Tag: nevin manimala

Proc Natl Acad Sci U S A. 2023 Aug 15;120(33):e2203828120. doi: 10.1073/pnas.2203828120. Epub 2023 Aug 7.

ABSTRACT

Cellular omics such as single-cell genomics, proteomics, and microbiomics allow the characterization of tissue and microbial community composition, which can be compared between conditions to identify biological drivers. This strategy has been critical to revealing markers of disease progression, such as cancer and pathogen infection. A dedicated statistical method for differential variability analysis is lacking for cellular omics data, and existing methods for differential composition analysis do not model some compositional data properties, suggesting there is room to improve model performance. Here, we introduce sccomp, a method for differential composition and variability analyses that jointly models data count distribution, compositionality, group-specific variability, and proportion mean-variability association, being aware of outliers. sccomp provides a comprehensive analysis framework that offers realistic data simulation and cross-study knowledge transfer. Here, we demonstrate that mean-variability association is ubiquitous across technologies, highlighting the inadequacy of the very popular Dirichlet-multinomial distribution. We show that sccomp accurately fits experimental data, significantly improving performance over state-of-the-art algorithms. Using sccomp, we identified differential constraints and composition in the microenvironment of primary breast cancer.

PMID:37549298 | DOI:10.1073/pnas.2203828120

Proc Natl Acad Sci U S A. 2023 Aug 15;120(33):e2304415120. doi: 10.1073/pnas.2304415120. Epub 2023 Aug 7.

ABSTRACT

Real-world healthcare data sharing is instrumental in constructing broader-based and larger clinical datasets that may improve clinical decision-making research and outcomes. Stakeholders are frequently reluctant to share their data without guaranteed patient privacy, proper protection of their datasets, and control over the usage of their data. Fully homomorphic encryption (FHE) is a cryptographic capability that can address these issues by enabling computation on encrypted data without intermediate decryptions, so the analytics results are obtained without revealing the raw data. This work presents a toolset for collaborative privacy-preserving analysis of oncological data using multiparty FHE. Our toolset supports survival analysis, logistic regression training, and several common descriptive statistics. We demonstrate using oncological datasets that the toolset achieves high accuracy and practical performance, which scales well to larger datasets. As part of this work, we propose a cryptographic protocol for interactive bootstrapping in multiparty FHE, which is of independent interest. The toolset we develop is general-purpose and can be applied to other collaborative medical and healthcare application domains.

PMID:37549296 | DOI:10.1073/pnas.2304415120

Proc Natl Acad Sci U S A. 2023 Aug 15;120(33):e2302661120. doi: 10.1073/pnas.2302661120. Epub 2023 Aug 7.

ABSTRACT

Polycystic Echinococcosis (PE), a neglected life-threatening zoonotic disease caused by the cestode Echinococcus vogeli, is endemic in the Amazon. Despite being treatable, PE reaches a case fatality rate of around 29% due to late or missed diagnosis. PE is sustained in Pan-Amazonia by a complex sylvatic cycle. The hunting of its infected intermediate hosts (especially the lowland paca Cuniculus paca) enables the disease to further transmit to humans, when their viscera are improperly handled. In this study, we compiled a unique dataset of host occurrences (~86000 records) and disease infections (~400 cases) covering the entire Pan-Amazonia and employed different modeling and statistical tools to unveil the spatial distribution of PE’s key animal hosts. Subsequently, we derived a set of ecological, environmental, climatic, and hunting covariates that potentially act as transmission risk factors and used them as predictors of two independent Maximum Entropy models, one for animal infections and one for human infections. Our findings indicate that temperature stability promotes the sylvatic circulation of the disease. Additionally, we show how El Niño-Southern Oscillation (ENSO) extreme events disrupt hunting patterns throughout Pan-Amazonia, ultimately affecting the probability of spillover. In a scenario where climate extremes are projected to intensify, climate change at regional level appears to be indirectly driving the spillover of E. vogeli. These results hold substantial implications for a wide range of zoonoses acquired at the wildlife-human interface for which transmission is related to the manipulation and consumption of wild meat, underscoring the pressing need for enhanced awareness and intervention strategies.

PMID:37549288 | DOI:10.1073/pnas.2302661120

Proc Natl Acad Sci U S A. 2023 Aug 15;120(33):e2210500120. doi: 10.1073/pnas.2210500120. Epub 2023 Aug 7.

ABSTRACT

Simulations can help unravel the complicated ways in which molecular structure determines function. Here, we use molecular simulations to show how slight alterations of a molecular motor’s structure can cause the motor’s typical dynamical behavior to reverse directions. Inspired by autonomous synthetic catenane motors, we study the molecular dynamics of a minimal motor model, consisting of a shuttling ring that moves along a track containing interspersed binding sites and catalytic sites. The binding sites attract the shuttling ring while the catalytic sites speed up a reaction between molecular species, which can be thought of as fuel and waste. When that fuel and waste are held in nonequilibrium steady-state concentrations, the free energy from the reaction drives directed motion of the shuttling ring along the track. Using this model and nonequilibrium molecular dynamics, we show that the shuttling ring’s direction can be reversed by simply adjusting the spacing between binding and catalytic sites on the track. We present a steric mechanism behind the current reversal, supported by kinetic measurements from the simulations. These results demonstrate how molecular simulation can guide future development of artificial molecular motors.

PMID:37549273 | DOI:10.1073/pnas.2210500120

J Vet Intern Med. 2023 Aug 7. doi: 10.1111/jvim.16831. Online ahead of print.

ABSTRACT

BACKGROUND: Attainment of adequate transfer of passive immunity (TPI) is critical to health of calves; however, studies comparing available tools for measurement of TPI in individual beef animals are limited.

OBJECTIVES: To report agreement between 4 tests evaluating individual TPI status in beef calves.

ANIMALS: One hundred ninety-six beef calves born to cows and heifers presenting for calving management or dystocia.

METHODS: Retrospective study to assess serum immunoglobulin (IgG) concentrations via turbidimetric immunoassay (TI), gamma-glutamyl transferase (GGT), serum total protein (TP), and single radial immunodiffusion (RID; reference standard). Test agreement was evaluated using Passing-Bablok regression, Bland-Altman analysis, Cohen’s kappa, and receiver operating characteristic (ROC) curves with and without covariate adjustment to determine optimal thresholds.

RESULTS: Correlation between RID and test results varied: TI, ρ = 0.757; TP, ρ = 0.715; GGT: ρ = 0.413. For the TI compared to RID, regression analysis identified a constant (intercept = -0.51 [CI: -2.63, 3.05]) and proportional (slope = 1.87 [CI: 1.69, 2.08]) bias. Based on ROC, TI concentrations of ≤9.89 and ≤13.76 g/L, and TP concentrations of ≤5.5 and ≤6.0 g/dL, indicated IgG concentrations <18.0 and <25.0 g/L, respectively.

CONCLUSIONS AND CLINICAL IMPORTANCE: Within this cohort of calves, TI demonstrated the best correlation with RID; however, significant bias was identified which led to frequent underestimation of IgG concentration. Serum total protein demonstrated less correlation with RID but had less misclassification than TI. Both TI and TP demonstrated less correlation for calves that received colostrum replacement prompting clinical awareness of colostrum type when evaluating individual TPI in beef calves.

PMID:37549250 | DOI:10.1111/jvim.16831

J Infect Dis. 2023 Aug 7:jiad297. doi: 10.1093/infdis/jiad297. Online ahead of print.

ABSTRACT

BACKGROUND: Our study aimed to determine the risk of herpes zoster reactivation and COVID-19 vaccination (mRNA vaccine [BNT162b2] and adenovirus-vectored vaccine [ChAdOx1 nCoV-19]).

METHODS: This retrospective study analyzed herpes zoster cases diagnosed between February 26, 2021 and June 30, 2021 and registered in the National Health Insurance Service database. A matched case-control study with a 1:3 matching ratio, and a propensity score matching (PSM) study with a 1:1 ratio of vaccinated and unvaccinated individuals were performed.

RESULTS: In the matched case control analysis, BNT162b2 was associated with an increased risk of herpes zoster reactivation (first dose, adjusted odds ratio [aOR]: 1.11 [95% confidence interval {CI}: 1.06-1.15]; second dose, aOR: 1.17 [95% CI: 1.12-1.23]). PSM analysis revealed a statistically significant increase in risk within 18 days following any vaccination (adjusted hazard ratio [aHR]: 1.09 [95% CI: 1.02-1.16]). BNT162b2 was associated with an increased risk at 18 days post-vaccination (aHR: 1.65 [95% CI: 1.35-2.02]) and second dose (aHR: 1.10 [95% CI: 1.02-1.19]). However, the risk did not increase in both analysis of ChAdOx1 vaccination.

CONCLUSIONS: mRNA COVID-19 vaccination possibly increases the risk of herpes zoster reactivation, and thus close follow-up for herpes zoster reactivation is required.

PMID:37549237 | DOI:10.1093/infdis/jiad297

Cochrane Database Syst Rev. 2023 Aug 7;8:CD011022. doi: 10.1002/14651858.CD011022.pub3.

ABSTRACT

BACKGROUND: Dementia is a syndrome of acquired cognitive impairment which is severe enough to interfere with independent living. Over the course of the illness, people with dementia also experience changes in emotions, behaviour and social relationships. According to Alzheimer’s Disease International, dementia affects approximately 55 million people worldwide. The latest NICE guideline for dementia highlights the value of diverse treatment options for the different stages and symptoms of dementia, including non-pharmacological treatments. Relevant literature also argues for the value of interventions that acknowledge the complexity of the condition and address the person as a whole, including their physical, emotional, social and cognitive processes. A growing literature highlights the capacity of the arts and has embodied practices to address this complexity. Dance movement therapy (DMT) is an embodied psychological intervention that can address complexity and thus may be useful for people with dementia, but its effectiveness remains unclear.

OBJECTIVES: To assess the effects of dance movement therapy on behavioural, social, cognitive and emotional symptoms of people with dementia in comparison to no treatment, standard care or any other treatment. Also, to compare different forms of dance movement therapy (e.g. Laban-based dance movement therapy, Chacian dance movement therapy or Authentic Movement) SEARCH METHODS: We searched the Cochrane Dementia and Cognitive Improvement Group’s register, MEDLINE (Ovid SP), Embase (Ovid SP), PsycINFO (Ovid SP), CINAHL (EBSCOhost), Web of Science Core Collection (Clarivate), LILACS (BIREME), ClinicalTrials.gov and the World Health Organization’s meta-register of the International Clinical Trials Registry Portal until 8 December 2022.

SELECTION CRITERIA: We included randomised controlled trials (RCTs) that included people with dementia, of any age and in any setting. The DMT intervention had to be delivered by a dance movement therapy practitioner who (i) had received formal training (ii) was a dance movement therapist in training or (iii) was otherwise recognised as a dance movement therapist in the country in which the study was conducted.

DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data and evaluated methodological quality. We expressed effect estimates using the mean difference (MD) between intervention groups and presented associated confidence intervals (CIs). We used GRADE methods to rate our certainty in the results.

MAIN RESULTS: We found only one study eligible for inclusion in this review. This was a 3-arm parallel-group RCT conducted in Hong Kong involving 204 adults with mild neurocognitive disorder or dementia. The study examined the effects of short-term (12 weeks) group DMT in comparison with exercise and a waiting-list control group immediately post-intervention and three and nine months later. We found that, at the end of the intervention, DMT may result in little to no difference in neuropsychiatric symptoms assessed with the 12-item Neuropsychiatric Inventory when compared with waiting list (MD 0.3, 95% CI -0.96 to 1.56; low-certainty evidence) or exercise (MD -0.30, 95% CI -1.83 to 1.23; low-certainty evidence). Nor was there any evidence of effects at later time points. Cognitive functioning was assessed with a variety of instruments and there were no statistically significant between-group differences (low-certainty evidence). When compared to exercise or waiting list, DMT may result in little to no difference in cognitive function immediately after the intervention or at follow-up. In comparison to waiting list, DMT may result in a slight reduction in depression assessed with the 4-item Geriatric Depression Scale at the end of therapy (MD -0.60, 95% CI -0.96 to -0.24; low-certainty evidence). This slight positive effect of DMT on depression scores was sustained at three and nine months after the completion of the intervention. DMT may also reduce depression slightly in comparison with exercise at the end of therapy (MD -0.40, 95% CI -0.76 to -0.04, low-certainty evidence), an effect also sustained at three and nine months. Our fourth primary outcome, quality of life, was not assessed in the included study. There were data for two of our secondary outcomes, social and occupational functioning and dropouts (which we used as a proxy for acceptability), but in both cases the evidence was of very low certainty and hence our confidence in the results was very low. For all outcomes, we considered the certainty of the evidence in relation to our review objectives to be low or very low in GRADE terms due to indirectness (because not all participants in the included study had a diagnosis of dementia) and imprecision.

AUTHORS’ CONCLUSIONS: This review included one RCT with a low risk of bias. Due to the low certainty of the evidence, the true effects of DMT as an intervention for dementia may be substantially different from those found. More RCTs are needed to determine with any confidence whether DMT has beneficial effects on dementia.

PMID:37549216 | DOI:10.1002/14651858.CD011022.pub3

Psychosom Med. 2023 Aug 7. doi: 10.1097/PSY.0000000000001242. Online ahead of print.

ABSTRACT

OBJECTIVE: eHealth is a useful tool to deliver lifestyle interventions for patients with cardiometabolic diseases. However, there are inconsistent findings about whether these eHealth interventions should be supported by a human professional, or whether self-help interventions are equally effective.

METHODS: Databases were searched between January 1995 and October 2021 for randomized controlled trials on cardiometabolic diseases (cardiovascular disease, chronic kidney disease, type 1 and 2 diabetes mellitus) and eHealth lifestyle interventions. A multilevel meta-analysis was used to pool clinical and behavioral health outcomes. Moderator analyses assessed the effect of intervention type (self-help vs. human-supported), dose of human support (minor vs. major part of intervention), and delivery mode of human support (remote vs. blended). 107 papers fulfilled eligibility criteria and 102 unique (N = 20,781) studies were included.

RESULTS: The analysis showed a positive effect of eHealth lifestyle interventions on clinical and behavioral health outcomes (p < .001). However, these effects were not moderated by intervention type (p = .169), dose (p = .698), or delivery mode of human support (p = .557).

CONCLUSION: This shows that self-help eHealth interventions are equally effective as human-supported ones in improving health outcomes among cardiometabolic disease patients. Future studies could investigate whether higher quality eHealth interventions compensate for a lack of human support.Meta-analysis registration: PROSPERO CRD42021269263.

PMID:37549197 | DOI:10.1097/PSY.0000000000001242

J Am Coll Health. 2023 Aug 7:1-12. doi: 10.1080/07448481.2023.2237585. Online ahead of print.

ABSTRACT

Objective: To investigate COVID-19’s impact on sleep, specifically insomnia, in college students. Participants: Students from a private university were eligible if they registered for Refresh, an online sleep-health program. Methods: A pre-intervention survey was distributed and assessed insomnia and COVID-19 factors using the Insomnia Severity Index (ISI) and a COVID-19 questionnaire. Baseline ISI scores from students enrolled in 2020-2021 were compared to scores from students enrolled in 2018-2019 using a two-sample t-test. Associations between insomnia and the COVID-19 factors were determined using chi-square tests. Results: There was no significant difference in baseline ISI scores when comparing 2018-2019 scores to those collected during the pandemic, p = 0.274. There was a statistically significant association between having insomnia and a student’s learning location, p = 0.006, as well as disturbances in sleep caused by the pandemic, p = 0.026. Conclusion: Our results indicate that the COVID-19 pandemic did not worsen baseline insomnia.

PMID:37549005 | DOI:10.1080/07448481.2023.2237585

JMIR Form Res. 2023 Aug 7;7:e43271. doi: 10.2196/43271.

ABSTRACT

BACKGROUND: Every year, one-fourth of the people in the United Kingdom experience diagnosable mental health concerns, yet only a proportion receive a timely diagnosis and treatment. With novel developments in digital technologies, the potential to increase access to mental health assessments and triage is promising.

OBJECTIVE: This study aimed to investigate the current state of mental health provision in the United Kingdom and understand the utility of, and interest in, digital mental health technologies.

METHODS: A web-based survey was generated using Qualtrics XM. Participants were recruited via social media. Data were explored using descriptive statistics.

RESULTS: The majority of the respondents (555/618, 89.8%) had discussed their mental health with a general practitioner. More than three-fourths (503/618, 81.4%) of the respondents had been diagnosed with a mental health disorder, with the most common diagnoses being depression and generalized anxiety disorder. Diagnostic waiting times from first contact with a health care professional varied by diagnosis. Neurodevelopmental disorders (30/56, 54%), bipolar disorder (25/52, 48%), and personality disorders (48/101, 47.5%) had the longest waiting times, with almost half (103/209, 49.3%) of these diagnoses taking >6 months. Participants stated that waiting times resulted in symptoms worsening (262/353, 74.2%), lower quality of life (166/353, 47%), and the necessity to seek emergency care (109/353, 30.9%). Of the 618 participants, 386 (62.5%) stated that they felt that their mental health symptoms were not always taken seriously by their health care provider and 297 (48.1%) were not given any psychoeducational information. The majority of the respondents (416/595, 77.5%) did not have the chance to discuss mental health support and treatment options. Critically, 16.1% (96/595) did not find any treatment or support provided at all helpful, with 63% (48/76) having discontinued treatment with no effective alternatives. Furthermore, 88.3% (545/617) of the respondents) had sought help on the web regarding mental health symptoms, and 44.4% (272/612) had used a web application or smartphone app for their mental health. Psychoeducation (364/596, 61.1%), referral to a health care professional (332/596, 55.7%), and symptom monitoring (314/596, 52.7%) were the most desired app features. Only 6.8% (40/590) of the participants said that they would not be interested in using a mental health assessment app. Respondents were the most interested to receive an overall severity score of their mental health symptoms (441/546, 80.8%) and an indication of whether they should seek mental health support (454/546, 83.2%).

CONCLUSIONS: Key gaps in current UK mental health care provision are highlighted. Assessment and treatment waiting times together with a lack of information regarding symptoms and treatment options translated into poor care experiences. The participants’ responses provide proof-of-concept support for the development of a digital mental health assessment app and valuable recommendations regarding desirable app features.

PMID:37549003 | DOI:10.2196/43271