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In nature, chemotactic interactions are ubiquitous and play a critical role in driving the collective behavior of living organisms. Reproducing these interactions in vitro is still a paramount challenge due to the complexity of mimicking and controlling cellular features, such as tangled metabolic networks, cytosolic macromolecular crowding, and cellular migration, on a microorganism size scale. Here, we generate enzymatically active cell-sized droplets able to move freely, and by following a chemical gradient, able to interact with the surrounding droplets in a collective manner. The enzyme within the droplets generates a pH gradient that extends outside the edge of the droplets. We discovered that the external pH gradient triggers droplet migration and controls its directionality, which is selectively toward the neighboring droplets. Hence, by changing the enzyme activity inside the droplet, we tuned the droplet migration speed. Furthermore, we showed that these cellular-like features can facilitate the reconstitution of a simple and linear protometabolic pathway and increase the final reaction product generation. Our work suggests that simple and stable membraneless droplets can reproduce complex biological phenomena, opening new perspectives as bioinspired materials and synthetic biology tools.
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Quimiotaxia , Concentração de Íons de Hidrogênio , Tamanho da PartículaRESUMO
Innate immune defense mechanisms against infection and cancer encompass the modulation of pattern recognition receptor (PRR)-mediated inflammation, including upregulation of various transcription factors and the activation of pro-inflammatory pathways important for immune surveillance. Dysfunction of PRRs-mediated signaling has been implicated in cancer and autoimmune diseases, while the overactivation of PRRs-driven responses during infection can lead to devastating consequences such as acute lung injury or sepsis. We used crystal structure-based design to develop immunomodulatory lipopolysaccharide (LPS) mimetics targeting one of the ubiquitous PRRs, Toll-like Receptor 4 (TLR4). Taking advantage of an exo-anomeric conformation and specific molecular shape of synthetic nonreducing ß,ß-diglucosamine, which was investigated by NMR, we developed two sets of lipid A mimicking glycolipids capable of either potently activating innate immune responses or inhibiting pro-inflammatory signaling. Stereoselective 1,1'-glycosylation towards fully orthogonally protected nonreducing GlcNß(1â1')ßGlcN followed by stepwise assembly of differently functionalised phosphorylated glycolipids provided biologically active molecules that were evaluated for their ability to trigger or to inhibit cellular innate immune responses. Two LPS mimetics, identified as potent TLR4-specific inducers of the intracellular signaling pathways, serve as vaccine adjuvant- and immunotherapy candidates, while anionic glycolipids with TLR4-inhibitory potential hold therapeutic promise for the management of acute or chronic inflammation.
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Humans are unique in their ability to think about themselves and carry a more or less clear notion of who they are in their mind. Here we review recent evidence suggesting that the birth, maintenance, and loss of the abstract concept of 'self' is deeply tied to interoception, the sense of internal physiological signals. Interoception influences multiple facets of the self-concept, cutting across its material, social, moral, and agentive components. Overall, we argue that interoception contributes to the stability of the self-concept over time, unifying its layers and constraining the degree to which it is susceptible to external influences. Hence, the core features of the self-concept are those that correlate more with inner bodily states. We discuss the implications that this may have for theories of embodied cognition as well as for the understanding of psychiatric disorders in which the concept of self appears fragmented or loose. Finally, we formulate some empirical predictions that could be tested in future studies to shed further light on this emerging field.
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Interocepção , Psicologia Clínica , Humanos , Interocepção/fisiologia , Cognição/fisiologia , AutoimagemRESUMO
Shear thickening in stable dense colloidal suspensions is a reversible phenomenon and no hysteresis is observed in the flow curve measurements. However, a reduction in the stability of colloids promotes particle aggregation and introduces a time dependent rheological response. In this work, by using a model colloidal system of hard spherical silica particles (average diameter of 415 nm) with varying particle volume fractions 0.2 ≤ Ï ≤ 0.56, we study the effect of particle stability on the hysteresis of the shear thickening behavior of these suspensions. The particle stability is manipulated by adding a simple monovalent salt (sodium chloride) in the silica suspension with varying concentrations α ∈ [0,0.5] M. For repulsive and weakly attractive suspensions, the flow behavior is history independent and the shear thickening behavior does not exhibit hysteresis. However, significant hysteresis is observed in rheological measurements for strongly attractive suspensions, with shear history playing a critical role due to the dynamic nature of particle clusters, resulting in time dependent hysteresis behavior. By performing numerical simulations, we find that this hysteresis behavior arises due to the competition among shear, electrostatic repulsive, van der Waals attractive, and frictional contact forces. The critical shear stress (i.e., the onset of shear thickening) decreases with increasing salt concentrations, which can be captured by a scaling relationship based on the force balance between particle-particle contact force and electrostatic repulsive force. Our combined experimental and simulation results imply the formation of particle contacts in our sheared suspensions.
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Recent theories posit that physiological signals contribute to corporeal awareness, the basic feeling that one has a body (body ownership) that acts according to one's will (body agency) and occupies a specific position (body location). Combining physiological recordings with immersive virtual reality, we found that an ecological mapping of real respiratory patterns onto a virtual body illusorily changes corporeal awareness. This new way of inducing a respiratory bodily illusion, called "embreathment," revealed that breathing is almost as important as visual appearance for inducing body ownership and more important than any other cue for body agency. These effects were moderated by individual levels of interoception, as assessed through a standard heartbeat-counting task and a new "pneumoception" task. By showing that respiratory, visual, and spatial signals exert a specific and weighted influence on the fundamental feeling that one is an embodied agent, we pave the way for a comprehensive hierarchical model of corporeal awareness.NEW & NOTEWORTHY Our body is the only object we sense from the inside; however, it is unclear how much inner physiology contributes to the global sensation of having a body and controlling it. We combine respiration recordings with immersive virtual reality and find that making a virtual body breathe like the real body gives an illusory sense of ownership and agency over the avatar, elucidating the role of a key physiological process like breathing in corporeal awareness.
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Conscientização/fisiologia , Ilusões/fisiologia , Interocepção/fisiologia , Respiração , Adulto , Humanos , Masculino , Realidade Virtual , Adulto JovemRESUMO
Coherent processing in synthetic aperture sonar (SAS) requires platform motion estimation and compensation with sub-wavelength accuracy for high-resolution imaging. Micronavigation, i.e., through-the-sensor platform motion estimation, is essential when positioning information from navigational instruments is absent or inadequately accurate. A machine learning method based on variational Bayesian inference has been proposed for unsupervised data-driven micronavigation. Herein, the multiple-input multiple-output arrangement of a multi-band SAS system is exploited and combined with a hierarchical variational inference scheme, which self-supervises the learning of platform motion and results in improved micronavigation accuracy.
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Although it is generally held that gastrointestinal (GI) signals are related to emotions, direct evidence for such a link is currently lacking. One of the reasons why the internal milieu of the GI system is poorly investigated is because visceral organs are difficult to access and monitor. To directly measure the influence of endoluminal markers of GI activity on the emotional experience, we asked a group of healthy male participants to ingest a pill that measured pH, pressure, and temperature of their GI tract while they watched video clips that consistently induced disgust, fear, happiness, sadness, or a control neutral state. In addition to the objective physiological markers of GI activity, subjective ratings of perceived emotions and visceral (i.e. gastric, respiratory and cardiac) sensations were recorded, as well as changes in heart rate (HR), heart rate variability (HRV) and spontaneous eyes blinks as non-gastric behavioral and autonomic markers of the emotional experience. We found that when participants observed fearful and disgusting video clips, they reported to perceive not only cardiac and respiratory sensations but also gastric sensations, such as nausea. Moreover, we found that there was a clear relation between the physiology of the stomach and the perceived emotions. Specifically, when disgusting video clips were displayed, the more acidic the pH, the more participants reported feelings of disgust and fear; the less acidic the pH, the more they reported happiness. Complementing the results found in the deep gastric realm, we found that disgusting stimuli induced a significant increase in HRV compared to the neutral scenarios, and together with fearful video clips a decrease in HR. Our findings suggest that gastric signals contribute to unique emotional states and that ingestible pills may open new avenues for exploring the deep-body physiology of emotions.
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Emoções , Humanos , Masculino , Emoções/fisiologia , Adulto , Adulto Jovem , Frequência Cardíaca/fisiologia , Concentração de Íons de HidrogênioRESUMO
We capitalized on the respiratory bodily illusion that we discovered in a previous study and called 'Embreathment' where we showed that breathing modulates corporeal awareness in men. Despite the relevance of the issue, no such studies are available in women. To bridge this gap, we tested whether the synchronization of avatar-participant respiration patterns influenced females' bodily awareness. We collected cardiac and respiratory interoceptive measures, administered body (dis)satisfaction questionnaires, and tracked participants' menstrual cycles via a mobile app. Our approach allowed us to characterize the 'Embreathment' illusion in women, and explore the relationships between menstrual cycle, interoception and body image. We found that breathing was as crucial as visual appearance in eliciting feelings of ownership and held greater significance than any other cue with respect to body agency in both women and men. Moreover, a positive correlation between menstrual cycle days and body image concerns, and a negative correlation between interoceptive sensibility and body dissatisfaction were found, confirming that women's body dissatisfaction arises during the last days of menstrual cycle and is associated with interoception. These findings have potential implications for corporeal awareness alterations in clinical conditions like eating disorders and schizophrenia.
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Conscientização , Imagem Corporal , Ilusões , Interocepção , Realidade Virtual , Humanos , Feminino , Imagem Corporal/psicologia , Adulto , Ilusões/fisiologia , Adulto Jovem , Interocepção/fisiologia , Masculino , Ciclo Menstrual/fisiologia , Ciclo Menstrual/psicologia , Inquéritos e Questionários , Respiração , Insatisfação Corporal/psicologiaRESUMO
We study the rheological behaviour of bidisperse suspensions in three dimensions under a non-uniform shear flow, made by the superimposition of a linear shear and a sinusoidal disturbance. Our results show that (i) only a streamwise disturbance in the shear-plane alters the suspension dynamics by substantially reducing the relative viscosity, (ii) with the amplitude of the disturbance determining a threshold value for the effect to kick-in and its wavenumber controlling the amount of reduction and which of the two phases is affected. We show that, (iii) the rheological changes are caused by the effective separation of the two phases, with the large or small particles layering in separate regions. We provide a physical explanation of the phase separation process and of the conditions necessary to trigger it. We test the results in the whole flow curve, and we show that the mechanism remains substantially unaltered, with the only difference being the nature of the interactions between particles modified by the phase separation.
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Flexible filamentous beds interacting with a turbulent flow represent a fundamental setting for many environmental phenomena, e.g., aquatic canopies in marine current. Exploiting direct numerical simulations at high Reynolds number where the canopy stems are modelled individually, we provide evidence on the essential features of the honami/monami collective motion experienced by hairy surfaces over a range of different flexibilities, i.e., Cauchy number. Our findings clearly confirm that the collective motion is essentially driven by fluid flow turbulence, with the canopy having in this respect a fully-passive behavior. Instead, some features pertaining to the structural response turn out to manifest in the motion of the individual canopy elements when focusing, in particular, on the spanwise oscillation and/or on sufficiently small Cauchy numbers.
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Trehalose-containing glycans play an essential role in bacterial pathogenesis, host-pathogen interaction, and cell signaling. The investigation of trehalose uptake and metabolism in Mycobacteria using synthetic desymmetrized trehalose probes is an important approach for the development of diagnostic tools and potential therapeutics for tuberculosis. Trehalose-derived mycobacterial glycolipids activate the innate immune response through recognition by the C-type lectin Mincle, justifying efforts to develop novel trehalose-based Mincle-dependent adjuvants. The chemical synthesis of trehalose-based glycoconjugates, glycolipids, and small-molecule trehalose probes requires the challenging chemical desymmetrization of eight hydroxyl groups in a C 2-symmetric disaccharide αGlc(1â1)αGlc. Using a novel set of orthogonal protecting groups, we developed a flexible multiscale synthetic approach to a collection of differently and variably protected fully desymmetrized trehalose derivatives, ready for final chemical modification with relevant functional or reporter groups. Using a regioselective and site-specific protecting group strategy, we performed multiple symmetry-breaking operations, resulting in a library of trehalose-derived orthogonally protected building blocks as a versatile source for the synthesis of complex trehalose-containing glycans.
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Viscous dissipation causes significant energy losses in fluid flows; in ducts, laminar flows provide the minimum resistance to the motion, whereas turbulence substantially increases the friction at the wall and the consequent energy requirements for pumping. Great effort is currently being devoted to find new strategies to reduce the energy losses induced by turbulence. Here we propose a simple and novel drag-reduction technique which achieves substantial energy savings in internal flows. Our approach consists in driving the flow with a temporally intermittent pumping, unlike the common practice of a constant pumping. We alternate "pump on" phases where the flow accelerates, and "pump off" phases where the flow decays freely. The flow cyclically enters a quasi-laminar state during the acceleration, and transitions to a more classic turbulent state during the deceleration. Our numerical results demonstrate that important energy savings can be achieved by simply modulating the power injection into the system over time. The physical understanding of this process can help the industry in reducing the waste of energy, creating economical benefits and preserving the environment by reducing harmful emissions.
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Movimento (Física) , ViscosidadeRESUMO
Non-localized impulsive sources are ubiquitous in underwater acoustic applications. However, analytical expressions of their acoustic field are usually not available. In this work, far-field analytical solutions of the non-homogeneous scalar Helmholtz and wave equations are developed for a class of spatially extended impulsive sources. The derived expressions can serve as benchmarks to verify the accuracy of numerical solvers.
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Background: Interoception - the processing of the internal state of the body - has been consistently tied to well-being and mental health, which in turn have been severely challenged by the COVID-19 pandemic. Moreover, the fact that symptoms of COVID-19 (high temperature, shortness of breath, fatigue, and even gastro-intestinal problems) directly alter interoceptive signals has fueled people's tendency to constantly check their internal bodily state. Objectives: In this longitudinal study we tested for changes in interoception and psychophysiological health and well-being during different stages of the pandemic in 2020 and assessed their potential association. To highlight this association, we combined both subjective (i.e., self-reported questionnaires) and objective (i.e., measures of heart rate variability, HRV and of interoceptive accuracy) measures. Methods: 245 Italian participants who had completed the Multidimensional Assessment of Interoceptive Awareness (MAIA-2) prior to the onset of the pandemic, repeated the questionnaire during the first national lockdown in Italy, and four months after restrictions. Participants also completed survey measures of depression (PHQ-9), anxiety (STAI), and sleep disturbance (PSQI). A sub-sample of 28 participants, who had completed the heartbeat counting task (HCT) and a measure of heart rate variability (HRV), was tested again remotely, in the same time windows, using phone applications and photoplethysmography. Results: While performance in the HCT remained unvaried, MAIA-2 scores consistently increased from before the pandemic to the national lockdown, and remained largely unvaried after four months. The national lockdown was associated with the lowest psychophysiological health and well-being, as evidenced by a decrease in HRV compared to before the pandemic and by higher scores in self-reported depression, anxiety, and sleep disturbance compared to four months after the lockdown. Interestingly, psychophysiological health and well-being were predicted by specific regulatory components of interoception (e.g., the ability to regulate distress by focusing on body sensations and experiencing one's body as safe and trustworthy). Conclusions: Our results suggest an increased attention towards visceral signals during the COVID-19 pandemic, and highlight the positive role of specific components of interoception in contributing to well-being, suggesting that novel interventions aimed at increasing interoception may be developed to protect against stressful life events such as COVID-19.
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The literature reports that there was a significant difference in the medical impact of the coronavirus disease (COVID-19) pandemic between European and East Asian countries; specifically, the mortality rate of COVID-19 in Europe was significantly higher than that in East Asia. Considering such a difference, our narrative review aimed to compare the prevalence and characteristics of residual lung abnormalities at one-year follow-up computed tomography (CT) after severe or critical COVID-19 in survivors of European and East Asian countries. A literature search was performed to identify articles focusing on the prevalence and characteristics of CT lung abnormalities in survivors of severe or critical COVID-19. Database analysis identified 16 research articles, 9 from Europe and 7 from East Asia (all from China). Our analysis found a higher prevalence of CT lung abnormalities in European than in Chinese studies (82% vs. 52%). While the most prevalent lung abnormalities in Chinese studies were ground-glass opacities (35%), the most prevalent lung abnormalities in European studies were linear (59%) and reticular opacities (55%), followed by bronchiectasis (46%). Although our findings required confirmation, the higher prevalence and severity of lung abnormalities in European than in Chinese survivors of COVID-19 may reflect a greater architectural distortion due to a more severe lung damage.
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COVID-19 , Pulmão , Humanos , COVID-19/complicações , COVID-19/diagnóstico por imagem , População do Leste Asiático , Seguimentos , Pulmão/diagnóstico por imagem , Sobreviventes , Tomografia Computadorizada por Raios X , Europa (Continente) , Ásia Oriental , População Europeia , Gravidade do PacienteRESUMO
Elastomer composites with low hysteresis are of great importance for sustainable development, as they find application in billions of tires. For these composites, a filler such as silica, able to establish a chemical bond with the elastomer chains, is used, in spite of its technical drawbacks. In this work, a furnace carbon black (CB) functionalized with polar groups was used in replacement of silica, obtaining lower hysteresis. CBN326 was functionalized with 2-(2,5-dimethyl-1H-pyrrol-1-yl)-1,3-propanediol (serinol pyrrole, SP), and samples of CB/SP adducts were prepared with different SP content, ranging from four to seven parts per hundred carbon (phc). The entire process, from the synthesis of SP to the preparation of the CB/SP adduct, was characterized by a yield close to 80%. The functionalization did not alter the bulk structure of CB. Composites were prepared, based on diene rubbers-poly(1,4-cis-isoprene) from Hevea Brasiliensis and poly(1,4-cis-butadiene) in a first study and synthetic poly(1,4-cis-isoprene) in a second study-and were crosslinked with a sulfur-based system. A CB/silica hybrid filler system (30/35 parts) was used and the partial replacement (66% by volume) of silica with CB/SP was performed. The composites with CB/SP exhibited more efficient crosslinking, a lower Payne effect and higher dynamic rigidity, for all the SP content, with the effect of the functionalized CB consistently increasing the amount of SP. Lower hysteresis was obtained for the composites with CB/SP. A CB/SP adduct with approximately 6 phc of SP, used in place of silica, resulted in a reduction in ΔG'/G' of more than 10% and an increase in E' at 70 °C and in σ300 in tensile measurements of about 35% and 30%, respectively. The results of this work increase the degrees of freedom for preparing elastomer composites with low hysteresis, allowing for the use of either silica or CB as filler, with a potentially great impact on an industrial scale.
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Background: Given their sensitivity to environmental alterations, odonates act as reliable bioindicators to assess the effects of changes in freshwater ecosystems and associated terrestrial habitats. The region comprised between Lario and Brianza (Provinces of Como, Lecco and Monza and Brianza - Lombardy, N Italy) is one of the most urbanised of the Italian peninsula and large parts of its territory have been heavily altered, especially at low elevation. Despite this pervasive anthropogenisation, the area is still characterised by a considerable variety of freshwater habitats, possibly harbouring rich odonate communities, which, however, have been never thoroughly investigated. This study aimed to produce the first commented checklist of the Odonata of this region, accompanied by distribution maps. New information: The work is based on 12,093 records spanning from 1981 and 2022, derived from literature (289), revision of collections (42), citizen-science projects (1249) and unpublished data from the authors and their collaborators (10,513). Overall, fifty-five species occur - or occurred in the past - in the study area (20 Zygoptera and 35 Anisoptera). One species, Erythrommanajas, was confirmed exclusively before 1978, while seven species (Lestesbarbarus, Coenagrionscitulum, Aeshnaaffinis, Anaxephippiger, Somatochloraarctica, Sympetrummeridionale and Trithemisannulata) have been recorded only after 2000. Records referring to Chalcolestesparvidens and Sympetrumflaveolum were considered questionable and excluded from the checklist. A list of species for each protected site is additionally provided. This work highlighted the importance for odonates of Lario and Brianza Regions from a national perspective, in particular for species of conservation priority/interest, such as Sympecmapaedisca, Oxygastracurtisii and Sympetrumdepressiusculum.
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Bodily self-consciousness, the state of mind that allows humans to be aware of their own body, forms the backdrop for almost every human experience, yet its underpinnings remain elusive. Here we combine an ingestible, minimally invasive capsule with surface electrogastrography to probe if gut physiology correlates with bodily self-consciousness in a sample of healthy men during a virtual bodily illusion. We discover that specific patterns of stomach and bowel activity (temperature, pressure, and pH) covary with specific facets of bodily self-consciousness (feelings of body location, agency, and disembodiment). These results uncover the hitherto untapped potential of minimally invasive probes to study the link between mental and gut states and show the significance of deep visceral organs in the self-conscious perception of ourselves as embodied beings.
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A pilot-scale membrane-enhanced biological phosphorus removal process accumulated substantial quantities of stable foam on the surface of the anoxic zone. The foam contained 4 to 6% dry matter, with specific nitrogen and phosphorus contents that were similar to those of the underlying anoxic zone mixed liquor. Kinetic studies demonstrated that the specific rate of phosphorus release from the foam was only 25 to 30% of that observed with mixed liquor from the aerobic zone. Molecular techniques demonstrated that the calculated similarity of the microbial communities in the foam and the underlying mixed liquor was approximately 80%, with two phylotypes (Gordonia amarae and Microthrix parvicella) being uniquely enriched in the foam and one phylotype (Epistylis sp.) more abundant in the underlying mixed liquor. The production of foam was demonstrated to be a consistent phenomenon that depended on the concentration of the suspended solids in the bioreactor.
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Reatores Biológicos , Fósforo/química , Eliminação de Resíduos Líquidos , Poluentes Químicos da Água/química , Aerobiose , Bactérias/genética , Bactérias/metabolismo , Monitoramento Ambiental , Hipóxia , Membranas Artificiais , Filogenia , Fatores de TempoRESUMO
PURPOSE: We assessed the immunogenicity and safety of the BNT162b2 vaccine in a large cohort of patients with cancer (CP). EXPERIMENTAL DESIGN: From March 1, 2021 to March 20, 2021, this prospective cohort study included 816 CP afferent to our institution and eligible for the vaccination. A cohort of 274 health care workers (HCW) was used as age- and sex-matched control group. BNT162b2 was administered as a two-dose regimen given 21 days apart. Blood samples to analyze anti-Spike (S) IgG antibodies (Ab) were collected prevaccination [timepoint (TP) 0], and at 3 weeks (TP1) and 7 weeks (TP2) after the first dose. RESULTS: Patients characteristics: median age 62 (range, 21-97); breast/lung cancer/others (31/21/48%); active treatment/follow-up (90/10%). In the whole CP cohort, the serologic response rate (RR) and the titre of anti-S IgG significantly increased across the TPs; at TP2, the responders (IgG >15 AU/mL) were 94.2%. Active chemotherapy and chronic use of steroids were independent predictors of lower RR. Adverse events (AE) after the booster predicted higher likelihood of response (OR, 4.04; 95% confidence interval, 1.63-9.99; P = 0.003). Comparing the matched cohorts, the responders were significantly lower in CP than in HCW at TP1 (61.2% vs. 93.2%) and TP2 (93.3% vs. 100%), while the geometric mean concentration of IgG did not significantly differ at TP2 being significantly lower in CP (23.3) than in HCW (52.1) at TP1. BNT162b2 was well tolerated in CP; severe-grade AEs were 3.5% and 1.3% after the first and second doses, respectively. CONCLUSIONS: BNT162b2 assures serologic immunization without clinically significant toxicity in CP. The second dose is needed to reach a satisfactory humoral response.