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RNA Velocity allows the inference of cellular differentiation trajectories from single-cell RNA sequencing (scRNA-seq) data. It would be highly interesting to study these differentiation dynamics in the spatial context of tissues. Estimating spatial RNA velocities is, however, limited by the inability to spatially capture spliced and unspliced mRNA molecules in high-resolution spatial transcriptomics. We present SIRV, a method to spatially infer RNA velocities at the single-cell resolution by enriching spatial transcriptomics data with the expression of spliced and unspliced mRNA from reference scRNA-seq data. We used SIRV to infer spatial differentiation trajectories in the developing mouse brain, including the differentiation of midbrain-hindbrain boundary cells and marking the forebrain origin of the cortical hem and diencephalon cells. Our results show that SIRV reveals spatial differentiation patterns not identifiable with scRNA-seq data alone. Additionally, we applied SIRV to mouse organogenesis data and obtained robust spatial differentiation trajectories. Finally, we verified the spatial RNA velocities obtained by SIRV using 10x Visium data of the developing chicken heart and MERFISH data from human osteosarcoma cells. Altogether, SIRV allows the inference of spatial RNA velocities at the single-cell resolution to facilitate studying tissue development.
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Background: Microvascular occlusions caused by sickle-shaped erythrocytes in patients with sickle cell disease (SCD) can lead to increased intraoperative and postoperative complications during total hip arthroplasty (THA). This systematic review and meta-analysis aimed to estimate the overall rate of complications following THA in patients with SCD and to identify the predictors of these complications including the surgical approach. Methods: The search was conducted across the grey literature, Google Scholar, and seven databases: Scopus, MEDLINE Central/PubMed, ProQuest, SciELO, SAGE, and Web of Science. All observational studies reporting the proportional THA complications in SCD were included. The Newcastle-Ottawa Scale quality assessment tool was used to assess the quality of the studies. The random effect model was applied to estimate the pooled outcomes. A sub-group analysis for the different approaches was performed. A sensitivity analysis and meta-regression were used to explain heterogeneity and to identify the THA complication predictors. Results: Of 3230 citations, only 23 studies were eligible for the meta-analysis. The pooled proportion of total primary THA complications in patients with SCD was 42% (95% CI: 30-56%, I2 = 95%). The sub-group analysis highlighted the anterolateral approach as the approach accompanied with the least complications. The meta-regression revealed that the anterolateral approach decreases the complications significantly, -28.67 (95%CI, -56.45--0.88, p = 0.044), while the number of hips increased the complications by 0.43 (95%CI, 0.30-0.57, p < 0.001). Male gender, age, lateral approach, and HbSS non-significantly affect the THA complications in SCD 52.05, 0.18, 6.06, and 55.78, respectively. The pooled proportions for an SCD crisis 9% (95%CI, 5-14%, I2 = 61%), dislocation 4% (95%CI: 2-7%, I2 = 66%), aseptic loosening 12% (95%CI, 7-20%, I2 = 91%), revision 6% (3-11, I2 = 92%), heterotopic ossification 12% (95%CI, 3-35%, I2 = 95%), and prosthetic joint infection (PJI) 6% (95%CI, 3-11%, I2 = 92%). The most fitted model of meta-regression illustrated that HbSS significantly increases PJI, 0.05 (95%CI: 0.02-0.08, p = 0.009), and male gender and age non-significantly increase PJI, 2.28 (95%CI: -4.99-13.56, p = 0.311) and 0.001 (95%CI: -0.27-0.27, p = 0.990), respectively. Meanwhile, the anterolateral, lateral, and posterior approaches non-significantly decrease PJI, -3.55, -0.92, and -1.27, respectively. The pooled proportion for a sickle cell disease crisis after revision was 16% (95%CI: 6-36%, I2 = 0) and for aseptic loosening after revision, it was 24% (95%CI: 12-43%, I2 = 0). Conclusions: This study revealed the high rate of complications in patients with SCD and highlighted that the anterolateral approach was associated with the lowest rate of complications. Furthermore, this study illustrated that homozygous (HbSS) individuals are more susceptible to prosthetic joint infection.
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Different dosing strategies exist to initiate warfarin, most commonly fixed warfarin dosing (FWD), clinical warfarin dosing (CWD), and genetic-guided warfarin dosing (GWD). Landmark trials have shown GWD to be superior when compared to FWD in the EU-PACT trial or CWD in the GIFT trial. COAG trial did not show differences between GWD and CWD. We aim to compare the anticoagulation quality outcomes of CWD and FWD. This is a prospective cohort study with a retrospective comparator. Recruited subjects in the CWD (prospective) arm were initiated on warfarin according to the clinical dosing component of the algorithm published in www.warfarindosing.org. The primary efficacy outcome was the percentage time in the therapeutic range (PTTR) from day 3 to 6 till day 28 to 35. The study enrolled 122 and 123 patients in the CWD and FWD, respectively. The PTTR did not differ statistically between CWD and FWD (62.2 ± 26.2% vs. 58 ± 25.4%, p = 0.2). There was also no difference between both arms in the percentage of visits with extreme subtherapeutic international normalized ratio (INR) (<1.5; 15 ± 18.3% vs. 16.8 ± 19.1%, p = 0.44) or extreme supratherapeutic INR (>4; 7.7 ± 14.7% vs. 7.5 ± 12.4%, p = 0.92). We conclude that CWD did not improve the anticoagulation quality parameters compared to the FWD method.
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Anticoagulantes , Coeficiente Internacional Normatizado , Varfarina , Humanos , Varfarina/administração & dosagem , Anticoagulantes/administração & dosagem , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Coagulação Sanguínea/efeitos dos fármacos , Algoritmos , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos/métodos , Monitoramento de Medicamentos/normas , Resultado do Tratamento , Idoso de 80 Anos ou maisRESUMO
This study employed a multifaceted approach to investigate the inhibitory potential of alpha-amyrin against TLR2, a key player in bacterial infection and sepsis. A high-resolution TLR2 model was constructed using Swiss-MODEL, exhibiting excellent quality with 100% sequence identity and coverage. Cavity detection revealed five significant cavities on TLR2. Molecular docking identifies alpha-amyrin as a potent inhibitor, displaying a strong binding affinity of -8.6 kcal/mol. Comprehensive analyses, including ADMET predictions, PASS analysis, and SwissTargetPrediction, affirm alpha-amyrin's drug-like properties and diverse biological activities. Cytotoxicity assays on HEK-293 cells confirm its safety, and fluorescence-based inhibition assays provide empirical evidence of its inhibitory potency on TLR2 enzymatic activity. Further validations in HUVECs show a significant decrease in TLR2 mRNA expression (p<0.01) and activity (p<0.05) upon alpha-amyrin treatment. In conclusion, this integrative study positions alpha-amyrin as a promising therapeutic candidate for TLR2 inhibition, emphasizing its potential in combating bacterial infections with safety and efficacy.
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Infecções Bacterianas , Simulação de Acoplamento Molecular , Ácido Oleanólico , Sepse , Receptor 2 Toll-Like , Receptor 2 Toll-Like/metabolismo , Humanos , Sepse/tratamento farmacológico , Sepse/microbiologia , Células HEK293 , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/farmacologia , Ácido Oleanólico/química , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Simulação por ComputadorRESUMO
Background: Acute coronary syndrome (ACS) remains a risk factor for heart failure (HF). Therefore, we aimed to assess the cardioprotective role of sodium-glucose cotransporter-2 (SGLT2) inhibitors post-ACS in patients with acute HF (AHF) and diabetes. Methods: We conducted a retrospective observational cohort study employing propensity score matching. This study involved patients with diabetes admitted with ACS complicated by AHF, defined as either new clinical HF requiring diuretics during the index admission or having an ejection fraction (EF) of <40%. The study population was divided into two groups; (1) SGLT2 inhibitor users and (2) SGLT2 inhibitor non-users. The Cox proportional hazard regression analysis was used to evaluate the outcomes. Results: A total of 465 patients (93% male; mean age, 55 ± 10 years) were included in this study. Using a 1 : 1 propensity score matching, 78 patients were included per arm with an absolute standardized difference of <0.1 for all baseline characteristics. The use of SGLT2 inhibitors resulted in lower composite outcomes of ACS, HF hospitalization, and all-cause mortality at 1 month and 12 months [1 month: 2.6% vs. 11.5%, HR = 0.20 (0.04-0.94), p = 0.041; 12 months: 14.1% vs. 23.1%, HR = 0.46 (0.22-0.99), p = 0.046]. Conclusion: The findings suggest that SGLT2 inhibitors may confer cardioprotective effects in ACS-induced AHF, thereby widening the spectrum for indications of SGLT2 inhibitors.
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Background and Objectives: Healthy eating is a crucial approach to improving overall health, encompassing a well-balanced diet of natural and fresh foods, plenty of fruits and vegetables, and foods rich in minerals and vitamins. This study aimed to assess the prevalence of obesity and associated dietary habits among medical students at King Khalid University, Aseer, Saudi Arabia. Materials and Methods: This observational cross-sectional study was conducted through face-to-face interviews. A structured predesigned questionnaire was used to collect data. Results: A total of 540 medical students were included; 43.3% of participants were aged 20-22 years, 24.8% were in the 3rd year, and 82.0% had an average income level. Of them, 21.9% were overweight and 14.6% were obese. There was a significant association between obesity and grade (p = 0.004). Significant differences were observed between males and females in adding sugar to beverages, the frequency of eating out, cooking meat, and drinking water (p < 0.05). The predictors of obesity were being male (OR = 3.5, 95% CI [1.6-7.8], p = 0.002), age (OR = 1.8, 95% CI [1.1-3.0, p = 0.019], being at grade 2 (OR = 38.8, 95% CI [4.0-375.8], p = 0.002), having grilled meat (OR = 0.42, 95% CI, [0.20-0.99], p = 0.048), using artificial sweeteners [OR = 0.24, 95% CI [0.08-0.73], p = 0.012], and drinking sparkling bottled water (OR 8.6, 95% CI [1.2 333-63.8], p = 0.034). Conclusions: The study revealed a high prevalence of obesity and overweight among medical students of both sexes. It recommends education on healthy eating habits, balanced nutrition, and regular physical activity, as well as gender-specific health initiatives, nutritional counseling, and the inclusion of physical activity.
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Sobrepeso , Estudantes de Medicina , Feminino , Masculino , Humanos , Sobrepeso/epidemiologia , Arábia Saudita/epidemiologia , Prevalência , Universidades , Índice de Massa Corporal , Obesidade/epidemiologia , Comportamento AlimentarRESUMO
OBJECTIVES: To compare maternal characteristics and outcomes among patients having major placenta previa (PP) with and without previous cesarean section (CS). And to determine if previous CS alone is a risk factor for associated adverse maternal outcomes in these patients. MATERIALS AND METHODS: This is a retrospective analysis including two groups of major PP patients, with previous CS (n = 184) and without CS (n = 115); who were admitted to Abha Maternity and Children's Hospital over the last ten-years (January 2012-December 2021), Aseer region, Saudi Arabia. RESULTS: Compared to those without previous CS, major PP patients with previous CS had significantly advanced ages with higher mean numbers of gravidity and parity, but significantly less rates of previous uterine surgery and IVF pregnancies. Moreover, they were more likely to acquire higher rates of adverse maternal outcomes. In the same way, these patients had an increased Odds Ratios of cesarean hysterectomy (OR of 20.462), urinary tract injuries (OR of 12.361), associated PAS (OR of 4.375), moderate/ heavy intra-operative bleeding (OR of 2.153) and the need for transfusion of 3+ units of packed RBCs (OR of 1.849). CONCLUSION: (1) Patients with combined existence of major PP and previous CS had significantly higher rates of adverse maternal outcomes (2) Alone, prior CS in major PP patients increased the Odds Ratios of cesarean hysterectomy, urinary tract injuries, diagnosis of PAS, excessive intra-operative bleeding and repeated packed RBCs transfusions. (3) Among our PP patients with previous CS, the increased rate and OR of PAS diagnosis could in-part explain the adverse maternal outcomes.
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Placenta Acreta , Placenta Prévia , Criança , Gravidez , Humanos , Feminino , Cesárea/efeitos adversos , Estudos Retrospectivos , Placenta Acreta/cirurgia , Fatores de Risco , Número de GestaçõesRESUMO
Most regulatory elements, especially enhancer sequences, are cell population-specific. One could even argue that a distinct set of regulatory elements is what defines a cell population. However, discovering which non-coding regions of the DNA are essential in which context, and as a result, which genes are expressed, is a difficult task. Some computational models tackle this problem by predicting gene expression directly from the genomic sequence. These models are currently limited to predicting bulk measurements and mainly make tissue-specific predictions. Here, we present a model that leverages single-cell RNA-sequencing data to predict gene expression. We show that cell population-specific models outperform tissue-specific models, especially when the expression profile of a cell population and the corresponding tissue are dissimilar. Further, we show that our model can prioritize GWAS variants and learn motifs of transcription factor binding sites. We envision that our model can be useful for delineating cell population-specific regulatory elements.
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The sporadic nature of DUX4 expression in FSHD muscle challenges comparative transcriptome analyses between FSHD and control samples. A variety of DUX4 and FSHD-associated transcriptional changes have been identified, but bulk RNA-seq strategies prohibit comprehensive analysis of their spatiotemporal relation, interdependence and role in the disease process. In this study, we used single-nucleus RNA-sequencing of nuclei isolated from patient- and control-derived multinucleated primary myotubes to investigate the cellular heterogeneity in FSHD. Taking advantage of the increased resolution in snRNA-sequencing of fully differentiated myotubes, two distinct populations of DUX4-affected nuclei could be defined by their transcriptional profiles. Our data provides insights into the differences between these two populations and suggests heterogeneity in two well-known FSHD-associated transcriptional aberrations: increased oxidative stress and inhibition of myogenic differentiation. Additionally, we provide evidence that DUX4-affected nuclei share transcriptome features with early embryonic cells beyond the well-described cleavage stage, progressing into the 8-cell and blastocyst stages. Altogether, our data suggests that the FSHD transcriptional profile is defined by a mixture of individual and sometimes mutually exclusive DUX4-induced responses and cellular state-dependent downstream effects.
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Distrofia Muscular Facioescapuloumeral , Humanos , Distrofia Muscular Facioescapuloumeral/genética , Distrofia Muscular Facioescapuloumeral/metabolismo , Transcriptoma/genética , Proteínas de Homeodomínio/metabolismo , RNA Nuclear Pequeno/genética , RNA Nuclear Pequeno/metabolismo , Estresse Oxidativo/genética , Apoptose , Músculo Esquelético/metabolismo , Regulação da Expressão Gênica/genéticaRESUMO
INTRODUCTION: Left ventricular thrombus (LVT) increases the risk of ischemic stroke. However, it remains uncertain if the percutaneous coronary intervention (PCI) in the confirmed LVT setting further augments the stroke risk. Therefore, in this study, we evaluated the risk of stroke among patients with LVT undergoing CAG +/- PCI. METHODS: This retrospective observational cohort study included all the patients encountered with LVT from 1st of April 2015, to 31st of March 2020. The study population was divided into two groups: Longobardo et al. (2018) [1] patients with LVT who underwent CAG +/- PCI; Solheim et al. (2010) [2] patients with LVT who did not undergo CAG +/- PCI. The primary outcome evaluated was stroke during the index admission, and the secondary outcomes included in-hospital mortality, all-cause mortality, and stroke at 12 months post-discharge. Logistic regression was used to determine the risk of stroke associated with PCI among patients with LVT, and a p-value<0.05 indicated statistical significance. RESULTS: Of the 210 patients included, 119 underwent CAG +/- PCI, while 91 patients did not undergo CAG +/- PCI. Most of the patients were Asian (67%), male (96%), with a mean age of 56 years. Ischemic cardiomyopathy was the primary etiology of LVT in both groups (96% in the CAG +/- PCI group and 80% in non CAG +/- PCI group). During the index admission, stroke among patients with LVT did not differ between the CAG +/- PCI and non CAG +/- PCI groups (5% versus 3.3%; odds ratio (OR) 1.6, 95% confidence interval (CI) 0.34-6.4, p = 0.539; adjusted OR 0.9, 95% CI 0.09-10.6, p = 0.968). Similarly, in-hospital mortality, all-cause mortality, and stroke at 12 months did not differ between the study groups. CONCLUSION: Performing CAG +/- PCI among patients with LVT was not associated with an increased risk of stroke during admission or within 12 months in comparison to patients who did not undergo CAG +/- PCI, which may reassure cardiologists to perform CAG +/- PCI among patients with LVT safely.
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Intervenção Coronária Percutânea , Acidente Vascular Cerebral , Trombose , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Intervenção Coronária Percutânea/efeitos adversos , Assistência ao Convalescente , Alta do Paciente , Trombose/epidemiologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Resultado do TratamentoRESUMO
Sustained low-efficiency dialysis (SLED) is usually performed over 6-12 h among hemodynamically unstable patients. Conduction of 4-h SLED may spare time and manpower during hospitalization. Therefore, we conducted a retrospective observational study to explore the appropriateness and clinical outcomes of 4-h SLED among critically ill patients admitted to our center from 1/06/2016 to 1/06/2020. Renal parameters including blood urea nitrogen, serum creatinine, sodium, phosphorus, potassium, and bicarbonate were determined on the day of dialysis before SLED and within 24 h after SLED, and clinical outcomes including, acute kidney injury (AKI) recovery, in-hospital mortality, 30-day mortality, 180-day mortality, and re-admission with AKI, were evaluated. Of the 304 patients included, 69.4% were male. The majority of patients were from the Middle East (65.8%), followed by 28.6% from Asia. Four-hour SLED resulted in a significant improvement in the renal parameters. Recovery from AKI was observed in 25.4%, in-hospital mortality rate was 48.7%, while the 30- and 180-day mortality outcomes were 3.2 and 9.6%, respectively, and re-admission with AKI was observed in 16.9%. Our findings suggest that 4-h SLED significantly improved renal parameters and was associated with favorable clinical outcomes in terms of survival and AKI recovery, suggesting possible utilization of SLED shorter than 6 h in the acute settings to preserve time and manpower for procedures.
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Motivation: Single-cell technologies allow deep characterization of different molecular aspects of cells. Integrating these modalities provides a comprehensive view of cellular identity. Current integration methods rely on overlapping features or cells to link datasets measuring different modalities, limiting their application to experiments where different molecular layers are profiled in different subsets of cells. Results: We present scTopoGAN, a method for unsupervised manifold alignment of single-cell datasets with non-overlapping cells or features. We use topological autoencoders (topoAE) to obtain latent representations of each modality separately. A topology-guided Generative Adversarial Network then aligns these latent representations into a common space. We show that scTopoGAN outperforms state-of-the-art manifold alignment methods in complete unsupervised settings. Interestingly, the topoAE for individual modalities also showed better performance in preserving the original structure of the data in the low-dimensional representations when compared to other manifold projection methods. Taken together, we show that the concept of topology preservation might be a powerful tool to align multiple single modality datasets, unleashing the potential of multi-omic interpretations of cells. Availability and implementation: Implementation available on GitHub (https://github.com/AkashCiel/scTopoGAN). All datasets used in this study are publicly available.
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Deep generative models, such as variational autoencoders (VAE), have gained increasing attention in computational biology due to their ability to capture complex data manifolds which subsequently can be used to achieve better performance in downstream tasks, such as cancer type prediction or subtyping of cancer. However, these models are difficult to train due to the large number of hyperparameters that need to be tuned. To get a better understanding of the importance of the different hyperparameters, we examined six different VAE models when trained on TCGA transcriptomics data and evaluated on the downstream tasks of cluster agreement with cancer subtypes and survival analysis. We studied the effect of the latent space dimensionality, learning rate, optimizer, initialization and activation function on the quality of subsequent downstream tasks on the TCGA samples. We found ß-TCVAE and DIP-VAE to have a good performance, on average, despite being more sensitive to hyperparameters selection. Based on these experiments, we derived recommendations for selecting the different hyperparameters settings. To ensure generalization, we tested all hyperparameter configurations on the GTEx dataset. We found a significant correlation (ρ = 0.7) between the hyperparameter effects on clustering performance in the TCGA and GTEx datasets. This highlights the robustness and generalizability of our recommendations. In addition, we examined whether the learned latent spaces capture biologically relevant information. Hereto, we measured the correlation and mutual information of the different representations with various data characteristics such as gender, age, days to metastasis, immune infiltration, and mutation signatures. We found that for all models the latent factors, in general, do not uniquely correlate with one of the data characteristics nor capture separable information in the latent factors even for models specifically designed for disentanglement.
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Benchmarking , Neoplasias , Humanos , Transcriptoma , Neoplasias/genética , Perfilação da Expressão Gênica , Análise por ConglomeradosRESUMO
PURPOSE: To investigate real-world prescribing trends and clinical outcomes based on body mass index (BMI) categorization in patients who received rivaroxaban therapy. METHODS: This was a retrospective cohort study involving all patients who received rivaroxaban therapy across all Hamad Medical Corporation (HMC) hospitals from 2015 to 2020. RESULTS: The number of patients initiated on rivaroxaban therapy significantly increased from 152 (3.3%) in 2015 to 1342 (28.9%) in 2020 (p <0.001). Within BMI categories, a similar increasing trend was observed in underweight, normal, and overweight patients, while from 2018 to 2020, there was a decreasing trend in rivaroxaban prescribing in all obese classes. The prevalence rate of all-cause mortality differed significantly between the BMI groups, with the highest mortality being among morbidly obese patients (BMI ≥ 40 kg/m2) (p< 0.001). On the other hand, no significant differences were found between the BMI groups in terms of bleeding, pulmonary embolism, deep vein thrombosis and stroke incidences. Multivariate logistic regression analyses showed that the likelihood of all-cause mortality was significantly higher in overweight and all categories of obese patients compared to underweight patients: overweight (OR: 5.3, 95% CI: 2.3-11.9, p< 0.001); obese class 1 (OR: 5.4, 95% CI: 2.3 - 12.2, p< 0.001); obese class 2 (OR: 6.5, 95% CI: 2.7 - 15.6, p< 0.001); and obese class 3 (OR: 3.7, 95% CI: 1.6 - 8.7, p = 0.003). CONCLUSIONS: Rivaroxaban prescribing has significantly increased over the years across general population, with a noticeable decline in obese population during the last few years (from 2018 onwards). Furthermore, an appreciable association was evident between all-cause mortality and BMI of these patients.
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Fibrilação Atrial , Obesidade Mórbida , Humanos , Rivaroxabana/uso terapêutico , Magreza/epidemiologia , Magreza/induzido quimicamente , Magreza/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Obesidade Mórbida/tratamento farmacológico , Obesidade Mórbida/epidemiologia , Estudos Retrospectivos , Fibrilação Atrial/tratamento farmacológico , Índice de Massa Corporal , Anticoagulantes/efeitos adversosRESUMO
OBJECTIVES: To determine the incidence, risk factors, and maternal outcomes of "major degree" placenta previa (PP)/placenta accreta spectrum (PAS) in Abha Maternity and Children's Hospital, Abha, Saudi Arabia. Secondly, to compare our findings to those of previous studies on PP/PAS in Saudi Arabia. METHODS: This is a retrospective study that included 299 patients diagnosed with major degree PP/PAS and admitted to Abha Maternity and Children's Hospital, Abha, Saudi Arabia, within 10 years (January 2012-December 2021). Also, we compared our results to the outcomes of PP/PAS patients in 6 previous Saudi studies. RESULTS: The total number of deliveries was 54,341; PP minor and major degrees were diagnosed in 376 (0.69%) patients. Of them, 299 patients had PP major degree (79.5%). The pattern of main risk factors for major PP/PAS included: elder age, high parity, and previous cesarean deliveries. Nearly 30.5% had evidence of PAS on antenatal MRI (n=91). Approximately 68.5% (n=205) of patients were delivered <37 weeks. Of 299 patients, 29 (9.7%)patients had emergency cesarean hysterectomy. The maternal mortality rate was 0.3% (n=1). Generally, in many aspects, our results are comparable to similar Saudi studies on PP/PAS. CONCLUSION: Major degree of PP/PAS is associated with high maternal morbidity but rare mortality. Over 30 years, our patients' obstetric characteristics did not change, including both elder age and high parity. A substantial increase in the rate of cesarean deliveries is a leading cause of major PP/PAS.
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Placenta Prévia , Gravidez , Criança , Humanos , Feminino , Idoso , Incidência , Placenta Prévia/epidemiologia , Estudos Retrospectivos , Cesárea , Fatores de RiscoRESUMO
BACKGROUND: Antenatal assessment of maternal risk factors and imaging evaluation can help in diagnosis and treatment of placenta accreta spectrum (PAS) in major placenta previa (PP). Recent evidence suggests that magnetic resonance imaging (MRI) could complement ultrasonography (US) in the PAS diagnosis. OBJECTIVES: Evaluate the incidence, risk factors, and maternal morbidity related to the MRI diagnosis of PAS in major PP. DESIGN: A 10-year retrospective cohort study. SETTING: Tertiary care hospital. PATIENTS AND METHODS: We report on patients with major PP who had cesarean delivery in Abha Maternity and Children's Hospital (AMCH) over a 10-year period (2012-2021). They were evaluated with ultrasonography (US) and color Doppler for evidence of PAS. Antenatal MRI was ordered either to confirm the diagnosis (if equivocal US) or to assess the depth of invasion/extra-uterine extension (if definitive US). MAIN OUTCOME MEASURES: Risk factors for PAS in major PP and maternal complications. SAMPLE SIZE: 299 patients RESULTS: Among 299 patients, MRI confirmed the PAS diagnosis in 91/299 (30.5%) patients. The independent risk factors for MRI diagnosis of PAS in major PP included only repeated cesarean sections and advanced maternal age. The commonest maternal morbidity in major PP with PAS was significantly excessive intraoperative bleeding. CONCLUSION: MRI may be a valuable adjunct in the evaluation of PAS in major PP; as a complement, but not substitute US. MRI may be suitable in major PP/PAS patients who are older and have repeated cesarean deliveries with equivocal results or deep/extra-uterine extension on US. LIMITATION: Single center, small sample size, lack of complete histopathological diagnosis. CONFLICT OF INTEREST: None.
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Placenta Acreta , Placenta Prévia , Criança , Gravidez , Feminino , Humanos , Placenta Acreta/diagnóstico por imagem , Placenta Acreta/epidemiologia , Placenta Prévia/diagnóstico por imagem , Placenta Prévia/epidemiologia , Incidência , Estudos Retrospectivos , Fatores de Risco , Imageamento por Ressonância MagnéticaRESUMO
Single-cell genomics is now producing an ever-increasing amount of datasets that, when integrated, could provide large-scale reference atlases of tissue in health and disease. Such large-scale atlases increase the scale and generalizability of analyses and enable combining knowledge generated by individual studies. Specifically, individual studies often differ regarding cell annotation terminology and depth, with different groups specializing in different cell type compartments, often using distinct terminology. Understanding how these distinct sets of annotations are related and complement each other would mark a major step towards a consensus-based cell-type annotation reflecting the latest knowledge in the field. Whereas recent computational techniques, referred to as 'reference mapping' methods, facilitate the usage and expansion of existing reference atlases by mapping new datasets (i.e. queries) onto an atlas; a systematic approach towards harmonizing dataset-specific cell-type terminology and annotation depth is still lacking. Here, we present 'treeArches', a framework to automatically build and extend reference atlases while enriching them with an updatable hierarchy of cell-type annotations across different datasets. We demonstrate various use cases for treeArches, from automatically resolving relations between reference and query cell types to identifying unseen cell types absent in the reference, such as disease-associated cell states. We envision treeArches enabling data-driven construction of consensus atlas-level cell-type hierarchies and facilitating efficient usage of reference atlases.
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BACKGROUND: Well-designed and well-maintained drug formularies serve as a reliable resource to guide prescribing decisions; they are associated with improved medicine safety and increased efficiency, while also serving as a cost-effective tool to help manage and predict medicine expenditure. Multiple studies have investigated the inappropriate prescribing of non-formulary drugs (NFDs) with statistics indicating that up to 70% of NFD usage being inappropriate or not following the ascribed NFD policies. AIM: To explore physicians' views and influences on their prescribing of non-formulary drugs. METHOD: Data collection and analysis were underpinned using the Theoretical Domains Framework (TDF). Thirteen semi-structured interviews were conducted within Hamad Medical Corporation, the main provider of secondary and tertiary healthcare in Qatar, with physicians who had submitted a NFD request in the preceding 12 months. RESULTS: Three overarching themes were identified: providing evidence-based care for individual patients; influences of others; and formulary management issues. Subthemes were mapped to specific TDF domains: environmental context and resources; social influences; professional role and identity; beliefs about consequences; goals; intentions. CONCLUSION: The behavioral influences identified in this study can be mapped to behavior change strategies facilitating the development of an intervention to promote appropriate prescribing of NFDs with implications for medicine safety and healthcare efficiency.
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Atitude do Pessoal de Saúde , Médicos , Humanos , Papel Profissional , Pesquisa QualitativaRESUMO
The kidney's cellular diversity is on par with its physiological intricacy; yet identifying cell populations and their markers remains challenging. Here, we created a comprehensive atlas of the healthy adult mouse kidney (MKA: Mouse Kidney Atlas) by integrating 140.000 cells and nuclei from 59 publicly available single-cell and single-nuclei RNA-sequencing datasets from eight independent studies. To harmonize annotations across datasets, we built a hierarchical model of the cell populations. Our model allows the incorporation of novel cell populations and the refinement of known profiles as more datasets become available. Using MKA and the learned model of cellular hierarchies, we predicted previously missing cell annotations from several studies. The MKA allowed us to identify reproducible markers across studies for poorly understood cell types and transitional states, which we verified using existing data from micro-dissected samples and spatial transcriptomics.
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MOTIVATION: Knowing the relation between cell types is crucial for translating experimental results from mice to humans. Establishing cell type matches, however, is hindered by the biological differences between the species. A substantial amount of evolutionary information between genes that could be used to align the species is discarded by most of the current methods since they only use one-to-one orthologous genes. Some methods try to retain the information by explicitly including the relation between genes, however, not without caveats. RESULTS: In this work, we present a model to transfer and align cell types in cross-species analysis (TACTiCS). First, TACTiCS uses a natural language processing model to match genes using their protein sequences. Next, TACTiCS employs a neural network to classify cell types within a species. Afterward, TACTiCS uses transfer learning to propagate cell type labels between species. We applied TACTiCS on scRNA-seq data of the primary motor cortex of human, mouse, and marmoset. Our model can accurately match and align cell types on these datasets. Moreover, our model outperforms Seurat and the state-of-the-art method SAMap. Finally, we show that our gene matching method results in better cell type matches than BLAST in our model. AVAILABILITY AND IMPLEMENTATION: The implementation is available on GitHub (https://github.com/kbiharie/TACTiCS). The preprocessed datasets and trained models can be downloaded from Zenodo (https://doi.org/10.5281/zenodo.7582460).