This paper presents the first photoplethysmographic (PPG) signal dynamic-based biometric authentication system with a Siamese convolutional neural network (CNN). Our method extracts the PPG signal's ...biometric characteristics from its diffusive dynamics, characterized by geometric patterns in the (p,q)-planes specific to the 0-1 test. PPG signal diffusive dynamics are strongly dependent on the vascular bed's biostructure, unique to each individual. The dynamic characteristics of the PPG signal are more stable over time than its morphological features, particularly in the presence of psychosomatic conditions. Besides its robustness, our biometric method is anti-spoofing, given the complex nature of the blood network. Our proposal trains using a national research study database with 40 real-world PPG signals measured with commercial equipment. Biometric system results for input data, raw and preprocessed, are studied and compared with eight primary biometric methods related to PPG, achieving the best equal error rate (ERR) and processing times with a single attempt, among all of them.
SARS‐CoV‐2 infection causes an abrupt response by the host immune system, which is largely responsible for the outcome of COVID‐19. We investigated whether the specific immune responses in the ...peripheral blood of 276 patients were associated with the severity and progression of COVID‐19. At admission, dramatic lymphopenia of T, B, and NK cells is associated with severity. Conversely, the proportion of B cells, plasmablasts, circulating follicular helper T cells (cTfh) and CD56–CD16+ NK‐cells increased. Regarding humoral immunity, levels of IgM, IgA, and IgG were unaffected, but when degrees of severity were considered, IgG was lower in severe patients. Compared to healthy donors, complement C3 and C4 protein levels were higher in mild and moderate, but not in severe patients, while the activation peptide of C5 (C5a) increased from the admission in every patient, regardless of their severity. Moreover, total IgG, the IgG1 and IgG3 isotypes, and C4 decreased from day 0 to day 10 in patients who were hospitalized for more than two weeks, but not in patients who were discharged earlier. Our study provides important clues to understand the immune response observed in COVID‐19 patients, associating severity with an imbalanced humoral response, and identifying new targets for therapeutic intervention.
The pathogenesis of SARS‐CoV‐2 involves both cellular and humoral immunity. The proportion of B cells, plasmablasts, circulating follicular helper T cells (cTfh), and CD56‐CD16+ NK‐cells is increased in COVID‐19 patients. However, levels of IgG, and complement proteins are diminished in severe patients, suggesting immunoglobulins and complement consumption.
Increased recruitment of transitional and non-classical monocytes in the lung during SARS-CoV-2 infection is associated with COVID-19 severity. However, whether specific innate sensors mediate the ...activation or differentiation of monocytes in response to different SARS-CoV-2 proteins remain poorly characterized. Here, we show that SARS-CoV-2 Spike 1 but not nucleoprotein induce differentiation of monocytes into transitional or non-classical subsets from both peripheral blood and COVID-19 bronchoalveolar lavage samples in a NFκB-dependent manner, but this process does not require inflammasome activation. However, NLRP3 and NLRC4 differentially regulated CD86 expression in monocytes in response to Spike 1 and Nucleoprotein, respectively. Moreover, monocytes exposed to Spike 1 induce significantly higher proportions of Th1 and Th17 CD4 + T cells. In contrast, monocytes exposed to Nucleoprotein reduce the degranulation of CD8 + T cells from severe COVID-19 patients. Our study provides insights in the differential impact of innate sensors in regulating monocytes in response to different SARS-CoV-2 proteins, which might be useful to better understand COVID-19 immunopathology and identify therapeutic targets.
Introduction
SARS-CoV-2 viral load has been related to COVID-19 severity. The main aim of this study was to evaluate the relationship between SARS-CoV-2 viremia and SNPs in genes previously studied ...by our group as predictors of COVID-19 severity.
Materials and methods
Retrospective observational study including 340 patients hospitalized for COVID-19 in the University Hospital La Princesa between March 2020 and December 2021, with at least one viremia determination. Positive viremia was considered when viral load was above the quantifiable threshold (20 copies/ml). A total of 38 SNPs were genotyped. To study their association with viremia a multivariate logistic regression was performed.
Results
The mean age of the studied population was 64.5 years (SD 16.6), 60.9% patients were male and 79.4% white non-Hispanic. Only 126 patients (37.1%) had at least one positive viremia. After adjustment by confounders, the presence of the minor alleles of rs2071746 (
HMOX1
; T/T genotype OR 9.9
p
< 0.0001), rs78958998 (probably associated with
SERPING1
expression; A/T genotype OR 2.3,
p
= 0.04 and T/T genotype OR 12.9,
p
< 0.0001), and rs713400 (eQTL for
TMPRSS2
; C/T + T/T genotype OR 1.86,
p
= 0.10) were associated with higher risk of viremia, whereas the minor alleles of rs11052877 (
CD69
; A/G genotype OR 0.5, p = 0.04 and G/G genotype OR 0.3,
p
= 0.01), rs2660 (
OAS1
; A/G genotype OR 0.6,
p
= 0.08), rs896 (
VIPR1
; T/T genotype OR 0.4,
p
= 0.02) and rs33980500 (
TRAF3IP2
; C/T + T/T genotype OR 0.3,
p
= 0.01) were associated with lower risk of viremia.
Conclusion
Genetic variants in
HMOX1
(rs2071746),
SERPING1
(rs78958998),
TMPRSS2
(rs713400),
CD69
(rs11052877),
TRAF3IP2
(rs33980500),
OAS1
(rs2660) and
VIPR1
(rs896) could explain heterogeneity in SARS-CoV-2 viremia in our population.
Bruton's tyrosine kinase inhibitor ibrutinib has significantly changed treatment landscape in chronic lymphocytic leukemia (CLL). Growing evidence supports ibrutinib to work beyond the effect on ...tumor cells by means of, for example, restoring functionality of the T-cell compartment and increasing circulating T-cell numbers. Recent evidence suggests T-cell enhanced expansion, rather than increased egress from secondary lymphoid organs (SLO), as a root cause for ibrutinib-induced lymphocytosis. However, whether the latter physiological change is also a consequence of a forced retention in blood remains undisclosed. Since CCR7 is the main chemokine receptor taking over the homing of T-cells from peripheral compartments to lymph nodes and other SLO, we aimed to investigate the impact of ibrutinib on CCR7 functionality in T-cells. To this end, we documented receptor expression in T-cells from a large cohort of ibrutinib-treated CLL patients, and performed different in vivo and in vitro migration models. Overall, our data confirm that CCR7 expression or receptor-mediated migration in CLL T-cells is not affected by ibrutinib. Furthermore, it does not modulate CCR7-driven homing nor nodal interstitial migration. Together, our results support that ibrutinib-induced CLL T-cell accumulation in the blood stream is not derived from an impairment of CCR7-driven recirculation between the SLO and bloodstream, and therefore T-cell expansion is the most plausible cause.
Graft-versus-host disease (GVHD) is the main complication after allogeneic hematopoietic stem cell transplantation. We previously unveiled a correlation between proportions of C-C motif chemokine ...receptor 7 (CCR7)
T cells in the apheresis and the risk of developing GVHD. We wanted to evaluate in vivo whether apheresis with low proportion of CCR7
cells or treatment with an anti-human CCR7 monoclonal antibody (mAb) were suitable strategies to prevent or treat acute GVHD in preclinical xenogeneic models. Therapeutic anti-CCR7 mAb was the most effective strategy in both prophylactic and therapeutic settings where antibody drastically reduced in vivo lymphoid organ infiltration of donor CCR7
T cells, extended lifespan and solved clinical signs. The antibody neutralized in vitro migration of naïve and central memory T cells toward CCR7 ligands and depleted target CCR7
subsets through complement activation. Both mechanisms of action spared CCR7
subsets, including effector memory and effector memory CD45RA
T cells which may mediate graft versus leukemia effect and immunity against infections. Accordingly, the numbers of donor CCR7
T cells in the apheresis were not associated to cytomegalovirus reactivation or the recurrence of the underlying disease. These findings provide a promising new strategy to prevent and treat acute GVHD, a condition where new specific, safety and effective treatment is needed.
•By promoting stromal cell contractility, dasatinib leads to a transient egress of lymphocytes from the spleen.•Dasatinib-induced spleen resizing and lymphocyte mobilization open new possibilities ...for clinical applications.
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The tyrosine kinase inhibitor dasatinib is approved for Philadelphia chromosome–positive leukemia, including chronic myeloid leukemia (CML). Although effective and well tolerated, patients typically exhibit a transient lymphocytosis after dasatinib uptake. To date, the underlying physiological process linking dasatinib to lymphocytosis remains unknown. Here, we used a small rodent model to examine the mechanism of dasatinib-induced lymphocytosis, focusing on lymphocyte trafficking into and out of secondary lymphoid organs. Our data indicate that lymphocyte homing to lymph nodes and spleen remained unaffected by dasatinib treatment. In contrast, dasatinib promoted lymphocyte egress from spleen with kinetics consistent with the observed lymphocytosis. Unexpectedly, dasatinib-induced lymphocyte egress occurred independently of canonical sphingosine-1-phosphate–mediated egress signals; instead, dasatinib treatment led to a decrease in spleen size, concomitant with increased splenic stromal cell contractility, as measured by myosin light chain phosphorylation. Accordingly, dasatinib-induced lymphocytosis was partially reversed by pharmacological inhibition of the contraction-promoting factor Rho-rho associated kinase. Finally, we uncovered a decrease in spleen size in patients with CML who showed lymphocytosis immediately after dasatinib treatment, and this reduction was proportional to the magnitude of lymphocytosis and dasatinib plasma levels. In summary, our work provides evidence that dasatinib-induced lymphocytosis is a consequence of drug-induced contractility of splenic stromal cells.
The aim of this study was to describe incidence, incidence trends and survival patterns of lymphoid neoplasms (LNs) and its subtypes in Spain in the period 2002-2013 using data from the Spanish ...Network of Cancer Registries (REDECAN).
Data were extracted from 13 Spanish population-based cancer registries. LNs incident cases were codified using the International Classification of Diseases for Oncology, third edition (ICD-O-3) and grouped according to the WHO 2008 classification. Age-standardized incidence rates to the 2013 European standard population (ASIRe) were obtained. Poisson regression models were used to analyze trends in incidence rates and estimate the annual percentage change (APC) for each subtype. The number of cases in Spain for 2023 was estimated by applying the estimated age-specific rates for the year 2023 to the 2023 Spanish population. Observed survival (OS) was estimated by the Kaplan-Meier method and net survival (NS) by the Pohar-Perme method. Sex- and age-specific estimates of 5-year NS were calculated, as well as its changes according to two periods of diagnosis (2002-2007 and 2008-2013).
LNs accounted for 69% (n=39,156) of all hematological malignancies (n=56,751) diagnosed during the period of study. Median age at diagnosis was 67 years (interquartile range (IQR) = 52-77). The overall ASIRe was 34.23 (95% confidence interval (CI): 33.89, 34.57) and showed a marked male predominance in almost all subtypes (global sex ratio = 1.45). During the study period, incidence trends of LNs remained stable (APC: 0.3; 95% CI: -0.1, 0.6), nevertheless some subtypes showed statistically significant variations, such as LNs NOS category (APC: -5.6; 95% CI: -6.8, -4.3). Around 17,926 new cases of LNs will be diagnosed in 2023 in Spain. Survival rates differed considerably across age-groups, while they were similar between men and women. Five- year NS was 62.81% (95% CI: 62.1, 63.52) for all LNs, and varied widely across LNs subtypes, ranging from 39.21% to 90.25%. NS for all LNs improved from the first period of diagnosis to the second one, being 61.57% (95% CI: 60.56, 62.61) in 2002-2007 and 64.17% (95% CI: 63.29, 65.07) in 2008-2013.
This study presents the first complete and extensive population-based analysis of LNs incidence and survival in Spain. These population-based data provide relevant information to better understand the epidemiology of LNs in Southern Europe and it features some useful points for public health authorities and clinicians. However, additional improvements regarding the registration of these hematological neoplasms can be implemented.
Patients with coronavirus disaese 2019 (COVID-19) can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome requiring invasive mechanical ventilation (IMV). ...Because IL-6 is a relevant cytokine in acute respiratory distress syndrome, the blockade of its receptor with tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19.
We sought to determine whether baseline IL-6 serum levels can predict the need for IMV and the response to TCZ.
A retrospective observational study was performed in hospitalized patients diagnosed with COVID-19. Clinical information and laboratory findings, including IL-6 levels, were collected approximately 3 and 9 days after admission to be matched with preadministration and postadministration of TCZ. Multivariable logistic and linear regressions and survival analysis were performed depending on outcomes: need for IMV, evolution of arterial oxygen tension/fraction of inspired oxygen ratio, or mortality.
One hundred forty-six patients were studied, predominantly males (66%); median age was 63 years. Forty-four patients (30%) required IMV, and 58 patients (40%) received treatment with TCZ. IL-6 levels greater than 30 pg/mL was the best predictor for IMV (odds ratio, 7.1; P < .001). Early administration of TCZ was associated with improvement in oxygenation (arterial oxygen tension/fraction of inspired oxygen ratio) in patients with high IL-6 (P = .048). Patients with high IL-6 not treated with TCZ showed high mortality (hazard ratio, 4.6; P = .003), as well as those with low IL-6 treated with TCZ (hazard ratio, 3.6; P = .016). No relevant serious adverse events were observed in TCZ-treated patients.
Baseline IL-6 greater than 30 pg/mL predicts IMV requirement in patients with COVID-19 and contributes to establish an adequate indication for TCZ administration.
Some patients with COVID-19 pneumonia develop an associated cytokine storm syndrome that aggravates the pulmonary disease. These patients may benefit of anti-inflammatory treatment. The role of ...colchicine in hospitalized patients with COVID-19 pneumonia and established hyperinflammation remains unexplored. In a prospective, randomized controlled, observer-blinded endpoint, investigator-initiated trial, 240 hospitalized patients with COVID-19 pneumonia and established hyperinflammation were randomly allocated to receive oral colchicine or not. The primary efficacy outcome measure was a composite of non-invasive mechanical ventilation (CPAP or BiPAP), admission to the intensive care unit, invasive mechanical ventilation requirement or death. The composite primary outcome occurred in 19.3% of the total study population. The composite primary outcome was similar in the two arms (17% in colchicine group vs. 20.8% in the control group; p = 0.533) and the same applied to each of its individual components. Most patients received steroids (98%) and heparin (99%), with similar doses in both groups. In this trial, including adult patients with COVID-19 pneumonia and associated hyperinflammation, no clinical benefit was observed with short-course colchicine treatment beyond standard care regarding the combined outcome measurement of CPAP/BiPAP use, ICU admission, invasive mechanical ventilation or death (Funded by the Community of Madrid, EudraCT Number: 2020-001841-38; 26/04/2020).
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