A Critical Review of Short Antimicrobial Peptides from Scorpion Venoms, Their Physicochemical Attributes, and Potential for the Development of New Drugs.

Scorpion venoms have proven to be excellent sources of antimicrobial agents. However, although many of them have been functionally characterized, they remain underutilized as pharmacological agents, despite their evident therapeutic potential. In this review, we discuss the physicochemical properties of short scorpion venom antimicrobial peptides (ssAMPs). Being generally short (13-25 aa) and amidated, their proven antimicrobial activity is generally explained by parameters such as their net charge, the hydrophobic moment, or the degree of helicity. However, for a complete understanding of their biological activities, also considering the properties of the target membranes is of great relevance. Here, with an extensive analysis of the physicochemical, structural, and thermodynamic parameters associated with these biomolecules, we propose a theoretical framework for the rational design of new antimicrobial drugs. Through a comparison of these physicochemical properties with the bioactivity of ssAMPs in pathogenic bacteria such as Staphylococcus aureus or Acinetobacter baumannii, it is evident that in addition to the net charge, the hydrophobic moment, electrostatic energy, or intrinsic flexibility are determining parameters to understand their performance. Although the correlation between these parameters is very complex, the consensus of our analysis suggests that there is a delicate balance between them and that modifying one affects the rest. Understanding the contribution of lipid composition to their bioactivities is also underestimated, which suggests that for each peptide, there is a physiological context to consider for the rational design of new drugs.

Multilevel analysis of positive emotional induction: Which is the role of gender and valence on cognitive control processes?

How emotions are processed affects people's cognition and behavior. One of the most used measures to study the physiological component of emotions is heart rate (HR), where greater HR variation (range) implies greater emotional processing. Several investigations established the importance of gender modulation of these processes due to the different cultural treatment given to emotions among genders. However, very heterogeneous results are reported today, and few studies incorporated these parameters when investigating emotion modulation of cognitive processes according to individual factors. The present work consists of two studies. In a pilot study, 97 young adults, through the Self-Assessment Manikin (SAM), ranged the valence and arousal to select two positive and neutral videos. The second study analyses the role of gender and valence in the variation of subjective (SAM) and physiological (HR) indicators of emotional processing associated with performance in two cognitive tasks (Stroop and Tower of London) under two different emotional conditions. Participants were 60 adults, who were randomly assigned to positive or neutral video visualization, and their HR was registered. There was a tendency for women to have higher HR during positive videos than in neutral. While the subjective reports indicated variances in the appraisal of the videos, the heart rate did not exhibit differences across the experimental conditions. Few studies integrate emotional and cognitive components, and include physiological and subjective measures of emotional processing. These findings illustrate the importance of including various measures of emotional and cognitive processing.

Asian Cohort for Alzheimer's Disease (ACAD) pilot study on genetic and non-genetic risk factors for Alzheimer's disease among Asian Americans and Canadians.

INTRODUCTION: Clinical research in Alzheimer's disease (AD) lacks cohort diversity despite being a global health crisis. The Asian Cohort for Alzheimer's Disease (ACAD) was formed to address underrepresentation of Asians in research, and limited understanding of how genetics and non-genetic/lifestyle factors impact this multi-ethnic population. METHODS: The ACAD started fully recruiting in October 2021 with one central coordination site, eight recruitment sites, and two analysis sites. We developed a comprehensive study protocol for outreach and recruitment, an extensive data collection packet, and a centralized data management system, in English, Chinese, Korean, and Vietnamese. RESULTS: ACAD has recruited 606 participants with an additional 900 expressing interest in enrollment since program inception. DISCUSSION: ACAD's traction indicates the feasibility of recruiting Asians for clinical research to enhance understanding of AD risk factors. ACAD will recruit > 5000 participants to identify genetic and non-genetic/lifestyle AD risk factors, establish blood biomarker levels for AD diagnosis, and facilitate clinical trial readiness. HIGHLIGHTS: The Asian Cohort for Alzheimer's Disease (ACAD) promotes awareness of under-investment in clinical research for Asians. We are recruiting Asian Americans and Canadians for novel insights into Alzheimer's disease. We describe culturally appropriate recruitment strategies and data collection protocol. ACAD addresses challenges of recruitment from heterogeneous Asian subcommunities. We aim to implement a successful recruitment program that enrolls across three Asian subcommunities.

Overexpression of Fut 2, 4, and 8, and nuclear localization of Fut 4 in ovarian cancer cell lines induced by ascitic fluids from epithelial ovarian cancer patients.

Fucosyltransferases (Fut) regulate the fucosylation process associated with tumorogenesis in different cancer types. Ascitic fluid (AF) from patients diagnosed with advanced stage of epithelial ovarian cancer (EOC) is considered as a dynamic tumor microenvironment associated with poor prognosis. Previous studies from our laboratory showed increased fucosylation in SKOV-3 and OVCAR-3, cancer-derived cell lines, when these cells were incubated with AFs derived from patients diagnosed with EOC. In the present work we studied three fucosyltransferases (Fut 2, Fut 4, and Fut 8) in SKOV-3, OVCAR-3 and CAOV-3 cell lines in combination with five different AFs from patients diagnosed with this disease, confirming that all tested AFs increased fucosylation. Then, we demonstrate that mRNAs of these three enzymes were overexpressed in the three cell lines under treatment with AFs. SKOV-3 showed the higher overexpression of Fut 2, Fut 4, and Fut 8 in comparison with the control condition. We further confirmed, in the SKOV-3 cell line, by endpoint PCR, WB, and confocal microscopy, that the three enzymes were overexpressed, being Fut 4 the most overexpressed enzyme compared to Fut 2 and Fut 8. These enzymes were concentrated in vesicular structures with a homogeneous distribution pattern throughout the cytoplasm. Moreover, we found that among the three enzymes, only Fut 4 was located inside the nuclei. The nuclear location of Fut 4 was confirmed for the three cell lines. These results allow to propose Fut 2, Fut 4, and Fut 8 as potential targets for EOC treatment or as diagnostic tools for this disease.

Cognitive and emotional processing in tasks with emotional valence: Analysis of age and gender role on child development variations.

Cognitive control consists of high-level cognitive processes regulating thoughts and actions during goal-directed behavior and problem-solving. This study analyzes the performance of 4- to 8-year-old children in Stroop-like and ToL tasks using stimuli with different emotional valence. Significant differences were found in the performance in the congruent block of the Stroop-like task, where 5-year-old children presented a higher performance in the neutral condition. Also, a significant difference was only found in the incongruent block (with higher demand for inhibition), which indicates that girls performed better than boys in both task conditions. Variations in the Stroop-like task performance were found in preschoolers but not in older children, especially in girls than in boys. Specifically, these variations were found between age groups with at least two years of difference. No statistically significant differences were found in performance nor planning time in ToL between the age and gender groups in any of the task conditions. The findings highlight the need to analyze the interaction between cognitive and emotional processing, individual differences, and task demands.

Extracellular Vesicles Secreted by Acanthamoeba culbertsoni Have COX and Proteolytic Activity and Induce Hemolysis.

Several species of Acanthamoeba genus are potential pathogens and etiological agents of several diseases. The pathogenic mechanisms carried out by these amoebae in different target tissues have been documented, evidencing the relevant role of contact-dependent mechanisms. With the purpose of describing the pathogenic processes carried out by these protozoans more precisely, we considered it important to determine the emission of extracellular vesicles (EVs) as part of the contact-independent pathogenicity mechanisms of A. culbertsoni, a highly pathogenic strain. Through transmission electronic microscopy (TEM) and nanoparticle tracking analysis (NTA), EVs were characterized. EVs showed lipid membrane and a size between 60 and 855 nm. The secretion of large vesicles was corroborated by confocal and TEM microscopy. The SDS-PAGE of EVs showed proteins of 45 to 200 kDa. Antigenic recognition was determined by Western Blot, and the internalization of EVs by trophozoites was observed through Dil-labeled EVs. In addition, some EVs biological characteristics were determined, such as proteolytic, hemolytic and COX activity. Furthermore, we highlighted the presence of leishmanolysin in trophozites and EVs. These results suggest that EVs are part of a contact-independent mechanism, which, together with contact-dependent ones, allow for a better understanding of the pathogenicity carried out by Acanthamoeba culbertsoni.

Generation of high oleic acid sunflower lines using gamma radiation mutagenesis and high-throughput fatty acid profiling.

Sunflower (Helianthus annuus L.) is the second most important oil seed crop in Europe. The seeds are used as confection seeds and, more importantly, to generate an edible vegetable oil, which in normal varieties is rich in the polyunsaturated fatty acid linoleic acid. Linoleic acid is biosynthesized from oleic acid through activity of the oleate desaturase FATTY ACID DESATURASE 2 (FAD2), which in seeds is encoded by FAD2-1, a gene that's present in single copy in sunflowers. Defective FAD2-1 expression enriches oleic acid, yielding the high oleic (HO) acid trait, which is of great interest in oil seed crops, since HO oil bears benefits for both food and non-food applications. Chemical mutagenesis has previously been used to generate sunflower mutants with reduced FAD2-1 expression and here it was aimed to produce further genetic material in which FAD2-1 activity is lost and the HO trait is stably expressed. For this purpose, a sunflower mutant population was created using gamma irradiation and screened for fad2-1 mutants with a newly developed HPLC-based fatty-acid profiling system that's suitable for high-throughput analyses. With this approach fad2-1 knock-out mutants could be isolated, which stably hyper-accumulate oleic acid in concentrations of 85-90% of the total fatty acid pool. The genetic nature of these new sunflower lines was characterized and will facilitate marker development, for the rapid introgression of the trait into elite sunflower breeding material.

Frequency of Helicobacter pylori Infection in Patients Requiring GI Endoscopy in Seven Units in Three Antioquia Subregions

Aim: To determine the frequency of Helicobacter pylori and sociodemographic factors, life habits, and personal and family history of gastroduodenal diseases in patients who required and were taken to GI endoscopy (symptomatic or by screening) in seven endoscopy units in three Antioquia subregions. Materials and methods: A cross-sectional study conducted between 2016 and 2018 included 272 participants. Sociodemographic factors, life habits, and personal and family history were related to H. pylori infection. Descriptive statistics and bivariate analysis were performed to establish the association between the variables, and multivariate analysis (binomial regression) was used to adjust the prevalence ratios of the associated factors. A p-value ≤ 0.05 was considered statistically significant. Results: The frequency of H. pylori infection was 55.9%, with differences by subregion (Valle de Aburrá metropolitan area: 54.3%, Oriente: 64%, and Urabá: 79.2%). Factors associated with H. pylori infection were male sex (adjusted prevalence ratio [APR] = 1.26; 95% confidence interval [CI] = 1.04-1.52), age 18-55 years (APR = 1.62; CI 95% = 1.22-2.16), absence of drinking water (APR = 1.40; 95% CI: 1.15-1.72) and educational level below university (APR = 1.73; 95% CI% = 1.26-2.38). Conclusion: The frequency of H. pylori was higher than in other recent studies because different diagnostic tests were used for its detection, and differences were found in the frequency of infection by region, which is explained by the heterogeneity in the populations analyzed. This study suggests the need to improve the population's living conditions to reduce H. pylori and direct measures of primary prevention of the infection, especially in family groups, men, individuals between 18 and 55 years old without drinking water, and with an educational level lower than university.

Objetivo: determinar la frecuencia de Helicobacter pylori y la presencia de factores sociodemográficos, hábitos de vida y antecedentes personales y familiares de enfermedades gastroduodenales en pacientes que requirieron y fueron llevados a endoscopia digestiva (sintomáticos o por tamización) en siete unidades de endoscopia de tres subregiones de Antioquia. Materiales y métodos: estudio transversal realizado entre 2016 y 2018 que incluyó a 272 participantes. Los factores sociodemográficos, hábitos de vida, antecedentes personales y familiares se relacionaron con la infección por H. pylori. Se realizó estadística descriptiva y análisis bivariado para establecer la asociación entre las variables y el análisis multivariado (regresión binomial) para ajustar las razones de prevalencia de los factores asociados. Un valor p ≤ 0,05 se consideró estadísticamente significativo. Resultados: la frecuencia de infección por H. pylori fue de 55,9%, con diferencias por subregión (área metropolitana del Valle de Aburrá: 54,3%, oriente: 64% y Urabá: 79,2%). Los factores asociados a la infección por H. pylori fueron sexo masculino (razón de prevalencia ajustada [RPA] = 1,26; intervalo de confianza [IC] del 95% = 1,04-1,52), edad de 18-55 años (RPA = 1,62; IC 95% = 1,22-2,16), ausencia de agua potable (RPA = 1,40; IC 95%: 1,15-1,72) y nivel educativo inferior al universitario (RPA = 1,73; IC 95% = 1,26-2,38). Conclusión: la frecuencia de H. pylori fue mayor que en otros estudios recientes porque se emplearon diferentes pruebas diagnósticas para su detección y se demostraron diferencias en la frecuencia de la infección por región, lo cual se explica por la heterogeneidad en las poblaciones analizadas. Este estudio sugiere la necesidad de mejorar las condiciones de vida de la población para reducir la infección por H. pylori y dirigir medidas de prevención primaria de la infección especialmente en los grupos familiares, en hombres, individuos entre 18 y 55 años, sin agua potable y con un nivel educativo inferior al universitario.

Social Motivation as a Moderator of the Relationship Between Problematic Internet Use and Alcohol Use Among Adolescents in Mexico.

BACKGROUND: Prior research shows a link between alcohol use and problematic Internet use among adolescents. This relationship likely indicates a vulnerability to addiction; however, little is known about factors that may increase this vulnerability. One potential factor is social motivation. Adolescents often engage in Internet use and alcohol use as a way of connecting socially. This study examines the moderating effects of social motivation for Internet use on the relationship between problematic Internet use and alcohol use among adolescents. METHODS: A cross-sectional survey was administered to 582 adolescents selected randomly from one middle school and one high school in Nuevo Laredo, Tamaulipas, Mexico. Participants answered questions related to demographics/background (including reasons for Internet use), problematic Internet use, and alcohol use. Hierarchical regression modeling examined the moderating effects of social Internet use on problematic Internet use and alcohol use, controlling for age and gender. RESULTS: Social Internet use and problematic Internet use accounted for a significant amount of variance in alcohol use (R2 = .126, F(4, 575) = 20.77, p < .001). When the interaction term was entered, social Internet use was found to moderate the relationship between problematic Internet use and alcohol use (ß = .525, t = 3.293, p = .001), and the direct effects of social Internet use (ß = -.062, t = -0.663, p = .507) and problematic Internet use (ß = -.129, t = -1.053, p = .293) were no longer significant. CONCLUSION: This study highlights the role that social connections may play in contributing to problematic Internet use and alcohol use among adolescents. Interventions aimed at preventing problematic and addictive behaviors among adolescents should address the role of social motivations.

A monoclonal antibody against a Leishmania mexicana COX-like enzymatic activity also recognizes similar proteins in different protozoa of clinical importance.

In Leishmania mexicana, the protease gp63 has been documented as the protein responsible for cyclooxygenase (COX) activity. The present work aimed to obtain a monoclonal antibody capable of recognizing this protein without blocking the COX-like enzymatic activity. The antibody produced by the selected hybridoma was named D12 mAb. The antigen recognized by the D12 mAb was characterized by the determination of COX activity associated with immune complexes in the presence of exogenous arachidonic acid (AA) using the commercial Activity Assay Abcam kit. LSM-SMS analysis validated the identity of the antigen associated with the D12 mAb as the L. mexicana protease gp63. Confocal microscopy assays with the D12 mAb detected, by cross-recognition, similar proteins in other protozoan parasites. COX-like molecules are located in vesicular structures, homogeneously distributed throughout the cytoplasm in amastigotes (intracellular infectious phase) and promastigotes of L. mexicana, and trophozoites of Entamoeba histolytica, Acanthamoeba castellanii, and Naegleria fowleri. However, in Giardia duodenalis trophozoites, the distribution of the COX-like molecule was also in perinuclear areas. In comparison, in Trypanosoma cruzi trypomastigotes, the distribution was mainly observed in the plasma membrane. Structural analyses of COX-2-like antigens revealed continuous and discontinuous epitopes for B cells, which could be relevant in the cross-reaction of D12 mAb with the analyzed parasites. These results indicate that the D12 mAb against the L. mexicana gp63 also recognizes a COX-like molecule in several protozoan parasites, suggesting that this D12 mAb could potentially be used in combined therapies against infectious diseases.

Illusory Responses across the Lewy Body Disease Spectrum.

OBJECTIVE: This study was undertaken to study pareidolias, or perceived meaningful objects in a meaningless stimulus, in patients across the Lewy body (LB) disease spectrum, where most do not report hallucinations or delusions. METHODS: We studied illusory responses on the Noise Pareidolia Task in 300 participants (38 cognitively impaired LB, 65 cognitively unimpaired LB, 51 Alzheimer disease spectrum [AD-s], 146 controls). Pairwise between-group comparisons examined how diagnosis impacts the number of illusory responses. Ordinal regression analysis compared the number of illusory responses across diagnosis groups, adjusting for age, sex, and education. Analyses were repeated after removing participants with reported hallucinations or delusions. RESULTS: Cognitively impaired LB participants were 12.3, 4.9, and 4.6 times more likely than control, cognitively unimpaired LB, and AD-s participants, respectively, to endorse illusory responses. After adjusting for age, sex, and education, the probability of endorsing 1 or more illusory responses was 61% in the cognitively impaired LB group, compared to 26% in AD-s, 25% in cognitively unimpaired LB, and 12% in control participants. All results were similar after repeated analysis only in participants without hallucinations or delusions. In LB without hallucinations or delusions, 52% with mild cognitive impairment and 66.7% with dementia endorsed at least 1 illusory response. INTERPRETATION: We found illusory responses are common in cognitively impaired LB patients, including those without any reported psychosis. Our data suggest that, prior to the onset of hallucinations and delusions, the Noise Pareidolia Task can easily be used to screen for unobtrusive pareidolias in all LB patients. ANN NEUROL 2023;93:702-714.

Performance of a fully-automated Lumipulse plasma phospho-tau181 assay for Alzheimer's disease.

BACKGROUND: The recent promise of disease-modifying therapies for Alzheimer's disease (AD) has reinforced the need for accurate biomarkers for early disease detection, diagnosis and treatment monitoring. Advances in the development of novel blood-based biomarkers for AD have revealed that plasma levels of tau phosphorylated at various residues are specific and sensitive to AD dementia. However, the currently available tests have shortcomings in access, throughput, and scalability that limit widespread implementation. METHODS: We evaluated the diagnostic and prognostic performance of a high-throughput and fully-automated Lumipulse plasma p-tau181 assay for the detection of AD. Plasma from older clinically unimpaired individuals (CU, n = 463) and patients with mild cognitive impairment (MCI, n = 107) or AD dementia (n = 78) were obtained from the longitudinal Stanford University Alzheimer's Disease Research Center (ADRC) and the Stanford Aging and Memory Study (SAMS) cohorts. We evaluated the discriminative accuracy of plasma p-tau181 for clinical AD diagnosis, association with amyloid ß peptides and p-tau181 concentrations in CSF, association with amyloid positron emission tomography (PET), and ability to predict longitudinal cognitive and functional change. RESULTS: The assay showed robust performance in differentiating AD from control participants (AUC 0.959, CI: 0.912 to 0.990), and was strongly associated with CSF p-tau181, CSF Aß42/Aß40 ratio, and amyloid-PET global SUVRs. Associations between plasma p-tau181 with CSF biomarkers were significant when examined separately in Aß+ and Aß- groups. Plasma p-tau181 significantly increased over time in CU and AD diagnostic groups. After controlling for clinical diagnosis, age, sex, and education, baseline plasma p-tau181 predicted change in MoCA overall and change in CDR Sum of Boxes in the AD group over follow-up of up to 5 years. CONCLUSIONS: This fully-automated and available blood-based biomarker assay therefore may be useful for early detection, diagnosis, prognosis, and treatment monitoring of AD.

Alpha-terthienyl increases filamentous actin of Entamoeba histolytica.

This study aimed to know if alpha terthienyl (α-T) affects E. histolytica viability and to analyze its effect on the actin cytoskeleton. Trophozoites of E. histolytica HM1-IMSS were treated with α-T, then, cell viability and morphology were evaluated using tetrazolium salts and scanning electron microscopy, respectively; while actin filaments (F-actin) were stained with rhodamine-phalloidin, observed by confocal microscopy and quantified by fluorometry. Data showed that α-T inhibited cell viability of trophozoites (IC50, 19.43 µg / mL), affected the cell morphology, and increased the F-actin in a dose-dependent manner. Production of reactive oxygen species and RhoA-GTP levels remained normal in α-T-treated amebas. Two inhibitors that affect the organization of the trophozoites cytoskeleton, one that interacts directly with actin, Cytochalasin D (CD), and one that affects the Rho signaling pathway by inhibiting the downstream effector Rock, Y27632, were tested. Y27632 did not affect the increase of polymerized actin observed with α-T, this compound partially ameliorates the potent disrupting effects of CD on actin filaments. Docking results suggest that α-T could be an antagonist of CD for the same interaction zone in actin, however, more studies are needed to define the action mechanism of this compound.

Report of Adverse Effects Following Population-Wide COVID-19 Vaccination: A Comparative Study between Six Different Vaccines in Baja-California, Mexico.

After emergency authorization, different COVID-19 vaccines were administered across Mexico in 2021, including mRNA, viral vector, and inactivated platform vaccines. In the state of Baja-California, 3,516,394 doses were administered, and 2285 adverse events (AE) were registered in the epidemiological surveillance system in 2021. Incidence rates per 100,000 doses were calculated for total, mild (local and systemic), and severe AE for each vaccine. Symptoms were compared between mRNA and viral vector/inactivated virus vaccines. The overall incidence rate for all AE was 64.98 per 100,000 administered doses; 79.05 AE per 100,000 doses for mRNA vaccines; and 56.9 AE per 100,000 doses for viral vector/inactivated virus vaccine platforms. AE were at least five times higher in recipients of the AstraZeneca vaccine from the Serum Institute of India (AZ from SII). Local injection site symptoms were more common in mRNA vaccines while systemic were more prevalent in viral vector/inactivated virus vaccines. Severe AE rates were similar across all administered vaccines (0.72-1.61 AE per 100,000 doses), except for AZ from SII, which documented 12.6 AE per 100,000 doses. Among 32 hospitalized severe cases, 28 (87.5%) were discharged. Guillain-Barré Syndrome was the most common serious AE reported (n = 7). Adverse events rates differed among vaccine manufacturers but were consistent with clinical trials and population-based reports in the literature.

Alcohol, age at first sexual intercourse and number of sexual partners in young Mexican women.

AIM: To identify the relationship between use of alcohol, number of sexual partners and age of sexual initiation. METHOD: Descriptive-correlational study. A random sample of 319 young women (age 18-25) from Nuevo Laredo, Mexico was recruited. A sociodemographic data sheet and the AUDIT questionnaire were used. Non-parametric Spearman's rank correlation coefficient and Kruskal-Wallis H test were selected. RESULTS: On average the participants were 20.70 years old (±2.1), had 1.86 sexual partners (±1.27), started drinking alcohol at the age of 16.82 (±1.79), and their first sexual intercourse was at the age of 17.38 (±1.65). There was a decrease in the age of onset of alcohol use (H=16.646, p<.001) and the age at first sexual intercourse (H=26.749, p<.001) on the lower their current age. The overall AUDIT score negatively correlated with the age of the participants on their first sexual intercourse (rs=-.168, p<.001) and positively correlated with the number of sexual partners (rs=.243, p<.001). The aforementioned correlations were more intense among the younger participants (18- and 19-year olds; p<.01). CONCLUSIONS: There was an association between higher use of alcohol, early age of sexual initiation and number of sexual partners. Nursing professionals may address such variables simultaneously through preventive strategies directed specifically at young women.

Subtle anomaly detection: Application to brain MRI analysis of de novo Parkinsonian patients.

With the advent of recent deep learning techniques, computerized methods for automatic lesion segmentation have reached performances comparable to those of medical practitioners. However, little attention has been paid to the detection of subtle physiological changes caused by evolutive pathologies, such as neurodegenerative diseases. In this work, we leverage deep learning models to detect anomalies in brain diffusion tensor imaging (DTI) parameter maps of recently diagnosed and untreated (de novo) patients with Parkinson's disease (PD). For this purpose, we trained auto-encoders on parameter maps of healthy controls (n = 56) and tested them on those of de novo PD patients (n = 129). We considered large reconstruction errors between the original and reconstructed images to be anomalies that, when quantified, allow discerning between de novo PD patients and healthy controls. The most discriminating brain macro-region was found to be the white matter with a ROC-AUC 68.3 (IQR 5.4) and the best subcortical structure, the GPi (ROC-AUC 62.6 IQR 5.4). Our results indicate that our deep learning-based model can detect potentially pathological regions in de novo PD patients, without requiring any expert delineation. This may enable extracting neuroimaging biomarkers of PD in the future, but further testing on larger cohorts is needed. Such models can be seamlessly extended with additional parameter maps and applied to study the physio-pathology of other neurological diseases.

PHD finger protein 20-like protein 1 (PHF20L1) in ovarian cancer: from its overexpression in tissue to its upregulation by the ascites microenvironment.

BACKGROUND: Ovarian cancer is the most aggressive gynecological malignancy. Transcriptional regulators impact the tumor phenotype and, consequently, clinical progression and response to therapy. PHD finger protein 20-like protein 1 (PHF20L1) is a transcriptional regulator with several isoforms, and studies on its role in ovarian cancer are limited. We previously reported that PHF20L1 is expressed as a fucosylated protein in SKOV-3 cells stimulated with ascites from patients with ovarian cancer. METHODS: We decided to analyze the expression of PHF20L1 in ovarian cancer tissues, determine whether a correlation exists between PHF20L1 expression and patient clinical data, and analyze whether ascites can modulate the different isoforms of this protein. Ovarian cancer biopsies from 29 different patients were analyzed by immunohistochemistry, and the expression of the isoforms in ovarian cancer cells with or without exposure to the tumor microenvironment, i.e., the ascitic fluid, was determined by western blotting assays. RESULTS: Immunohistochemical results suggest that PHF20L1 exhibits increased expression in sections of tumor tissues from patients with ovarian cancer and that higher PHF20L1 expression correlates with shorter progression-free survival and shorter overall survival. Furthermore, western blotting assays determined that protein isoforms are differentially regulated in SKOV-3 cells in response to stimulation with ascites from patients with epithelial ovarian cancer. CONCLUSION: The results suggest that PHF20L1 could play a relevant role in ovarian cancer given that higher PHF20L1 protein expression is associated with lower overall patient survival.

User Experience, Engagement, and Popularity in Mental Health Apps: Secondary Analysis of App Analytics and Expert App Reviews.

BACKGROUND: User experience and engagement are critical elements of mental health apps' abilities to support users. However, work examining the relationships among user experience, engagement, and popularity has been limited. Understanding how user experience relates to engagement with and popularity of mental health apps can demonstrate the relationship between subjective and objective measures of app use. In turn, this may inform efforts to develop more effective and appealing mental health apps and ensure that they reach wide audiences. OBJECTIVE: We aimed to examine the relationship among subjective measures of user experience, objective measures of popularity, and engagement in mental health apps. METHODS: We conducted a preregistered secondary data analysis in a sample of 56 mental health apps. To measure user experience, we used expert ratings on the Mobile App Rating Scale (MARS) and consumer ratings from the Apple App Store and Google Play. To measure engagement, we acquired estimates of monthly active users (MAU) and user retention. To measure app popularity, we used download count, total app revenue, and MAU again. RESULTS: MARS total score was moderately positively correlated with app-level revenue (Kendall rank [T]=0.30, P=.002), MAU (T=0.39, P<.001), and downloads (T=0.41, P<.001). However, the MARS total score and each of its subscales (Engagement, Functionality, Aesthetics, and Information) showed extremely small correlations with user retention 1, 7, and 30 days after downloading. Furthermore, the total MARS score only correlated with app store rating at T=0.12, which, at P=.20, did not meet our threshold for significance. CONCLUSIONS: More popular mental health apps receive better ratings of user experience than less popular ones. However, user experience does not predict sustained engagement with mental health apps. Thus, mental health app developers and evaluators need to better understand user experience and engagement, as well as to define sustained engagement, what leads to it, and how to create products that achieve it. This understanding might be supported by better collaboration between industry and academic teams to advance a science of engagement.

Individual Differences in Emotional Appraisal during Development: Analysis of the Role of Age, Gender, and Appraisal Accuracy.

Emotional appraisal is the process by which different responses are generated from subjective assessments of different stimuli. Children and adults can react differently to the same stimulus. Emotional appraisal is crucial to define emotional processing and its consequent response rather than the properties of the stimulus itself. Age and gender modulate emotional appraisal during development. This study analyzed emotional appraisal in children aged 4 to 8-years-old. The children's emotional appraisal responses and the appraisal accuracy to images with positive, negative, and neutral valence be compared between the different age groups, and according to the gender of the participants. About the appraisal accuracy, the comparisons indicated significant differences for positive and negative images according to the age of the participants, with no differences in the appraisal accuracy of neutral images. Differences in appraisal accuracy for negative images were observed between the 4-years-old group compared to the 7- and 8-years-old group, as well as in 5-years-old participants compared to 7-years-old. Significant differences were found for the positive and negative images between girls and boys, but no differences were found for neutral images. Girls had more appraisals accuracy for positive and negative images. This work highlights the importance of analyzing individual differences associated with emotional processing at different stages of development. This interrogates research findings in which emotional appraisal is carried out considering the valence assigned by adults and highlights the need for a methodological approach that includes individual differences in the appraisal of stimuli used during development.

Bacillus cereus MH778713 elicits tomato plant protection against Fusarium oxysporum.

AIM: The genus Fusarium comprises plant pathogenic species with agricultural relevance. Fusarium oxysporum causes tomato wilt disease with significant production losses. The use of agrochemicals to control the Fusarium wilt of tomato is not environmentally friendly. Bacillus species, as biocontrol agents, provide a safe and sustainable means to control Fusarium-induced plant diseases. In this study, the ability of Bacillus cereus MH778713, a strain isolated from root nodules of Prosopis laevigata, to protect tomato plants against Fusarium wilt was evaluated. METHODS AND RESULTS: Bacillus cereus MH778713 and its volatiles inhibited the radial growth of F. oxysporum and stimulated tomato seedling growth in in vitro and in vivo tests. When tomato plants growing in the greenhouse were inoculated with B. cereus MH778713, the percentage of wilted plants decreased from 96% to 12%, indicating an effective crop protection against Fusarium wilt. Among the metabolites produced by B. cereus MH778713, hentriacontane and 2,4-di-tert-butylphenol promoted tomato seedling growth and showed antifungal activity against the target pathogen. CONCLUSION: The inoculation of B. cereus MH778713 on tomato seedlings helped plants to manage Fusarium wilt, suggesting the potential of B. cereus MH778713 as a biocontrol agent. SIGNIFICANCE AND IMPACT OF THE STUDY: These results complement our previous studies on chromium tolerance and bioremediation traits of B. cereus MH778713 by highlighting the potential of this metal-resistant micro-organism to boost crop growth and disease resistance.