Spatial Deconvolution of Cell Types and Cell States at Scale Utilizing TACIT.

Identifying cell types and states remains a time-consuming and error-prone challenge for spatial biology. While deep learning is increasingly used, it is difficult to generalize due to variability at the level of cells, neighborhoods, and niches in health and disease. To address this, we developed TACIT, an unsupervised algorithm for cell annotation using predefined signatures that operates without training data, using unbiased thresholding to distinguish positive cells from background, focusing on relevant markers to identify ambiguous cells in multiomic assays. Using five datasets (5,000,000-cells; 51-cell types) from three niches (brain, intestine, gland), TACIT outperformed existing unsupervised methods in accuracy and scalability. Integration of TACIT-identified cell with a novel Shiny app revealed new phenotypes in two inflammatory gland diseases. Finally, using combined spatial transcriptomics and proteomics, we discover under- and overrepresented immune cell types and states in regions of interest, suggesting multimodality is essential for translating spatial biology to clinical applications.

Single-cell and spatially resolved interactomics of tooth-associated keratinocytes in periodontitis.

Periodontitis affects billions of people worldwide. To address relationships of periodontal niche cell types and microbes in periodontitis, we generated an integrated single-cell RNA sequencing (scRNAseq) atlas of human periodontium (34-sample, 105918-cell), including sulcular and junctional keratinocytes (SK/JKs). SK/JKs displayed altered differentiation states and were enriched for effector cytokines in periodontitis. Single-cell metagenomics revealed 37 bacterial species with cell-specific tropism. Fluorescence in situ hybridization detected intracellular 16 S and mRNA signals of multiple species and correlated with SK/JK proinflammatory phenotypes in situ. Cell-cell communication analysis predicted keratinocyte-specific innate and adaptive immune interactions. Highly multiplexed immunofluorescence (33-antibody) revealed peri-epithelial immune foci, with innate cells often spatially constrained around JKs. Spatial phenotyping revealed immunosuppressed JK-microniches and SK-localized tertiary lymphoid structures in periodontitis. Here, we demonstrate impacts on and predicted interactomics of SK and JK cells in health and periodontitis, which requires further investigation to support precision periodontal interventions in states of chronic inflammation.

A comparison of severity of illness between the SARS-CoV-2 Omicron variant and Delta variant.

Background: The COVID-19 pandemic has disproportionally affected traditionally marginalized groups. Both the Delta and Omicron variants raised concern amongst public health officials due to potentially higher infectivity rates and disease severity than prior variants. This study sought to compare disease severity between adults infected with the Omicron variant and adults infected with the Delta variant who presented to the Emergency Department at an academic, safety-net hospital in Virginia. Methods: This retrospective cohort study used electronic medical record data of patients who presented to the Emergency Department and received a positive SARS-CoV-2 test between September 1, 2021, and January 31, 2022. Positive tests were stratified by genotypic variant through whole genome sequencing. Participants with the Omicron variant were propensity scores matched with individuals with the Delta variant. Results: Among 500 Delta and 500 Omicron participants, 279 propensity score-matched pairs were identified. Participants were predominantly unvaccinated, with medical comorbidities, and self-identified as Black. Individuals infected with the Delta variant had more severe disease compared to those with the Omicron variant, regardless of vaccination status. Patients with kidney, liver, and respiratory disease, as well as cancer, are at higher risk for severe disease. Patients with 2 doses of COVID-19 immunization trended toward less severe disease. Conclusions: Overall, these data further support the literature regarding the disproportionate effects of the COVID-19 pandemic on vulnerable patient populations - such as those with limited access to care, people of color, and those with chronic medical conditions - and can be used to inform public health interventions.

Prevalence and impact of metabolic syndrome on in-hospital outcomes in patients with acute myocardial infarction: A perspective from a developing country.

Acute myocardial infarction (AMI) often suffers from a high prevalence of metabolic syndrome (MetS). However, few studies in developing countries have focused on the effect of MetS on in-hospital outcomes in patients with AMI. We analyzed 199 patients with AMI who underwent primary percutaneous coronary intervention. This study aimed to determine the impact of MetS and factors related to in-hospital outcomes in patients with AMI. The study included 199 patients who met the criteria, with a mean age of 64.5 ±â€…11.3 years. Out Of the total number of patients, 136 (68.3%) were found to have MetS. Patients with MetS were more likely to be female, have a higher body mass index, larger waist circumference, and a higher prevalence of hypertension and diabetes than those without MetS. The rates of major complications, such as cardiogenic shock, heart failure, mechanical complications, and arrhythmias, were not significantly different between the 2 groups. MetS was not associated with in-hospital mortality with OR, 4.92 (95% CI 0.62-39.31, P = .13). In this study, increased waist circumference was associated with an increased all-cause mortality rate. However, the MetS group had a significantly higher rate of cardiovascular mortality than the group without MetS (P = .03). Among patients with AMI, the prevalence of metabolic syndrome was high. Patients with MetS did not exhibit an increased all-cause in-hospital mortality rate. Increased waist circumference is associated with increased all-cause mortality.

Prediction of obstructive coronary artery disease in patients undergoing heart valve surgery: A cross-sectional study in a tertiary care hospital.

Introduction: Estimating the probability of obstructive coronary artery disease in patients undergoing noncoronary cardiac surgery should be considered compulsory. Our study sought to evaluate the prevalence of obstructive coronary artery disease in patients undergoing valvular heart surgery and to utilize predictive methodology of concomitant obstructive coronary artery disease in these patients. Methods: The retrospective study cohort was derived from a tertiary care hospital registry of patients undergoing coronary angiogram prior to valvular heart operations. Decision tree, logistic regression, and support vector machine models were built to predict the probability of the appearance of obstructive coronary artery disease. A total of 367 patients from 2016 to 2019 were analyzed. Results: The mean age of the study population was 57.3±9.3 years, 45.2% of the patients were male. Of 367 patients, 76 (21%) patients had obstructive coronary artery disease. The decision tree, logistics regression, and support vector machine models had an area under the curve of 72% (95% CI: 62% - 81%), 67% (95% CI: 56% - 77%), and 78% (95% CI: 68% - 87%), respectively. Multivariate analysis indicated that hypertension (OR 1.98; P=0.032), diabetes (OR 2.32; P=0.040), age (OR 1.05; P=0.006), and typical angina (OR 5.46; P<0.001) had significant role in predicting the presence of obstructive coronary artery disease. Conclusion: Our study revealed that approximately one-fifth of patients who underwent valvular heart surgery had concomitant obstructive coronary artery disease. The support vector machine model showed the highest accuracy compared to the other model.

GZMK+CD8+ T cells Target a Specific Acinar Cell Type in Sjögren's Disease.

Sjögren's Disease (SjD) is a systemic autoimmune disease without a clear etiology or effective therapy. Utilizing unbiased single-cell and spatial transcriptomics to analyze human minor salivary glands in health and disease we developed a comprehensive understanding of the cellular landscape of healthy salivary glands and how that landscape changes in SjD patients. We identified novel seromucous acinar cell types and identified a population of PRR4+CST3+WFDC2- seromucous acinar cells that are particularly targeted in SjD. Notably, GZMK+CD8 T cells, enriched in SjD, exhibited a cytotoxic phenotype and were physically associated with immune-engaged epithelial cells in disease. These findings shed light on the immune response's impact on transitioning acinar cells with high levels of secretion and explain the loss of this specific cell population in SjD. This study explores the complex interplay of varied cell types in the salivary glands and their role in the pathology of Sjögren's Disease.

The global response: How cities and provinces around the globe tackled Covid-19 outbreaks in 2021.

Background: Tackling the spread of COVID-19 remains a crucial part of ending the pandemic. Its highly contagious nature and constant evolution coupled with a relative lack of immunity make the virus difficult to control. For this, various strategies have been proposed and adopted including limiting contact, social isolation, vaccination, contact tracing, etc. However, given the heterogeneity in the enforcement of these strategies and constant fluctuations in the strictness levels of these strategies, it becomes challenging to assess the true impact of these strategies in controlling the spread of COVID-19. Methods: In the present study, we evaluated various transmission control measures that were imposed in 10 global urban cities and provinces in 2021- Bangkok, Gauteng, Ho Chi Minh City, Jakarta, London, Manila City, New Delhi, New York City, Singapore, and Tokyo. Findings: Based on our analysis, we herein propose the population-level Swiss cheese model for the failures and pitfalls in various strategies that each of these cities and provinces had. Furthermore, whilst all the evaluated cities and provinces took a different personalized approach to managing the pandemic, what remained common was dynamic enforcement and monitoring of breaches of each barrier of protection. The measures taken to reinforce the barriers were adjusted continuously based on the evolving epidemiological situation. Interpretation: How an individual city or province handled the pandemic profoundly affected and determined how the entire country handled the pandemic since the chain of transmission needs to be broken at the very grassroot level to achieve nationwide control. Funding: The present study did not receive any external funding.

Predicting Anxiety and Depression Among Patients With COVID-19 in Concentrated Isolation at Medical Camps in Vietnam: A Descriptive Cross-Sectional Study.

Introduction: This study aims to assess the requirement for anxiety and depression treatment for patients with coronavirus disease 2019 (COVID-19) in medical camps in Bac Giang province, Vietnam. This information can help improve the government policy to reduce anxiety and depression in patients with COVID-19. Methods: A total of patients with 427 COVID-19 participated in the survey conducted from 5 to 15 June 2021 in Bac Giang province. The survey included 17 questions about the general characteristics of the patients, 15 questions to assess common COVID-19 symptoms, the Patient Health Questionnaire-9 (PHQ-9), and General Anxiety Disorder-7 (GAD-7) scores, and four questions to assess hospital reviews, including facilities, food, medical staff, and living conditions. Logistics regression analyses were conducted to assess the association between COVID-19 symptoms and high anxiety and depression (HAD) status. Results: A logistic regression analysis evaluated the risk factors in need of intervention. Our study showed that lower hospital review scores (odd ratio = 0.98; 95% confident interval = 0.97-0.99) were found to be a risk needing intervention. It was also identified that older patients (odd ratio = 1.1; 95% confident interval = 1.03-1.18), women (odd ratio = 1.31; 95% confident interval = 1.09-1.31), patients who were primary income earners in the family (odd ratio = 1.15; 95% confident interval = 1.03-1.28), patients who had headaches (odd ratio = 1.16; 95% confident interval = 1.06-1.21), and patients who had joint pain (odd ratio = 1.17; 95% confident interval = 1.06- 1.3) were risk factors for HAD status. Conclusion: Our research shows that every 10-year age increase was associated with a 10% increase in the likelihood of HAD status. Study subjects being primary income earners were also associated with a 15% increased risk of having HAD status. This study showed that a decrease in family income due to COVID-19 caused an increase in high-level anxiety/depression status.

Chest X-ray Severity Score as a Putative Predictor of Clinical Outcome in Hospitalized Patients: An Experience From a Vietnamese COVID-19 Field Hospital.

Background Through the coronavirus disease 2019 (COVID-19) pandemic, portable radiography was particularly useful for assessing and monitoring the COVID-19 disease in Vietnamese field hospitals. It provides a convenient and precise picture of the progression of the disease. The purpose of this study was to evaluate the predictive value of chest radiograph reporting systems (Brixia and total severity score (TSS)) and the National Early Warning Score (NEWS) clinical score in a group of hospitalized patients with COVID-19. Methods This retrospective cohort study used routinely collected clinical data from polymerase chain reaction (PCR)-positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients admitted to Field Hospital District 8, Ho Chi Minh City, Vietnam, from August 2021 to September 2021. The initial chest radiographs were scored based on the TSS and Brixia scoring systems to quantify the extent of lung involvement. After the chest radiograph score was reported, two residents calculated the rate of all-cause in-hospital mortality with the consultation of expert radiologists. In this study, NEWS2 scores on hospital admission were calculated. The gradient boosting machines (GBMs) and Shapley additive exPlanations (SHAP) were applied to access the important variable and improve the accuracy of mortality prediction. The adjusted odds ratio for predictor was presented by univariate analysis and multivariate analysis. Results The chest X-rays (CXRs) at the admission of 273 patients (mean age 59 years +/-16, 42.1% were male) were scored. In the univariate analysis, age, vaccination status, previous disease, NEWS2, a saturation of peripheral oxygen (Sp02), the Brixia and TSS scores were significant predictors of mortality (p-value < 0.05). In multivariate analysis, there were statistically significant differences in mortality between age, Sp02, Brixia score, and patients with previous diseases were independent predictors of mortality and hospitalization. A gradient boosting machine was performed in the train data set, which showed that the best hyperparameters for predicting the mortality of patients are the Brixia score (exclude TSS score). In the top five predictors, an increase in Brixia, age, and BMI increased the logarithmic number of probability clarifying as death status. Although the TSS and Brixia scores evaluated chest imaging, the TSS score was not essential as the Brixia score (rank 6/11). It was clear that the BMI and NEWS2 score was positively correlated with the Brixia score, and age did not affect this correlation. Meanwhile, we did not find any trend between the TSS score versus BMI and NEWS2. Conclusion When integrated with the BMI and NEWS2 clinical classification systems, the severity score of COVID-19 chest radiographs, particularly the Brixia score, was an excellent predictor of all-cause in-hospital mortality.

The effects of the COVID-19 lockdown on patients with chronic cardiovascular disease in Vietnam.

INTRODUCTION: We evaluated the impact of the lockdown policy during the COVID-19 pandemic on cardiovascular outpatients of a cardiology clinic in Vietnam from April to June 2020. We estimated the occurrence of different cardiovascular problems in general and the stability of blood pressure. METHODOLOGY: During the Covid-19 outbreak in Vietnam, we conducted a cross-sectional study to evaluate its impact on blood pressure stability of hypertensive patients treated as outpatients at the clinic of the University Medical Center (UMC), Ho Chi Minh City. RESULTS: The mean age of the recruited 493 patients was 62.2 ± 10.2 years. The stable blood pressure group consisted of 87% patients, while the unstable blood pressure group consisted of 13% patients. We found that 68% of the study population attended their follow-up appointments as scheduled: 87% with stable blood pressure versus only 13% with unstable blood pressure. Significant differences were noticed in body weight changes and cardiovascular problems between the two groups: body weight increase (22.6% vs. 10.2%), body weight decrease (3.2% vs. 6.7%), worsening of cardiovascular problems (35.5% vs. 17.9%) in the unstable and stable blood pressure groups, respectively. Multivariable regression analysis reflected the impact of the increase in body weight and occurrence of cardiovascular problems on the patients with unstable blood pressure. CONCLUSIONS: Our study provided concrete proof of the impact of the lockdown on chronic patients, which should warrant further surveys, and evaluation of the lockdown policy.

White matter abnormalities across different epilepsy syndromes in adults: an ENIGMA-Epilepsy study.

The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate patterns of neuroimaging abnormalities in common epilepsy syndromes, including temporal lobe epilepsy, extratemporal epilepsy, and genetic generalized epilepsy. Our goal was to rank the most robust white matter microstructural differences across and within syndromes in a multicentre sample of adult epilepsy patients. Diffusion-weighted MRI data were analysed from 1069 healthy controls and 1249 patients: temporal lobe epilepsy with hippocampal sclerosis (n = 599), temporal lobe epilepsy with normal MRI (n = 275), genetic generalized epilepsy (n = 182) and non-lesional extratemporal epilepsy (n = 193). A harmonized protocol using tract-based spatial statistics was used to derive skeletonized maps of fractional anisotropy and mean diffusivity for each participant, and fibre tracts were segmented using a diffusion MRI atlas. Data were harmonized to correct for scanner-specific variations in diffusion measures using a batch-effect correction tool (ComBat). Analyses of covariance, adjusting for age and sex, examined differences between each epilepsy syndrome and controls for each white matter tract (Bonferroni corrected at P < 0.001). Across 'all epilepsies' lower fractional anisotropy was observed in most fibre tracts with small to medium effect sizes, especially in the corpus callosum, cingulum and external capsule. There were also less robust increases in mean diffusivity. Syndrome-specific fractional anisotropy and mean diffusivity differences were most pronounced in patients with hippocampal sclerosis in the ipsilateral parahippocampal cingulum and external capsule, with smaller effects across most other tracts. Individuals with temporal lobe epilepsy and normal MRI showed a similar pattern of greater ipsilateral than contralateral abnormalities, but less marked than those in patients with hippocampal sclerosis. Patients with generalized and extratemporal epilepsies had pronounced reductions in fractional anisotropy in the corpus callosum, corona radiata and external capsule, and increased mean diffusivity of the anterior corona radiata. Earlier age of seizure onset and longer disease duration were associated with a greater extent of diffusion abnormalities in patients with hippocampal sclerosis. We demonstrate microstructural abnormalities across major association, commissural, and projection fibres in a large multicentre study of epilepsy. Overall, patients with epilepsy showed white matter abnormalities in the corpus callosum, cingulum and external capsule, with differing severity across epilepsy syndromes. These data further define the spectrum of white matter abnormalities in common epilepsy syndromes, yielding more detailed insights into pathological substrates that may explain cognitive and psychiatric co-morbidities and be used to guide biomarker studies of treatment outcomes and/or genetic research.

Quantification of total concentration of thiol functional groups in environmental samples by titration with monobromo(trimethylammonio)bimane and determination with tandem mass spectrometry.

Thiol compounds (R-SH) have many important biological functions and are principal controls of the speciation of several toxic metals in the environment. However, determining the concentration of thiols associated with environmental matrices is challenging due to the compounds' low abundance and interferences from non-thiol compounds for many available methods. Here a novel method has been developed and validated to quantify the total concentration of thiol functional groups in aqueous samples using derivatization with monobromo(trimethylammonio)bimane (qBBr) and quantification with tandem mass spectrometry. The thiol concentration was determined by titration of the sample with qBBr, which reacts selectively with thiols, and quantification of the residual qBBr. We systematically evaluated potential interferences from various organic compounds, inorganic ions (including sea water matrices), sulfide and mercury (Hg) species, and demonstrate that the method is highly sensitive, selective and robust. The limit of detection (LOD) for total thiols is in the nanomolar concentration range (~6 nM). The method performance was also demonstrated by determination of the total thiol concentration in different natural samples including boreal stream water (1.16 µM), wetland porewater (0.96 µM) and the Suwanee River natural organic matter (NOM) reference material SR101 N (7.9 µmol g-1). The developed method represents a combination of low LOD and high selectivity and robustness that is unsurpassed for total thiol concentration measurements.

The ENIGMA-Epilepsy working group: Mapping disease from large data sets.

Epilepsy is a common and serious neurological disorder, with many different constituent conditions characterized by their electro clinical, imaging, and genetic features. MRI has been fundamental in advancing our understanding of brain processes in the epilepsies. Smaller-scale studies have identified many interesting imaging phenomena, with implications both for understanding pathophysiology and improving clinical care. Through the infrastructure and concepts now well-established by the ENIGMA Consortium, ENIGMA-Epilepsy was established to strengthen epilepsy neuroscience by greatly increasing sample sizes, leveraging ideas and methods established in other ENIGMA projects, and generating a body of collaborating scientists and clinicians to drive forward robust research. Here we review published, current, and future projects, that include structural MRI, diffusion tensor imaging (DTI), and resting state functional MRI (rsfMRI), and that employ advanced methods including structural covariance, and event-based modeling analysis. We explore age of onset- and duration-related features, as well as phenomena-specific work focusing on particular epilepsy syndromes or phenotypes, multimodal analyses focused on understanding the biology of disease progression, and deep learning approaches. We encourage groups who may be interested in participating to make contact to further grow and develop ENIGMA-Epilepsy.

Determination of picomolar concentrations of thiol compounds in natural waters and biological samples by tandem mass spectrometry with online preconcentration and isotope-labeling derivatization.

We present a sensitive, selective and robust method for the determination of 14 thiol compounds in aqueous samples. Thiols were derivatized with ω-bromoacetonylquinolinium bromide (BQB) and its deuterium labeled equivalent D7-ω-bromoacetonylquinolinium bromide (D7). Derivatized thiols were preconcentrated by online solid-phase extraction (SPE) followed by liquid chromatography separation and electrospray ionization tandem mass spectrometry determination (SPE/LC-ESI-MS/MS). The robustness of the method was validated for wide ranges in pH, salinity, and concentrations of sulfide and dissolved organic carbon (DOC) to cover contrasting natural water types. The limits of detection (LODs) for the thiols were 3.1-66 pM. Between 6 and 14 of the thiols were detected in different natural sample types at variable concentrations: boreal wetland porewater (0.7-51 nM), estuarine sediment porewater (50 pM-11 nM), coastal sea water (60 pM-16 nM), and sulfate reducing bacterium cultures (80 pM-4 nM). MS/MS fragmentation of the compounds produces two pairs of common product ions, m/z 130.2/137.1 and 218.1/225.1, which enables scanning for unknown thiols in precursor ion scan mode. Using this approach, we identified cysteine, mercaptoacetic acid, N-acetyl-L-cysteine and sulfurothioic S-acid in boreal wetland porewater. The performance of the developed method sets a new state of the art for the determination of thiol compounds in environmental and biological samples.

Physicians' adherence to acute coronary syndrome prescribing guidelines in Vietnamese hospital practice: a cross-sectional study.

OBJECTIVES: To determine the extent of physicians' adherence to prescribing guidelines for acute coronary syndrome in Vietnamese hospitals. METHODS: Retrospective cross-sectional study of medical records of all patients with ACS admitted to two public hospitals in Ho Chi Minh City, Vietnam, from January to December 2013. Percentages of eligible patients receiving guideline-recommended medications were determined. Factors associated with non-adherence were identified using multivariate logistic regression. RESULTS: Overall, 711 medical records were reviewed and 284 patients fulfilled inclusion criteria (mean age 64 years; 69.4% male). Of those patients eligible for treatment, aspirin was prescribed for 97.9% at arrival and 96.3% at discharge; dual antiplatelet therapy was prescribed for 92.3% at arrival and 91.7% at discharge; loading doses were prescribed for 79.5% (aspirin) and 55.8% (clopidogrel); beta blockers were prescribed for 58.7% at arrival and 76.7% at discharge; angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) were prescribed for 89.1% at arrival or discharge; and statins were prescribed for 94.1% at arrival and 90.7% at discharge. Patients undergoing an invasive procedure were more likely to receive guideline-recommended medications at discharge: dual antiplatelet therapy (OR 3.77; 95% CI 1.23-11.52), beta blocker (OR 3.95; 95% CI 1.86-8.40) and ACEI/ARB (OR 4.01; 95% CI 1.30-12.41). Ninety of the excluded patients were discharged without completing treatment. CONCLUSIONS: In general, physicians closely adhered to ACS prescribing guidelines in Vietnamese hospital practice. Prescribing of beta blockers and clopidogrel loading doses was probably suboptimal. Why patients do not complete treatment needs to be investigated.