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

Arturo Tozzi

Blood pressure regulation is commonly addressed in terms of local mechanisms such as vascular resistance, compliance and neurohumoral control. However, the human vasculature encompasses multiple quasi-closed flow loops under both physiological and pathological conditions. To test whether these loops could influence pressure dynamics beyond local control, we address the role of vascular topology in blood pressure regulation. Using one dimensional flow simulation models, we compared pressure dynamics in open vascular segments and closed vascular loops. We found that in open segments pressure fades away and remains spatially localized, whereas in closed loops pressure can keep circulating around the loop even if resistance in one spot is modified. Since parallel pathways within loops are dynamically coupled rather than independent, pressure changes in one place can affect the entire closed loop, allowing system level pressure patterns to emerge. Also, we assessed the temporal evolution of pressure fluctuations within closed vascular loops in normotensive and hypertensive parameter regimes, before and after loop breaking intervention. This topological approach helps clarifying why drugs or local interventions may fail to lower blood pressure in looped vascular architectures, providing a theoretical interpretation of some forms of resistant hypertension. Because disrupting a loop restores pressure relaxation, it may also help explain the disproportionate pressure changes observed after topology altering events like thrombosis, vascular surgery or embolization of arteriovenous malformations and shunts. Therefore, vascular topology can influence cardiovascular physiology by coupling local pressure flow relations to global constraints on blood pressure regulation, with physiological, pathological and clinical implications.

Lo Kai Shun John, Riya Nagar, Abicumaran Uthamacumaran et al.

Early detection of cancer and cardiovascular diseases is fundamental to improving patient outcomes and reducing healthcare expenditure. Current cancer screening programs are targeted towards specific cancers and are often inaccessible to large parts of the population, particularly in remote regions. This project aimed to develop digital blood twins: machine learning models that leverage routinely collected blood test data, demographics, comorbidities, and prescribed medications, for scalable and cost-effective disease screening. Digital blood twins were constructed using the UK Biobank dataset (n = 373,269). Using age, sex, comorbidities, medication profiles, and blood test z-scores, three iterations of XGBoost classifiers were trained for broad cancer, colorectal cancer, and cardiovascular disease prediction. Model interpretability was achieved through SHAP and dimensionality reduction analyses (UMAP, t-SNE). Broad-category cancer models achieved ROC-AUC = 0.607-0.706. Colorectal cancer prediction demonstrated excellent discrimination (ROC-AUC = 0.816-0.993), and cardiovascular models showed clinical utility, notably for hypertension (ROC-AUC = 0.813, F1 = 0.861). SHAP revealed consistent importance of age, sex, basophil count, and cystatin C. Immune digital blood twins as an agnostic tool demonstrate proof-of-concept feasibility for accessible, low-cost, and scalable screening of cancer and cardiovascular diseases, supporting future integration into predictive and preventive healthcare.

Abduz Zami, Shadman Sobhan, Rounaq Hossain et al.

Image segmentation plays a vital role in the medical field by isolating organs or regions of interest from surrounding areas. Traditionally, segmentation models are trained on a specific organ or a disease, limiting their ability to handle other organs and diseases. At present, few advanced models can perform multi-organ or multi-disease segmentation, offering greater flexibility. Also, recently, prompt-based image segmentation has gained attention as a more flexible approach. It allows models to segment areas based on user-provided prompts. Despite these advances, there has been no dedicated work on prompt-based interactive multi-organ and multi-disease segmentation, especially for Chest X-rays. This work presents two main contributions: first, generating doodle prompts by medical experts of a collection of datasets from multiple sources with 23 classes, including 6 organs and 17 diseases, specifically designed for prompt-based Chest X-ray segmentation. Second, we introduce Prompt2SegCXR, a lightweight model for accurately segmenting multiple organs and diseases from Chest X-rays. The model incorporates multi-stage feature fusion, enabling it to combine features from various network layers for better spatial and semantic understanding, enhancing segmentation accuracy. Compared to existing pre-trained models for prompt-based image segmentation, our model scores well, providing a reliable solution for segmenting Chest X-rays based on user prompts.

Clotilde Joubert, Alexei Grichine, Monika Dolega et al.

The functional role of platelets is intricately linked to the dynamic organization of two main components of the cytoskeleton, microtubules and actin fibers. Throughout the phases of platelet activation, spreading, and retraction, both of these essential polymers undergo continuous and orchestrated reorganization. Our investigation of the dynamic cytoskeletal changes during these phases highlights a sequential remodeling of the actin cytoskeleton in adherent platelets from the formation of initial actin nodules through the development of stress fibers and a subsequent return to nodular structures. Concurrently, the marginal ring of microtubules, characteristic of resting platelets, undergoes a re-organization induced by marginal band extension and coiling toward the formation of star-like bundles of microtubules. Subsequently, these bundles are dispersed into individual microtubules, which are re-bundled at later stages before ring-like structures are formed again. These findings suggest a compelling tendency for both cytoskeletal components to revert to their original configurations. Notably, the early steps of platelet cytoskeleton reorganizations have previously been shown to be regulated by the signaling cascade triggered during platelet activation, which leads to an increase of cytosolic calcium concentrations. We show here that later steps are potentially regulated by a progressive decrease of intracellular calcium concentrations as platelets approach the end of their functional lifespan.

Ayfer Gedük

CAR-T (chimeric antigen receptor T-cell) therapy represents a revolutionary advance in treating hematologic cancers, offering promising outcomes for lymphoma patients, especially those with relapsed or refractory disease. Initially approved for diffuse large B-cell lymphoma (DLBCL), CAR-T therapy is expanding to address a broader range of lymphomas, including other B-cell and T-cell subtypes. As CAR-T technology evolves, researchers are exploring innovative delivery strategies and engineering methods to enhance efficacy and address the unique challenges of treating different lymphoma types.CAR-T cell therapy works by genetically modifying a patient's T cells to express a receptor targeting specific cancer cell antigens. In B-cell lymphomas, CD19 has proven an effective target, with CAR-T therapies such as axicabtagene ciloleucel and tisagenlecleucel demonstrating remarkable responses. Recent studies reveal high remission rates in DLBCL, mantle cell lymphoma, and follicular lymphoma when using CD19-targeted CAR-T therapy, even in patients who have exhausted other treatment options. The success of these therapies has catalyzed research into additional lymphoma subtypes and new antigen targets, allowing CAR-T cell therapy to benefit an expanding patient population (Denlinger et al., 2022).One notable development is the investigation of CAR-T cell therapy in T-cell lymphomas. T-cell lymphomas pose unique challenges due to their antigen overlap with healthy T cells, leading to risks like T-cell fratricide, where CAR-T cells inadvertently destroy each other. To address this, researchers are designing CAR-T cells targeting less common antigens, such as CD30, which is often overexpressed in Hodgkin lymphoma and some T-cell lymphomas, but not in normal T cells. CD30-directed CAR-T therapies have shown early success in clinical trials, offering hope for relapsed Hodgkin lymphoma patients who lack other viable options (Brudno et al., 2024, Ramos et al., 2020).Localized CAR-T cell therapy is another emerging strategy, particularly for lymphomas affecting the central nervous system (CNS). CNS lymphomas present an additional barrier because CAR-T cells administered intravenously may struggle to cross the blood-brain barrier (BBB) and reach tumor cells. Direct intrathecal CAR-T administration, which bypasses the BBB, has shown promising early results for CNS lymphoma, providing high CAR-T cell concentrations directly within the CNS and improving patient outcomes. This approach may reduce systemic side effects like cytokine release syndrome (CRS) and neurotoxicity, although localized neurotoxicity remains a concern (Sagnella et al., 2022).Engineering advancements are also helping address antigen escape, where cancer cells evade CAR-T cells by losing the targeted antigen. Dual-target CAR-T cells can recognize multiple antigens, reducing the risk of relapse due to antigen loss. For example, dual CD19/CD22 CAR-T therapies are being studied for their ability to sustain long-term remission by targeting two markers common to B-cell lymphomas, thus enhancing durability and reducing escape mutations. Also combining CAR-T with immune checkpoint inhibitors improve CAR-T cell efficacy. (Roddie et al., 2023).In summary, CAR-T cell therapy has transformed the lymphoma treatment landscape, extending beyond DLBCL to address Hodgkin lymphoma, follicular lymphoma, and other challenging subtypes. As new approaches evolve—such as local delivery for CNS lymphoma, dual-target CAR-T constructs, and novel T-cell lymphoma strategies—CAR-T therapy's role continues to expand, offering new hope to patients with previously untreatable lymphomas. Continued innovation will be crucial for refining CAR-T technology, overcoming barriers, and realizing its full potential across diverse lymphoma types.

FG Barbosa, FZ Piazera, GO Borges et al.

Introdução: A terapia de alta dose (HDT) seguida de TCTH é o tratamento padrão para LH recidivado ou refratário. Até recentemente, carmustina, etoposídeo, citarabina e melfalano (BEAM) era o regime de condicionamento mais comumente utilizado, dada sua eficácia e tolerabilidade aceitáveis. Apesar do sucesso com BEAM, a carmustina está associada a uma série de toxicidades agudas e tardias. Além disso, problemas recentes de fornecimento criaram uma necessidade urgente de regimes de condicionamento alternativos. Vários novos regimes de condicionamento que substituem a carmustina por outros agentes estão sob investigação, o que pode fornecer alternativas eficazes ao BEAM. Ao considerar novos agentes para substituir a carmustina, a lomustina pode uma alternativa, conforme demonstrado pelos resultados de vários estudos prévios. No estudo atual apresentamos uma análise retrospectiva da série histórica de uma instituição privada comparando BEAM vs. LEAM como condicionamento para LH. Objetivo: O objetivo foi avaliar toxicidades hematologicase não hematológicas entre os dois condicionamentos citados. Materiais e métodos: Realizou-se uma análise retrospectiva de 28 pacientes submetidos ao TCTH autólogo no período de 2000 a 2024 numa instituição privada do DF. As variáveis epidemiológicas, clínicas do LH, viabilidade celular das células CD34+, tipo de condicionamento, tempo de enxertia foram analisados. A análise estatística uni e multivariada foi realizada pelo programa PRISM®. O teste de Mann-Whitney-Wilcoxon foi usado para comparar 2 grupos distribuídos não normalmente. O teste de Fisher foi usado para comparar categorias. Resultados: A mediana de idade foi 28,3 anos (variando de 18 a 55 anos); sendo 60,3% de pacientes sexo masculino e 39,7% do sexo feminino. Quanto ao estadiamento clínico Ann Arbor ao diagnóstico: II = 14,2% (n = 4), III = 50% (n = 14), IV = 36,8%(n = 10), Quanto ao tipo de Condicionamento: LEAM = 64,2% (n = 18) e BEAM = 36,8% (n = 10); quanto ao número de terapias previas ao TCTH: 2 esquemas = 85,8% (n = 24) e 3 esquemas = 14,2% (n = 4), quanto ao esquema de resgate utilizado: ABVD = 100% (n = 28 pacientes), GDP = 64,2% (n = 18), IGEV = 7,14% (n = 2), DHAP = 21,42% (n = 6), ICE = 7,14% (n = 2); quanto a avaliação de resposta pré TCTH: DE = 10,8% (n = 3), RP = 39,2% (n = 11), RC = 50% (n = 14); quanto a terapia de manutenção pós TCTH: 64,2% (n = 18) (tal terapia só foi ofertada após 2019). Quanto ao tipo de mobilização: os pacientes do grupo BEAM (devido ao periodohistorico) foram mobilizados com ciclofosfamida + GCSF (n = 10) apresentando mediana de celulas CD34+ coletadas de 2,9 × 10.6/Kg (variando de 1,64 a 9,9) com mediana de 2 coletas de aferese (variando de 1 a 4) e viabilidade celular de 95%. O grupo do LEAM foram mobilizados com protocolo de plerixafor +GCSF (n = 18) com mediana de células CD34+ de 9,2 (variando de 3,7 a 85,2) com mediana de coletas de aferese de 1,5 (variando 1 a 3) e viabilidade celulas de 98%. Quanto análise em subgrupos do tipo de condicionamento com tempo de enxertia, grupo BEAM apresentou mediana de 16 dias (variando de 11 a 24 dias) e sobrevida em 100 dias de 100 % e LEAM com 11 dias (variando de 9 a 28 dias) com sobrevida em 100 dias de 95% (1 óbito por falha de enxertia) com p = 0,001. Conclusão: Neste estudo, apresentamos a análise comparativa retrospectiva de pacientes com LH R/R submetidos a ASCT com condicionamento BEAM/LEAM. Os dados apresentados analisam apenas o estado clínico e as variáveis celulares dos pacientes nos primeiros 100 dias após o transplante. Assim, estudos futuros devem ser realizados para comparar os três regimes de condicionamento além do dia +100 após o transplante.

Gideon A. Ngwa, Bime M. Ghakanyuy, Miranda I. Teboh-Ewungkem et al.

A deterministic nonlinear ordinary differential equation model for mosquito dynamics in which the mosquitoes can quest for blood either within a human population or within non-human/vertebrate populations is derived and studied. The model captures both the mosquito's aquatic and terrestrial forms and includes a mechanism to investigate the impact of mating on mosquito dynamics. The model uses a restricted form of homogeneous mixing based on the idea that the mosquito has a blood-feeding habit by accounting for the mosquitoes' blood-feeding preferences as well as its gonotrophic cycle. This characterization allows us to compartmentalise the total mosquito population into distinct compartments according to the spatial location of the mosquito (breeding site, resting places and questing places) as well as blood-fed status. Issues of overcrowding and intraspecific competition both within the aquatic and the terrestrial stages of the mosquito's life forms are addressed and considered in the model. Results show that the inclusion of mating induces bi-stability; a phenomenon whereby locally stable trivial and non-trivial equilibria co-exist with an unstable non-zero equilibrium. The local nature of the stable equilibria is demonstrated by numerically showing that the long-term state of the system is sensitive to initial conditions. The bi-stability state is analogous to the phenomenon of the Allee effect that has been reported in population biology. The model's results, including the derivation of the threshold parameter of the system, are comprehensively tested via numerical simulations. The output of our model has direct application to mosquito control strategies, for it clearly shows key points in the mosquito's developmental pathway that can be targeted for control purposes.

B. Kuehn

As a young person, Joseph C. Wu, MD, PhD, the Simon Stertzer, MD, Professor of Medicine and Radiology and Director of Stanford Cardiovascular Institute, was drawn to cardiology because he was fascinated by the beating heart— “the center of melodic, rhythmic motion that makes it the most palpable organ of the human body.” Now, Joe (as he is known to colleagues and friends) regularly observes the behavior of beating cardiomyocytes grown from patients’ cells in his laboratory at the Biomedical Innovation building across from the Stanford University Hospital. “We take patient’s blood cells, convert them into induced pluripotent stem cells and differentiate them into heart cells in a dish,” he said. “We can also grow human engineered heart tissues in a dish.” His work on human induced pluripotent stem cells (iPSCs) is on the cusp of revolutionizing cardiovascular drug studies. It is also bringing personalized medicine into reach for patients with genetic forms of heart disease. As he continues his ambitious research agenda, Dr Wu hopes to share his passion for cardiovascular health and science with the public, policymakers, and the next generation of cardiovascular researchers as he steps into the role of the 2023– 2024 president of the American Heart Association. “I want to raise public awareness about the importance of cardiovascular health because heart disease is the number one cause of mortality,” he said during an interview. “I also want to emphasize the importance of investing in biomedical research that will benefit our patients in the future and training the next generation of scientific researchers who will do this critical work for decades to come.”

R Conserva, VM Sthel, VLP Figueiredo

Objective: To report the clinical evolution of AML with complex karyotype in an elderly individual using the AZAVIT-ABCDEF protocol. Method: Information was obtained through electronic medical record review (HSPE–IAMSPE-SP). Introduction: The cellular proliferation that occurs in AMLs requires significant energy access. Warburg described in 1956 that neoplastic cells, even in the presence of O2, utilize anaerobic metabolism. Improving the use of aerobic pathways with high doses of vitamins may favor the differentiation of hematopoietic cells. The AZAVIT-ABCDEF protocol (AZACYTIDINE 75 mg/m2 subcutaneously for 7 days associated with high intravenous doses of Vitamins B1 (15-20 mg/kg every 12/12 hours), C (300 - 400 mg/kg intravenously every 12/12 hours), calcitriol 0.25 mcg orally every 6/6 hours, erythropoietin 10,000 IU subcutaneously once a day, and filgrastim 5-10 mcg/kg subcutaneously once a day) in a 28/28-day cycle. Between cycles, oral use includes Vitamin C 2 g every 8/8 hours, Benfotiamine 150 mg every 12/12 hours, Vitamin D 50,000 IU once a day until levels reach 80-100 ng/mL, and Famotidine 40 mg every 12/12 hours - (Plataforma Brasil CAAE: 53015421.0.0000.5463). After obtaining informed consent. Case report: Male 80-year-old in NOV/22 presented with anemic syndrome, Hb = 5.5 g/dL; Leukocytes = 3719/mm3 (20/11/0/55/14); Platelets = 38,000/mm3. Bone marrow: 30% blasts with phenotype: CD10, CD13, CD33, CD34, CD38, CD71, CD117, CD123, HLA-DR, and MPO. Karyotype: 45 XY add (3) (q21), del5, add(7) (p11.2), -9, der (12)t(1214) (p11.2q11.2), -14, +2mar [17] /46, XY [4]. FISH: Deletion of Chromosome 5 in 130/200 metaphases. He received 4 cycles of the protocol. Progressed with Hemogram: Hb = 14.1 g/dL; leukocytes = 13,670/mm3 (neutrophils = 10,130) and platelets = 273,000/mm3. Bone marrow: Hypercellular and normomaturative with negative minimal residual disease. Karyotype: 46, XY [20] and FISH: normal. As of August 2023, he is on the 8th cycle with stable hemogram. Discussion: Vitamins are closely linked to the Krebs cycle, not providing energy but releasing it through intense redox mechanisms. This may contribute to better epigenetic regulation of primitive hematopoietic cells. Genes linked to epigenetics: DNMT3A, TET2, ASXL1, IDH1, and IDH2 are frequently mutated in AML and are considered important for directly or indirectly leading to DNA methylation. Azacytidine: inhibits DNMT3A and promotes cell differentiation. Vitamin: An effective guardian of aerobic metabolism, serving as a cofactor for pyruvate dehydrogenase complex (PDHC), the enzyme allowing pyruvate to enter the Krebs cycle. It also acts on alpha-ketoglutarate metabolism, reducing 2-Hydroxyglutarate (2-HG) formation and DNA methylation. Vitamin C: Cofactor of TET2 gene in DNA demethylation. Vitamin D: Binds to VDR, which heterodimerizes with retinoid-X receptor (RXR) within the cell nucleus, serving as a transcription factor for numerous target genes. Conclusions: The patient exhibited an excellent response, and the AZAVIT-ABCDEF protocol should be studied in a prospective cohort to better define its role in treating AML in patients without performance status for intensive treatment. The main objective is to reduce transfusion dependence and extend survival in this population.

PC Gontijo, ABGC Silva, ALAC Freitas et al.

Introdução/Objetivo: O sistema linfocítico tem um papel fundamental na defesa do organismo, entretanto pode se tornar disfuncional em alguns casos, levando ao surgimento de doenças graves, como os linfomas. O objetivo deste trabalho é relatar a evolução de um paciente de 27 anos com Linfoma de Hodgkin Predominância Linfocitária Nodular de padrão difuso (LHPLN) transformado para Linfoma Difuso de Grandes Células B rico em T (LBRCT), além de evidenciar a dificuldade no tratamento desse subtipo de doença. Material e métodos: Trata-se de um Relato de Caso, em que as informações do paciente foram obtidas por meio de revisão do prontuário, entrevista com o paciente, discussão do caso com a equipe médica responsável e revisão da literatura. Resultados: Em 2016, o paciente foi internado após procurar por atendimento médico devido a paraparesia súbita de MMII ao despertar, sem hipoestesia ou outros sintomas associados. Nesse período, foi notada massa axilar esquerda de rápida evolução e emagrecimento significativo, de 42 kg em dois meses, ou seja, aproximadamente, 50% do peso corporal. Aos exames de imagem, biópsia e imuno-histoquímica, foi diagnosticado com LHPLN transformado para LBRCT. A neoplasia apresentou focos neoplásicos unilaterais e bilaterais em linfonodos paravertebrais, axilares, cervicais, esplênicos, hilares e outras regiões, sendo o estadiamento da doença IVB. O paciente apresentou refratariedade à quimioterapia e não obteve sucesso no transplante autólogo, apresentando 4 recidivas da doença. Atualmente, encontra-se em controle do quadro, relatando como sintoma fadiga associada a atividades intensas do dia a dia, como arrumar casa, além de outros dois casos de paraparesia dos MMII no final de 2022 e em maio de 2023, com melhora do quadro após internação em ambos os casos. A última sessão de quimioterapia foi em julho de 2023. Discussão: A terapêutica envolvida nos LHPLN transformado para LBRCT é complexa, pois esse tipo de câncer pode estar associado a uma diversidade de características moleculares e bioquímicas das células neoplásicas, variando as condutas e os tratamentos prescritos. Dessa forma, os sintomas podem se manifestar de várias formas, inclusive serem sutis e isolados, dificultando o diagnóstico e limitando as possibilidades terapêuticas, tal como ocorre nos casos em que há resistência à quimioterapia. Devido a essas questões, essa doença deve ser acompanhada por uma equipe multidisciplinar, que visa a individualidade de cada caso clínico. Conclusão: A transição de LHPLN a LBRCT é uma condição que predispõe a agressividade do linfoma e a refratariedade aos tratamentos existentes. Desta forma, o conhecimento e o contato com pacientes que apresentam essa patologia são vitais para a ampliação do manejo clínico e melhora do prognóstico. As manifestações clínicas da doença devem ser sempre consideradas e avaliados criteriosamente, devido às frequentes dúvidas diagnósticas dos exames complementares em casos de transição de LHPLN a LBRCT. A determinação do diagnóstico rapidamente é de suma importância devido à frequente apresentação avançada com pior prognóstico do LBRCT.

Himangshu Sonowal, Rafael Bejar, William Rice et al.

Andrii Voshchepynets, Oleksiy Agapitov, Lynn Wilson et al.

We present the results of processing the effects of the powerful Gamma Ray Burst GRB221009A captured by the charged particle detectors (electrostatic analyzers and solid-state detectors) onboard spacecraft at different points in the heliosphere on October 9, 2022. To follow the GRB221009A propagation through the heliosphere we used the electron and proton flux measurements from solar missions Solar Orbiter and STEREO-A; Earth magnetosphere and the solar wind missions THEMIS and Wind; meteorological satellites POES15, POES19, MetOp3; and MAVEN - a NASA mission orbiting Mars. GRB221009A had a structure of four bursts: less intense Pulse 1 - the triggering impulse - was detected by gamma-ray observatories at 131659 UT (near the Earth); the most intense Pulses 2 and 3 were detected on board all the spacecraft from the list, and Pulse 4 detected in more than 500 s after Pulse 1. Due to their different scientific objectives, the spacecraft, which data was used in this study, were separated by more than 1 AU (Solar Orbiter and MAVEN). This enabled tracking GRB221009A as it was propagating across the heliosphere. STEREO-A was the first to register Pulse 2 and 3 of the GRB, almost 100 seconds before their detection by spacecraft in the vicinity of Earth. MAVEN detected GRB221009A Pulses 2, 3, and 4 at the orbit of Mars about 237 seconds after their detection near Earth. By processing the time delays observed we show that the source location of the GRB221009A was at RA 288.5 degrees, Dec 18.5 degrees (J2000) with an error cone of 2 degrees

older, Austrian, C. T Panzera 1 et al.

Abstract Background Cardiovascular disease and cancer share modifiable risk factors and, potentially, molecular mechanisms of disease, as postulated by the “common soil” hypothesis. We examined whether the American Heart Association's Life's Simple 7 (LS7) metrics to assess and promote cardiovascular health, is associated with cancer risk, defined as first hospital admission for any cancer obtained through record linkage with hospital discharge forms. Methods Longitudinal analyses on 21,705 apparently cancer-free participants (mean age 55.2±11.6; 51.9% women) at cohort entry in the Moli-sani Study (2005-2010). Components of the LS7 include cigarette smoking, physical activity, diet, body mass index, blood pressure, cholesterol and glucose: each ideal CV health metric was assigned 2 points, and all points were summed to compute a CV health score ranging between 0 to 14 points. CV health scores were then classified as poor (0 to 6), average (7 to 9), and ideal (10 to 14). Results Over a median follow up of 13 y, a total of 1,918 hospital admissions for any cancer were recorded. The proportion of poor, intermediate and ideal CV health were respectively 33.2%, 47.6%, and 19.2%. In a multivariable-adjusted COX analysis controlled for known risk factors, participants in the ideal CV health category experienced 29% lower risk of cancer hospitalization (HR = 0.71; 95%CI 0.61-0.83) compared with the poor CV health category. These associations tended to be stronger in men (HR = 0.60; 95%CI 0.48-0.76) than in women (HR = 0.80; 95%CI 0.64-0.99), but were of the same magnitude in both the elderly (aged ≥65 y; HR = 0.74; 0.55-0.99) and younger participants (aged <65 y; HR = 0.75; 95%CI 0.63-0.90). Conclusions Results from this large cohort of middle-aged and elderly Italians suggest that improving cardiovascular health could also reduce the future burden of cancer, supporting the hypothesis of a common soil of underlying risk factors for these two groups of diseases. Key messages • The Life’s Simple 7 metric initially developed to promote cardiovascular health is associated with future cancer risk in a large population of middle-aged and elderly Italians. • These findings reinforce the notion of a “common soil” of underlying risk factors for cardiovascular disease and cancer, and support common public health strategies for prevention.

T. Lekva, T. Ueland, B. Halvorsen et al.

Abstract Background The lungs are the organ most likely to sustain serious injury from coronavirus disease 2019 (COVID-19). However, the mechanisms for long-term complications are not clear. Patients with severe COVID-19 have shorter telomere lengths and higher levels of cellular senescence, and we hypothesized that circulating levels of the telomere-associated senescence markers chitotriosidase, β-galactosidase, cathelicidin antimicrobial peptide and stathmin 1 (STMN1) were elevated in hospitalized COVID-19 patients compared to controls and could be associated with pulmonary sequelae following hospitalization. Methods Ninety-seven hospitalized patients with COVID-19 who underwent assessment for pulmonary sequelae at three-month follow-up were included in the study. β-Galactosidase and chitotriosidase were analysed by fluorescence; stathmin 1 and cathelicidin antimicrobial peptide were analysed by enzyme immuno-assay in plasma samples from the acute phase and after three-months. In addition, the classical senescence markers cyclin-dependent kinase inhibitor 1A and 2A were analysed by enzyme immuno-assay in peripheral blood mononuclear cell lysate after three months. Results We found elevated plasma levels of the senescence markers chitotriosidase and stathmin 1 in patients three months after hospitalization with COVID-19, and these markers in addition to protein levels of cyclin-dependent kinase inhibitor 2A in cell lysate, were associated with pulmonary pathology. The elevated levels of these markers seem to reflect both age-dependent (chitotriosidase) and age-independent (stathmin 1, cyclin-dependent kinase inhibitor 2A) processes. Conclusions We suggest that accelerated ageing or senescence could be important for long-term pulmonary complications of COVID-19, and our findings may be relevant for future research exploring the pathophysiology and management of these patients.

Martin Dreyling, Marc André, Nicola Gökbuget et al.

Ting Zhang, Jun Li, Yi Zhao et al.

Accurate segmentation of the blood vessels of the retina is an important step in clinical diagnosis of ophthalmic diseases. Many deep learning frameworks have come up for retinal blood vessels segmentation tasks. However, the complex vascular structure and uncertain pathological features make the blood vessel segmentation still very challenging. A novel U-shaped network named Multi-module Concatenation which is based on Atrous convolution and multi-kernel pooling is put forward to retinal vessels segmentation in this paper. The proposed network structure retains three layers the essential structure of U-Net, in which the atrous convolution combining the multi-kernel pooling blocks are designed to obtain more contextual information. The spatial attention module is concatenated with dense atrous convolution module and multi-kernel pooling module to form a multi-module concatenation. And different dilation rates are selected by cascading to acquire a larger receptive field in atrous convolution. Adequate comparative experiments are conducted on these public retinal datasets: DRIVE, STARE and CHASE_DB1. The results show that the proposed method is effective, especially for microvessels. The code will be put out at https://github.com/Rebeccala/MC-UNet

Changmin Lee, Bon-Hong Koo, Chan-Byoung Chae et al.

In this paper, we investigate the Internet of Bio-Nano Things (IoBNT) which relates to networks formed by molecular communications. By providing a means of communication through the ubiquitously connected blood vessels (arteries, veins, and capillaries), molecular communication-based IoBNT enables a host of new eHealth applications. For example, an organ monitoring sensor can transfer internal body signals through the IoBNT for health monitoring applications. We empirically show that blood vessel channels introduce a new set of challenges for the design of molecular communication systems in comparison to free-space channels. We then propose cylindrical duct channel models and discuss the corresponding system designs conforming to the channel characteristics. Furthermore, based on prototype implementations, we confirm that molecular communication techniques can be utilized for composing the IoBNT. We believe that the promising results presented in this work, together with the rich research challenges that lie ahead, are strong indicators that IoBNT with molecular communications can drive novel applications for emerging eHealth systems.

Shaowei Jiang, Chengfei Guo, Tianbo Wang et al.

Blu-ray drive is an engineering masterpiece that integrates disc rotation, pickup head translation, and three lasers in a compact and portable format. Here we integrate a blood-coated image sensor with a modified Blu-ray drive for high-throughput cytometric analysis of various bio-specimens. In this device, samples are mounted on the rotating Blu-ray disc and illuminated by the built-in lasers from the pickup head. The resulting coherent diffraction patterns are then recorded by the blood-coated image sensor. The rich spatial features of the blood-cell monolayer help down-modulate the object information for sensor detection, thus forming a high-resolution computational bio-lens with a theoretically unlimited field of view. With the acquired data, we develop a lensless coherent diffraction imaging modality termed rotational ptychography for image reconstruction. We show that our device can resolve the 435 nm linewidth on the resolution target and has a field of view only limited by the size of the Blu-ray disc. To demonstrate its applications, we perform high-throughput urinalysis by locating disease-related calcium oxalate crystals over the entire microscope slide. We also quantify different types of cells on a blood smear with an acquisition speed of ~10,000 cells per second. For in vitro experiment, we monitor live bacterial cultures over the entire Petri dish with single-cell resolution. Using biological cells as a computational lens could enable new intriguing imaging devices for point-of-care diagnostics. Modifying a Blu-ray drive with the blood-coated sensor further allows the spread of high-throughput optical microscopy from well-equipped laboratories to citizen scientists worldwide.

Sarah Galien, Michael Hultström, Miklós Lipcsey et al.

Abstract Background Deep vein thrombosis (DVT) is common in critically ill patients with Coronavirus disease 2019 (COVID-19) and may cause fatal pulmonary embolism (PE) prior to diagnosis due to subtle clinical symptoms. The aim of this study was to explore the feasibility of bedside screening for DVT in critically ill COVID-19 patients performed by physicians with limited experience of venous ultrasound. We further aimed to compare inflammation, coagulation and organ dysfunction in patients with and without venous thromboembolism (VTE). Methods This observational study included patients with COVID-19 admitted to the intensive care unit (ICU) of a tertiary hospital in Sweden and screened for DVT with proximal compression ultrasound of the lower extremities between April and July 2020. Screening was performed by ICU residents having received a short online education and one hands-on-session. Pathological screening ultrasound was confirmed by formal ultrasound whereas patients with negative screening underwent formal ultrasound on clinical suspicion. Clinical data, laboratory findings and follow-up were extracted from medical records. Results Of 90 eligible patients, 56 were screened by seven ICU residents with no (n = 5) or limited (n = 2) previous experience of DVT ultrasound who performed a median of 4 (IQR 2–19) examinations. Four (7.1%) patients had pathological screening ultrasound of which three (5.6%) were confirmed by formal ultrasound. None of the 52 patients with negative screening ultrasound were diagnosed with DVT during follow-up. Six patients were diagnosed with PE of which four prior to negative screening and two following negative and positive screening respectively. Patients with VTE (n = 8) had higher median peak D-dimer (24.0 (IQR 14.2–50.5) vs. 2.8 (IQR 1.7–7.2) mg/L, p = 0.004), mean peak C-reactive protein (363 (SD 80) vs. 285 (SD 108) mg/L, p = 0.033) and median peak plasma creatinine (288 (IQR 131–328) vs. 94 (IQR 78–131) μmol/L, p = 0.009) compared to patients without VTE (n = 48). Five patients (63%) with VTE received continuous renal replacement therapy compared to six patients (13%) without VTE (p = 0.005). Conclusion ICU residents with no or limited experience could detect DVT with ultrasound in critically ill COVID-19 patients following a short education. VTE was associated with kidney dysfunction and features of hyperinflammation and hypercoagulation. Trial registration ClinicalTrials ID: NCT04316884 . Registered 20 March 2020.

Amirhossein Arzani, Jian-Xun Wang, Roshan M. D'Souza

Near-wall blood flow and wall shear stress (WSS) regulate major forms of cardiovascular disease, yet they are challenging to quantify with high fidelity. Patient-specific computational and experimental measurement of WSS suffers from uncertainty, low resolution, and noise issues. Physics-informed neural networks (PINN) provide a flexible deep learning framework to integrate mathematical equations governing blood flow with measurement data. By leveraging knowledge about the governing equations (herein, Navier-Stokes), PINN overcomes the large data requirement in deep learning. In this study, it was shown how PINN could be used to improve WSS quantification in diseased arterial flows. Specifically, blood flow problems where the inlet and outlet boundary conditions were not known were solved by assimilating very few measurement points. Uncertainty in boundary conditions is a common feature in patient-specific computational fluid dynamics models. It was shown that PINN could use sparse velocity measurements away from the wall to quantify WSS with very high accuracy even without full knowledge of the boundary conditions. Examples in idealized stenosis and aneurysm models were considered demonstrating how partial knowledge about the flow physics could be combined with partial measurements to obtain accurate near-wall blood flow data. The proposed hybrid data-driven and physics-based deep learning framework has high potential in transforming high-fidelity near-wall hemodynamics modeling in cardiovascular disease.