Nevin Manimala

Ann Am Thorac Soc. 2024 Aug 21. doi: 10.1513/AnnalsATS.202311-955OC. Online ahead of print.

ABSTRACT

Rationale: Growing evidence suggests that air pollution exposure is a major risk factor in chronic obstructive pulmonary disease (COPD) that is associated with an increased prothrombotic state and adverse cardiovascular outcomes. However, much of this work is based on observational data or human exposure studies involving younger participants. The biological causality and mechanism of air pollution-induced prothrombotic response in patients with COPD remain to be explored. Objective: The main aim of this work was to investigate the impact of short-term diesel exhaust (DE) exposure on circulating prothrombotic markers-fibrinogen and plasminogen activator inhibitor-1 (PAI-1)-and urinary eicosanoids in patients with COPD. Methods: Twenty-nine research participants were recruited in this randomized, double-blinded, crossover, controlled human exposure study to DE. Participants included former smokers with and without mild or moderate COPD (ES and COPD group) and healthy never-smokers without COPD (NS group). Each participant was exposed to DE (300 µg/m³ of PM_2.5) and filtered air (FA) for 2 hours on different occasions, in randomized order, separated by a 4-week washout. Blood and urine samples were collected prior to and 24 hours after each exposure. Plasma fibrinogen and serum PAI-1 concentrations were quantified using ELISAs. Urinary eicosanoid concentrations were quantified using ultra- performance liquid chromatography coupled to tandem mass spectrometry. Linear mixed-effects models were used for statistical comparisons. Results: Participants with COPD showed an increase in plasma fibrinogen (effect estimate: 1.27 [1.06 to 1.53], p=0.01) after DE relative to FA, but no significant DE-associated change in serum PAI-1 (0.95 [0.87 to 1.04], p=0.26). In never-smokers and ex-smokers without COPD, fibrinogen (NS group: 1.10 [0.99 to 1.23], p=0.08; ES group: 0.86 [0.68 to 1.09], p=0.08] and PAI-1 (NS group: 1.12 [ 0.96 to 1.32], p=0.15; ES group: 0.90 [0.79 to 1.03], p=0.13) were not changed after DE exposure. COPD participants showed a DE-attributable increase in urinary thromboxane B₂ (TXB₂) metabolites concentrations as follows: 11-dehydro TXB₂ (1.45 [1.02 to 2.08], p=0.04); 2,3-dinor-TXB₂ (1.45 [1.05 to 2.00], p=0.03). Conclusions: Participants with COPD had increased plasma fibrinogen and urinary TXB₂ metabolites after short-term DE exposure, suggesting they may be more susceptible to pollution-attributable prothrombotic response compared to healthy controls or ex-smokers without COPD. Clinical trial registration available at www.clinicaltrials.gov, ID: NCT02236039.

PMID:39167788 | DOI:10.1513/AnnalsATS.202311-955OC

J Med Internet Res. 2024 Aug 21;26:e56500. doi: 10.2196/56500.

ABSTRACT

BACKGROUND: Large language models including GPT-4 (OpenAI) have opened new avenues in health care and qualitative research. Traditional qualitative methods are time-consuming and require expertise to capture nuance. Although large language models have demonstrated enhanced contextual understanding and inferencing compared with traditional natural language processing, their performance in qualitative analysis versus that of humans remains unexplored.

OBJECTIVE: We evaluated the effectiveness of GPT-4 versus human researchers in qualitative analysis of interviews with patients with adult-acquired buried penis (AABP).

METHODS: Qualitative data were obtained from semistructured interviews with 20 patients with AABP. Human analysis involved a structured 3-stage process-initial observations, line-by-line coding, and consensus discussions to refine themes. In contrast, artificial intelligence (AI) analysis with GPT-4 underwent two phases: (1) a naïve phase, where GPT-4 outputs were independently evaluated by a blinded reviewer to identify themes and subthemes and (2) a comparison phase, where AI-generated themes were compared with human-identified themes to assess agreement. We used a general qualitative description approach.

RESULTS: The study population (N=20) comprised predominantly White (17/20, 85%), married (12/20, 60%), heterosexual (19/20, 95%) men, with a mean age of 58.8 years and BMI of 41.1 kg/m². Human qualitative analysis identified “urinary issues” in 95% (19/20) and GPT-4 in 75% (15/20) of interviews, with the subtheme “spray or stream” noted in 60% (12/20) and 35% (7/20), respectively. “Sexual issues” were prominent (19/20, 95% humans vs 16/20, 80% GPT-4), although humans identified a wider range of subthemes, including “pain with sex or masturbation” (7/20, 35%) and “difficulty with sex or masturbation” (4/20, 20%). Both analyses similarly highlighted “mental health issues” (11/20, 55%, both), although humans coded “depression” more frequently (10/20, 50% humans vs 4/20, 20% GPT-4). Humans frequently cited “issues using public restrooms” (12/20, 60%) as impacting social life, whereas GPT-4 emphasized “struggles with romantic relationships” (9/20, 45%). “Hygiene issues” were consistently recognized (14/20, 70% humans vs 13/20, 65% GPT-4). Humans uniquely identified “contributing factors” as a theme in all interviews. There was moderate agreement between human and GPT-4 coding (κ=0.401). Reliability assessments of GPT-4’s analyses showed consistent coding for themes including “body image struggles,” “chronic pain” (10/10, 100%), and “depression” (9/10, 90%). Other themes like “motivation for surgery” and “weight challenges” were reliably coded (8/10, 80%), while less frequent themes were variably identified across multiple iterations.

CONCLUSIONS: Large language models including GPT-4 can effectively identify key themes in analyzing qualitative health care data, showing moderate agreement with human analysis. While human analysis provided a richer diversity of subthemes, the consistency of AI suggests its use as a complementary tool in qualitative research. With AI rapidly advancing, future studies should iterate analyses and circumvent token limitations by segmenting data, furthering the breadth and depth of large language model-driven qualitative analyses.

PMID:39167785 | DOI:10.2196/56500

Blood Adv. 2024 Aug 21:bloodadvances.2024013746. doi: 10.1182/bloodadvances.2024013746. Online ahead of print.

ABSTRACT

BMT CTN 1506 was a phase III randomized trial comparing gilteritinib versus placebo after allogeneic HCT for FLT3-ITD-positive AML. The primary analysis comparing relapse-free survival (RFS) was not statistically significant, however, patients with detectable FLT3-ITD MRD peri-HCT had significantly longer RFS with gilteritinib. The aim of this analysis is to describe the effect of post-HCT gilteritinib versus placebo on health-related quality of life (HRQOL). HRQOL was measured using the Functional Assessment of Cancer Therapy (FACT)-BMT, FACT-Leukemia (-Leu), and EQ-5D-5L at post-HCT randomization, day 29, month 3, 6, 12, 18, 24, and/or end of therapy. HRQOL and clinically meaningful differences were summarized using descriptive statistics and compared using mixed model repeated measures to evaluate longitudinal change from baseline and stratified Cox model to evaluate time to improvement. Between 8/2017 and 7/2020, 356 patients were randomized. HRQOL completion rate was acceptable (>70%) across all time points and measures. There were no differences in FACT-BMT, FACT-Leu, or EQ-5D-5L scores at any time point between cohorts. There was an increase in scores over time, indicating improvement in HRQOL post-HCT. Clinically meaningful improvement and time to improvement in HRQOL was similar in both arms. Despite higher TEAEs with gilteritinib, response to the question of being “bothered by side effects of treatment” did not differ between groups. Subgroup analysis of MRD detectable and negative patients demonstrated no differences in HRQOL between arms. For FLT3-ITD+ AML patients undergoing HCT, gilteritinib maintenance was not associated with any difference in HRQOL or patient-reported impact of side effects. Trial Registration: NCT02997202.

PMID:39167766 | DOI:10.1182/bloodadvances.2024013746

Eur J Public Health. 2024 Aug 21:ckae128. doi: 10.1093/eurpub/ckae128. Online ahead of print.

ABSTRACT

Smoking prevalence remains high in Europe and widening socioeconomic group differences are driving health inequalities. While plain packaging policies disrupt tobacco industry tactics that sustain smoking, evidence of their equity impact is sparse. This study evaluated the implementation of plain packaging in Ireland in 2018 on consumer responses, overall and by the socioeconomic group. Consecutive nationally representative cross-sectional surveys (2018, n = 7701 and 2019, n = 7382) measured changes in 13 consumer responses among respondents who smoked across three domains: product appeal, health warnings effectiveness, and perceived harmfulness of smoking. Multiple logistic regression-derived adjusted odds ratios with 95% confidence intervals to compare responses post- versus pre-implementation adjusting for age, gender, educational level, and heaviness of smoking. A stratified analysis examined changes by socioeconomic group indexed using educational level. There were statistically significant changes in consumer responses to plain packaging policy implementation across 7/13 outcomes studied. Five changes were aligned with expected policy impacts (2/6 product appeal outcomes and 3/4 health warning effectiveness outcomes). Two responses were also observed which were not expected policy impacts (1 appeal-related and 1 perceived harm-related outcome). There was no change in five outcomes. Differences in consumer responses between educational groups were generally small, mixed in nature, and indistinguishable when interval estimates of effect were compared. Implementation of plain packaging in Ireland had intended impacts on consumer responses. Including plain packaging requirements in revising the European Union’s legislative frameworks for tobacco control will help build progress towards a Tobacco-Free Europe without exacerbating smoking inequalities.

PMID:39167744 | DOI:10.1093/eurpub/ckae128

Database (Oxford). 2024 Aug 21;2024:baae076. doi: 10.1093/database/baae076.

ABSTRACT

MicroRNAs are key players involved in stress responses in plants and reports are available on the role of miRNAs in drought stress response in rice. This work reports the development of a database, RiceMetaSys: Drought-miR, based on the meta-analysis of publicly available sRNA datasets. From 28 drought stress-specific sRNA datasets, we identified 216 drought-responsive miRNAs (DRMs). The major features of the database include genotype-, tissue- and miRNA ID-specific search options and comparison of genotypes to identify common miRNAs. Co-localization of the DRMs with the known quantitative trait loci (QTLs), i.e., meta-QTL regions governing drought tolerance in rice pertaining to different drought adaptive traits, narrowed down this to 37 promising DRMs. To identify the high confidence target genes of DRMs under drought stress, degradome datasets and web resource on drought-responsive genes (RiceMetaSys: DRG) were used. Out of the 216 unique DRMs, only 193 had targets with high stringent parameters. Out of the 1081 target genes identified by Degradome datasets, 730 showed differential expression under drought stress in at least one accession. To retrieve complete information on the target genes, the database has been linked with RiceMetaSys: DRG. Further, we updated the RiceMetaSys: DRGv1 developed earlier with the addition of DRGs identified from RNA-seq datasets from five rice genotypes. We also identified 759 putative novel miRNAs and their target genes employing stringent criteria. Novel miRNA search has all the search options of known miRNAs and additionally, it gives information on their in silico validation features. Simple sequence repeat markers for both the miRNAs and their target genes have also been designed and made available in the database. Network analysis of the target genes identified 60 hub genes which primarily act through abscisic acid pathway and jasmonic acid pathway. Co-localization of the hub genes with the meta-QTL regions governing drought tolerance narrowed down this to 16 most promising DRGs. Database URL: http://14.139.229.201/RiceMetaSys_miRNA Updated database of RiceMetaSys URL: http://14.139.229.201/RiceMetaSysA/Drought/.

PMID:39167719 | DOI:10.1093/database/baae076

J Aging Health. 2024 Aug 21:8982643241273298. doi: 10.1177/08982643241273298. Online ahead of print.

ABSTRACT

BACKGROUND: The well-known disablement process has been conceptualized as a series of transitions between progressive states of functional decline. We studied joint patterns of change within disablement states defined as walking speed, grip strength, and self-reported disability.

METHODS: 1702 participants aged 65 and over were included from the Longitudinal Aging Study Amsterdam, spanning seven waves over 20 years (1996-2016). Group-based multi-trajectory modeling yielded trajectory clusters (TCs) of different patterns of change, further characterized by baseline sociodemographic characteristics, physical and cognitive health, and survival rate.

RESULTS: Five TCs were identified, distinguished by increasing baseline age. Walking speed and disability showed generally concomitant trajectories. Women had poorer trajectories in grip strength than men, but not in walking speed and disability. Poor physical health distinguished especially the poorest, and cognitive impairment distinguished especially the one-before-poorest from the better TCs.

DISCUSSION: The findings suggest that the disablement states are not generally distinct or sequential.

PMID:39167684 | DOI:10.1177/08982643241273298

Sci Adv. 2024 Aug 23;10(34):eadl1079. doi: 10.1126/sciadv.adl1079. Epub 2024 Aug 21.

ABSTRACT

Peaty sediments in coastal wetlands play an important role in the sequestration of atmospheric carbon dioxide and its belowground storage. Sediment cores are used to quantify organic matter (OM) density, estimated by multiplying the bulk density of a core segment by its OM fraction. This method can be imprecise, as repeated samples often differ widely. Recent studies have shown that sediment bulk density and OM fraction are not independent but tightly related by a function called the ideal-mixing model. Thus, the bulk density of the sediment can be directly estimated from its OM fraction. Statistical theory and simulations demonstrate that the high variance in the product estimation of OM density is the result of error propagation in the product of two functionally related variables with independent errors. Estimating OM density in wetland sediments using the ideal-mixing model is more precise than the traditionally used product estimate, especially in highly organic sediments.

PMID:39167659 | DOI:10.1126/sciadv.adl1079

Sci Adv. 2024 Aug 23;10(34):eado9059. doi: 10.1126/sciadv.ado9059. Epub 2024 Aug 21.

ABSTRACT

Dynamic nuclear polarization (DNP) has revolutionized the field of nuclear magnetic resonance spectroscopy, expanding its reach and capabilities to investigate diverse materials, biomolecules, and complex dynamic processes. Bringing high-efficiency DNP to the nanometer scale would open exciting avenues for studying nanoscale nuclear spin ensembles, such as single biomolecules, virus particles, and condensed matter systems. Combining pulsed DNP with nanoscale force-detected magnetic resonance measurements, we demonstrated a 100-fold enhancement in the Boltzmann polarization of proton spins in nanoscale sugar droplets at 6 kelvin and 0.33 tesla. Crucially, this enhancement corresponds to a factor of 200 reduction in the averaging time compared to measurements that rely on the detection of statistical fluctuations in nanoscale nuclear spin ensembles. These results substantially advance the capabilities of force-detected magnetic resonance detection as a practical tool for nanoscale imaging.

PMID:39167648 | DOI:10.1126/sciadv.ado9059

Cornea. 2024 Aug 21. doi: 10.1097/ICO.0000000000003679. Online ahead of print.

ABSTRACT

PURPOSE: To analyze the corneal phenotypes of Japanese patients with myotonic dystrophy type 1 (DM1).

METHODS: We included patients with DM1 who were diagnosed with clinical neuromuscular symptoms by neurologists and CTG trinucleotide repeat (TNR) expansion of the (myotonic dystrophy protein kinase) DMPK gene. We analyzed the corneal phenotype using slit-lamp examination, specular microscopy, and anterior segment optical coherence tomography. We evaluated TNR expansion in the TCF4 gene of leukocyte-derived genomic DNA by fragment analysis using polymerase chain reaction and triplet-repeat primed polymerase chain reaction.

RESULTS: Nineteen eyes from 10 patients with DM1 (DM1 group) and 72 eyes from 37 healthy participants (control group) were analyzed. The average age was 49.3 ± 11.9 and 51.8 ± 12.9 years in the DM1 and control groups, respectively (P = 0.11). Slit-lamp examination demonstrated that 2 patients with DM1 had bilateral corneal guttae equivalent to modified Krachmer grade 1 of Fuchs endothelial corneal dystrophy. Dark areas on specular microscopy were observed in 4 of 19 eyes (21.1%) and 0 of 72 eyes (0%) in the DM1 and control groups, respectively, with statistically significant differences (P = 0.002). The average endothelial cell density in the DM1 group (3536 ± 722 cells/mm2) was significantly higher than that in the control group (3026 ± 412 cells/mm2) (P = 0.0006). TNR expansion in TCF4 was not detected in eyes with corneal guttae or in the dark areas in the DM1 group.

CONCLUSIONS: Japanese patients with DM1 without TNR expansion in TCF4 have a mild phenotype equivalent to Fuchs endothelial corneal dystrophy. Endothelial cell density is higher in DM1 patients than in normal participants.

PMID:39167633 | DOI:10.1097/ICO.0000000000003679

Cornea. 2024 Aug 21. doi: 10.1097/ICO.0000000000003675. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of this study was to evaluate the efficacy of temporary conjunctival flap with topical natamycin and oral voriconazole compared with medical treatment only in reducing the rate of perforation in high-risk fungal keratitis.

METHODS: Sixty-two eyes of 62 patients with severe fungal keratitis were examined; only 54 patients were enrolled and divided randomly into 2 groups. The first group received medical treatment only in the form of topical natamycin 5% together with oral voriconazole 200 mg, while the second group received the same medical treatment plus a temporary conjunctival flap that was removed after 2 weeks. Five patients were lost during the follow-up, and only 49 patients were statistically analyzed. All patients were examined frequently until reepithelialization or the development of perforation.

RESULTS: Fifteen perforations were reported, with a higher rate among the medical group (48%) compared with the conjunctival flap group (12.5%), with P value <0.05. A significant delay was noted in reepithelialization time in the medical group compared with the conjunctival flap group (mean time was 21.69 ± 5.41 and 15.36 ± 2.2 days, respectively), with P value = 0.001. Significant improvement in visual acuity was reported over time when comparing baseline versus 3-month visual acuity in the same group using paired t sample test (P value was 0.003 and <0.001 in the first and second group, respectively).

CONCLUSIONS: Temporary conjunctival flap is associated with a lower perforation rate compared with medical treatment only in severe fungal keratitis, which can provide a cheap and available alternative to therapeutic penetrating keratoplasty.

PMID:39167631 | DOI:10.1097/ICO.0000000000003675