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Nevin Manimala Statistics

Recognition and reconstruction of cell differentiation patterns with deep learning

PLoS Comput Biol. 2023 Oct 27;19(10):e1011582. doi: 10.1371/journal.pcbi.1011582. Online ahead of print.

ABSTRACT

Cell lineage decisions occur in three-dimensional spatial patterns that are difficult to identify by eye. There is an ongoing effort to replicate such patterns using mathematical modeling. One approach uses long ranging cell-cell communication to replicate common spatial arrangements like checkerboard and engulfing patterns. In this model, the cell-cell communication has been implemented as a signal that disperses throughout the tissue. On the other hand, machine learning models have been developed for pattern recognition and pattern reconstruction tasks. We combined synthetic data generated by the mathematical model with spatial summary statistics and deep learning algorithms to recognize and reconstruct cell fate patterns in organoids of mouse embryonic stem cells. Application of Moran’s index and pair correlation functions for in vitro and synthetic data from the model showed local clustering and radial segregation. To assess the patterns as a whole, a graph neural network was developed and trained on synthetic data from the model. Application to in vitro data predicted a low signal dispersion value. To test this result, we implemented a multilayer perceptron for the prediction of a given cell fate based on the fates of the neighboring cells. The results show a 70% accuracy of cell fate imputation based on the nine nearest neighbors of a cell. Overall, our approach combines deep learning with mathematical modeling to link cell fate patterns with potential underlying mechanisms.

PMID:37889897 | DOI:10.1371/journal.pcbi.1011582

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Nevin Manimala Statistics

Predictors of treatment intensification in uncontrolled hypertension

J Hypertens. 2023 Oct 20. doi: 10.1097/HJH.0000000000003598. Online ahead of print.

ABSTRACT

PURPOSE: Prior studies have shown that treatment intensification for patients presenting with uncontrolled hypertension (HTN) rarely occurs, even during visits to the patient’s own primary care physicians (PCPs). In this article, we identified predictors of treatment intensification for uncontrolled HTN.

METHODS: We conducted a cross-sectional study using nationally representative survey data on visits by patients aged 18 or above with uncontrolled HTN, defined as a recorded SBP at least 140 and/or a DBP at least 90 using data from the National Ambulatory Medical Care Survey (NAMCS) 2008-2018. Our outcome is treatment intensification defined as the addition of a new blood pressure medication.

RESULTS: We analyzed 22 559 visits to PCPs where uncontrolled HTN was noted, representing 801 023 786 visits nationally. Among these encounters, 2138 (10.3%) of the visits resulted in treatment intensification. Visits with the patient’s own PCP had higher rates of treatment intensification than visits to another PCP (10.8 vs. 5.9%, P < 0.0001). Visits for patients previously on antihypertensive medications had lower rates of treatment intensification (11% for no medications, 10.4% for one medication, 6.6% for ≥2 medications, P < 0.0001), but there were no statistically significant differences in rates of intensification for those with relevant comorbidities (9.4% for no chronic conditions, 10.8% for one to two chronic conditions, 8.9% for at least three chronic conditions, P = 0.12). Multivariable adjusted results were similar to the unadjusted findings.

CONCLUSION: Visits for patients with uncontrolled HTN rarely result in treatment intensification. Substantial opportunity exists to improve management of HTN, particularly for patients on fewer medications or seen by a covering provider.

PMID:37889569 | DOI:10.1097/HJH.0000000000003598

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Nevin Manimala Statistics

The effect of experimental emotion induction on experimental pain: a systematic review and meta-analysis

Pain. 2023 Oct 25. doi: 10.1097/j.pain.0000000000003073. Online ahead of print.

ABSTRACT

The idea that emotions can influence pain is generally recognized. However, a synthesis of the numerous individual experimental studies on this subject is lacking. The aim of the present systematic review and meta-analysis was to synthesize the existing evidence on the effect of experimental emotion induction on experimental pain in nonclinical adults. PsycInfo and PubMed were searched up until April 10, 2023, for studies assessing differences in self-reported pain between emotion induction groups and/or control groups or between conditions within group. Risk of bias was assessed for the individual studies. The literature search yielded 78 relevant records of 71 independent studies. When compared with control conditions, the pooled results revealed a statistically significant pain-attenuating effect of positive emotion induction (between-group: Hedges g = -0.48, 95% CI: -0.72; -0.25, K = 9; within-group: g = -0.24, 95% CI: -0.32; -0.15, K = 40), and a statistically significant pain-exacerbating effect of negative emotion induction in within-group analyses but not between-group analyses (between-group: g = -0.29, 95% CI: -0.66; 0.07, K = 10; within-group: g = 0.14, 95% CI: 0.06; 0.23, K = 39). Bayesian meta-analysis provided strong support for an effect of positive emotion induction but weak support for an effect of negative emotion induction. Taken together, the findings indicate a pain-attenuating effect of positive emotion induction, while the findings for negative emotion induction are less clear. The findings are discussed with reference to theoretical work emphasizing the role of motivational systems and distraction for pain. Limitations include considerable heterogeneity across studies limiting the generalizability of the findings.

PMID:37889565 | DOI:10.1097/j.pain.0000000000003073

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Nevin Manimala Statistics

Influence of Subclinical Corneal Edema on Contrast Sensitivity in Fuchs Endothelial Corneal Dystrophy

Cornea. 2023 Oct 27. doi: 10.1097/ICO.0000000000003414. Online ahead of print.

ABSTRACT

PURPOSE: The aim of this study was to compare visual function, with a focus on contrast sensitivity, between patients with Fuchs endothelial corneal dystrophy (FECD) with and without subclinical corneal edema.

METHODS: In this cross-sectional, observational, single-center study, 46 pseudophakic eyes of 31 patients with FECD were divided into 2 groups depending on the presence of subclinical corneal edema. All eyes presented with a Krachmer grade of 5 and no clinical corneal edema. The criteria for subclinical corneal edema were loss of regular isopachs, displacement of the thinnest point, and focal posterior surface depression in Scheimpflug tomography. If more than 1 criterion was present, subclinical corneal edema was diagnosed. The corrected distance visual acuity, contrast sensitivity (Pelli-Robson chart and CSV-1000 test with optional glare), and straylight were measured. The differences between both groups were analyzed using clustered Wilcoxon rank-sum tests.

RESULTS: The corrected distance visual acuity and the contrast sensitivity, measured with a Pelli-Robson chart, were significantly inferior in eyes with subclinical corneal edema compared with eyes without subclinical edema (P < 0.05). At all spatial frequencies, eyes with subclinical edema demonstrated lower contrast sensitivity with a statistically significantly reduction in total contrast sensitivity when tested with (P = 0.005) and without (P = 0.002) glare. The straylight did not significantly differ between both groups (P > 0.05).

CONCLUSIONS: The corrected distance visual acuity and contrast sensitivity were significantly reduced in FECD eyes with subclinical corneal edema compared with those with no subclinical edema. This decrease in visual quality may be considered when evaluating the need for surgical intervention at earlier stages of FECD.

PMID:37889563 | DOI:10.1097/ICO.0000000000003414

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Effect of combined tobacco use and type 2 diabetes mellitus on prevalent fibrosis in patients with MASLD

Hepatol Commun. 2023 Oct 27;7(11):e0300. doi: 10.1097/HC9.0000000000000300. eCollection 2023 Nov 1.

ABSTRACT

BACKGROUND: Several studies have investigated the independent effect of cigarette smoking or type 2 diabetes mellitus (T2DM) on MASLD. However, the interaction effect between tobacco consumption and T2DM on MASLD severity remains underexplored. In this study, we assessed the combined effect of tobacco use and T2DM on hepatic fibrosis in MASLD.

METHODS: We conducted a single-center retrospective cross-sectional analysis of eligible participants from the Mass General Brigham Fibroscan© database. The participants were divided into 3 groups: those with T2DM and a history of tobacco use (primary exposure group), those with T2DM but no history of tobacco use (secondary exposure group), and those without T2DM and no history of tobacco use (reference group). An additional model was developed, which included a fourth group, participants with a history of tobacco use but no T2DM. The likelihood of fibrosis was determined using a defined fibrosis-4 index cutoff value of 1.3. In addition, we computed the estimated marginal means for liver stiffness measurement and compared the values among the exposure groups. Bivariable and multivariable logistic regression models were used to explore the associations between the exposure groups and the risk for hepatic fibrosis.

RESULTS: Overall, 598 individuals were enrolled in the study. The bivariable logistic regression model revealed a significant independent association between T2DM, combined smoking and T2DM, and the outcome of interest, fibrosis. Age, sex, metabolic syndrome, aspirin use, statin use, hemoglobin A1C (A1C), and total bilirubin level were also significantly associated with fibrosis. In the adjusted fibrosis-4 multivariable model (comparing exposure groups to controls), cigarette smoking and T2DM interaction had higher odds of prevalent fibrosis (aOR, 3.04; 95% CI, 1.62-5.76), compared to those with T2DM alone (aOR 2.28; 95% CI, 1.37-3.85). The continuous liver stiffness measurement comparison across the exposure group showed an estimated marginal means of 6.26 (95% CL: 5.58-6.94), 7.54 (95% CL: 6.78-8.30), and 7.88 (6.78-8.99) for the reference group, T2DM only group, and tobacco-T2DM group, respectively. The diabetes-only group and the combined tobacco-T2DM group had statistically significant associations with liver stiffness measurement (p values: 0.013 and 0.014, respectively).

CONCLUSION: Although diabetes is independently associated with hepatic fibrosis in patients with MASLD, the combination of tobacco consumption and diabetes is associated with a higher prevalence of fibrosis. Therefore, lifestyle change through tobacco use cessation in patients with diabetes could be beneficial in reducing the incidence of liver fibrosis among individuals with MASLD.

PMID:37889558 | DOI:10.1097/HC9.0000000000000300

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A Mobile App to Assist the Mentors of African American Young Men Who Have Sex With Men: Usability Study

JMIR Form Res. 2023 Oct 27;7:e48515. doi: 10.2196/48515.

ABSTRACT

BACKGROUND: Mentoring can promote positive youth development. Owing to social and structural factors, young people in underresourced communities often lack adequate access to mentors, and naturally occurring mentors are more common than formal, programmatic mentors. There is little information on the impact of naturally occurring mentors on youth in general and even less on the role that mentors may play in promoting healthy outcomes in sexual and gender minority youth. African American young men who have sex with men (YMSM) are more likely to reside in communities with limited access to formalized mentorship programs and may benefit from naturally occurring mentoring relationships that address health outcomes, specifically related to HIV.

OBJECTIVE: This study is a usability test of a mobile app designed for the mentors of African American YMSM to increase mentors’ knowledge of and confidence in talking about HIV prevention and related topics with mentees.

METHODS: Following consent, eligible and naturally occurring mentoring pairs involving African American YMSM in Baltimore; Philadelphia; and Washington, District of Columbia, tested the app, UrbanMentorHub, for usability. Participants downloaded the app and used it for 1 month, completed pre- and postintervention surveys, and participated in a follow-up focus group discussion. Participants’ sociodemographic characteristics and HIV- and mentorship-related measures were characterized using descriptive statistics. Wilcoxon signed rank tests were used to test for pre- and postintervention differences in knowledge, confidence, and outcome expectancy measures. Focus group discussions were audio recorded and transcribed. Transcripts were thematically coded and analyzed to identify ways that UrbanMentorHub could be improved in the mentoring context.

RESULTS: Nine mentorship pairs participated in this usability study (N=18). Mentors obtained high scores on knowledge, confidence, outcome expectancies, skills, and intentions related to HIV and mentoring. No pre- or postintervention changes were observed in these measures. Mentors reported usually initiating conversations around HIV testing and pre-exposure prophylaxis; mentees and mentors equally initiated conversations on sexual practices and same-sex relationships. Mentors reported sexual practices as the most frequently discussed topic in the past month and pre-exposure prophylaxis being the least discussed. Mentees reported high comfort with HIV-related conversations. No pre- or postintervention change was observed regarding HIV knowledge. Most mentees reported having discussed most HIV-related topics with their mentor in the past month. Mentor feedback on the app was mostly neutral, although they reported positive perceptions of the idea of the app, indicating the potential for addressing a need in their communities. Mentors suggested ways to improve the app content and design elements.

CONCLUSIONS: Although there was no observed statistical change in measured outcomes, and qualitative feedback was overall neutral, the results of this usability study can inform future work to design and promote interventions and resources that support mentoring relationships for African American YMSM.

PMID:37889552 | DOI:10.2196/48515

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Varenicline Combined With Oral Nicotine Replacement Therapy and Smartphone-Based Medication Reminders for Smoking Cessation: Feasibility Randomized Controlled Trial

JMIR Form Res. 2023 Oct 27;7:e48857. doi: 10.2196/48857.

ABSTRACT

BACKGROUND: Varenicline and oral nicotine replacement therapy (NRT) have each been shown to increase the likelihood of smoking cessation, but their combination has not been studied. In addition, smoking cessation medication adherence is often poor, thus, challenging the ability to evaluate medication efficacy.

OBJECTIVE: This study examined the effects of combined varenicline and oral NRT and smartphone medication reminders on pharmacotherapy adherence and smoking abstinence among adults enrolled in smoking cessation treatment.

METHODS: A 2×2 factorial design was used. Participants (N=34) were randomized to (1) varenicline + oral NRT (VAR+NRT) or varenicline alone (VAR) and (2) smartphone medication reminder messages (REM) or no reminder messages (NREM) over 13 weeks. Participants assigned to VAR+REM received varenicline reminder prompts, and those assigned to VAR+NRT+REM also received reminders to use oral NRT. The other 2 groups (VAR+NREM and VAR+NRT+NREM) did not receive medication reminders. Participants were not blinded to intervention groups. All participants received tobacco cessation counseling. Smartphone assessments of smoking as well as varenicline and NRT use (if applicable) were prompted daily through the first 12 weeks after a scheduled quit date. Descriptive statistics were generated to characterize the relations between medication and reminder group assignments with daily smoking, daily varenicline adherence, and daily quantity of oral NRT used. Participants completed follow-up assessments for 26 weeks after the quit date.

RESULTS: Participants were predominantly White (71%), and half were female (50%). On average, participants were 54.2 (SD 9.4) years of age, they smoked an average of 19.0 (SD 9.0) cigarettes per day and had smoked for 34.6 (SD 12.7) years. Descriptively, participants assigned to VAR+NRT reported more days of smoking abstinence compared to VAR (29.3 vs 26.3 days). Participants assigned to REM reported more days of smoking abstinence than those assigned to NREM (40.5 vs 21.8 days). Participants assigned to REM were adherent to varenicline on more days compared to those assigned to NREM (58.6 vs 40.5 days), and participants assigned to VAR were adherent to varenicline on more days than those assigned to VAR + NRT (50.7 vs 43.3 days). In the subsample of participants assigned to VAR+NRT, participants assigned to REM reported more days where ≥5 pieces of NRT were used than NREM (14.0 vs 7.4 days). Average overall medication adherence (assessed via the Medication Adherence Questionnaire) showed the same pattern as the daily smartphone-based adherence assessments.

CONCLUSIONS: Preliminary findings indicated that smoking cessation interventions may benefit from incorporating medication reminders and combining varenicline with oral NRT, though combining medications may be associated with poorer adherence. Further study is warranted.

TRIAL REGISTRATION: ClinicalTrials.gov NCT03722966; https://classic.clinicaltrials.gov/ct2/show/NCT03722966.

PMID:37889541 | DOI:10.2196/48857

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Manual Superficial Keratectomy Is the First Choice Treatment for Salzmann Nodular Degeneration

Cornea. 2023 Oct 26. doi: 10.1097/ICO.0000000000003413. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to describe the optical and topographic changes after manual superficial keratectomy (MSK) for Salzmann nodular degeneration.

METHODS: This was a descriptive, retrospective study. All patients with a clinical diagnosis of Salzmann nodular degeneration were examined at the Cornea Service of the Instituto Clínico Quirúrgico de Oftalmología (ICQO), Bilbao, Spain, and treated with MSK after presenting ocular discomfort and/or decreased visual acuity. The clinical characteristics (including anterior segment optical coherence tomography and Pentacam topography), treatment regimens, surgical procedures, and outcomes were recorded. Descriptive statistics were constructed using mean ± SD, minimum, maximum, and median. The Shapiro-Wilk normality test was used. The Student t test was used to determine significance.

RESULTS: Ten eyes of 9 patients were included in this study: 6 patients (66.6%) were female and 3 were male (33.3%). The mean age was 62.2 years, and the follow-up time was between 5 and 21 months. The best-corrected visual acuity before MSK was 0.20 LogMAR (median) and improved to 0.10 after the surgical procedure. The mean spherical equivalent was reduced from -0.23 ± 3.39 D preoperatively to -1.3 ± 3.0 D postoperatively. Astigmatism decreased between 0.5 and 3.75 D. Topographic irregularity normalized total root mean square from 11,596.4 ± 6854.01 to 4817.2 ± 2725.68 μm.

CONCLUSIONS: MSK is an effective and safe technique for the treatment of Salzmann nodular degeneration when the Bowman layer is preserved. Anterior segment optical coherence tomography and corneal topography are essential tools for the surgical plan and for the detection of corneal aberrations.

PMID:37889535 | DOI:10.1097/ICO.0000000000003413

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Optimization of a Transdiagnostic Mobile Emotion Regulation Intervention for University Students: Protocol for a Microrandomized Trial

JMIR Res Protoc. 2023 Oct 27;12:e46603. doi: 10.2196/46603.

ABSTRACT

BACKGROUND: Many university students experience mental health problems such as anxiety and depression. To support their mental health, a transdiagnostic mobile app intervention has been developed. The intervention provides short exercises rooted in various approaches (eg, positive psychology, mindfulness, self-compassion, and acceptance and commitment therapy) that aim to facilitate adaptive emotion regulation (ER) to help students cope with the various stressors they encounter during their time at university.

OBJECTIVE: The goals of this study are to investigate whether the intervention and its components function as intended and how participants engage with them. In addition, this study aims to monitor changes in distress symptoms and ER skills and identify relevant contextual factors that may moderate the intervention’s impact.

METHODS: A sequential explanatory mixed methods design combining a microrandomized trial and semistructured interviews will be used. During the microrandomized trial, students (N=200) will be prompted via the mobile app twice a day for 3 weeks to evaluate their emotional states and complete a randomly assigned intervention (ie, an exercise supporting ER) or a control intervention (ie, a health information snippet). A subsample of participants (21/200, 10.5%) will participate in interviews exploring their user experience with the app and the completed exercises. The primary outcomes will be changes in emotional states and engagement with the intervention (ie, objective and subjective engagement). Objective engagement will be evaluated through log data (eg, exercise completion time). Subjective engagement will be evaluated through exercise likability and helpfulness ratings as well as user experience interviews. The secondary outcomes will include the distal outcomes of the intervention (ie, ER skills and distress symptoms). Finally, the contextual moderators of intervention effectiveness will be explored (eg, the time of day and momentary emotional states).

RESULTS: The study commenced on February 9, 2023, and the data collection was concluded on June 13, 2023. Of the 172 eligible participants, 161 (93.6%) decided to participate. Of these 161 participants, 137 (85.1%) completed the first phase of the study. A subsample of participants (18/172, 10.5%) participated in the user experience interviews. Currently, the data processing and analyses are being conducted.

CONCLUSIONS: This study will provide insight into the functioning of the intervention and identify areas for improvement. Furthermore, the findings will shed light on potential changes in the distal outcomes of the intervention (ie, ER skills and distress symptoms), which will be considered when designing a follow-up randomized controlled trial evaluating the full-scale effectiveness of this intervention. Finally, the results and data gathered will be used to design and train a recommendation algorithm that will be integrated into the app linking students to relevant content.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05576883; https://www.clinicaltrials.gov/study/NCT05576883.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46603.

PMID:37889525 | DOI:10.2196/46603

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Management of de Quervain Tenosynovitis: A Systematic Review and Network Meta-Analysis

JAMA Netw Open. 2023 Oct 2;6(10):e2337001. doi: 10.1001/jamanetworkopen.2023.37001.

ABSTRACT

IMPORTANCE: There is a plethora of treatment options for patients with de Quervain tenosynovitis (DQT), but there are limited data on their effectiveness and no definitive management guidelines.

OBJECTIVE: To assess and compare the effectiveness associated with available treatment options for DQT to guide musculoskeletal practitioners and inform guidelines.

DATA SOURCES: Medline, Embase, PubMed, Cochrane Central, Scopus, OpenGrey.eu, and WorldCat.org were searched for published studies, and the World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, The European Union Clinical Trials Register, and the ISRCTN registry were searched for unpublished and ongoing studies from inception to August 2022.

STUDY SELECTION: All randomized clinical trials assessing the effectiveness of any intervention for the management of DQT.

DATA EXTRACTION AND SYNTHESIS: This study was prospectively registered on PROSPERO and conducted and reported per Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-analyses of Health Care Interventions (PRISMA-NMA) and PRISMA in Exercise, Rehabilitation, Sport Medicine and Sports Science (PERSIST) guidance. The Cochrane Risk of Bias tool and the Grading of Recommendations, Assessment, Development, and Evaluations tool were used for risk of bias and certainty of evidence assessment for each outcome.

MAIN OUTCOMES AND MEASURES: Pairwise and network meta-analyses were performed for patient-reported pain using a visual analogue scale (VAS) and for function using the quick disabilities of the arm, shoulder, and hand (Q-DASH) scale. Mean differences (MD) with their 95% CIs were calculated for the pairwise meta-analyses.

RESULTS: A total of 30 studies with 1663 patients (mean [SD] age, 46 [7] years; 80% female) were included, of which 19 studies were included in quantitative analyses. From the pairwise meta-analyses, based on evidence of moderate certainty, adding thumb spica immobilization for 3 to 4 weeks to a corticosteroid injection (CSI) was associated with statistically but not clinically significant functional benefits in the short-term (MD, 10.5 [95% CI, 6.8-14.1] points) and mid-term (MD, 9.4 [95% CI, 7.0-11.9] points). In the network meta-analysis, interventions that included ultrasonography-guided CSI ranked at the top for pain. CSI with thumb spica immobilization had the highest probability of being the most effective intervention for short- and mid-term function.

CONCLUSIONS AND RELEVANCE: This network meta-analysis found that adding a short period of thumb spica immobilization to CSI was associated with statistically but not clinically significant short- and mid-term benefits. These findings suggest that administration of CSI followed by 3 to 4 weeks immobilization should be considered as a first-line treatment for patients with DQT.

PMID:37889490 | DOI:10.1001/jamanetworkopen.2023.37001