Long-Term Effect of Home Blood Pressure Self-Monitoring Plus Medication Self-Titration for Patients With Hypertension: A Secondary Analysis of the ADAMPA Randomized Clinical Trial.

Importance: Patient empowerment through pharmacologic self-management is a common strategy for some chronic diseases such as diabetes, but it is rarely used for controlling blood pressure (BP). Several trials have shown its potential for reducing BP in the short term, but evidence in the longer term is scarce. Objective: To evaluate the longer-term effectiveness of BP self-monitoring plus self-titration of antihypertensive medication vs usual care for patients with poorly controlled hypertension, with passive follow-up and primary-care nursing involvement. Design, Setting, and Participants: The ADAMPA (Impact of Self-Monitoring of Blood Pressure and Self-Titration of Medication in the Control of Hypertension) study was a randomized, unblinded clinical trial with 2 parallel arms conducted in Valencia, Spain. Included participants were patients 40 years or older, with systolic BP (SBP) over 145 mm Hg and/or diastolic BP (DBP) over 90 mm Hg, recruited from July 21, 2017, to June 30, 2018 (study completion, August 25, 2020). Statistical analysis was conducted on an intention-to-treat basis from August 2022 to February 2024. Interventions: Participants were randomized 1:1 to usual care vs an individualized, prearranged plan based on BP self-monitoring plus medication self-titration. Main Outcomes and Measures: The main outome was the adjusted mean difference (AMD) in SBP between groups at 24 months of follow-up. Secondary outcomes were the AMD in DBP between groups at 24 months of follow-up, proportion of patients reaching the BP target (SBP <140 mm Hg and DBP <90 mm Hg), change in behaviors, quality of life, health service use, and adverse events. Results: Among 312 patients included in main trial, data on BP measurements at 24 months were available for 219 patients (111 in the intervention group and 108 in the control group). The mean (SD) age was 64.3 (10.1) years, and 120 patients (54.8%) were female; the mean (SD) SBP was 155.6 (13.1) mm Hg, and the mean (SD) diastolic BP was 90.8 (7.7) mm Hg. The median follow-up was 23.8 months (IQR, 19.8-24.5 months). The AMD in SBP at the end of follow-up was -3.4 mm Hg (95% CI, -4.7 to -2.1 mm Hg; P < .001), and the AMD in DBP was -2.5 mm Hg (95% CI, -3.5 to -1.6 mm Hg; P < .001). Subgroup analysis for the main outcome showed consistent results. Sensitivity analyses confirmed the robustness of the main findings. No differences were observed between groups in behaviors, quality of life, use of health services, or adverse events. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, BP self-monitoring plus self-titration of antihypertensive medication based on an individualized prearranged plan used in primary care reduced BP in the longer term with passive follow-up compared with usual care, without increasing health care use or adverse events. These results suggest that simple, inexpensive, and easy-to-implement self-management interventions have the potential to improve the long-term control of hypertension in routine clinical practice. Trial Registration: ClinicalTrials.gov Identifier: NCT03242785.

Pharmacokinetics and Safety of Lurbinectedin Administrated with Itraconazole in Cancer Patients: A Drug-Drug Interaction Study.

This open-label, two-part, phase Ib drug-drug interaction study investigated whether the pharmacokinetic (PK) and safety profiles of lurbinectedin (LRB), a marine-derived drug, are affected by co-administration of itraconazole (ITZ), a strong CYP3A4 inhibitor, in adult patients with advanced solid tumors. In Part A, three patients were sequentially assigned to Sequence 1 (LRB 0.8 mg/m2, 1-h intravenous [IV] + ITZ 200 mg/day oral in Cycle 1 [C1] and LRB alone 3.2 mg/m2, 1 h, IV in Cycle 2 [C2]). In Part B, 11 patients were randomized (1:1) to receive either Sequence 1 (LRB at 0.9 mg/m2 + ITZ in C1 and LRB alone in C2) or Sequence 2 (LRB alone in C1 and LRB + ITZ in C2). Eleven patients were evaluable for PK analysis: three in Part A and eight in Part B (four per sequence). The systemic total exposure of LRB increased with ITZ co-administration: 15% for Cmax, area under the curve (AUC) 2.4-fold for AUC0-t and 2.7-fold for AUC0-∞. Co-administration with ITZ produced statistically significant modifications in the unbound plasma LRB PK parameters. The LRB safety profile was consistent with the toxicities described in previous studies. Co-administration with multiple doses of ITZ significantly altered LRB systemic exposure. Hence, to avoid LRB overexposure when co-administered with strong CYP3A4 inhibitors, an LRB dose reduction proportional to CL reduction should be applied.

Maternal, Perinatal and Neonatal Outcomes of Triplet Pregnancies According to Chorionicity: Our 15-Year Experience in a Tertiary-Level Center.

Introduction: The goal of this study was to evaluate the effect of chorionicity on maternal, fetal and neonatal morbidity and mortality in triplet pregnancies in our environment. Methods: A retrospective observational study was carried out on triplet pregnancies that were delivered in a tertiary center between 2006 and 2020. A total of 76 pregnant women, 228 fetuses and 226 live newborns were analyzed. Of these triplet pregnancies, half were non-trichorionic. We analyzed maternal characteristics and obstetric, fetal, perinatal and neonatal complications based on their chorionicity, comparing trichorionic vs. non-trichorionic triplet pregnancies. Prematurity was defined as <34 weeks. We measured perinatal and neonatal mortality, composite neonatal morbidity and composite maternal morbidity. Results: Newborns with a monochorionic component had a lower gestational age at birth, presented greater prematurity under 34 weeks, lower birth weight, greater probability of birth weight under 2000 g and an APGAR score below 7 at 5 min after birth, more respiratory distress syndrome and, overall, higher composite neonatal morbidity. The monochorionic component of triple pregnancies may entail the development of complications intrinsic to shared circulation and require premature elective termination. This greater prematurity is also associated with a lower birth weight and to the main neonatal complications observed. These findings are in line with those that were previously published in the meta-analysis by our research group and previous literature. Discussion: Triplet gestations with a monochorionic component present a higher risk of obstetric, fetal and neonatal morbidity and mortality.

SUMOylation controls Hu antigen R posttranscriptional activity in liver cancer.

The posttranslational modification of proteins critically influences many biological processes and is a key mechanism that regulates the function of the RNA-binding protein Hu antigen R (HuR), a hub in liver cancer. Here, we show that HuR is SUMOylated in the tumor sections of patients with hepatocellular carcinoma in contrast to the surrounding tissue, as well as in human cell line and mouse models of the disease. SUMOylation of HuR promotes major cancer hallmarks, namely proliferation and invasion, whereas the absence of HuR SUMOylation results in a senescent phenotype with dysfunctional mitochondria and endoplasmic reticulum. Mechanistically, SUMOylation induces a structural rearrangement of the RNA recognition motifs that modulates HuR binding affinity to its target RNAs, further modifying the transcriptomic profile toward hepatic tumor progression. Overall, SUMOylation constitutes a mechanism of HuR regulation that could be potentially exploited as a therapeutic strategy for liver cancer.

Genomic and Immunologic Correlates in Prostate Cancer with High Expression of KLK2.

The identification of surfaceome proteins is a main goal in cancer research to design antibody-based therapeutic strategies. T cell engagers based on KLK2, a kallikrein specifically expressed in prostate cancer (PRAD), are currently in early clinical development. Using genomic information from different sources, we evaluated the immune microenvironment and genomic profile of prostate tumors with high expression of KLK2. KLK2 was specifically expressed in PRAD but it was not significant associated with Gleason score. Additionally, KLK2 expression did not associate with the presence of any immune cell population and T cell activating markers. A mild correlation between the high expression of KLK2 and the deletion of TMPRSS2 was identified. KLK2 expression associated with high levels of surface proteins linked with a detrimental response to immune checkpoint inhibitors (ICIs) including CHRNA2, FAM174B, OR51E2, TSPAN1, PTPRN2, and the non-surface protein TRPM4. However, no association of these genes with an outcome in PRAD was observed. Finally, the expression of these genes in PRAD did not associate with an outcome in PRAD and any immune populations. We describe the immunologic microenvironment on PRAD tumors with a high expression of KLK2, including a gene signature linked with an inert immune microenvironment, that predicts the response to ICIs in other tumor types. Strategies targeting KLK2 with T cell engagers or antibody-drug conjugates will define whether T cell mobilization or antigen release and stimulation of immune cell death are sufficient effects to induce clinical activity.

Impact of a Moderate CYP3A4 Inducer (Bosentan) on Lurbinectedin Pharmacokinetics and Safety in Patients with Advanced Solid Tumors: An Open-Label, Two-Way, Crossover, Phase Ib Drug-Drug Interaction Study.

This open-label, two-way, crossover, phase Ib drug-drug interaction study investigated whether the pharmacokinetics (PKs) and safety profile of lurbinectedin (LRB) are affected by co-administration of a moderate CYP3A4 inducer (bosentan, BOS) in adult patients with advanced solid tumors. Eleven patients were randomly assigned to Sequence 1 (LRB + BOS in Cycle 1 [C1] and LRB alone in Cycle 2 [C2]) or Sequence 2 (LRB alone in C1 and LRB + BOS in C2), and finally, eight patients (four per sequence) were considered evaluable for PK assessment. LRB (3.2 mg/m2, 1 h [h], intravenous) was administered alone or combined with multiple BOS administration (125 mg/12 h oral; 5.5 days). Co-administration with BOS decreased the systemic total exposure (area under the curve, AUC) of LRB by 21% for AUC0-t and 20% for AUC0-∞ and increased clearance by 25%. Co-administration with BOS did not significantly modify the unbound plasma LRB PK parameters. BOS increased the conversion of LRB to its metabolite M1, with no changes on its metabolite M4. The LRB safety profile was consistent with the toxicities previously described for this drug. No differences in terms of toxicity were found between LRB with and without BOS. In summary, the magnitude of the observed changes precludes a clinically relevant effect of BOS co-administration on LRB exposure and its safety profile.

Deciphering the role of Zn2+ -binding histidines from TIA-1 on the assembly and dynamics of stress granules.

T-cell intracellular antigen-1 (TIA-1) is a key RNA-binding protein that participates in translation regulation and RNA splicing. TIA-1 undergoes liquid-liquid phase separation as a fundamental mechanism that enables the condensation of RNA and proteins into membraneless organelles called stress granules (SGs). However, this dynamic behavior can lead to aberrant fibril formation, implicated in neurodegenerative disorders, and must be tightly regulated. In this study, we investigated the role in the cell of histidine residues His94 and His96, responsible for Zn2+ binding. Using fluorescence microscopy, we found that the specific binding site formed by these residues is critical for SG assembly. Furthermore, it also plays a role maintaining the dynamic behavior of SG-assembled TIA-1. Collectively, our findings confirm the physiological relevance of TIA-1 His94 and His96 in the Zn2+ -mediated regulatory mechanism for protection against fibril formation in SGs.

The Histone Chaperones SET/TAF-1ß and NPM1 Exhibit Conserved Functionality in Nucleosome Remodeling and Histone Eviction in a Cytochrome c-Dependent Manner.

Chromatin homeostasis mediates essential processes in eukaryotes, where histone chaperones have emerged as major regulatory factors during DNA replication, repair, and transcription. The dynamic nature of these processes, however, has severely impeded their characterization at the molecular level. Here, fluorescence optical tweezers are applied to follow histone chaperone dynamics in real time. The molecular action of SET/template-activating factor-Iß and nucleophosmin 1-representing the two most common histone chaperone folds-are examined using both nucleosomes and isolated histones. It is shown that these chaperones present binding specificity for fully dismantled nucleosomes and are able to recognize and disrupt non-native histone-DNA interactions. Furthermore, the histone eviction process and its modulation by cytochrome c are scrutinized. This approach shows that despite the different structures of these chaperones, they present conserved modes of action mediating nucleosome remodeling.

Neddylation of phosphoenolpyruvate carboxykinase 1 controls glucose metabolism.

Neddylation is a post-translational mechanism that adds a ubiquitin-like protein, namely neural precursor cell expressed developmentally downregulated protein 8 (NEDD8). Here, we show that neddylation in mouse liver is modulated by nutrient availability. Inhibition of neddylation in mouse liver reduces gluconeogenic capacity and the hyperglycemic actions of counter-regulatory hormones. Furthermore, people with type 2 diabetes display elevated hepatic neddylation levels. Mechanistically, fasting or caloric restriction of mice leads to neddylation of phosphoenolpyruvate carboxykinase 1 (PCK1) at three lysine residues-K278, K342, and K387. We find that mutating the three PCK1 lysines that are neddylated reduces their gluconeogenic activity rate. Molecular dynamics simulations show that neddylation of PCK1 could re-position two loops surrounding the catalytic center into an open configuration, rendering the catalytic center more accessible. Our study reveals that neddylation of PCK1 provides a finely tuned mechanism of controlling glucose metabolism by linking whole nutrient availability to metabolic homeostasis.

Cytochrome c lysine acetylation regulates cellular respiration and cell death in ischemic skeletal muscle.

Skeletal muscle is more resilient to ischemia-reperfusion injury than other organs. Tissue specific post-translational modifications of cytochrome c (Cytc) are involved in ischemia-reperfusion injury by regulating mitochondrial respiration and apoptosis. Here, we describe an acetylation site of Cytc, lysine 39 (K39), which was mapped in ischemic porcine skeletal muscle and removed by sirtuin5 in vitro. Using purified protein and cellular double knockout models, we show that K39 acetylation and acetylmimetic K39Q replacement increases cytochrome c oxidase (COX) activity and ROS scavenging while inhibiting apoptosis via decreased binding to Apaf-1, caspase cleavage and activity, and cardiolipin peroxidase activity. These results are discussed with X-ray crystallography structures of K39 acetylated (1.50 Å) and acetylmimetic K39Q Cytc (1.36 Å) and NMR dynamics. We propose that K39 acetylation is an adaptive response that controls electron transport chain flux, allowing skeletal muscle to meet heightened energy demand while simultaneously providing the tissue with robust resilience to ischemia-reperfusion injury.

High blood levels of brain-derived neurotrophic factor (BDNF) mRNA in early psychosis are associated with inflammatory markers.

The brain-derived neurotrophic factor (BDNF) single nucleotide polymorphism (SNP) rs6265C > T, Val66Met, affects BDNF secretion and has been related to inflammatory processes. Both the rs6265 and BDNF protein levels have been widely investigated in neuropsychiatric disorders with conflicting results. In the present study we examined BDNF mRNA expression in blood considering the SNP rs6265 and its relationship with inflammatory markers in the early stages of psychosis. The rs6265 genotype and blood BDNF mRNA levels were measured in 34 at-risk mental states (ARMS) individuals, 37 patients with first-episode psychosis (FEP) and 42 healthy controls (HCs) by quantitative PCR and reverse transcription (RT)-qPCR using validated TaqMan assays. We also obtained measures of interleukin-6 (IL6) mRNA levels, fibrinogen, neutrophil-to-lymphocyte ratio (NLR) and high-sensitivity C-reactive protein. We identified that BDNF mRNA levels were associated with the rs6265 genotype in an allele-dose-dependent manner, with low expression levels associated with the T allele (Met substitution). Thus, we controlled for the rs6265 genotype in all analyses. Blood BDNF mRNA levels differed between diagnostic groups: patients with FEP exhibited higher blood BDNF mRNA levels than ARMS individuals, and the lowest levels were observed in HC. In addition, we observed significant correlations between BDNF mRNA levels and inflammatory markers (IL6 mRNA levels and NLR), controlled by the rs6265 genotype, in ARMS and FEP groups. This exploratory study suggests that the rs6265 genotype is associated with differential blood mRNA expression of BDNF that increases with illness progression and correlated with inflammation in the early stages of psychosis.

A first-in-human study of the fibroblast activation protein-targeted, 4-1BB agonist RO7122290 in patients with advanced solid tumors.

This first-in-human study evaluated RO7122290, a bispecific fusion protein carrying a split trimeric 4-1BB (CD137) ligand and a fibroblast activation protein α (FAP) binding site that costimulates T cells for improved tumor cell killing in FAP-expressing tumors. Patients with advanced or metastatic solid tumors received escalating weekly intravenous doses of RO7122290 as a single agent (n = 65) or in combination with a 1200-milligram fixed dose of the anti-programmed death-ligand 1 (anti-PD-L1) antibody atezolizumab given every 3 weeks (n = 50), across a tested RO7122290 dose range of 5 to 2000 milligrams and 45 to 2000 milligrams, respectively. Three dose-limiting toxicities were reported, two at different RO7122290 single-agent doses (grade 3 febrile neutropenia and grade 3 cytokine release syndrome) and one for the combination (grade 3 pneumonitis). No maximum tolerated dose was identified. The pharmacokinetic profile of RO7122290 suggested nonlinearity in elimination. The observed changes in peripheral and tissue pharmacodynamic (PD) biomarkers were consistent with the postulated mechanism of action. Treatment-induced PD changes included an increase in proliferating and activated T cells in peripheral blood both in the single-agent and combination arms. Increased infiltration of intratumoral CD8+ and Ki67+CD8+ T cells was observed for both treatment regimens, accompanied by the up-regulation of T cell activation genes and gene signatures. Eleven patients experienced a complete or partial response, six of whom were confirmed to be immune checkpoint inhibitor naive. These results support further evaluation of RO7122290 in combination with atezolizumab or other immune-oncology agents for the treatment of solid tumors.

Nicotinamide N-methyltransferase (NNMT) regulates the glucocorticoid signaling pathway during the early phase of adipogenesis.

Obesity is associated with adipose tissue dysfunction through the differentiation and expansion of pre-adipocytes to adipocytes (hyperplasia) and/or increases in size of pre-existing adipocytes (hypertrophy). A cascade of transcriptional events coordinates the differentiation of pre-adipocytes into fully differentiated adipocytes; the process of adipogenesis. Although nicotinamide N-methyltransferase (NNMT) has been associated with obesity, how NNMT is regulated during adipogenesis, and the underlying regulatory mechanisms, remain undefined. In present study we used genetic and pharmacological approaches to elucidate the molecular signals driving NNMT activation and its role during adipogenesis. Firstly, we demonstrated that during the early phase of adipocyte differentiation NNMT is transactivated by CCAAT/Enhancer Binding Protein beta (CEBPB) in response to glucocorticoid (GC) induction. We found that Nnmt knockout, using CRISPR/Cas9 approach, impaired terminal adipogenesis by influencing the timing of cellular commitment and cell cycle exit during mitotic clonal expansion, as demonstrated by cell cycle analysis and RNA sequencing experiments. Biochemical and computational methods showed that a novel small molecule, called CC-410, stably binds to and highly specifically inhibits NNMT. CC-410 was, therefore, used to modulate protein activity during pre-adipocyte differentiation stages, demonstrating that, in line with the genetic approach, chemical inhibition of NNMT at the early stages of adipogenesis impairs terminal differentiation by deregulating the GC network. These congruent results conclusively demonstrate that NNMT is a key component of the GC-CEBP axis during the early stages of adipogenesis and could be a potential therapeutic target for both early-onset obesity and glucocorticoid-induced obesity.

Home Blood Pressure Self-monitoring plus Self-titration of Antihypertensive Medication for Poorly Controlled Hypertension in Primary Care: the ADAMPA Randomized Clinical Trial.

BACKGROUND: Patient empowerment through pharmacological self-management is a common strategy in some chronic diseases such as diabetes, but it is rarely used for controlling blood pressure. OBJECTIVE: This study aimed to assess self-monitoring plus self-titration of antihypertensive medication versus usual care for reducing systolic blood pressure (SBP) at 12 months in poorly controlled hypertensive patients. DESIGN: The ADAMPA study was a pragmatic, controlled, randomized, non-masked clinical trial with two parallel arms in Valencia, Spain. PARTICIPANTS: Hypertensive patients older than 40 years, with SBP over 145 mmHg and/or diastolic blood pressure (DBP) over 90 mmHg, were recruited from July 2017 to June 2018. INTERVENTION: Participants were randomized 1:1 to usual care versus an individualized, pre-arranged plan based on self-monitoring plus self-titration. MAIN MEASURE: The primary outcome was the adjusted mean difference (AMD) in SBP between groups at 12 months. KEY RESULTS: Primary outcome data were available for 312 patients (intervention n=156, control n=156) of the 366 who were initially recruited. The AMD in SBP at 12 months (main analysis) was -2.9 mmHg (95% CI, -5.9 to 0.1, p=0.061), while the AMD in DBP was -1.9 mmHg (95% CI, -3.7 to 0.0, p=0.052). The results of the subgroup analysis were consistent with these for the main outcome measures. More patients in the intervention group achieved good blood pressure control (<140/90 mmHg) at 12 months than in the control group (55.8% vs 42.3%, difference 13.5%, 95% CI, 2.5 to 24.5%, p=0.017). At 12 months, no differences were observed in behavior, quality of life, use of health services, or adverse events. CONCLUSION: Self-monitoring plus self-titration of antihypertensive medication based on an individualized pre-arranged plan used in primary care may be a promising strategy for reducing blood pressure at 12 months compared to usual care, without increasing healthcare utilization or adverse events. TRIAL REGISTRATION: EudraCT, number 2016-003986-25 (registered 17 March 2017) and clinicaltrials.gov , NCT03242785.

Corneal tissue changes following short-term soft contact lens wear of different materials.

PURPOSE: To study the effect of different soft contact lens (CL) materials during short-term wear on corneal tissue. METHODS: Twenty-two healthy participants wore both silicone hydrogel (MyDay, CooperVision) and hydrogel soft CLs (Biomedics 1 day extra, CooperVision) for 8 h per lens. In each session, Scheimpflug images were captured before and immediately after CL removal. Images were analysed using the densitometry distribution analysis, a technique from which two parameters, α (corneal transparency) and ß (corneal homogeneity), were estimated. In addition, the central corneal thickness changes after CL wear and the influence of the CL material on corneal transparency were evaluated. RESULTS: The ß parameter (homogeneity) increased by 5% after wearing both CL materials (paired t-test, p < 0.001). However, the α parameter (transparency) only increased in half of the participants. No material was found to be more determinant in causing the corneal densitometry changes. Statistically significant but not clinically relevant changes in corneal thickness were observed. CONCLUSIONS: Biomarkers of corneal tissue integrity (α and ß) were affected by short-term soft contact lens wear. The observed changes in corneal transparency and homogeneity were not clinically relevant but support the importance of participant-material biocompatibility.

Distal Endarterectomy Combined With Endovascular Proximal Treatment: The Hybrid DEEP Retrograde Technique for High-Complexity Infrainguinal Disease.

Purpose: We present a hybrid technique for the treatment of chronic limb-threatening ischemia (CLTI) due to complex, multilevel infrainguinal disease. It consists of an open distal endarterectomy combined with endovascular proximal treatment (the DEEP technique). Materials and Methods: This was a prospective cohort study. Thirty-three limbs (30 patients) were treated. Main inclusion criteria were absence of significant disease in femoral bifurcation associated with a complex infrainguinal pattern. This approach was specially considered in absence of suitable vein for bypass, obesity, hostile groin, and overall high surgical risk. Results: Mean age was 72.8 ± 10 years (ranging 50-93). Most cases presented with severe limb threatening onset (90.9% Rutherford >4 and 81.8% WIfi >3) due to high-complexity infrainguinal disease pattern (Global Limb Anatomic Staging System [GLASS] stage III) in 31/33 (93.9%), chronic total occlusions (CTOs) in 24/33 (72.7%), and severe calcification (Peripheral Arterial Calcium Scoring System [PACSS] grade 4) in 22/33 (66.6%). Mean lesion length was 228.2 mm ± 83 (ranging 40-340 mm). In all procedures, a covered-stent (25 cm length Viabahn) was implanted in a retrograde fashion as the endovascular component. Effective revascularization was achieved in all cases, showing significant clinical and hemodynamic improvement (median pre- and postprocedure ankle-brachial index [ABI]: 0.3 and 0.9, respectively). Results at 12 months follow-up were as follows: 93.9% limb salvage ratio, 75.7% primary patency, 84.6% assisted primary patency, and 90.9% secondary patency. Major adverse limb events (MALE) and cardiovascular events (MACE) occurred in 8/33 (24.2%) and 2/33 (6%), respectively. Mean length of postoperative stay was 7.5 ± 6.92 days (3-27). Conclusion: This less invasive hybrid technique has promising short-term results for limb salvage and it is worth to be included in vascular armamentarium for CLTI revascularization in selected patients.

Emoji-SP, the Spanish emoji database: Visual complexity, familiarity, frequency of use, clarity, and emotional valence and arousal norms for 1031 emojis.

This article presents subjective norms for 1031 emojis in six dimensions: visual complexity, familiarity, frequency of use, clarity, emotional valence, and emotional arousal. This is the largest normative study conducted so far that relies on subjective ratings. Unlike the few existing normative studies, which mainly comprise face emojis, here we present a wide range of emoji categories. We also examine the correlations between the dimensions assessed. Our results show that, in terms of their affective properties, emojis are analogous to other stimuli, such as words, showing the expected U-shaped relationship between valence and arousal. The relationship between affective properties and other dimensions (e.g., between valence and familiarity) is also similar to the relationship observed in words, in the sense that positively valenced emojis are more familiar than negative ones. These findings suggest that emojis are suitable stimuli for studying affective processing. Emoji-SP will be highly valuable for researchers of various fields interested in emojis, including computer science, communication, linguistics, and psychology. The full set of norms is available at: https://osf.io/dtfjv/ .

GWAS of genetic factors affecting white blood cell morphological parameters in Sardinians uncovers influence of chromosome 11 innate immunity gene cluster on eosinophil morphology.

Few genome-wide association studies (GWAS) analyzing genetic regulation of morphological traits of white blood cells have been reported. We carried out a GWAS of 12 morphological traits in 869 individuals from the general population of Sardinia, Italy. These traits, included measures of cell volume, conductivity and light scatter in four white-cell populations (eosinophils, lymphocytes, monocytes, neutrophils). This analysis yielded seven statistically significant signals, four of which were novel (four novel, PRG2, P2RX3, two of CDK6). Five signals were replicated in the independent INTERVAL cohort of 11 822 individuals. The most interesting signal with large effect size on eosinophil scatter (P-value = 8.33 x 10-32, beta = -1.651, se = 0.1351) falls within the innate immunity cluster on chromosome 11, and is located in the PRG2 gene. Computational analyses revealed that a rare, Sardinian-specific PRG2:p.Ser148Pro mutation modifies PRG2 amino acid contacts and protein dynamics in a manner that could possibly explain the changes observed in eosinophil morphology. Our discoveries shed light on genetics of morphological traits. For the first time, we describe such large effect size on eosinophils morphology that is relatively frequent in Sardinian population.