Combined Flow-Fluorescence in situ hybridization to HHV-8 and EBV reveals the viral heterogeneity of primary effusion lymphoma.

Primary effusion lymphoma (PEL) is a rare B-cell non-Hodgkin lymphoma associated with Kaposi Sarcoma-associated herpesvirus (KSHV/HHV8) infection. Lymphoma cells are coinfected with Epstein-Barr virus (EBV) in 60-80% of cases. Tools allowing a reliable PEL diagnosis are lacking. This study reports PEL diagnosis in 4 patients using a Flow-Fluorescence in situ hybridization (FlowFISH) technique that allowed detection of differentially expressed EBV and HHV8 transcripts within the same sample, revealing viral heterogeneity of the disease. Moreover, infected cells exhibited variable expressions of CD19, CD38, CD40, and CD138. Therefore, FlowFISH is a promising tool to diagnose and characterize complex viral lymphoproliferations.

Accurate Internal Monitoring of Batteries by Embedded Piezoelectric Sensors.

Advancements in operando techniques have unraveled the complexities of the Electrode Electrolyte Interface (EEI) in electrochemical energy storage devices. However, each technique has inherent limitations, often necessitating adjustments to experimental conditions, which may compromise accuracy. To address this challenge, a novel battery cell design is introduced, integrating piezoelectric sensors with electrochemical analysis for surface-sensitive operando measurements. This innovative approach aims to overcome conventional limitations by accommodating commercial-grade battery electrodes within a single body, alongside a piezoelectric sensor. This enables operando electrogravimetric measurements to be realized, and the electrochemistry of a battery to be more faithfully reproduced at the sensor level. A proof of concept is carried out on both Li-ion (LiFePO4//Graphite) and Na-ion (Na3V2(PO4)2F3//Hard carbon) systems, utilizing commercially available powder electrodes. In both cases, the results reveal rational mass variations at the sensor level during the cycling of commercial electrodes with mass loadings several orders of magnitude higher, while performing Galvanostatic Charge Discharge (GCD) tests across various C-rates. This innovative design opens up possibilities for a broader application of operando electrogravimetry within the battery community, to enhance the understanding of EEI behavior and facilitate the development of more efficient energy storage solutions.

Laminar organization of neocortical activities during systemic anoxia.

The neocortex is highly susceptible to metabolic dysfunction. When exposed to global ischemia or anoxia, it suffers a slowly propagating wave of collective neuronal depolarization that ultimately impairs its structure and function. While the molecular signature of anoxic depolarization (AD) is well documented, little is known about the brain states that precede and follow AD onset. Here, by means of multisite extracellular local field potentials and intracellular recordings from identified pyramidal cells, we investigated the laminar expression of cortical activities induced by transient anoxia in rat primary somatosensory cortex. Soon after the interruption of brain oxygenation, we observed a well-organized sequence of stereotyped activity patterns across all cortical layers. This sequence included an initial period of beta-gamma activity, rapidly replaced by delta-theta oscillations followed by a decline in all spontaneous activites, marking the entry into a sustained period of electrical silence. Intracellular recordings revealed that cortical pyramidal neurons were depolarized and highly active during high-frequency activity, became inactive and devoid of synaptic potentials during the isoelectric state, and showed subthreshold composite synaptic depolarizations during the low-frequency period. Contrasting with the strong temporal coherence of pre-AD activities along the vertical axis of the cortical column, the onset of AD was not uniform across layers. AD initially occurred in layer 5 or 6 and then propagated bidirectionally in the upward and downward direction. Conversely, the post-anoxic waves that indicated the repolarization of cortical neurons upon brain reoxygenation did not exhibit a specific spatio-temporal profile. Pyramidal neurons from AD initiation site had a more depolarized resting potential and higher spontaneous firing rate compared to superficial cortical cells. We also found that the propagation pattern of AD was reliably reproduced by focal injection of an inhibitor of sodium­potassium ATPases, suggesting that cortical AD dynamics could reflect layer-dependent variations in cellular metabolic regulations.

UBTF tandem duplications define a distinct subtype of adult de novo acute myeloid leukemia.

Tandem duplications (TDs) of the UBTF gene have been recently described as a recurrent alteration in pediatric acute myeloid leukemia (AML). Here, by screening 1946 newly diagnosed adult AML, we found that UBTF-TDs occur in about 3% of patients aged 18-60 years, in a mutually exclusive pattern with other known AML subtype-defining alterations. The characteristics of 59 adults with UBTF-TD AML included young age (median 37 years), low bone marrow (BM) blast infiltration (median 25%), and high rates of WT1 mutations (61%), FLT3-ITDs (51%) and trisomy 8 (29%). BM morphology frequently demonstrates dysmyelopoiesis albeit modulated by the co-occurrence of FLT3-ITD. UBTF-TD patients have lower complete remission (CR) rates (57% after 1 course and 76% after 2 courses of intensive chemotherapy [ICT]) than UBTF-wild-type patients. In patients enrolled in the ALFA-0702 study (n = 614 patients including 21 with UBTF-TD AML), the 3-year disease-free survival (DFS) and overall survival of UBTF-TD patients were 42.9% (95%CI: 23.4-78.5%) and 57.1% (95%CI: 39.5-82.8%) and did not significantly differ from those of ELN 2022 intermediate/adverse risk patients. Finally, the study of paired diagnosis and relapsed/refractory AML samples suggests that WT1-mutated clones are frequently selected under ICT. This study supports the recognition of UBTF-TD AML as a new AML entity in adults.

Allogeneic transplantation in acute myelogenous leukemia: a comprehensive single institution's experience.

Debates on the role and timing of allogeneic hemtopoietic stem cell transplantation (HSCT) in acute myelogenous leukemia (AML) have persisted for decades. Time to transplant introduces an immortal time and current treatment algorithm mainly relies on the European LeukemiaNet disease risk classification. Previous studies are also limited to age groups, remission status and other ill-defined parameters. We studied all patients at diagnosis irrespective of age and comorbidities to estimate the cumulative incidence and potential benefit or disadvantage of HSCT in a single center. As a time-dependent covariate, HSCT improved overall survival in intermediate- and poor-risk patients (hazard ratio =0.51; P=0.004). In goodrisk patients only eight were transplanted in first complete remission. Overall, the 4-year cumulative incidence of HSCT was only 21.9% but was higher (52.1%) for patients in the first age quartile (16-57 years old) and 26.4% in older patients (57-70 years old) (P<0.001). It was negligible in patients older than 70 years reflecting our own transplant policy but also barriers to transplantation (comorbidities and remission status). However, HSCT patients need to survive, be considered eligible both by the referring and the HSCT physicians and have a suitable donor to get transplantation. We, thus, comprehensively analyzed the complete decision-making and outcome of all our AML patients from diagnosis to last followup to decipher how patient allocation and therapy inform the value of HSCT. The role of HSCT in AML is shifting with broad access to different donors including haploidentical ones. Thus, it may (or may not) lead to increased numbers of allogeneic HSCT in AML in adults.

Machine learning-based improvement of MDS-CBC score brings platelets into the limelight to optimize smear review in the hematology laboratory.

BACKGROUND: Myelodysplastic syndromes (MDS) are clonal hematopoietic diseases of the elderly characterized by chronic cytopenias, ineffective and dysplastic haematopoiesis, recurrent genetic abnormalities and increased risk of progression to acute myeloid leukemia. A challenge of routine laboratory Complete Blood Counts (CBC) is to correctly identify MDS patients while simultaneously avoiding excess smear reviews. To optimize smear review, the latest generations of hematology analyzers provide new cell population data (CPD) parameters with an increased ability to screen MDS, among which the previously described MDS-CBC Score, based on Absolute Neutrophil Count (ANC), structural neutrophil dispersion (Ne-WX) and mean corpuscular volume (MCV). Ne-WX is increased in the presence of hypogranulated/degranulated neutrophils, a hallmark of dysplasia in the context of MDS or chronic myelomonocytic leukemia. Ne-WX and MCV are CPD derived from leukocytes and red blood cells, therefore the MDS-CBC score does not include any platelet-derived CPD. We asked whether this score could be improved by adding the immature platelet fraction (IPF), a CPD used as a surrogate marker of dysplastic thrombopoiesis. METHODS: Here, we studied a cohort of more than 500 individuals with cytopenias, including 168 MDS patients. In a first step, we used Breiman's random forests algorithm, a machine-learning approach, to identify the most relevant parameters for MDS prediction. We then designed Classification And Regression Trees (CART) to evaluate, using resampling, the effect of model tuning parameters on performance and choose the "optimal" model across these parameters. RESULTS: Using random forests algorithm, we identified Ne-WX and IPF as the strongest discriminatory predictors, explaining 37 and 33% of diagnoses respectively. To obtain "simplified" trees, which could be easily implemented into laboratory middlewares, we designed CART combining MDS-CBC score and IPF. Optimal results were obtained using a MDS-CBC score threshold equal to 0.23, and an IPF threshold equal to 3%. CONCLUSIONS: We propose an extended MDS-CBC score, including CPD from the three myeloid lineages, to improve MDS diagnosis on routine laboratory CBCs and optimize smear reviews.

Probing the Electrode-Electrolyte Interface of a Model K-Ion Battery Electrode─The Origin of Rate Capability Discrepancy between Aqueous and Non-Aqueous Electrolytes.

Li-ion batteries are the electrochemical energy storage technology of choice of today's electrical vehicles and grid applications with a growing interest for Na-ion and K-ion systems based on either aqueous or non-aqueous electrolyte for power, cost, and sustainable reasons. The rate capability of alkali-metal-ion batteries is influenced by ion transport properties in the bulk of the electrolyte, as well as by diverse effects occurring at the vicinity of the electrode and electrolyte interface. Therefore, identification of the predominant factor affecting the rate capability of electrodes still remains a challenge and requires suitable experimental and computational methods. Herein, we investigate the mechanistic of the K+ insertion process in the Prussian blue phase, Fe4III[FeII(CN)6]3 in both aqueous and non-aqueous electrolytes, which reveals drastic differences. Through combined electrochemical characterizations, electrochemical-quartz-crystal-microbalance and ac-electrogravimetric analyses, we provide evidences that what matters the most for fast ion transport is the positioning of the partially solvated cations adsorbed at the material surface in aqueous as opposed to non-aqueous electrolytes. We rationalized such findings by molecular dynamics simulations that establish the K+ repartition profile within the electrochemical double layer. A similar trend was earlier reported by our group for the aqueous versus non-aqueous insertion of Li+ into LiFePO4. Such a study unveils the critical but overlooked role of the electrode-electrolyte interface in ruling ion transport and insertion processes. Tailoring this interface structuring via the proper salt-solvent interaction is the key to enabling the best power performances in alkali-metal-ion batteries.

UBA1 Variations in Neutrophilic Dermatosis Skin Lesions of Patients With VEXAS Syndrome.

IMPORTANCE: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a recently described severe adult-onset autoinflammatory disease that is associated with myeloid lineage-restricted ubiquitin-activating enzyme 1 (UBA1) somatic variations that primarily affect the skin (Sweet syndrome), cartilage, and bone marrow. Skin symptoms have been poorly described. OBJECTIVE: To better describe clinical and pathological skin manifestations and their pathophysiology in VEXAS syndrome. DESIGN, SETTING, AND PARTICIPANTS: This multicenter retrospective case series study of clinical and histological features of 8 patients with VEXAS syndrome and skin involvement was conducted in France from December 2007 to March 2021, with molecular data obtained from March to April 2022. Any UBA1 variations were detected by Sanger or next-generation sequencing that was performed on bone marrow and formalin-fixed paraffin-embedded tissue sections of skin lesion biopsies. RESULTS: All 8 patients were men, and the median age at symptom onset was 65.5 years (interquartile range, 54-76 years). All patients had neutrophilic dermatosis skin lesions, including tender red or violaceous papules, sometimes edematous, without fever, arthralgia, recurrence or pathergy, inflammatory edematous papules on the neck and trunk (sometimes umbilicated), and firm erythematous purpuric or pigmented infiltrated plaques and nodules. Three patients had livedo racemosa. The infiltrates were perivascular and consisted of mature neutrophils with leukocytoclasia, which were admixed with myeloperoxidase-positive CD163-positive myeloid cells with indented nuclei and lymphoid cells in all cases. A sequencing analysis of paired bone marrow samples and skin lesion biopsies identified the same loss-of-function UBA1 variation in both samples for all patients. CONCLUSIONS AND RELEVANCE: This case series study describes the different clinical presentations of skin lesions found in VEXAS syndrome, which is characterized histologically by neutrophilic dermatosis. The findings suggested that the dermal infiltrates seen in VEXAS skin lesions are derived from the pathological myeloid clone. This suggests that using therapies that target the pathological clone may be effective in the long-term management of the disease.

Registering Unmanned Aerial Vehicle Videos in the Long Term.

Unmanned aerial vehicles (UAVs) have become a very popular way of acquiring video within contexts such as remote data acquisition or surveillance. Unfortunately, their viewpoint is often unstable, which tends to impact the automatic processing of their video flux negatively. To counteract the effects of an inconsistent viewpoint, two video processing strategies are classically adopted, namely registration and stabilization, which tend to be affected by distinct issues, namely jitter and drifting. Following our prior work, we suggest that the motion estimators used in both situations can be modeled to take into account their inherent errors. By acknowledging that drifting and jittery errors are of a different nature, we propose a combination that is able to limit their influence and build a hybrid solution for jitter-free video registration. In this work, however, our modeling was restricted to 2D-rigid transforms, which are rather limited in the case of airborne videos. In the present paper, we extend and refine the theoretical ground of our previous work. This addition allows us to show how to practically adapt our previous work to perspective transforms, which our study shows to be much more accurate for this problem. A lightweight implementation enables us to automatically register stationary UAV videos in real time. Our evaluation includes traffic surveillance recordings of up to 2 h and shows the potential of the proposed approach when paired with background subtraction tasks.

Clinical and biological features of B-cell neoplasms with CDK6 translocations: an association with a subgroup of splenic marginal zone lymphomas displaying frequent CD5 expression, prolymphocytic cells, and TP53 abnormalities.

A translocation involving the cyclin-dependent kinase 6 (CDK6) gene [t(CDK6)] is a rare but recurrent abnormality in B-cell neoplasms. To further characterise this aberration, we studied 57 cases; the largest series reported to date. Fluorescence in situ hybridisation analysis confirmed the involvement of CDK6 in all cases, including t(2;7)(p11;q21) immunoglobulin kappa locus (IGK)/CDK6 (n = 51), t(7;14)(q21;q32) CDK6/immunoglobulin heavy locus (IGH) (n = 2) and the previously undescribed t(7;14)(q21;q11) CDK6/T-cell receptor alpha locus (TRA)/T-cell receptor delta locus (TRD) (n = 4). In total, 10 patients were diagnosed with chronic lymphocytic leukaemia, monoclonal B-cell lymphocytosis or small lymphocytic lymphoma, and 47 had small B-cell lymphoma (SmBL) including 36 cases of marginal zone lymphoma (MZL; 34 splenic MZLs, one nodal MZL and one bronchus-associated lymphoid tissue lymphoma). In all, 18 of the 26 cytologically reviewed cases of MZL (69%) had an atypical aspect with prolymphocytic cells. Among the 47 patients with MZL/SmBL, CD5 expression was found in 26 (55%) and the tumour protein p53 (TP53) deletion in 22 (47%). The TP53 gene was mutated in 10/30 (33%); the 7q deletion was detected in only one case, and no Notch receptor 2 (NOTCH2) mutations were found. Immunoglobulin heavy-chain variable-region (IGHV) locus sequencing revealed that none harboured an IGHV1-02*04 gene. Overall survival was 82% at 10 years and not influenced by TP53 aberration. Our present findings suggest that most t(CDK6)+ neoplasms correspond to a particular subgroup of indolent marginal zone B-cell lymphomas with distinctive features.

Innate local response and tissue recovery following application of high density microarray patches to human skin.

The development of microarray patches for vaccine application has the potential to revolutionise vaccine delivery. Microarray patches (MAP) reduce risks of needle stick injury, do not require reconstitution and have the potential to enhance immune responses using a fractional vaccine dose. To date, the majority of research has focused on vaccine delivery with little characterisation of local skin response and recovery. Here we study in detail the immediate local skin response and recovery of the skin post high density MAP application in 12 individuals receiving 3 MAPs randomly assigned to the forearm and upper arm. Responses were characterised by clinical scoring, dermatoscopy, evaporimetry and tissue viability imaging (TiVi). MAP application resulted in punctures in the epidermis, a significant transepidermal water loss (TEWL), the peak TEWL being concomitant with peak erythema responses visualised by TiVi. TEWL and TiVi responses reduced over time, with TEWL returning to baseline by 48 h and erythema fading over the course of a 7 day period. As MAPs for vaccination move into larger clinical studies more variation of individual subject phenotypic or disease propensity will be encountered which will require consideration both in regard to reliability of dose delivery and degree of inherent skin response.

Making Advanced Electrogravimetry as an Affordable Analytical Tool for Battery Interface Characterization.

Numerous sophisticated diagnostic techniques have been designed to monitor electrode-electrolyte interfaces that mainly govern the lifetime and reliability of batteries. Among them is the electrochemical quartz crystal microbalance (EQCM) that offers valuable insights of the interfaces once the required conditions of the deposited film in terms of viscoelastic and hydrodynamic properties are fulfilled. Herein, we propose a friendly protocol that includes the elaboration of a homogeneous deposit by spray coating followed by QCM measurements at multiharmonic frequencies to ensure the film flatness and rigidity for collecting meaningful data. Moreover, for easiness of the measurements, we report the design of a versatile and airtight EQCM cell setup that can be used either with aqueous or non-aqueous electrolytes. We also present, using a model battery material, LiFePO4, how dual frequency and motional resistance monitoring during electrochemical cycling can be used as a well-suitable indicator for achieving reliable and reproducible electrogravimetric measurements. We demonstrate through this study the essential role of the solvent assisting lithium-ion insertion at the LiFePO4 interface with a major outcome of solvent-dependent interfacial behavior. Namely, in aqueous media, we prove a near-surface desolvation of lithium ions from their water solvation shell as compared with organic molecules. This spatial dissimilarity leads to a smoother Li-ion transport across the LFP-H2O interface, hence accounting for the difference in rate capability of LFP in the respective electrolytes. Overall, we hope our analytical insights on interfacial mechanisms will help in gaining a wider acceptance of EQCM-based methods from the battery community.

Puberty and Inhibin B in 35 Adolescents With Pituitary Stalk Interruption Syndrome.

Background: In patients with pituitary stalk interruption syndrome (PSIS), long-term follow-up is necessary to address their gonadotrophic status. The objectives of this study were (1) to describe pubertal features of and (2) to assess the ability of serum inhibin B concentration to predict hypogonadotropic hypogonadism (HH) in patients with PSIS. Methods: This retrospective single-center study included 35 patients with PSIS and known gonadotrophic status for whom a serum sample preserved at -22°C (collected at initial evaluation or later) was available for measuring inhibin B by the same hormonal immunoassay method. Results: Among the 21 boys, 15 had normal puberty (early in two), and six had partial (n = 2) or complete (n = 4) HH. Among the 14 girls, five had normal puberty (early in one)-four with regular menses and one in the process of puberty-, four had complete HH, and five had amenorrhea (primary in three and secondary in two) after normal pubertal development, despite a normal pubertal gonadotropin response to gonadotropin-releasing hormone test. These were considered as having partial HH. Only three boys had values over the normal lower range for serum inhibin B concentrations despite partial (n = 2) or complete (n = 1) HH. Inhibin B concentrations were low in all girls with complete HH, normal in all those with partial HH except in one and in those with normal puberty except in two. Considering boys and girls together, the occurrence of under-range inhibin B was significantly higher in those with HH than in those without (47 vs. 10%, p = 0.02). All 15 patients with HH had associated thyroid-stimulating hormone and adrenocorticotropic hormone deficiency except for 3 girls with partial HH. Conclusions: Under-range inhibin B concentrations in patients with PSIS might be suggestive of HH. These concentrations provide a simple first-line predictive test, especially in boys.

Elucidating the Origin of the Electrochemical Capacity in a Proton-Based Battery HxIrO4 via Advanced Electrogravimetry.

Recently, because of sustainability issues dictated by societal demands, more importance has been given to aqueous systems and especially to proton-based batteries. However, the mechanisms behind the processes leading to energy storage in such systems are still not elucidated. Under this scope, our study is structured on the selection of a model electrode material, the protonic phase HxIrO4, and the scrutiny of the interfacial processes through suitable analytical tools. Herein, we employed operando electrochemical quartz crystal microbalance (EQCM) combined with electrochemical impedance spectroscopy (EIS) to provide new insights into the mechanism intervening at the electrode-electrolyte interface. First, we demonstrated that not only the surface or near surface but the whole particle participates in the cationic redox process. Second, we proved that the contribution of the proton on the overall potential window together with the incorporation of water at low potentials solely. This is explained by the fact that water molecules permit a further insertion of protons in the material by shielding the proton charge but at the expense of the proton kinetic properties. These findings shed a new light on the importance of water molecules in the ion-insertion mechanisms taking place at the electrode-electrolyte interface of aqueous proton-based batteries. Overall, the present results further highlight the richness of the EQCM-based methods for the battery field in offering mechanistic insights that are crucial for the understanding of interfaces and charge storage in insertion compounds.

Pain assessment and factors influencing pain during bone marrow aspiration: A prospective study.

Although bone marrow aspiration (BMA) is still considered a painful procedure, pain level remains poorly documented. We therefore conducted a prospective study intended to evaluate pain level in adult patients undergoing BMA at the sternal or iliac crest site to identify factors associated with pain. We enrolled a total of 448 patients who underwent 461 BMA and asked those patients to score their pain intensity after BMA using numerical pain rating scale (NPRS). The following factors: level of anxiety, quality of the information given to the patient, operator's experience, and bone texture were recorded using a standardized questionnaire. The median NPRS score was 3.5 (IQR [2.0; 5.0]) the sternal site (n = 405) was associated with an increased median NPRS score (3.5 [2.0; 5.0]) compared to the iliac crest (n = 56, 2.5 [1.0; 4.0]; p<0.0001). For those patients who underwent sternal BMA, the median NPRS score was significantly lower when using lidocaine infiltration (p = 0.0159) as compared with no anesthetic use. Additionally there was no significant effect of anesthetic cream found. After multivariate analysis, the model of NPRS score at the sternal site included patient anxiety (p<0.0001) and the use of lidocaine infiltration (0.0378). This study underlines the usefulness of a comprehensive management including pain relief and efforts to reduce anxiety including appropriate information given to the patient during BMA.