Tag: pubmed

Proc Natl Acad Sci U S A. 2023 Aug 8;120(32):e2308935120. doi: 10.1073/pnas.2308935120. Epub 2023 Jul 31.

ABSTRACT

The instability of Stokes waves, steady propagating waves on the surface of an ideal fluid of infinite depth, is a fundamental problem in the field of nonlinear science. The dominant instability of these waves depends on their steepness. For small amplitude waves, it is well known that the Benjamin-Feir or modulational instability dominates the dynamics of a wave train. We demonstrate that for steeper waves, an instability caused by disturbances localized at the wave crest vastly surpasses the growth rate of the modulational instability. These dominant localized disturbances are either coperiodic with the Stokes wave or have twice its period. In either case, the nonlinear evolution of the instability leads to the formation of plunging breakers. This phenomenon explains why long propagating ocean swell consists of small-amplitude waves.

PMID:37523557 | DOI:10.1073/pnas.2308935120

Proc Natl Acad Sci U S A. 2023 Aug 8;120(32):e2300828120. doi: 10.1073/pnas.2300828120. Epub 2023 Jul 31.

ABSTRACT

Traditionally, nuclear spin is not considered to affect biological processes. Recently, this has changed as isotopic fractionation that deviates from classical mass dependence was reported both in vitro and in vivo. In these cases, the isotopic effect correlates with the nuclear magnetic spin. Here, we show nuclear spin effects using stable oxygen isotopes (¹⁶O, ¹⁷O, and ¹⁸O) in two separate setups: an artificial dioxygen production system and biological aquaporin channels in cells. We observe that oxygen dynamics in chiral environments (in particular its transport) depend on nuclear spin, suggesting future applications for controlled isotope separation to be used, for instance, in NMR. To demonstrate the mechanism behind our findings, we formulate theoretical models based on a nuclear-spin-enhanced switch between electronic spin states. Accounting for the role of nuclear spin in biology can provide insights into the role of quantum effects in living systems and help inspire the development of future biotechnology solutions.

PMID:37523549 | DOI:10.1073/pnas.2300828120

Proc Natl Acad Sci U S A. 2023 Aug 8;120(32):e2303402120. doi: 10.1073/pnas.2303402120. Epub 2023 Jul 31.

ABSTRACT

The endoplasmic reticulum (ER) and mitochondria form a unique subcellular compartment called mitochondria-associated ER membranes (MAMs). Disruption of MAMs impairs Ca²⁺ homeostasis, triggering pleiotropic effects in the neuronal system. Genome-wide kinase-MAM interactome screening identifies casein kinase 2 alpha 1 (CK2A1) as a regulator of composition and Ca²⁺ transport of MAMs. CK2A1-mediated phosphorylation of PACS2 at Ser207/208/213 facilitates MAM localization of the CK2A1-PACS2-PKD2 complex, regulating PKD2-dependent mitochondrial Ca²⁺ influx. We further reveal that mutations of PACS2 (E209K and E211K) associated with developmental and epileptic encephalopathy-66 (DEE66) impair MAM integrity through the disturbance of PACS2 phosphorylation at Ser207/208/213. This, in turn, causes the reduction of mitochondrial Ca²⁺ uptake and the dramatic increase of the cytosolic Ca²⁺ level, thereby, inducing neurotransmitter release at the axon boutons of glutamatergic neurons. In conclusion, our findings suggest a molecular mechanism that MAM alterations induced by pathological PACS2 mutations modulate Ca²⁺-dependent neurotransmitter release.

PMID:37523531 | DOI:10.1073/pnas.2303402120

Proc Natl Acad Sci U S A. 2023 Aug 8;120(32):e2303647120. doi: 10.1073/pnas.2303647120. Epub 2023 Jul 31.

ABSTRACT

Multimodal single-cell technologies profile multiple modalities for each cell simultaneously, enabling a more thorough characterization of cell populations. Existing dimension-reduction methods for multimodal data capture the “union of information,” producing a lower-dimensional embedding that combines the information across modalities. While these tools are useful, we focus on a fundamentally different task of separating and quantifying the information among cells that is shared between the two modalities as well as unique to only one modality. Hence, we develop Tilted Canonical Correlation Analysis (Tilted-CCA), a method that decomposes a paired multimodal dataset into three lower-dimensional embeddings-one embedding captures the “intersection of information,” representing the geometric relations among the cells that is common to both modalities, while the remaining two embeddings capture the “distinct information for a modality,” representing the modality-specific geometric relations. We analyze single-cell multimodal datasets sequencing RNA along surface antibodies (i.e., CITE-seq) as well as RNA alongside chromatin accessibility (i.e., 10x) for blood cells and developing neurons via Tilted-CCA. These analyses show that Tilted-CCA enables meaningful visualization and quantification of the cross-modal information. Finally, Tilted-CCA’s framework allows us to perform two specific downstream analyses. First, for single-cell datasets that simultaneously profile transcriptome and surface antibody markers, we show that Tilted-CCA helps design the target antibody panel to complement the transcriptome best. Second, for developmental single-cell datasets that simultaneously profile transcriptome and chromatin accessibility, we show that Tilted-CCA helps identify development-informative genes and distinguish between transient versus terminal cell types.

PMID:37523521 | DOI:10.1073/pnas.2303647120

Vascular. 2023 Jul 31:17085381231192377. doi: 10.1177/17085381231192377. Online ahead of print.

ABSTRACT

INTRODUCTION: Iliac aneurysms occur in 10% of patients with abdominal aortic aneurysms (AAA). There are three different endovascular approaches to their treatment in the context of infrarenal Endovascular Aortic Aneurysm Repair (EVAR): occlusion by coiling the internal iliac, incorporation using an iliac branch device, and delaying repair using a bell bottom limb. We sought to determine outcomes associated with these three strategies in our practice.

METHODOLOGY: The study was a combined prospective cohort study with a retrospective arm: prospective patient recruitment was done for 1 year from September 2019 and ended by September 2020, and retrospective data was collected from 2017 to 2019. Demographic, procedural, and imaging data was collected. SPSS was used to analyze data as patients were classified by limbs in four groups: iliac branched, bell bottom, coil and cover technique, and standard treated limbs.

RESULTS: There were 65 male and 4 female patients included in this study incorporating 137 limbs with a mean age of 78 years (SD ± 8 years). Two patients died after discharge (at 3 and 21 months postoperatively, without hospital admission) and five patients were lost to long-term follow-up. Three patients had operations that deviated from the plan: one was an IBD converted to bell bottom, one was an IBD that was converted to coil and cover, and one was a bell bottom that did not seal. Follow-up revealed late type IB endoleak in three bell bottom limbs and one limb treated with coil and cover. Common iliac occlusion occurred in one IBD, three bell bottom limbs, and two limbs treated with coil/cover technique. There were four additional ischemic events (buttock claudication in three and intestinal ischemia in one): all ischemic events occurred in the coil and cover group (p = .001).

CONCLUSIONS: Given the small population size examined in this study, there is no statistical difference between treatment groups; however, there was a trend toward bell bottom technique being associated with higher incidence of type IB endoleak. Coil and cover technique was associated with decreased IB endoleak; however, Buttock claudication and intestinal ischemia occurred more significantly in this group. Using IBD may be the best strategy to improve short- and long-term outcomes in patients with iliac aneurysms.

PMID:37523224 | DOI:10.1177/17085381231192377

J Comput Biol. 2023 Jul 31. doi: 10.1089/cmb.2023.0096. Online ahead of print.

ABSTRACT

International Classification of Diseases (ICD) serves as the foundation for generating comparable global disease statistics across regions and over time. The process of ICD coding involves assigning codes to diseases based on clinical notes, which can describe a patient’s condition in a standard way. However, this process is complicated by the vast number of codes and the intricate taxonomy of ICD codes, which are hierarchically organized into various levels, including chapter, category, subcategory, and its subdivisions. Many existing studies focus solely on predicting subcategory codes, ignoring the hierarchical relationships among codes. To address this limitation, we propose a multitask learning model that trains multiple classifiers for different code levels, while also capturing the relations between coarser and finer-grained labels through a reinforcement mechanism. Our approach is evaluated on both English and Chinese benchmark dataset, and we demonstrate that our method achieves competitive performance with baseline models, particularly in terms of macro-F1 results. These findings suggest that our approach effectively leverages the hierarchical structure of ICD codes to improve disease code prediction accuracy. Analysis of attention mechanism shows that multigranularity attention of our model captures crucial feature of input text on different granularity levels, which can provide reasonable explanations for the prediction results.

PMID:37523219 | DOI:10.1089/cmb.2023.0096

Ergonomics. 2023 Jul 31:1-21. doi: 10.1080/00140139.2023.2240048. Online ahead of print.

ABSTRACT

Accident analysis methods are used to model the multifactorial cause of adverse incidents. Methods such as AcciMap, STAMP-CAST and recently AcciNet, are systemic approaches that support the identification of safety interventions across sociotechnical system levels. Despite their growing popularity, little is known about how reliable systems-based methods are when used to describe, model and classify contributory factors and relationships. Here, we conducted an intra-rater and inter-rater reliability assessment of AcciMap, STAMP-CAST and AcciNet using the Signal Detection Theory (SDT) paradigm. A total of 180 hours’ worth of analyses across 360 comparisons were performed by 30 expert analysts. Findings revealed that all three methods produced a weak to moderate positive correlation coefficient, however the inter-rater reliability of STAMP-CAST was significantly higher compared to AcciMap and AcciNet. No statistically significant or practically meaningful differences were found between methods in the overall intra-rater reliability analyses. Implications and future research directions are discussed.

PMID:37523211 | DOI:10.1080/00140139.2023.2240048

JAMA Neurol. 2023 Jul 31. doi: 10.1001/jamaneurol.2023.2392. Online ahead of print.

ABSTRACT

IMPORTANCE: Outcome prediction after endovascular treatment (EVT) for ischemic stroke is important to patients, family members, and physicians.

OBJECTIVE: To develop and validate a model based on preprocedural and postprocedural characteristics to predict functional outcome for individual patients after EVT.

DESIGN, SETTING, AND PARTICIPANTS: A prediction model was developed using individual patient data from 7 randomized clinical trials, performed between December 2010 and December 2014. The model was developed within the Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) collaboration and external validation in data from the Dutch Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry of patients treated in clinical practice between March 2014 and November 2017. Participants included patients from multiple centers throughout different countries in Europe, North America, East Asia, and Oceania (derivation cohort), and multiple centers in the Netherlands (validation cohort). Included were adult patients with a history of ischemic stroke from an intracranial large vessel occlusion in the anterior circulation who underwent EVT within 12 hours of symptom onset or last seen well. Data were last analyzed in July 2022.

MAIN OUTCOME(S) AND MEASURE(S): A total of 19 variables were assessed by multivariable ordinal regression to predict functional outcome (modified Rankin Scale [mRS] score) 90 days after EVT. Variables were routinely available 1 day after EVT. Akaike information criterion (AIC) was used to optimize model fit vs model complexity. Probabilities for functional independence (mRS 0-2) and survival (mRS 0-5) were derived from the ordinal model. Model performance was expressed with discrimination (C statistic) and calibration.

RESULTS: A total of 781 patients (median [IQR] age, 67 [57-76] years; 414 men [53%]) constituted the derivation cohort, and 3260 patients (median [IQR] age, 72 [61-80] years; 1684 men [52%]) composed the validation cohort. Nine variables were included in the model: age, baseline National Institutes of Health Stroke Scale (NIHSS) score, prestroke mRS score, history of diabetes, occlusion location, collateral score, reperfusion grade, NIHSS score at 24 hours, and symptomatic intracranial hemorrhage 24 hours after EVT. External validation in the MR CLEAN Registry showed excellent discriminative ability for functional independence (C statistic, 0.91; 95% CI, 0.90-0.92) and survival (0.89; 95% CI, 0.88-0.90). The proportion of functional independence in the MR CLEAN Registry was systematically higher than predicted by the model (41% vs 34%), whereas observed and predicted survival were similar (72% vs 75%). The model was updated and implemented for clinical use.

CONCLUSION AND RELEVANCE: The prognostic tool MR PREDICTS@24H can be applied 1 day after EVT to accurately predict functional outcome for individual patients at 90 days and to provide reliable outcome expectations and personalize follow-up and rehabilitation plans. It will need further validation and updating for contemporary patients.

PMID:37523199 | DOI:10.1001/jamaneurol.2023.2392

JAMA Pediatr. 2023 Jul 31. doi: 10.1001/jamapediatrics.2023.2584. Online ahead of print.

NO ABSTRACT

PMID:37523191 | DOI:10.1001/jamapediatrics.2023.2584

JAMA Netw Open. 2023 Jul 3;6(7):e2324969. doi: 10.1001/jamanetworkopen.2023.24969.

ABSTRACT

IMPORTANCE: Limited data describe the health status of sexual or gender minority (SGM) people due to inaccurate and inconsistent ascertainment of gender identity, sex assigned at birth, and sexual orientation.

OBJECTIVE: To evaluate whether the prevalence of 12 health conditions is higher among SGM adults in the All of Us Research Program data compared with cisgender heterosexual (non-SGM) people.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from a multidisciplinary research consortium, the All of Us Research Program, that links participant-reported survey information to electronic health records (EHR) and physical measurements. In total, 372 082 US adults recruited and enrolled at an All of Us health care provider organization or by directly visiting the enrollment website from May 31, 2017, to January 1, 2022, and were assessed for study eligibility.

EXPOSURES: Self-identified gender identity and sexual orientation group.

MAIN OUTCOMES AND MEASURES: Twelve health conditions were evaluated: 11 using EHR data and 1, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), using participants’ physical measurements. Logistic regression (adjusting for age, income, and employment, enrollment year, and US Census division) was used to obtain adjusted odds ratios (AORs) for the associations between each SGM group and health condition compared with a non-SGM reference group.

RESULTS: The analytic sample included 346 868 participants (median [IQR] age, 55 [39-68] years; 30 763 [8.9%] self-identified as SGM). Among participants with available BMI (80.2%) and EHR data (69.4%), SGM groups had higher odds of anxiety, depression, HIV diagnosis, and tobacco use disorder but lower odds of cardiovascular disease, kidney disease, diabetes, and hypertension. Estimated associations for asthma (AOR, 0.39 [95% CI, 0.24-0.63] for gender diverse people assigned male at birth; AOR, 0.51 [95% CI, 0.38-0.69] for transgender women), a BMI of 25 or higher (AOR, 1.65 [95% CI, 1.38-1.96] for transgender men), cancer (AOR, 1.15 [95% CI, 1.07-1.23] for cisgender sexual minority men; AOR, 0.88 [95% CI, 0.81-0.95] for cisgender sexual minority women), and substance use disorder (AOR, 0.35 [95% CI, 0.24-0.52] for gender diverse people assigned female at birth; AOR, 0.65 [95% CI, 0.49-0.87] for transgender men) varied substantially across SGM groups compared with non-SGM groups.

CONCLUSIONS AND RELEVANCE: In this cross-sectional analysis of data from the All of Us Research Program, SGM participants experienced health inequities that varied by group and condition. The All of Us Research Program can be a valuable resource for conducting health research focused on SGM people.

PMID:37523187 | DOI:10.1001/jamanetworkopen.2023.24969