinning and yield stress behaviors, exert a considerable influence on the hemodynamics around a mechanical heart valve.

W. Y. Ho, H. Hartmann, Shuo-Chien Ling

Cholesterol is a ubiquitous and essential component of cellular membranes, as it regulates membrane structure and fluidity. Furthermore, cholesterol serves as a precursor for steroid hormones, oxysterol, and bile acids, that are essential for maintaining many of the body's metabolic processes. The biosynthesis and excretion of cholesterol is tightly regulated in order to maintain homeostasis. Although virtually all cells have the capacity to make cholesterol, the liver and brain are the two main organs producing cholesterol in mammals. Once produced, cholesterol is transported in the form of lipoprotein particles to other cell types and tissues. Upon formation of the blood–brain barrier (BBB) during embryonic development, lipoproteins cannot move between the central nervous system (CNS) and the rest of the body. As such, cholesterol biosynthesis and metabolism in the CNS operate autonomously without input from the circulation system in normal physiological conditions. Nevertheless, similar regulatory mechanisms for maintaining cholesterol homeostasis are utilized in both the CNS and peripheral systems. Here, we discuss the functions and metabolism of cholesterol in the CNS. We further focus on how different CNS cell types contribute to cholesterol metabolism, and how ApoE, the major CNS apolipoprotein, is involved in normal and pathophysiological functions. Understanding these basic mechanisms will aid our ability to elucidate how CNS cholesterol dysmetabolism contributes to neurogenerative diseases.

Christian Steidl, Robert Kridel, Michael Binkley et al.

Abstract Lymphoid cancers are among the most frequent cancers diagnosed in adolescents and young adults (AYA), ranging from approximately 30%–35% of cancer diagnoses in adolescent patients (age 10–19) to approximately 10% in patients aged 30–39 years. Moreover, the specific distribution of lymphoid cancer types varies by age with substantial shifts in the subtype distributions between pediatric, AYA, adult, and older adult patients. Currently, biology studies specific to AYA lymphomas are rare and therefore insight into age‐related pathogenesis is incomplete. This review focuses on the paradigmatic epidemiology and pathogenesis of select lymphomas, occurring in the AYA patient population. With the example of posttransplant lymphoproliferative disorders, nodular lymphocyte‐predominant Hodgkin lymphoma, follicular lymphoma (incl. pediatric‐type follicular lymphoma), and mediastinal lymphomas (incl. classic Hodgkin lymphoma, primary mediastinal large B cell lymphoma and mediastinal gray zone lymphoma), we here illustrate the current state‐of‐the‐art in lymphoma classification, recent molecular insights including genomics, and translational opportunities. To improve outcome and quality of life, international collaboration in consortia dedicated to AYA lymphoma is needed to overcome challenges related to siloed biospecimens and data collections as well as to develop studies designed specifically for this unique population.

Sandeep Padala, Jorge Cortes

Asciminib is a novel tyrosine kinase inhibitor (TKI) that specifically targets the myristoyl pocket. It has increased selectivity and potent activity against BCR-ABL1 and the mutants that most frequently prevent the activity of the ATPbinding competitive inhibitors. Results for clinical trials in patients with chronic myeloid leukemia that have received two or more TKI (randomized against bosutinib) or who have a T315I mutation (single arm study) have shown high levels of activity and a favorable toxicity profile. Its approval has offered new options for patients with these disease features. There are, however, a number of unanswered questions that remain to be defined, including the optimal dose, understanding the mechanisms of resistance, and, importantly, how it compares to ponatinib in these patient populations for whom we now have these two options available. Ultimately, a randomized trial is needed to answer questions to which we currently offer speculative informed guesses. The novelty of its mechanism of action and the exciting early data offer the potential for asciminib to address some of the remaining needs in the management of patients with chronic myeloid leukemia, including second-line therapy after resistance to a front-line second-generation TKI and improving successful treatment-free remission. Multiple studies are ongoing in these areas, and one can only hope that the desired randomized trial comparing asciminib to ponatinib will be conducted soon.