98 research outputs found
Sharp Spectral Rates for Koopman Operator Learning
Non-linear dynamical systems can be handily described by the associated
Koopman operator, whose action evolves every observable of the system forward
in time. Learning the Koopman operator and its spectral decomposition from data
is enabled by a number of algorithms. In this work we present for the first
time non-asymptotic learning bounds for the Koopman eigenvalues and
eigenfunctions. We focus on time-reversal-invariant stochastic dynamical
systems, including the important example of Langevin dynamics. We analyze two
popular estimators: Extended Dynamic Mode Decomposition (EDMD) and Reduced Rank
Regression (RRR). Our results critically hinge on novel minimax estimation
bounds for the operator norm error, that may be of independent interest. Our
spectral learning bounds are driven by the simultaneous control of the operator
norm error and a novel metric distortion functional of the estimated
eigenfunctions. The bounds indicates that both EDMD and RRR have similar
variance, but EDMD suffers from a larger bias which might be detrimental to its
learning rate. Our results shed new light on the emergence of spurious
eigenvalues, an issue which is well known empirically. Numerical experiments
illustrate the implications of the bounds in practice.Comment: 10 pages, 3 figures, 6 appendice
Transfer learning for atomistic simulations using GNNs and kernel mean embeddings
Interatomic potentials learned using machine learning methods have been
successfully applied to atomistic simulations. However, deep learning pipelines
are notoriously data-hungry, while generating reference calculations is
computationally demanding. To overcome this difficulty, we propose a transfer
learning algorithm that leverages the ability of graph neural networks (GNNs)
in describing chemical environments, together with kernel mean embeddings. We
extract a feature map from GNNs pre-trained on the OC20 dataset and use it to
learn the potential energy surface from system-specific datasets of catalytic
processes. Our method is further enhanced by a flexible kernel function that
incorporates chemical species information, resulting in improved performance
and interpretability. We test our approach on a series of realistic datasets of
increasing complexity, showing excellent generalization and transferability
performance, and improving on methods that rely on GNNs or ridge regression
alone, as well as similar fine-tuning approaches. We make the code available to
the community at https://github.com/IsakFalk/atomistic_transfer_mekrr.Comment: 18 pages, 3 figures, 5 table
No evidence for allelic association between Covid-19 and ACE2 genetic variants by direct exome sequencing in 99 SARS-CoV-2 positive patients
Expression analysis of miRNA hsa-let7b-5p in naso-oropharyngeal swabs of COVID-19 patients supports its role in regulating ACE2 and DPP4 receptors
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the novel coronavirus responsible for worldwide coronavirus disease (COVID-19). We previously observed that Angiotensin-converting enzyme 2 (ACE2) and Dipeptidyl peptidase-4 (DPP4) are significantly overexpressed in naso-oropharyngeal swabs (NPS) of COVID-19 patients, suggesting their putative functional role in the disease progression. ACE2 and DPP4 overexpression in COVID-19 patients may be associated to epigenetic mechanism, such as miRNA differential expression. We investigated if hsa-let7b-5p, reported to target both ACE2 and DPP4 transcripts, could be involved in the regulation of these genes. We verified that the inhibition and overexpression of hsa-let7b-5p matched to a modulation of both ACE2 and DPP4 levels. Then, we observed a statistically significant downregulation (FC = -1.5; p < 0.05) of hsa-let7b-5p in the same COVID-19 and control samples of our previous study. This is the first study that shows hsa-let7b-5p low expression in naso-oropharyngeal swabs of COVID-19 patients and demonstrates a functional role of this miR in regulating ACE2 and DPP4 levels. These data suggest the involvement of hsa-let7b-5p in the regulation of genes necessary for SARS-CoV-2 infections and its putative role as a therapeutic target for COVID-19
Elevated left and reduced right orbitomedial prefrontal fractional anisotropy in adults with bipolar disorder revealed by tract-based spatial statistics
Context - Diffusion tensor imaging (DTI) studies in adults with bipolar disorder (BD) indicate altered white matter (WM) in the orbitomedial prefrontal cortex (OMPFC), potentially underlying abnormal prefrontal corticolimbic connectivity and mood dysregulation in BD. Objective - To use tract-based spatial statistics (TBSS) to examine WM skeleton (ie, the most compact whole-brain WM) in subjects with BD vs healthy control subjects. Design - Cross-sectional, case-control, whole-brain DTI using TBSS. Setting - University research institute. Participants - Fifty-six individuals, 31 having a DSM-IV diagnosis of BD type I (mean age, 35.9 years [age range, 24-52 years]) and 25 controls (mean age, 29.5 years [age range, 19-52 years]). Main Outcome Measures - Fractional anisotropy (FA) longitudinal and radial diffusivities in subjects with BD vs controls (covarying for age) and their relationships with clinical and demographic variables. Results - Subjects with BD vs controls had significantly greater FA (t > 3.0, P = .05 corrected) in the left uncinate fasciculus (reduced radial diffusivity distally and increased longitudinal diffusivity centrally), left optic radiation (increased longitudinal diffusivity), and right anterothalamic radiation (no significant diffusivity change). Subjects with BD vs controls had significantly reduced FA (t > 3.0, P = .05 corrected) in the right uncinate fasciculus (greater radial diffusivity). Among subjects with BD, significant negative correlations (P < .01) were found between age and FA in bilateral uncinate fasciculi and in the right anterothalamic radiation, as well as between medication load and FA in the left optic radiation. Decreased FA (P < .01) was observed in the left optic radiation and in the right anterothalamic radiation among subjects with BD taking vs those not taking mood stabilizers, as well as in the left optic radiation among depressed vs remitted subjects with BD. Subjects having BD with vs without lifetime alcohol or other drug abuse had significantly decreased FA in the left uncinate fasciculus. Conclusions - To our knowledge, this is the first study to use TBSS to examine WM in subjects with BD. Subjects with BD vs controls showed greater WM FA in the left OMPFC that diminished with age and with alcohol or other drug abuse, as well as reduced WM FA in the right OMPFC. Mood stabilizers and depressed episode reduced WM FA in left-sided sensory visual processing regions among subjects with BD. Abnormal right vs left asymmetry in FA in OMPFC WM among subjects with BD, likely reflecting increased proportions of left-sided longitudinally aligned and right-sided obliquely aligned myelinated fibers, may represent a biologic mechanism for mood dysregulation in BD
Epstein-Barr Virus in Cutaneous T-Cell Lymphomas: Evaluation of the Viral Presence and Significance in Skin and Peripheral Blood
The importance of viral agents in the development of cutaneous T-cell lymphomas (CTCL) is still debated. For this purpose, we retrospectively evaluated the Epstein-Barr virus (EBV) presence in Sézary syndrome (SS), mycosis fungoides (MF), inflammatory dermatoses (ID), and healthy donors (HD) using different approaches: EBV-DNA was quantified in skin biopsies and peripheral blood using real-time PCR, EBV-encoded small RNA (EBER) transcripts were detected by in situ hybridization (ISH), and latent membrane protein1-2 antigens were detected by immunohistochemistry. Skin biopsies were EBV-DNA-positive in 8/30 (27%) SS, 7/71 (10%) MF, and 2/18 (11%) ID patients and in none of the 25 normal skin samples. Positive mRNA (EBER) signals, always confined to cerebriform T lymphocytes, were found in 5/30 SS patients (17%), whereas signals in all MF and ID patients were negative. The presence of EBV-DNA in skin and blood samples was associated with a significantly lower survival in MF/SS patients. In evaluating EBV serological status, most (>70%) SS, MF, and ID patients showed a serological reactivation demonstrated by the presence of anti-EA IgG. In conclusion, although the finding of EBV-DNA in CTCL does not prove its etiopathogenetic role and may be related instead to immunosuppression, our study demonstrates that it has prognostic relevance
Image enhanced endoscopy and molecular biomarkers vs Seattle protocol to diagnose dysplasia in Barrett's esophagus
BACKGROUND: Dysplasia in Barrett's esophagus (BE) is often invisible on high-resolution white-light endoscopy (HRWLE). We compared the diagnostic accuracy for inconspicuous dysplasia of the combination of autofluorescence (AFI)-guided probe-based confocal laser endomicroscopy (pCLE) and molecular biomarkers versus HRWLE with Seattle protocol biopsies. METHODS: BE patients with no dysplastic lesions were block randomized to standard endoscopy (HRWLE with Seattle protocol) or AFI-guided pCLE with targeted biopsies for molecular biomarkers (p53 and cyclin A by immunohistochemistry; aneuploidy by image cytometry), with crossover to the other arm after 6-12 weeks. Histological endpoint was diagnosis from all study biopsies (trial histology). Sensitivity analysis was performed for overall histology, which included diagnoses within 12 months from first study endoscopy. Endoscopists were blinded to the referral endoscopy and histology results. Primary outcome was diagnostic accuracy for dysplasia by real-time pCLE versus HRWLE biopsies. RESULTS: Of 154 patients recruited, 134 completed both arms. In the primary outcome analysis (trial histology analysis), AFI-guided pCLE had similar sensitivity for dysplasia compared to standard endoscopy [74.3% (95%CI, 56.7-87.5) vs 80.0% (95%CI 63.1-91.6), p=0.48]. Multivariate logistic regression showed pCLE optical dysplasia, aberrant p53 and aneuploidy had strongest correlation with dysplasia (secondary outcome). This 3-biomarker panel had higher sensitivity for any grade of dysplasia than Seattle protocol (81.5% vs 51.9%, p<0.001) in the overall histology analysis, but not in the trial histology analysis (91.4% vs 80.0%; p=0.16) with an area under receiver operating curve of 0.83. CONCLUSIONS: Seattle protocol biopsies miss dysplasia in approximately half of patients with inconspicuous neoplasia. AFI-guided pCLE has similar accuracy to the current gold standard. Addition of molecular biomarkers could improve diagnostic accuracy
British Society of Gastroenterology guidelines on the diagnosis and management of patients at risk of gastric adenocarcinoma
Gastric adenocarcinoma carries a poor prognosis, in part due to the late stage of diagnosis. Risk factors include Helicobacter pylori infection, family history of gastric cancer - in particular, hereditary diffuse gastric cancer and pernicious anaemia. The stages in the progression to cancer include chronic gastritis, gastric atrophy (GA), gastric intestinal metaplasia (GIM) and dysplasia. The key to early detection of cancer and improved survival is to non-invasively identify those at risk before endoscopy. However, although biomarkers may help in the detection of patients with chronic atrophic gastritis, there is insufficient evidence to support their use for population screening. High-quality endoscopy with full mucosal visualisation is an important part of improving early detection. Image-enhanced endoscopy combined with biopsy sampling for histopathology is the best approach to detect and accurately risk-stratify GA and GIM. Biopsies following the Sydney protocol from the antrum, incisura, lesser and greater curvature allow both diagnostic confirmation and risk stratification for progression to cancer. Ideally biopsies should be directed to areas of GA or GIM visualised by high-quality endoscopy. There is insufficient evidence to support screening in a low-risk population (undergoing routine diagnostic oesophagogastroduodenoscopy) such as the UK, but endoscopic surveillance every 3 years should be offered to patients with extensive GA or GIM. Endoscopic mucosal resection or endoscopic submucosal dissection of visible gastric dysplasia and early cancer has been shown to be efficacious with a high success rate and low rate of recurrence, providing that specific quality criteria are met
British Society of Gastroenterology guidelines on the diagnosis and management of patients at risk of gastric adenocarcinoma
Gastric adenocarcinoma carries a poor prognosis, in part due to the late stage of diagnosis. Risk factors include Helicobacter pylori infection, family history of gastric cancer - in particular, hereditary diffuse gastric cancer and pernicious anaemia. The stages in the progression to cancer include chronic gastritis, gastric atrophy (GA), gastric intestinal metaplasia (GIM) and dysplasia. The key to early detection of cancer and improved survival is to non-invasively identify those at risk before endoscopy. However, although biomarkers may help in the detection of patients with chronic atrophic gastritis, there is insufficient evidence to support their use for population screening. High-quality endoscopy with full mucosal visualisation is an important part of improving early detection. Image-enhanced endoscopy combined with biopsy sampling for histopathology is the best approach to detect and accurately risk-stratify GA and GIM. Biopsies following the Sydney protocol from the antrum, incisura, lesser and greater curvature allow both diagnostic confirmation and risk stratification for progression to cancer. Ideally biopsies should be directed to areas of GA or GIM visualised by high-quality endoscopy. There is insufficient evidence to support screening in a low-risk population (undergoing routine diagnostic oesophagogastroduodenoscopy) such as the UK, but endoscopic surveillance every 3 years should be offered to patients with extensive GA or GIM. Endoscopic mucosal resection or endoscopic submucosal dissection of visible gastric dysplasia and early cancer has been shown to be efficacious with a high success rate and low rate of recurrence, providing that specific quality criteria are met
Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting: evidence from the REPOSI Register
Diabetes is an increasing global health burden with the highest prevalence (24.0%) observed in elderly people. Older diabetic adults have a greater risk of hospitalization and several geriatric syndromes than older nondiabetic adults. For these conditions, special care is required in prescribing therapies including anti- diabetes drugs. Aim of this study was to evaluate the appropriateness and the adherence to safety recommendations in the prescriptions of glucose-lowering drugs in hospitalized elderly patients with diabetes. Data for this cross-sectional study were obtained from the REgistro POliterapie-Società Italiana Medicina Interna (REPOSI) that collected clinical information on patients aged ≥ 65 years acutely admitted to Italian internal medicine and geriatric non-intensive care units (ICU) from 2010 up to 2019. Prescription appropriateness was assessed according to the 2019 AGS Beers Criteria and anti-diabetes drug data sheets.Among 5349 patients, 1624 (30.3%) had diagnosis of type 2 diabetes. At admission, 37.7% of diabetic patients received treatment with metformin, 37.3% insulin therapy, 16.4% sulfonylureas, and 11.4% glinides. Surprisingly, only 3.1% of diabetic patients were treated with new classes of anti- diabetes drugs. According to prescription criteria, at admission 15.4% of patients treated with metformin and 2.6% with sulfonylureas received inappropriately these treatments. At discharge, the inappropriateness of metformin therapy decreased (10.2%, P < 0.0001). According to Beers criteria, the inappropriate prescriptions of sulfonylureas raised to 29% both at admission and at discharge. This study shows a poor adherence to current guidelines on diabetes management in hospitalized elderly people with a high prevalence of inappropriate use of sulfonylureas according to the Beers criteria
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