Category: Nevin Manimala

Proc Natl Acad Sci U S A. 2024 Mar 19;121(12):e2317284121. doi: 10.1073/pnas.2317284121. Epub 2024 Mar 13.

ABSTRACT

Since its emergence in late 2019, SARS-CoV-2 has diversified into a large number of lineages and caused multiple waves of infection globally. Novel lineages have the potential to spread rapidly and internationally if they have higher intrinsic transmissibility and/or can evade host immune responses, as has been seen with the Alpha, Delta, and Omicron variants of concern. They can also cause increased mortality and morbidity if they have increased virulence, as was seen for Alpha and Delta. Phylogenetic methods provide the “gold standard” for representing the global diversity of SARS-CoV-2 and to identify newly emerging lineages. However, these methods are computationally expensive, struggle when datasets get too large, and require manual curation to designate new lineages. These challenges provide a motivation to develop complementary methods that can incorporate all of the genetic data available without down-sampling to extract meaningful information rapidly and with minimal curation. In this paper, we demonstrate the utility of using algorithmic approaches based on word-statistics to represent whole sequences, bringing speed, scalability, and interpretability to the construction of genetic topologies. While not serving as a substitute for current phylogenetic analyses, the proposed methods can be used as a complementary, and fully automatable, approach to identify and confirm new emerging variants.

PMID:38478692 | DOI:10.1073/pnas.2317284121

Sci Adv. 2024 Mar 15;10(11):eadk0785. doi: 10.1126/sciadv.adk0785. Epub 2024 Mar 13.

ABSTRACT

Cell migration is a critical contributor to metastasis. Cytokine production and its role in cancer cell migration have been traditionally associated with immune cells. We find that the histone methyltransferase Mixed-Lineage Leukemia 1 (MLL1) controls 3D cell migration via cytokines, IL-6, IL-8, and TGF-β1, secreted by the cancer cells themselves. MLL1, with its scaffold protein Menin, controls actin filament assembly via the IL-6/8/pSTAT3/Arp3 axis and myosin contractility via the TGF-β1/Gli2/ROCK1/2/pMLC2 axis, which together regulate dynamic protrusion generation and 3D cell migration. MLL1 also regulates cell proliferation via mitosis-based and cell cycle-related pathways. Mice bearing orthotopic MLL1-depleted tumors exhibit decreased lung metastatic burden and longer survival. MLL1 depletion leads to lower metastatic burden even when controlling for the difference in primary tumor growth rates. Combining MLL1-Menin inhibitor with paclitaxel abrogates tumor growth and metastasis, including preexistent metastasis. These results establish MLL1 as a potent regulator of cell migration and highlight the potential of targeting MLL1 in patients with metastatic disease.

PMID:38478601 | DOI:10.1126/sciadv.adk0785

PLoS One. 2024 Mar 13;19(3):e0299645. doi: 10.1371/journal.pone.0299645. eCollection 2024.

ABSTRACT

Monodominant tree communities can have phenotypic trait variation (intraspecific variation) as extreme as the trait variation across a forest with higher species diversity. An example of such forests is those composed of Quercus, an important genus of woody angiosperms in the montane neotropical forest. The Andean oak, or Quercus humboldtii Bonpl., is the sole member of this genus in South America and a characteristic component of montane ecosystems. Although there are several studies on the ecology and genetic structure of this species, there are few studies on the functional trait diversity among populations. Understanding functional traits can improve our comprehension of how organisms respond to various environmental conditions. In this study, we aimed to evaluate differences in six functional traits in individuals of the Andean oak, in two ontogenetic stages (juveniles and adults) from three populations with contrasting environmental conditions. Additionally, using T-statistics, we assessed the impact of external filters (e.g., climate, resource availability, large-scale biotic interactions) on population assembly. We found a remarkable level of functional differentiation among Andean oak forests, with all traits differing between populations and five traits differing between ontogenetic stages. External filters had a stronger influence in populations with more extreme environmental conditions. These findings emphasize the dynamic and context-dependent nature of functional traits in this species. However, given the limited exploration of functional diversity in Andean oak populations, further studies are needed to inform conservation efforts.

PMID:38478564 | DOI:10.1371/journal.pone.0299645

PLoS One. 2024 Mar 13;19(3):e0299459. doi: 10.1371/journal.pone.0299459. eCollection 2024.

ABSTRACT

China’s tourism economy has experienced significant regional disparities. However, little attention has been paid to understanding the intricate mechanisms through which the interplay of influential factors gives rise to such disparities. Utilizing statistical data from the tourism economy of 31 provinces in mainland China, this study investigates regional tourism economic disparity through the asymmetric modeling of fuzzy set qualitative comparative analysis (fsQCA). The findings reveal that the causes of regional tourism economic disparity exhibit asymmetry; varying approaches contribute to the formation of high and low levels of tourism economy; the functioning of the most influential factors is impacted by other antecedent conditions, presenting an asymmetric non-linear effect; favorable transportation convenience is a necessary condition for a high level of tourism economy, while poor tourism attraction is a necessary condition for a low level of tourism economy. This research not only introduces a fresh perspective on regional tourism economic disparities, enabling an in-depth comprehension of the complex interactions and nonlinear functional mechanisms of influential factors, but also explores a region-based tourism development model, offering valuable practical guidance for policymakers in the tourism sector.

PMID:38478560 | DOI:10.1371/journal.pone.0299459

PLoS One. 2024 Mar 13;19(3):e0299484. doi: 10.1371/journal.pone.0299484. eCollection 2024.

ABSTRACT

Little is known about the effect of statin use in lung cancer development in idiopathic pulmonary fibrosis (IPF). We analyzed the database of the National Health Insurance Service to further investigate the clinical impacts of statin on lung cancer development and overall survival (OS) in IPF patients. The analysis included 9,182 individuals diagnosed with IPF, of which 3,372 (36.7%) were statin users. Compared to statin non-users, the time from diagnosis of IPF to lung cancer development and OS were longer in statin users in IPF patients. In Cox proportional hazard regression models, higher statin compliance, statin use, and being female had an inverse association with lung cancer risk, while older age at diagnosis of IPF and smoking history were associated with higher risk of lung cancer in IPF patients. For OS, statin use, female sex, higher physical activity frequency, and diabetes were associated with longer survival. In contrast, older age at diagnosis of IPF and smoking history were associated with shorter OS in IPF patients. These data from a large population indicate that statin had an independent protective association with lung cancer development and mortality in IPF patients.

PMID:38478558 | DOI:10.1371/journal.pone.0299484

JMIR Res Protoc. 2024 Mar 13;13:e54251. doi: 10.2196/54251.

ABSTRACT

BACKGROUND: Social cognitive impairments are prevalent in schizophrenia spectrum disorder (SSD) and have detrimental effects on functioning. Cognitive remediation (CR) has shown its efficacy in improving social cognitive impairments, although the transfer of these skills to daily life and the personalization of these interventions remain challenging. RC2S (Remédiation Cognitive de la Cognition Sociale dans la Schizophrénie; Cognitive remediation of social cognition in Schizophrenia) is a French CR that combines the learning of strategies and practice using paper-and-pencil exercises and digital relational simulations. This French program was designed as an in-person intervention.

OBJECTIVE: This project aims to culturally adapt the RC2S program, in French-Canadian and North American English and to assess the feasibility, acceptability, safety, and implementation of a remote version in people with SSD. An exploratory objective is to assess the preliminary effect of remote RC2S on goal attainment, social cognition, and psychosocial outcomes.

METHODS: We will use a pre-post quasi-experimental design. First, the translation and cultural adaptation in North American English and French-Canadian of RC2S is presented. Then, 20 participants aged ≥18 years with a diagnosis of SSD, presenting with a subjective or an objective impairment in social cognition, will be included to receive RC2S. In addition, 5 therapists will be included as research participants to assess their perspective on RC2S. Participants with SSD will undergo a baseline remote assessment of their social cognition, clinical symptoms, and functioning. They will then start remote RC2S for 24 biweekly individual 1-hour sessions with a therapist. Following the case formulation and goal setting, participants will complete personalized paper-and-pencil exercises to develop strategies and integrative digital relational simulations, during which they will help an avatar navigate through a variety of social contexts and relationships. The last 2 sessions are dedicated to the transfer to daily life. All participants will complete in-session questionnaires assessing therapeutic alliance, motivation, acceptability, feasibility, and implementation. Following RC2S, the participants with SSD will repeat the same assessment as the baseline. Descriptive statistics will be used to summarize the data about acceptability, feasibility, safety, and implementation. To assess the preliminary effect of RC2S, an intention-to-treat approach will be used with linear mixed models for repeated measures with fixed effects of time.

RESULTS: So far, 45% (9/20) of participants with SSD (mean age 37.9, SD 9.3 years) have completed the project. They received a mean of 20.5 out of 24 (SD 3.5) sessions of RC2S. A total of 5 therapists also completed the project.

CONCLUSIONS: Improving social cognitive impairments is an important target in SSD to promote functional recovery. Using digital technologies to address these impairments and deliver the intervention is a promising approach to increase the ecological validity of CR and access to the intervention.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05017532; https://classic.clinicaltrials.gov/ct2/show/NCT05017532.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54251.

PMID:38477975 | DOI:10.2196/54251

JMIR Form Res. 2024 Mar 13;8:e49462. doi: 10.2196/49462.

ABSTRACT

BACKGROUND: To safeguard the most vulnerable individuals during the COVID-19 pandemic, numerous governments enforced measures such as stay-at-home orders, social distancing, and self-isolation. These social restrictions had a particularly negative effect on older adults, as they are more vulnerable and experience increased loneliness, which has various adverse effects, including increasing the risk of mental health problems and mortality. Chatbots can potentially reduce loneliness and provide companionship during a pandemic. However, existing chatbots do not cater to the specific needs of older adult populations.

OBJECTIVE: We aimed to develop a user-friendly chatbot tailored to the specific needs of older adults with anxiety or depressive disorders during the COVID-19 pandemic and to examine their perspectives on mental health chatbot use. The primary research objective was to investigate whether chatbots can mitigate the psychological stress of older adults during COVID-19.

METHODS: Participants were older adults belonging to two age groups (≥65 years and <65 years) from a psychiatric outpatient department who had been diagnosed with depressive or anxiety disorders by certified psychiatrists according to the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5) criteria. The participants were required to use mobile phones, have internet access, and possess literacy skills. The chatbot’s content includes monitoring and tracking health data and providing health information. Participants had access to the chatbot for at least 4 weeks. Self-report questionnaires for loneliness, depression, and anxiety were administered before and after chatbot use. The participants also rated their attitudes toward the chatbot.

RESULTS: A total of 35 participants (mean age 65.21, SD 7.51 years) were enrolled in the trial, comprising 74% (n=26) female and 26% (n=9) male participants. The participants demonstrated a high utilization rate during the intervention, with over 82% engaging with the chatbot daily. Loneliness significantly improved in the older group ≥65 years. This group also responded positively to the chatbot, as evidenced by changes in University of California Los Angeles Loneliness Scale scores, suggesting that this demographic can derive benefits from chatbot interaction. Conversely, the younger group, <65 years, exhibited no significant changes in loneliness after the intervention. Both the older and younger age groups provided good scores in relation to chatbot design with respect to usability (mean scores of 6.33 and 6.05, respectively) and satisfaction (mean scores of 5.33 and 5.15, respectively), rated on a 7-point Likert scale.

CONCLUSIONS: The chatbot interface was found to be user-friendly and demonstrated promising results among participants 65 years and older who were receiving care at psychiatric outpatient clinics and experiencing relatively stable symptoms of depression and anxiety. The chatbot not only provided caring companionship but also showed the potential to alleviate loneliness during the challenging circumstances of a pandemic.

PMID:38477965 | DOI:10.2196/49462

Iran J Allergy Asthma Immunol. 2023 Dec 28;22(6):536-550. doi: 10.18502/ijaai.v22i6.14643.

ABSTRACT

MicroRNAs (miRs) play a role in several diseases, such as rheumatoid arthritis (RA). The purpose of this study was to discover new microRNAs and investigate their involvement in RA, examining their connections with inflammation and metabolic markers. New microRNAs related to RA were predicted using Mirbase and TargetScan databases based on RA target genes. The relationships between miRNAs and targets were visualized with Cytoscape software. Real-time polymerase chain reaction confirmed detectable miRNAs and metabolic factors were assessed using immunoassay and spectrometry methods in RA patients and healthy subjects. Four microRNAs (hsa-miR-153-5p, hsa-miR-4270, hsa-miR-4441, and hsa-miR-6754-5p) showed the highest correlation with RA target genes among millions of microRNAs. The expression of miR-146b (fold change=1.8) and miR-4441 (fold change=1.7) was notably reduced, while miR-4270 showed upregulation (fold change=1.8) in plasma from RA patients compared to healthy individuals. MiR-6754 exhibited a decrease (fold change=1.3) but was statistically insignificant. MiR-153-5p expression was undetectable in plasma. Receiver operating characteristic (ROC) curve analysis indicated that miR-4441, with an area under the ROC curve (AUC) of 0.7728, and miR-4270 (AUC=0.7353) were promising biomarkers for RA. The expression of these studied miRNAs significantly correlated with essential clinical characteristics, including liver enzymes, cholesterol, phosphorus, and vitamin D3. Our findings suggest that miR-4270 and miR-4441, present in the circulation, exhibit distinct expression patterns in RA. These microRNAs may serve as links between inflammation and metabolism and represent promising new biomarkers for this disease.

PMID:38477951 | DOI:10.18502/ijaai.v22i6.14643

Iran J Allergy Asthma Immunol. 2023 Dec 28;22(6):527-535. doi: 10.18502/ijaai.v22i6.14642.

ABSTRACT

The aim of asthma treatment is to reduce airway inflammation by avoiding environmental triggers and using daily anti-inflammatory medications. This study aimed to compare the effects of fluticasone propionate (FP) and budesonide (Bud) on the clinical symptoms and control of asthma in children with moderate to severe asthma. In this open-label study, children with moderate to severe asthma were randomly selected to receive either FP 250 mcg or Bud 400 mcg for 3 months. Asthma control test scores were measured in both groups monthly. The clinical symptoms, drug adherence, and rescue medication were also evaluated. A total of 50 patients with ages between 4 and 7 years old were included in the study (25 cases received Bud and 25 cases received FP). Asthma control test scores, daily and nocturnal symptoms, and cough rates were significantly improved in both groups. The average asthma control scores for the fluticasone group were 21.68±3.32 in the second month and 24.84±2.67 in the third month, whereas the budesonide group had scores of 18.52±3.32 and 22.48±4.12 during the same periods. These variances were statistically significant. Additionally, the requirement for salbutamol use was notably reduced in the fluticasone group compared to the budesonide group throughout all three months. The efficacy of fluticasone propionate in decreasing the need for rescue medication and enhancing asthma control test scores was markedly superior to that of budesonide.

PMID:38477950 | DOI:10.18502/ijaai.v22i6.14642

JAMA Netw Open. 2024 Mar 4;7(3):e241784. doi: 10.1001/jamanetworkopen.2024.1784.

ABSTRACT

IMPORTANCE: Although the cognitive components of behavioral therapy for overactive bladder (OAB) are widely recognized, there is a lack of studies evaluating the effectiveness of multicomponent interventions that include cognitive components as a treatment for OAB.

OBJECTIVE: To examine the efficacy of a multicomponent intervention in improving health-related quality of life (HRQOL) for women with moderate to severe OAB.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, open-label, randomized clinical trial was conducted in Japan among women aged 20 to 80 years who had moderate to severe OAB. Participants were recruited from 4 institutions between January 16, 2020, and December 31, 2022, through self-referral via advertisement or referral from the participating institutions.

INTERVENTIONS: Participants were randomized 1:1 by minimization algorithm using an internet-based central cloud system to four 30-minute weekly sessions of a multicomponent intervention or waiting list. Both groups continued to receive baseline treatment throughout the study period.

MAIN OUTCOMES AND MEASURES: The primary outcome was the least-squares mean changes from baseline through week 13 in HRQOL total scores of the OAB questionnaire between 2 groups. Secondary outcomes included OAB symptom score and frequency volume chart.

RESULTS: A total of 79 women were randomized to either the intervention group (39 participants; mean [SD] age, 63.5 [14.6] years) or the waiting list control group (40 participants; mean [SD] age, 63.5 [12.9] years). One participant from each group dropped out from the allocated intervention, while 5 participants in the intervention group and 2 in the control group dropped out from the primary outcome assessment at week 13. Thirty-six participants (92.3%) in the intervention group and 35 (87.5%) in the control group had moderate OAB. The change in HRQOL total score from baseline to week 13 was 23.9 points (95% CI, 18.4-29.5 points) in the intervention group and 11.3 points (95% CI, 6.2-16.4 points) in the waiting list group, a significant difference of 12.6 points (95% CI, 6.6-18.6 points; P < .001). Similar superiority of the intervention was confirmed for frequency of micturition and urgency but not for OAB symptom score.

CONCLUSIONS AND RELEVANCE: These findings demonstrate that a multicomponent intervention improves HRQOL for women with moderate to severe OAB and suggest that the cognitive component may be an effective treatment option for women with OAB.

TRIAL REGISTRATION: UMIN Clinical Trials Registry Identifier: UMIN000038513.

PMID:38477920 | DOI:10.1001/jamanetworkopen.2024.1784