Impact of immune parameters and immune dysfunctions on the prognosis of patients with chronic lymphocytic leukemia

SIMPLE SUMMARY: In chronic lymphocytic leukemia (CLL), immune alterations—affecting both the innate and adaptive immunity—are very common. As a clinical consequence, patients with CLL frequently present with autoimmune phenomena, increased risk of infections and second malignancies. The aim of this review article is to present available data on CLL-associated alterations of immune parameters that correlate with known prognostic markers and with clinical outcome. Also, data on the impact of immune-related clinical manifestations on the prognosis of patients with CLL will be discussed. ABSTRACT: Chronic lymphocytic leukemia (CLL) is characterized by a wide spectrum of immune alterations, affecting both the innate and adaptive immunity. These immune dysfunctions strongly impact the immune surveillance, facilitate tumor progression and eventually affect the disease course. Quantitative and functional alterations involving conventional T cells, γδ T cells, regulatory T cells, NK and NKT cells, and myeloid cells, together with hypogammaglobulinemia, aberrations in the complement pathways and altered cytokine signature have been reported in patients with CLL. Some of these immune parameters have been shown to associate with other CLL-related characteristics with a known prognostic relevance or to correlate with disease prognosis. Also, in CLL, the complex immune response dysfunctions eventually translate in clinical manifestations, including autoimmune phenomena, increased risk of infections and second malignancies. These clinical issues are overall the most common complications that affect the course and management of CLL, and they also may impact overall disease prognosis

More Than Accuracy: Towards Trustworthy Machine Learning Interfaces for Object Recognition

This paper investigates the user experience of visualizations of a machine learning (ML) system that recognizes objects in images. This is important since even good systems can fail in unexpected ways as misclassifications on photo-sharing websites showed. In our study, we exposed users with a background in ML to three visualizations of three systems with different levels of accuracy. In interviews, we explored how the visualization helped users assess the accuracy of systems in use and how the visualization and the accuracy of the system affected trust and reliance. We found that participants do not only focus on accuracy when assessing ML systems. They also take the perceived plausibility and severity of misclassification into account and prefer seeing the probability of predictions. Semantically plausible errors are judged as less severe than errors that are implausible, which means that system accuracy could be communicated through the types of errors.Comment: UMAP '20: Proceedings of the 28th ACM Conference on User Modeling, Adaptation and Personalizatio

Building Credibility, Trust, and Safety on Video-Sharing Platforms

Video-sharing platforms (VSPs) such as YouTube, TikTok, and Twitch attract millions of users and have become influential information sources, especially among the young generation. Video creators and live streamers make videos to engage viewers and form online communities. VSP celebrities obtain monetary benefits through monetization programs and affiliated markets. However, there is a growing concern that user-generated videos are becoming a vehicle for spreading misinformation and controversial content. Creators may make inappropriate content for attention and financial benefits. Some other creators also face harassment and attack. This workshop seeks to bring together a group of HCI scholars to brainstorm technical and design solutions to improve the credibility, trust, and safety of VSPs. We aim to discuss and identify research directions for technology design, policy-making, and platform services for video-sharing platforms. © 2023 Owner/Author

Inter-individual differences in foraging tactics of a colonial raptor : consistency, weather effects, and fitness correlates

Background: Consistent inter-individual differences in behavioural phenotypes may entail differences in energy efficiency and expenditure, with different fitness payoffs. In colonial-breeding species, inter-individual differences in foraging behaviour may evolve to reduce resource use overlap among conspecifics exploiting shared foraging areas. Furthermore, individual differences in foraging behaviour may covary with individual characteristics, such as sex or physiological conditions. Methods: We investigated individual differences in foraging tactics of a colonial raptor, the lesser kestrel (Falco naumanni). We tracked foraging trips of breeding individuals using miniaturized biologgers. We classified behaviours from GPS data and identified tactics at the foraging trip level by cluster analysis. We then estimated energy expenditure associated to each tactic from tri-axial accelerometer data. Results: We obtained 489 foraging trips by 36 individuals. Two clusters of trips were identified, one (SF) characterized by more static foraging behaviour and the other (DF) by more dynamic foraging behaviour, with a higher proportion of flying activity and a higher energy expenditure compared to SF. Lesser kestrels showed consistent inter-individual differences in foraging tactics across weather condition gradients, favouring DF trips as solar radiation and crosswind intensity increased. DF trips were more frequent during the nestling-rearing than during the egg incubation stage. Nestlings whose tracked parent was more prone to perform DF trips experienced higher daily mass increase, irrespective of nestling feeding rates. Conclusions: Our study provided evidence that breeding lesser kestrels flexibly adopted different foraging tactics according to contingent weather landscapes, with birds showing consistent inter-individual differences in the tendency to adopt a given tactic. The positive correlation between the tendency to perform more energy-demanding DF trips and nestling growth suggests that individual differences in foraging behaviour may play a role in maintaining key life-history trade-offs between reproduction and self-maintenance

Molecular basis of autotrophic vs mixotrophic growth in Chlorella sorokiniana

In this work, we investigated the molecular basis of autotrophic vs. mixotrophic growth of Chlorella sorokiniana, one of the most productive microalgae species with high potential to produce biofuels, food and high value compounds. To increase biomass accumulation, photosynthetic microalgae are commonly cultivated in mixotrophic conditions, adding reduced carbon sources to the growth media. In the case of C. sorokiniana, the presence of acetate enhanced biomass, proteins, lipids and starch productivity when compared to autotrophic conditions. Despite decreased chlorophyll content, photosynthetic properties were essentially unaffected while differential gene expression profile revealed transcriptional regulation of several genes mainly involved in control of carbon flux. Interestingly, acetate assimilation caused upregulation of phosphoenolpyruvate carboxylase enzyme, enabling potential recovery of carbon atoms lost by acetate oxidation. The obtained results allowed to associate the increased productivity observed in mixotrophy in C. sorokiniana with a different gene regulation leading to a fine regulation of cell metabolism

Party Face Congratulations! Exploring Design Ideas to Help Sighted Users with Emoji Accessibility when Messaging with Screen Reader Users

Emoji are a popular, expressive form of non-verbal communication. However, people often use emoji in ways that result in confusing or cumbersome screen reader output. We created two accessibility support designs: (1) Preview, which displays a basic text transcript of a message with emoji that a screen reader would narrate, and (2) Alert, which summarises potential accessibility issues caused by emoji within a message. We explored our designs using an online survey and provided participants with the option to edit messages that contained emoji, should they choose to do so. We collected 1508 modified messages from 116 sighted participants and conducted a qualitative analysis of the data to identify the strategies participants used when asked to edit a message for accessibility issues and their appreciation of each design. We found that participants preferred the Preview design over Alert since it allows for subjective interpretations of what constitutes an accessible message. We report sighted users' rewriting strategies (e.g., editing the message to move the emoji to the end) and incorrect assumptions about screen readers that would lead to using textual markers that are incompatible with screen readers. We discuss the design implications for future systems for accessible messaging

A new case manager for diabetic patients: a pilot observational study of the role of community pharmacists and pharmacy services in the case management of diabetic patients

The adherence of type 2 diabetes mellitus (DM2) patients with an individual care plan (ICP) is often not satisfactory, nor does it allow for a significant improvement in outcome, because of poor accessibility to services, poor integration of pathway articulations, poor reconciliation with the patient's life, or the lack of a constant reference person. The purpose of this study was to evaluate the contribution of community pharmacists and pharmacy services in improving adherence with periodic controls in DM2. The study was conducted at a rural pharmacy. A sample of 40 patients was calculated with respect to a historical cohort and subsequently enrolled. Clinical and personal data were collected in an electronic case report form. Pharmacists acting as a case manager followed patients carrying out their ICP developed by an attending physician. Some of the activities foreseen by the ICP, such as electrocardiogram, fundus examination, and self-analysis of blood and urine, were carried out directly in the pharmacy by the pharmacist through the use of telemedicine services and point of care units. Activities that could not be performed in the pharmacy were booked by the pharmacist at the accredited units. Examination results were electronically reported by the pharmacist to the attending physician. The primary endpoint was the variation in patient adherence with the ICP compared to a historical cohort. Secondary endpoints were variation in waiting time for the examinations, mean percentage change in glycated hemoglobin (HbA1c) and low-density lipoprotein (LDL) cholesterol levels and blood pressure, impact on healthcare-related costs, and perceived quality of care. Adherence to the ICP significantly increased. Waiting times were reduced and clinical outcomes improved with conceivable effects on costs. Patients appreciated the easier access to services. Community pharmacists and pharmacy services represent ideal actors and context that, integrated in the care network, can really favor ICP adherence and obtain daily morbidity reduction and cost savings through proper disease control and an early diagnosis of complications

Only females in poor condition display a clear preference and prefer males with an average badge

<p>Abstract</p> <p>Background</p> <p>Female condition-dependent variation in mate preference may have important evolutionary implications, not only within the same population but also among populations. There are few experiments, however, on how condition and/or genotype influences female mate preferences. The black throat patch of the male house sparrow, <it>Passer domesticus</it>, is an intensively studied plumage trait. It is often referred to as a 'badge of status' and seems to be involved in female mate choice, but differences exist among populations. Between-population variation in mate preference may occur for condition-dependent mate preferences. We tested the hypothesis that female preference may vary with female quality (body condition). Therefore, we measured female preference for badge size using an aviary two-choice test in which females were presented with two males that had different sizes of badges (enlarged or averaged).</p> <p>Results</p> <p>Overall we did not find a female preference for enlarged or average badges, but low-quality females spent more time near average badge males. Conversely, high-quality females did not show a clear preference.</p> <p>Conclusions</p> <p>Collectively, these results indicate that female preference varies with female quality. Differences in female condition are causes of within-population variation in mating preferences. To our knowledge, our results provide one of the first experimental evidences that variation in preference for a male ornament is associated with female condition. In our study, however, only females of low condition displayed a clear mate preference. Differences observed among populations could be partly explained by differences in female condition.</p

Cyclic nucleotide-dependent relaxation in human umbilical vessels

Umbilical vessels have a low sensitivity to dilate, and this property is speculated to have physiological implications. We aimed to investigate the different relaxing responses of human umbilical arteries (HUAs) and veins (HUVs) to agonists acting through the cAMP and cGMP pathways. Vascular rings were suspended in organ baths for isometric force measurement. Following precontraction with the thromboxane prostanoid (TP) receptor agonist U44069, concentration-response curves to the nitric oxide (NO) donor sodium nitroprusside (SNP), the soluble guanylate cyclase (sGC) stimulator BAY 41-2272, the adenylate cyclase (AC) activator forskolin, the \u3b2-adrenergic receptor agonists isoproterenol (ADRB1), salmeterol (ADRB2), and BRL37344 (ADRB3), and the phosphodiesterase (PDE) inhibitors milrinone (PDE3), rolipram (PDE4), and sildenafil (PDE5) were performed. None of the tested drugs induced a relaxation higher than 30% of the U44069-induced tone. Rings from HUAs and HUVs showed a similar relaxation to forskolin, SNP, PDE inhibitors, and ADRB agonists. BAY 41-2272 was significantly more efficient in relaxing veins than arteries. ADRB agonists evoked weak relaxations (&lt; 20%), which were impaired in endothelium-removed vessels or in the presence of the NO synthase inhibitor L-NAME, sGC inhibitor ODQ. PKA and PKG inhibitors impaired ADBR1-mediated relaxation but did not affect ADRB2-mediated relaxation. ADRB3-mediated relaxation was impaired by PKG inhibition in HUAs and by PKA inhibition in HUVs. Although HUA and HUV rings were relaxed by BRL37344, immunohistochemistry and RT-qPCR analysis showed that, compared to ADRB1 and ADRB2, ADRB3 receptors are weakly or not expressed in umbilical vessels. In conclusion, our study confirmed the low relaxing capacity of HUAs and HUVs from term infants. ADRB-induced relaxation is partially mediated by endothelium-derived NO pathway in human umbilical vessels

Targeting hif-1&#945; regulatory pathways as a strategy to hamper tumor-microenvironment interactions in cll

The hypoxia-inducible factor 1 (HIF-1) and the CXCL12/CXCR4 axis regulate the interaction of chronic lymphocytic leukemia cells and the tumor microenvironment. However, the interconnections occurring between HIF-1 and the CXCL12/CXCR4 axis are not fully elucidated. Here, we demonstrate that the CXCL12/CXCR4 axis plays a pivotal role in the positive regulation of the α subunit of HIF-1 (HIF-1α) that occurs in CLL cells co-cultured with stromal cells (SC). Inhibitors acting at different levels on CXCR4 downstream signalling counteract the SC-induced HIF-1α upregulation in CLL cells, also hindering the SC-mediated pro-survival effect. HIF-1α inhibition also exerts off-tumor effects on the SC component, inducing the downregulation of target genes, including CXCL12. Consistently, our data show that pretreatment of leukemic cells and/or SC with idelalisib effectively abrogates the SC-mediated survival support. A combined on-tumor and off-tumor inhibition of HIF-1α was also observed in idelalisib-treated patients, who showed, along with a downregulation of HIF-1α target genes in leukemic cells, a significant decrease in CXCL12 serum concentration and changes in the bone marrow microenvironment. Our data demonstrate that the targeting of HIF-1α or its regulatory pathways acts at the tumor- and SC-level, and may be an appealing strategy to overcome the microenvironment-mediated protection of CLL cells