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Spatial transcriptomics (ST) technologies generate multiple data types from biological samples, namely gene expression, physical distance between data points, and/or tissue morphology. Here we developed three computational-statistical algorithms that integrate all three data types to advance understanding of cellular processes. First, we present a spatial graph-based method, pseudo-time-space (PSTS), to model and uncover relationships between transcriptional states of cells across tissues undergoing dynamic change (e.g. neurodevelopment, brain injury and/or microglia activation, and cancer progression). We further developed a spatially-constrained two-level permutation (SCTP) test to study cell-cell interaction, finding highly interactive tissue regions across thousands of ligand-receptor pairs with markedly reduced false discovery rates. Finally, we present a spatial graph-based imputation method with neural network (stSME), to correct for technical noise/dropout and increase ST data coverage. Together, the algorithms that we developed, implemented in the comprehensive and fast stLearn software, allow for robust interrogation of biological processes within healthy and diseased tissues. The integration of spatial, imaging, and sequencing information enables the mapping of cellular dynamics within a tissue. Here, authors show three algorithms in stLearn software to accurately reveal spatial trajectory, detect cell-cell interactions, and impute missing data.

To investigate factors associated with survival after out-of-hospital cardiac arrest in Viet Nam. We did a multicentre prospective observational study of people (> 18 years) presenting with out-of-hospital cardiac arrest (not caused by trauma) to three tertiary hospitals in Viet Nam from February 2014 to December 2018. We collected data on characteristics, management and outcomes of patients with out-of-hospital cardiac arrest and compared these data by type of transportation to hospital and survival to hospital admission. We assessed factors associated with survival to admission to and discharge from hospital using logistic regression analysis. Of 590 eligible people with out-of-hospital cardiac arrest, 440 (74.6%) were male and the mean age was 56.1 years (standard deviation: 17.2). Only 24.2% (143/590) of these people survived to hospital admission and 14.1% (83/590) survived to hospital discharge. Most cardiac arrests (67.8%; 400/590) occurred at home, 79.4% (444/559) were witnessed by bystanders and 22.3% (124/555) were given cardiopulmonary resuscitation by a bystander. Only 8.6% (51/590) of the people were taken to hospital by the emergency medical services and 32.2% (49/152) received pre-hospital defibrillation. Pre-hospital defibrillation (odds ratio, OR: 3.90; 95% confidence interval, CI: 1.54-9.90) and return of spontaneous circulation in the emergency department (OR: 2.89; 95% CI: 1.03-8.12) were associated with survival to hospital admission. Hypothermia therapy during post-resuscitation care was associated with survival to discharge (OR: 5.44; 95% CI: 2.33-12.74). Improvements are needed in the emergency medical services in Viet Nam such as increasing bystander cardiopulmonary resuscitation and public access defibrillation, and improving ambulance and post-resuscitation care.

Next-generation humanised mouse models and single-cell RNA sequencing (scRNAseq) approaches enable in-depth studies into human immune cell biology. Here we used NSG-SGM3 mice engrafted with human umbilical cord haematopoietic stem cells to investigate how human immune cells respond to and/or are changed by traumatic spinal cord injury (SCI). We hypothesised that the use of such mice could help advance our understanding of spinal cord injury-induced immune depression syndrome (SCI-IDS), and also how human leukocytes change as they migrate from the circulation into the lesion site. Our scRNAseq experiments, supplemented by flow cytometry, demonstrate the existence of up to 11 human immune cell (sub-) types and/or states across the blood and injured spinal cord (7 days post-SCI) of humanised NSG-SGM3 mice. Further comparisons of human immune cell transcriptomes between naïve, sham-operated and SCI mice identified a total of 579 differentially expressed genes, 190 of which were ‘SCI-specific’ (that is, genes regulated only in response to SCI but not sham surgery). Gene ontology analysis showed a prominent downregulation of immune cell function under SCI conditions, including for T cell receptor signalling and antigen presentation, confirming the presence of SCI-IDS and the transcriptional signature of human leukocytes in association with this phenomenon. We also highlight the activating influence of the local spinal cord lesion microenvironment by comparing the transcriptomes of circulating versus infiltrated human immune cells; those isolated from the lesion site were enriched for genes relating to both immune cell activity and function (e.g., oxidative phosphorylation, T cell proliferation and antigen presentation). We lastly applied an integrated bioinformatics approach to determine where immune responses in humanised NSG-SGM3 mice appear congruent to the native responses of human SCI patients, and where they diverge. Collectively, our study provides a valuable resource and methodological framework for the use of these mice in translational research.

Background. Gastric cancer (GC) is the fifth most common type of cancer and the fourth most common cause of cancer-related mortality. Although the risk of GC and peptic ulcer disease (PUD) is known to be increased by H. pylori infection, evidence regarding the direct relationship between PUD and GC across ethnicities is inconclusive. Therefore, we investigated the association between PUD and GC in the Stomach cancer Pooling (StoP) consortium. Methods. History of peptic ulcer disease was collected using a structured questionnaire in 11 studies in the StoP consortium, including 4106 GC cases and 6922 controls. The two-stage individual-participant data meta-analysis approach was adopted to generate a priori. Unconditional logistic regression and Firth’s penalized maximum likelihood estimator were used to calculate study-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between gastric ulcer (GU)/duodenal ulcer (DU) and risk of GC. Results. History of GU and DU was thoroughly reported and used in association analysis, respectively, by 487 cases (12.5%) and 276 controls (4.1%), and 253 cases (7.8%) and 318 controls (6.0%). We found that GU was associated with an increased risk of GC (OR = 3.04, 95% CI: 2.07–4.49). No association between DU and GC risk was observed (OR = 1.03, 95% CI: 0.77–1.39). Conclusions. In the pooled analysis of 11 case–control studies in a large consortium (i.e., the Stomach cancer Pooling (StoP) consortium), we found a positive association between GU and risk of GC and no association between DU and GC risk.

Spatial omics enables the molecular profiling of cells with the tissue context preserved. A new analytic approach shows how cellular neighborhood analysis and feature augmentation can spatially connect and cluster millions of cells into higher-order functional units.

We used single cell sequencing technology to characterize the transcriptomes of 1,174 human embryonic stem cell-derived retinal ganglion cells (RGCs) at the single cell level. The human embryonic stem cell line BRN3B-mCherry (A81-H7), was differentiated to RGCs using a guided differentiation approach. Cells were harvested at day 36 and prepared for single cell RNA sequencing. Our data indicates the presence of three distinct subpopulations of cells, with various degrees of maturity. One cluster of 288 cells showed increased expression of genes involved in axon guidance together with semaphorin interactions, cell-extracellular matrix interactions and ECM proteoglycans, suggestive of a more mature RGC phenotype.

In many countries, water distribution systems consist of large, highly pressurized pipe networks that require an excessive amount of energy and that are vulnerable to large-scale contamination. To imagine the future of water distribution, we can learn from Hanoi, Vietnam, where water is distributed at low pressures and most buildings are equipped with a basement tank, a rooftop tank, and separate water treatment processes, resulting in a system that consumes less energy and that is more resilient.

Alveolar macrophages (AM) must perform three seemingly opposing roles including homeostasis, driving inflammation, and facilitating tissue repair. Whilst there is now consensus (supported by a large body of human single cell RNA sequencing (scRNA-seq) data) that the cell subsets that perform these tasks can readily be found based on their transcriptome, their ontogeny has remained unclear. Moreover, there is agreement that in all types of pulmonary fibrosis (PF) there is an expanded population of profibrotic AM that may aberrantly drive PF. From a therapeutic viewpoint, there is great appeal in the notion that the transcriptional program in different AM subsets is not fixed but remains plastic and amenable to pharmacological reprogramming. Accordingly, this study addresses this question by performing scRNA-seq on human AM following treatment with drugs or perturbagens including pioglitazone, trametinib, nintedanib, lipopolysaccharide and the natural compound endiandrin A. Each treatment induced a unique global transcriptional change, driving the cells towards distinct subsets, further supported by trajectory analysis, confirming a high level of plasticity. Confirmatory experiments using qPCR demonstrated that single exposure to a compound induced a relatively stable transcriptome, whereas serial exposure to a different compound allowed the cells to be reprogrammed yet again to a different phenotype. These findings add new insight into the biology of AM and support the development of novel therapies to treat PF.

Objective To investigate factors associated with survival after out-of-hospital cardiac arrest in Viet Nam. Methods We did a multicentre prospective observational study of people (> 18 years) presenting with out-of-hospital cardiac arrest (not caused by trauma) to three tertiary hospitals in Viet Nam from February 2014 to December 2018. We collected data on characteristics, management and outcomes of patients with out-of-hospital cardiac arrest and compared these data by type of transportation to hospital and survival to hospital admission. We assessed factors associated with survival to admission to and discharge from hospital using logistic regression analysis. Findings Of 590 eligible people with out-of-hospital cardiac arrest, 440 (74.6%) were male and the mean age was 56.1 years (standard deviation: 17.2). Only 24.2% (143/590) of these people survived to hospital admission and 14.1% (83/590) survived to hospital discharge. Most cardiac arrests (67.8%; 400/590) occurred at home, 79.4% (444/559) were witnessed by bystanders and 22.3% (124/555) were given cardiopulmonary resuscitation by a bystander. Only 8.6% (51/590) of the people were taken to hospital by the emergency medical services and 32.2% (49/152) received pre-hospital defibrillation. Pre-hospital defibrillation (odds ratio, OR: 3.90; 95% confidence interval, CI: 1.54-9.90) and return of spontaneous circulation in the emergency department (OR: 2.89; 95% CI: 1.03-8.12) were associated with survival to hospital admission. Hypothermia therapy during post-resuscitation care was associated with survival to discharge (OR: 5.44; 95% CI: 2.33-12.74). Conclusion Improvements are needed in the emergency medical services in Viet Nam such as increasing bystander cardiopulmonary resuscitation and public access defibrillation, and improving ambulance and post-resuscitation care. Objectif Examiner les facteurs associes a la survie apres un arret cardiaque hors hopital au Viet Nam. Methodes Nous avons mene une etude d'observation prospective multicentrique sur des personnes (> 18 ans) ayant subi un arret cardiaque hors hopital (non traumatique) et admis dans trois hopitaux tertiaires au Viet Nam entre fevrier 2014 et decembre 2018. Nous avons recolte des donnees sur les caracteristiques, la gestion et l'issue de ces patients, puis les avons compares en fonction du moyen de transport vers l'hopital et de la survie apres leur admission. Enfin, nous avons mesure des facteurs associes a la survie lors de l'admission et de la sortie de l'etablissement a l'aide d'une analyse de regression logistique. Resultats Sur les 590 patients eligibles ayant subi un arret cardiaque hors hopital, 440 (74,6%) etaient des hommes et l'age moyen s'elevait a 56,1 ans (ecart type: 17.2). Seulement 24,2% (143/590) d'entre eux ont survecu a leur admission a l'hopital, et 14,1% (83/590) a leur sortie. La plupart des arrets cardiaques (67,8%; 400/590) ont eu lieu a domicile, 79,4% (444/559) se sont deroules en presence de passants et 22,3% (124/555) ont fait l'objet d'une reanimation cardiopulmonaire pratiquee par un temoin. A peine 8,6% (51/590) des patients ont ete emmenes a l'hopital par les services medicaux d'urgence, et 32,2% (49/152) ont recu une defibrillation avant d'arriver a l'hopital. La defibrillation prehospitaliere (odds ratio, OR: 3,90; intervalle de confiance de 95%, IC: 1,54-9,90) et le retablissement d'une circulation spontanee aux urgences (OR: 2,89; IC de 95%: 1,03-8,12) allaient de pair avec la survie apres admission. Lhypothermie therapeutique administree durant les soins post-reanimation etait liee a un meilleur taux de survie au moment de la sortie (OR: 5,44; IC de 95%: 2,33-12,74). Conclusion Des amenagements sont requis en matiere de services medicaux d'urgence au Viet Nam, notamment pour encourager la pratique de la reanimation cardiopulmonaire aupres de la population, garantir l'acces a des defibrillateurs publics, mais aussi ameliorer les soins en ambulance et en post-reanimation. Objetivo Investigar los factores relacionados con la supervivencia despues de un paro cardiaco extrahospitalario en Vietnam. Metodos Se realizo un estudio observacional prospectivo multicentrico de personas (>18 anos) que sufrieron un paro cardiaco extrahospitalario (no causado por traumatismo) en tres hospitales terciarios de Vietnam entre febrero de 2014 y diciembre de 2018. Se recopilaron los datos sobre las caracteristicas, el tratamiento y los resultados de los pacientes con paro cardiaco extrahospitalario y se compararon segun el tipo de transporte hasta el hospital y la supervivencia hasta el ingreso en el hospital. Se evaluaron los factores de supervivencia hasta el ingreso y el alta hospitalaria mediante un analisis de regresion logistica. Resultados De las 590 personas que cumplian los requisitos y sufrieron un paro cardiaco extrahospitalario, 440 (74,6 %) eran hombres, cuya edad media era de 56,1 anos (desviacion estandar: 17,2). Solo el 24,2 % (143/590) de estas personas sobrevivieron al ingreso en el hospital y el 14,1 % (83/590) sobrevivieron al alta hospitalaria. La mayoria de los paros cardiacos (67,8 %; 400/590) ocurrieron en el hogar, el 79,4 % (444/559) fueron presenciados por transeuntes y el 22,3 % (124/555) recibieron reanimacion cardiopulmonar por un transeunte. Solo el 8,6 % (51/590) de las personas fueron trasladadas al hospital por los servicios medicos de emergencia y el 32,2 % (49/152) recibieron desfibrilacion prehospitalaria. La desfibrilacion prehospitalaria (oportunidad relativa, OR: 3,90; intervalo de confianza del 95 %, IC: 1,54-9,90) y la recuperacion de la circulacion espontanea en el servicio de urgencias (OR: 2,89; IC del 95 %: 1,03-8,12) se asociaron a la supervivencia hasta el ingreso hospitalario. La hipotermia terapeutica durante la atencion posterior a la reanimacion se asocio a la supervivencia hasta el alta (OR: 5,44; IC del 95 %: 2,33-12,74). Conclusion Se necesitan mejoras en los servicios medicos de emergencia de Vietnam, como el aumento de las intervenciones de reanimacion cardiopulmonar para transeuntes y de desfibrilacion de acceso publico, asi como el mejoramiento de la atencion en las ambulancias y de los cuidados posteriores a la reanimacion. [phrase omitted]

Background Acute traumatic spinal cord injury (SCI) induces a systemic immune response involving circulating white blood cells (WBCs). How this response is influenced by overall trauma severity, the neurological level of injury and/or correlates with patient outcomes is poorly understood. The objective of this study was to identify relationships between early changes in circulating WBCs, injury characteristics and long‐term patient outcomes in individuals with traumatic SCI. Methods We retrospectively analysed data from 161 SCI patients admitted to Brisbane's Princess Alexandra Hospital (exploration cohort). Logistic regression models in conjunction with receiver operating characteristic (ROC) analyses were used to assess the strength of specific links between the WBC response, respiratory infection incidence and neurological outcomes (American Spinal Injury Association Impairment Scale (AIS) grade conversion). An independent validation cohort from the Trauma Hospital Berlin, Germany (n = 49) was then probed to assess the robustness of effects and disentangle centre effects. Results We find that the extent of acute neutrophilia in human SCI patients is positively correlated with New Injury Severity Scores but inversely with the neurological outcome (AIS grade). Multivariate analysis demonstrated that acute SCI‐induced neutrophilia is an independent predictor of AIS grade conversion failure, with an odds ratio (OR) of 4.16 and ROC area under curve (AUC) of 0.82 (P < 0.0001). SCI‐induced lymphopenia was separately identified as an independent predictor of better recovery (OR = 24.15; ROC AUC = 0.85, P < 0.0001). Acute neutrophilia and increased neutrophil‐lymphocyte ratios were otherwise significantly associated with respiratory infection presentation in both patient cohorts. Conclusions Our findings demonstrate the prognostic value of modelling early circulating neutrophil and lymphocyte counts with patient characteristics for predicting the longer term recovery after SCI. We describe the systemic white blood cell (WBC) response to human spinal cord injury (SCI) and demonstrate how this is influenced by overall trauma severity, lesion level, and neurological grade on admission. We identify acute neutrophilia as a negative predictor for patient outcomes, the occurrence of which reduces the likelihood of American Spinal Injury Association Impairment Scale (AIS) grade conversion. We further show that lymphopenia during the first week of SCI is typically associated with better recovery, but that higher neutrophil to lymphocyte ratios early after SCI are associated with infection presentation in at‐risk patients. Collectively, the multi‐factorial models described in this work allow for better patient stratification and more accurate prediction of their outcomes.