Platelet extraction requires whole blood to be processed within six hours of donation. To meet this deadline, blood collection organizations must optimally route a fleet of vehicles to pick up blood units from donation sites and deliver them to a processing center. This paper introduces a drone-aided blood collection routing problem in which a fleet of trucks, each equipped with a drone, operates in a synchronized manner to collect blood units before their processing time limit expires. Each truck-drone tandem can perform multiple trips throughout the planning horizon, allowing donation sites to be visited repeatedly as new blood units become available over time. We formulate this problem as a mixed-integer linear program that jointly optimizes the routing of trucks and drones, pickup schedules, and timing decisions to maximize the total number of viable blood units collected. We also develop a column generation approach that decomposes the problem into a master problem to select the optimal set of truck-drone tours and a pricing subproblem, which is solved using a tailored memetic algorithm to generate promising new columns. Through a comprehensive computational study, we show the operational benefits of integrating drones into the blood collection system. In addition, we demonstrate the superior performance of the proposed algorithm over Gurobi and two metaheuristics from the literature, namely the hybrid genetic algorithm and the invasive weed optimization, in both the drone-aided and truck-only settings.
Accurate classification of blood cells plays a key role in improving automated blood analysis for both medical and veterinary applications. This work presents a two-stage deep clustering method for classifying blood cells from high-dimensional signal data. In the first stage, red blood cells (RBCs) and platelets (PLTs) are separated using a combination of an improved autoencoder and the IDEC algorithm. The second stage further classifies RBC subtypes, pure RBCs, reticulocytes, and clumped RBCs, through a variational deep embedding (VaDE) approach. Due to the lack of detailed cell-level labels, soft classification probabilities are generated from sample-level data to approximate the true distributions. The aim is to contribute to the development of low-cost, automated blood analysis systems suitable for veterinary and biomedical use. Initial results indicate this method shows promise in effectively distinguishing different blood cell populations, even with limited supervision.
Muhammad Umaid Rauf, Steven Law, Marisa Santostefano
et al.
Renal prognosis in light-chain amyloidosis (AL) is determined by categorizing patients into three renal stages at diagnosis and assessing Renal Response or Renal Progression following chemotherapy after 6 months. We evaluated, in a test (N=1935) cohort of patients with renal AL amyloidosis who were followed for a median of 95 months, a modified 4-stage model where Renal Stage 2 was sub-categorized according to preserved (2A) or reduced (2B) estimated Glomerular Filtration Rate (eGFR). A hybrid model for evaluation of Renal Progression was also introduced, using an eGFR cut-off of 30ml/min/1.73 m2. These models were compared with existing models; namely those of Palladini and Kastritis, and results were validated in a multicenter cohort (N=438).
The risk of progression to renal replacement therapy (RRT) increased progressively across all Renal Stages of the revised staging model (Hazard ratio [HR]: 3.25, 5.13, 10.66 for Stages 2A, 2B and 3 respectively vs Stage 1, each p
The process of collecting blood from donors and making it available for transfusion requires a complex series of operations involving multiple actors and resources at each step. Ensuring hospitals receive adequate and safe blood for transfusion is a common challenge across low- and middle-income countries, but is rarely addressed from a system level. This paper presents the first use of discrete event simulation to study the blood system in Kenya and to explore the effect of variations and perturbations at different steps of the system on meeting patient blood demand. A process map of the Kenyan blood system was developed to capture critical steps from blood donation to transfusion using interviews with blood bank, hospital, and laboratory personnel at four public hospitals across three counties in Kenya. The blood system was simulated starting with blood collection, a blood bank where blood is tested and stored before it is issued, a major hospital attached to the blood bank, and several smaller hospitals served by the same blood bank. Values for supply-side parameters were based mainly on expert opinion; demand-side parameters were based on data from blood requisitions made in hospital wards, and dispatch of blood from the hospital laboratory. Illustrative examples demonstrate how the model can be used to explore the impacts of changes in blood collection (e.g., prioritising different donor types), blood demand (e.g., differing clinical case mix), and blood distribution (e.g., restocking strategies) on meeting demand at patient level. The model can reveal potential process impediments in the blood system and aid in choosing strategies for improving blood collection, distribution or use. Such a systems approach allows for interventions at different steps in the blood continuum to be tested on blood availability for different patients presenting at diverse hospitals across the country.
Xiaopo Cheng, Dell Zimmerman, Elizabeth Iffrig
et al.
Recent clinical results indicate that aberrant erythrocyte aggregation in hematological disorders is accompanied by endothelial damage and glycocalyx disruption, but the underlying biophysical mechanisms remain unclear. This study uses direct computational modeling to explore how red blood cell (RBC) aggregation impacts shear stress in small blood vessels, highlighting the increased risk of vascular damage. RBC aggregation creates a heterogeneous distribution, leading to variations in the cell-free layer thickness and fluctuating wall shear stress, especially near vessel walls. This effect aligns with experimental findings on endothelial disruption linked to RBC clustering near the wall, potentially reducing the protective glycocalyx layer. The power spectral density analysis of wall shear stress fluctuations reveals that, with RBC aggregation, there is a distinct peak near frequency f = 0.04, indicating increased fluctuations due to aggregated RBC clusters traveling close to the vessel wall. The presence of aberrant cells in blood disorders, modeled here by sickle cells, further amplifies these effects, as aggregation-enhanced margination drives sickle cells closer to vessel walls, exacerbating shear stress fluctuations and increasing the likelihood of vascular injury and inflammation. Simulations show that curved vascular geometry, with curvature accentuating RBC clustering near vessel walls, intensifies aggregation-induced wall shear stress fluctuations and increases the risk of vascular damage, particularly in sickle cell disease where sickle cells marginate closer to the wall.
Oncay Yasa, Fikru M. Tiruneh, Miriam Filippi
et al.
Hydrogels engineered for medical use within the human body need to be delivered in a minimally invasive fashion without altering their biochemical and mechanical properties to maximize their therapeutic outcomes. In this regard, key strategies applied for creating such medical hydrogels include formulating precursor solutions that can be crosslinked in situ with physical or chemical cues following their delivery or forming macroporous hydrogels at sub-zero temperatures via cryogelation prior to their delivery. Here, we present a new class of injectable composite materials with shape recovery ability. The shape recovery is derived from the physical properties of red blood cells (RBCs) that are first modified via hypotonic swelling and then integrated into the hydrogel scaffolds before polymerization. The RBCs' hypotonic swelling induces the formation of nanometer-sized pores on their cell membranes, which enable fast liquid release under compression. The resulting biocomposite hydrogel scaffolds display high deformability and shape-recovery ability. The scaffolds can repeatedly compress up to ~87% of their original volumes during injection and subsequent retraction through syringe needles of different sizes; this cycle of injection and retraction can be repeated up to ten times without causing any substantial mechanical damage to the scaffolds. Our biocomposite material system and fabrication approach for injectable materials will be foundational for the minimally invasive delivery of drug-loaded scaffolds, tissue-engineered constructs, and personalized medical platforms that could be administered to the human body with conventional needle-syringe systems.
The morphology of retinal blood vessels can indicate various diseases in the human body, and researchers have been working on automatic scanning and segmentation of retinal images to aid diagnosis. This project compares the performance of four neural network architectures in segmenting retinal images, using a combined dataset from different databases, namely the UNet, DR-VNet, UNet-ResNet and UNet-VGG.
Muhammad Zubair Khan, Oleg E. Peil, Apoorva Sharma
et al.
In the rapidly expanding field of two-dimensional materials, magnetic monolayers show great promise for the future applications in nanoelectronics, data storage, and sensing. The research in intrinsically magnetic two-dimensional materials mainly focuses on synthetic iodide and telluride based compounds, which inherently suffer from the lack of ambient stability. So far, naturally occurring layered magnetic materials have been vastly overlooked. These minerals offer a unique opportunity to explore air-stable complex layered systems with high concentration of local moment bearing ions. We demonstrate magnetic ordering in iron-rich two-dimensional phyllosilicates, focusing on mineral species of minnesotaite, annite, and biotite. These are naturally occurring van der Waals magnetic materials which integrate local moment baring ions of iron via magnesium/aluminium substitution in their octahedral sites. Due to self-inherent capping by silicate/aluminate tetrahedral groups, ultra-thin layers are air-stable. Chemical characterization, quantitative elemental analysis, and iron oxidation states were determined via Raman spectroscopy, wavelength disperse X-ray spectroscopy, X-ray absorption spectroscopy, and X-ray photoelectron spectroscopy. Superconducting quantum interference device magnetometry measurements were performed to examine the magnetic ordering. These layered materials exhibit paramagnetic or superparamagnetic characteristics at room temperature. At low temperature ferrimagnetic or antiferromagnetic ordering occurs, with the critical ordering temperature of 38.7 K for minnesotaite, 36.1 K for annite, and 4.9 K for biotite. In-field magnetic force microscopy on iron bearing phyllosilicates confirmed the paramagnetic response at room temperature, present down to monolayers.
Arterial deformations arise in blood flow when surrounding tissue invades the space available for a blood vessel to maintain its circular cross section, the most immediate effects being a reduction in blood flow and redistribution of shear stress. Here we consider deformations from circular to elliptic cross sections. Solution of this problem in steady flow is fairly straightforward. The focus in the present paper is on pulsatile flow where the change from circular to elliptic cross sections is associated with a transition in the character of the equations governing the flow from Bessel to Mathieu equations. The study of this problem has been hampered in the past because of difficulties involved in the solution of the governing equations. In the present study we describe methods we have used to overcome some of these difficulties and present a comprehensive set of results based on these methods. In particular, vessel deformation is examined under two different conditions relevant to blood flow regulation: (i) keeping cross sectional area constant and (ii) keeping cross sectional circumference constant. The results provide an important context for the mechanism of neurovascular control of blood flow under the pathological conditions of vessel deformation.
Introdução/objetivo: Acredita-se que o Emicizumabe possa induzir uma hemostasia equivalente ao nível de Fator VIII (FVIII) de 15 a 20 UI/mL na corrente sanguínea e pode ter sido um fator contribuinte para o desfecho positivo observado no caso relatado. Esse caso envolveu um paciente com hemofilia A grave (FVIII<1%) e inibidor, em tratamento com Emicizumabe, que sobreviveu mesmo após sofrer múltiplas perfurações por arma de fogo e arma branca. O objetivo deste estudo foi documentar e apresentar esse caso como evidência dos possíveis benefícios do uso de Emicizumabe em situações de trauma grave em pacientes com hemofilia A e inibidor. Material e métodos: Relato de caso de paciente com hemofilia A grave e inibidor em uso de Emicizumabe de forma profilática. Resultados: Jovem de 22 anos de idade, com hemofilia A grave e inibidor, em uso de Emicizumabe após falha de resposta à imunotolerãncia. Recentemente, ele sofreu uma situação crítica ao ser vítima de 6 perfurações por arma de fogo e 2 por arma branca. O resgate levou cerca de 40 minutos para chegar até ele. Ao chegar no hospital, o paciente apresentava múltiplos ferimentos por arma de fogo no braço direito, na região do hemitórax esquerdo abaixo do mamilo, no ombro esquerdo, na mão esquerda e uma perfuração tangencial no couro cabeludo occipital. Adicionalmente, ele apresentava duas perfurações por arma branca, uma no braço direito e outra na região cervical posterior. Além disso, o paciente também sofreu uma fratura nos ossos da mão esquerda, resultante de um trauma causado por um martelo. Os sinais vitais do paciente se mantiveram estáveis, apesar de apresentar hemopneumotórax à esquerda, o que demandou drenagem torácica. Inicialmente, foi administrada uma dose de concentrado de fator VII recombinante ativado (rFVIIa) de 90 mg/kg (3 doses), mas posteriormente a terapia foi ajustada para Fator VIII (FVIII) a cada 12 horas, devido ao resultado de inibidor disponível mais recente ser de 3,8 Unidades Bethesda (UB). O débito do dreno torácico estava elevado e a hemoglobina do paciente caiu de 10,2 g/dL para 4,9 g/dL durante a internação, resultando na transfusão de 7 unidades de concentrado de hemácias. Os pontos de entrada dos projéteis de arma de fogo foram suturados após uma reavaliação, visando melhor hemostasia, apesar de terem passado mais de 6 horas desde o ocorrido. Novo resultado de inibidor colhido de rotina um dia antes do incidente foi de 21,9 UB e o tratamento com o rFVIIa foi retomado, resultando em controle efetivo do sangramento. O dreno torácico foi removido após 5 dias e o paciente teve alta após 7 dias de internação. Durante o período no hospital, a dose semanal de Emicizumabe foi mantida em 1,5 mg/kg. O consumo de rFVIIa durante a hospitalização totalizou 1750 mg (35 mg/kg), enquanto o consumo do concentrado de FVIII foi de 12.000 UI (240 UI/kg). Conclusão: O paciente conseguiu sobreviver apesar da gravidade da doença hemorrágica e da presença de inibidor, provavelmente devido à profilaxia com Emicizumabe, que permitiu o tempo necessário para a implementação do tratamento hospitalar adequado.
Aims: Chromosomal banding analysis is the standard technique to identify cytogenetic abnormalities in both constitutional chromosomal disorders and hematological malignancies. Karyotyping is a laborious and manual technique. The development of image (metaphases) capture systems and software for karyotyping had a great impact on the routine of cytogenetic laboratories, and recently artificial intelligence (deep neural networks, DNN) has helped in the correct segmentation and chromosome classification, allowing the performance of karyotypes more quickly, with final supervision by experienced cytogeneticists. Some systems using AI are commercially available and our objective was to validate and implement one of these models in our laboratory and measure its productivity. Materials and methods: IA DNN –PC/GTX 1650 version 1.1.40 was configured in the automated metaphase image scanning equipment (Metafer), which uses the software for image analysis (Ikaros), all developed by Metasystems (Altlussheim, Germany). Sixteen machine learning models (classifiers) were tested for bone marrow (oncohematological karyotype) and another 16 for peripheral blood (constitutional karyotype), eight of them with the function of chromosome segmentation in metaphase (separation) and 8 of them with the function of classify chromosomes (chromosomal pairing). 55 metaphases from routine studies of bone marrow for hematological malignancies [300-400 bands, 8 with numerical (−Y, −7) or structural (20q−) chromosomal alterations] and 65 metaphases from PHA-stimulated peripheral blood [550 bands, 7 cases with multiple overlapping chromosomes and 9 with numerical (−X, +13, +21) chromosomal alterations]. The time for manual and automated analysis (time for segmentation + classification + review) was compared. The chromosomal mispairing was noted. Productivity was evaluated (percentage difference in seconds manual-automated analysis/ manual analysis in seconds ×100). Results: The average time for manual analysis of one metaphase in bone marrow samples was 74 ± 30 seconds (segmentation 34 seconds and classification 40 seconds) and in DNN it was 23 ± 19 seconds (segmentation 13 seconds, classification 10 seconds), with a gain of 51 ± 26 seconds and productivity gain of 68.6%, and mismatch of 1 ± 1.5 chromosomes. The average time for manual analysis of one metaphase in peripheral blood samples was 138 ± 56 seconds (segmentation 85 seconds and classification 52 seconds) and in DNN it was 29 ± 16 seconds (segmentation 15 seconds, classification 14 seconds), with a gain of 108 ± 49 seconds and productivity gain of 78.7%, and pairing error of 2.6 ± 2. Discussion: AI allowed a significantly gain in productivity and TAT reduction in karyotype, the constitutional from 21 days to 15 days and the oncohematological karyotype from 14 days to 7 days (5 days for acute leukemias at diagnosis). Conclusion: The use of AI in karyotype analysis proved to be effective and efficient in our laboratory, even using a commercial image bank (DNN). There was an important gain in productivity and the possibility of reducing the TAT, adapting to international quality standards.
Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell lymphoma curable even in advanced stages. DLBCL involving the central nervous system (CNS) is more difficult to cure and fewer treatment options exist. Primary CNS lymphoma (PCNSL) refers to aggressive lymphomas confined to the CNS, and are almost always DLBCL. Standard approaches for PCNSL use high-dose methotrexate-based combinations as induction therapy and younger patients often receive dose-intensive consolidation. However, dose-intensive therapies are not suitable for all patients, and older patients have fewer effective treatment options. Patients with relapsed or chemotherapy-refractory disease have a very poor prognosis. Secondary CNS lymphoma (SCNSL) describes aggressive lymphomas involving the CNS at initial presentation or relapses within the CNS after treatment for systemic DLBCL. Isolated CNS relapse is often managed as PCNSL, but patients with synchronous involvement of DLBCL in both the periphery and the CNS pose a unique clinical challenge. Insights into the molecular circuitry of DLBCL have identified distinct genetic subtypes including cases with a predilection for CNS invasion. PCNSL and subsets of SCNSL are characterized by chronically activated B-cell receptor and NFκB signaling along with genetic evidence of immune evasion which may be exploited therapeutically. Improved mechanistic understanding of targetable pathways underpinning CNS lymphomas has led to numerous clinical trials testing targeted agent combinations and immunotherapy approaches with promising early results. Biologically rational strategies may further improve the cure rate of CNS lymphomas, either by overcoming intrinsic or acquired treatment resistance and/or by being broadly applicable to patients of all ages.