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1.
J Theor Biol ; 532: 110923, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34606876

RESUMO

Dynamic models of gene expression are urgently required. In this paper, we describe the time evolution of gene expression by learning a jump diffusion process to model the biological process directly. Our algorithm needs aggregate gene expression data as input and outputs the parameters of the jump diffusion process. The learned jump diffusion process can predict population distributions of gene expression at any developmental stage, obtain long-time trajectories for individual cells, and offer a novel approach to computing RNA velocity. Moreover, it studies biological systems from a stochastic dynamic perspective. Gene expression data at a time point, which is a snapshot of a cellular process, is treated as an empirical marginal distribution of a stochastic process. The Wasserstein distance between the empirical distribution and predicted distribution by the jump diffusion process is minimized to learn the dynamics. For the learned jump diffusion process, its trajectories correspond to the development process of cells, the stochasticity determines the heterogeneity of cells, its instantaneous rate of state change can be taken as "RNA velocity", and the changes in scales and orientations of clusters can be noticed too. We demonstrate that our method can recover the underlying nonlinear dynamics better compared to previous parametric models and the diffusion processes driven by Brownian motion for both synthetic and real world datasets. Our method is also robust to perturbations of data because the computation involves only population expectations.

2.
Nucleic Acids Res ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34850092

RESUMO

Recent developments of single cell RNA-sequencing technologies lead to the exponential growth of single cell sequencing datasets across different conditions. Combining these datasets helps to better understand cellular identity and function. However, it is challenging to integrate different datasets from different laboratories or technologies due to batch effect, which are interspersed with biological variances. To overcome this problem, we have proposed Single Cell Integration by Disentangled Representation Learning (SCIDRL), a domain adaption-based method, to learn low-dimensional representations invariant to batch effect. This method can efficiently remove batch effect while retaining cell type purity. We applied it to thirteen diverse simulated and real datasets. Benchmark results show that SCIDRL outperforms other methods in most cases and exhibits excellent performances in two common situations: (i) effective integration of batch-shared rare cell types and preservation of batch-specific rare cell types; (ii) reliable integration of datasets with different cell compositions. This demonstrates SCIDRL will offer a valuable tool for researchers to decode the enigma of cell heterogeneity.

3.
Neuro Oncol ; 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34850171

RESUMO

BACKGROUND: The risk profile for posterior fossa ependymoma (EP) depends on surgical and molecular status [Group A (PFA) versus Group B (PFB)]. While subtotal tumor resection is known to confer worse prognosis, MRI-based EP risk-profiling is unexplored. We aimed to apply machine learning strategies to link MRI-based biomarkers of high-risk EP and also to distinguish PFA from PFB. METHODS: We extracted 1800 quantitative features from presurgical T2-weighted (T2-MRI) and gadolinium-enhanced T1-weighted (T1-MRI) imaging of 157 EP patients. We implemented nested cross-validation to identify features for risk score calculations and apply a Cox model for survival analysis. We conducted additional feature selection for PFA versus PFB and examined performance across three candidate classifiers. RESULTS: For all EP patients with GTR, we identified four T2-MRI-based features and stratified patients into high- and low-risk groups, with 5-year overall survival rates of 62% and 100%, respectively (p < 0.0001). Among presumed PFA patients with GTR, four T1-MRI and five T2-MRI features predicted divergence of high- and low-risk groups, with 5-year overall survival rates of 62.7% and 96.7%, respectively (p = 0.002). T1-MRI-based features showed the best performance distinguishing PFA from PFB with an AUC of 0.86. CONCLUSIONS: We present machine learning strategies to identify MRI phenotypes that distinguish PFA from PFB, as well as high- and low-risk PFA. We also describe quantitative image predictors of aggressive EP tumors that might assist risk-profiling after surgery. Future studies could examine translating radiomics as an adjunct to EP risk assessment when considering therapy strategies or trial candidacy.

4.
Nucleic Acids Res ; 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34850940

RESUMO

Clustering cells and depicting the lineage relationship among cell subpopulations are fundamental tasks in single-cell omics studies. However, existing analytical methods face challenges in stratifying cells, tracking cellular trajectories, and identifying critical points of cell transitions. To overcome these, we proposed a novel Markov hierarchical clustering algorithm (MarkovHC), a topological clustering method that leverages the metastability of exponentially perturbed Markov chains for systematically reconstructing the cellular landscape. Briefly, MarkovHC starts with local connectivity and density derived from the input and outputs a hierarchical structure for the data. We firstly benchmarked MarkovHC on five simulated datasets and ten public single-cell datasets with known labels. Then, we used MarkovHC to investigate the multi-level architectures and transition processes during human embryo preimplantation development and gastric cancer procession. MarkovHC found heterogeneous cell states and sub-cell types in lineage-specific progenitor cells and revealed the most possible transition paths and critical points in the cellular processes. These results demonstrated MarkovHC's effectiveness in facilitating the stratification of cells, identification of cell populations, and characterization of cellular trajectories and critical points.

5.
Adv Sci (Weinh) ; : e2102092, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34723439

RESUMO

Combinational therapy is used for a long time in cancer treatment to overcome drug resistance related to monotherapy. Increased pharmacological data and the rapid development of deep learning methods have enabled the construction of models to predict and screen drug pairs. However, the size of drug libraries is restricted to hundreds to thousands of compounds. The ScaffComb framework, which aims to bridge the gaps in the virtual screening of drug combinations in large-scale databases, is proposed here. Inspired by phenotype-based drug design, ScaffComb integrates phenotypic information into molecular scaffolds, which can be used to screen the drug library and identify potent drug combinations. First, ScaffComb is validated using the US food and drug administration dataset and known drug combinations are successfully reidentified. Then, ScaffComb is applied to screen the ZINC and ChEMBL databases, which yield novel drug combinations and reveal an ability to discover new synergistic mechanisms. To our knowledge, ScaffComb is the first method to use phenotype-based virtual screening of drug combinations in large-scale chemical datasets.

6.
Am J Cardiol ; 161: 42-50, 2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34794617

RESUMO

Plasma proteomic profiling may aid in the discovery of novel biomarkers upstream of the development of atrial fibrillation (AF). We used data from the Atherosclerosis Risk in Communities study to examine the relation between large-scale proteomics and incident AF in a cohort of older-aged adults in the United States. We quantified 4,877 plasma proteins in Atherosclerosis Risk in Communities participants at visit 5 (2011-2013) using an aptamer-based proteomic profiling platform. We used Cox proportional hazards models to assess the association between protein levels and incident AF, and explored relation of selected protein biomarkers using annotated pathway analysis. Our study included 4,668 AF-free participants (mean age 75 ± 5 years; 59% female; 20% Black race) with proteomic measures. A total of 585 participants developed AF over a mean follow-up of 5.7 ± 1.7 years. After adjustment for clinical factors associated with AF, N-terminal pro-B-type natriuretic peptide (NT-proBNP) was associated with the risk of incident AF (hazard ratio, 1.82; 95% CI, 1.68 to 1.98; p, 2.91 × 10-45 per doubling of NT-proBNP). In addition, 36 other proteins were also significantly associated with incident AF after Bonferroni correction. We further adjusted for medication use and estimated glomerular filtration rate and found 17 proteins, including angiopoietin-2 and transgelin, that remained significantly associated with incident AF. Pathway analyses implicated the inhibition of matrix metalloproteases as the top canonical pathway in AF pathogenesis. In conclusion, using a large-scale proteomic platform, we identified both novel and established proteins associated with incident AF and explored mechanistic pathways of AF development.


Assuntos
Aterosclerose/sangue , Fibrilação Atrial/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Proteômica/métodos , Medição de Risco/métodos , Aterosclerose/complicações , Aterosclerose/epidemiologia , Fibrilação Atrial/complicações , Fibrilação Atrial/epidemiologia , Biomarcadores/sangue , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Precursores de Proteínas , Fatores de Risco , Fatores de Tempo , Estados Unidos/epidemiologia
7.
Front Neurosci ; 15: 741571, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34720863

RESUMO

Vestibular evoked myogenic potentials (VEMP) have been used to assess otolith function in clinics worldwide. However, there are accumulating evidence suggesting that the clinically used sound stimuli activate not only the otolith afferents, but also the canal afferents, indicating canal contributions to the VEMPs. To better understand the neural mechanisms underlying the VEMPs and develop discriminative VEMP protocols, we further examined sound-evoked responses of the vestibular nucleus neurons and the abducens neurons, which have the interneurons and motoneurons of the vestibulo-ocular reflex (VOR) pathways. Air-conducted clicks (50-80 dB SL re ABR threshold, 0.1 ms duration) or tone bursts (60-80 dB SL, 125-4,000 Hz, 8 ms plateau, 1 ms rise/fall) were delivered to the ears of Sprague-Dawley or Long-Evans rats. Among 425 vestibular nucleus neurons recorded in anesthetized rats and 18 abducens neurons recorded in awake rats, sound activated 35.9% of the vestibular neurons that increased discharge rates for ipsilateral head rotation (Type I neuron), 15.7% of the vestibular neurons that increased discharge rates for contralateral head rotation (Type II neuron), 57.2% of the vestibular neurons that did not change discharge rates during head rotation (non-canal neuron), and 38.9% of the abducens neurons. Sound sensitive vestibular nucleus neurons and abducens neurons exhibited characteristic tuning curves that reflected convergence of canal and otolith inputs in the VOR pathways. Tone bursts also evoked well-defined eye movements that increased with tone intensity and duration and exhibited peak frequency of ∼1,500 Hz. For the left eye, tone bursts evoked upward/rightward eye movements for ipsilateral stimulation, and downward/leftward eye movements for contralateral stimulation. These results demonstrate that sound stimulation results in activation of the canal and otolith VOR pathways that can be measured by eye tracking devices to develop discriminative tests of vestibular function in animal models and in humans.

8.
World Neurosurg ; 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34844008

RESUMO

BACKGROUND: In 2016, the World Health Organization (WHO) revised its guidelines to retain only gemistocytic astrocytoma (GemA) as a distinct variant of diffuse astrocytoma (DA). In the past, grade 2 GemAs have been linked with a worse prognosis than DA. However, it is unclear how consistently the tumor subtype has been diagnosed over time. We used more recent data to compare outcomes between grade 2 GemA and DA. METHODS: WHO grade 2 DA and GemA patients were extracted from the SEER database between 1973-2016. Kaplan-Meier curves estimated survival differences across different eras, with a focus on patients diagnosed between 2000-2016, and propensity score matching (PSM) was used to balance baseline characteristics between DA and GemA cohorts RESULTS: Of 2,467 grade 2 astrocytoma patients between 2000-2016, 132 (5.35%) were diagnosed with GemA, and 2,335 (94.65%) were diagnosed with DA. At baseline, marked demographic and treatment differences were noted between tumor subtypes, including age of diagnosis and female sex. GemA patients did not have worse survival compared to DA patients at baseline (p=0.349) or after PSM (p=0.497). Multivariate Cox models found that surgical extent of resection was associated with a survival benefit for DA patients, and both DA and GemA patients aged >65 years had dramatically inferior survival. CONCLUSIONS: Our data suggest that the impact of GemA versus DA histopathology depends more upon the decade of queried data rather than patient-specific demographics. Using more recent longitudinal data, we found that grade 2 GemA and DA tumors did not have significant differences in survival. These data may prove useful for clinicians counseling patients diagnosed with grade 2 GemA.

9.
Mol Imaging Biol ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34846678

RESUMO

PURPOSE: Current checkpoint inhibitor immunotherapy strategies in glioblastoma are challenged by mechanisms of resistance including an immunosuppressive tumor microenvironment. T cell immunoglobulin domain and mucin domain 3 (TIM3) is a late-phase checkpoint receptor traditionally associated with T cell exhaustion. We apply fluorescent imaging techniques to explore feasibility of in vivo visualization of the immune state in a glioblastoma mouse model. PROCEDURES: TIM3 monoclonal antibody was conjugated to a near-infrared fluorescent dye, IRDye-800CW (800CW). The TIM3 experimental conjugate and isotype control were assessed for specificity with immunofluorescent staining and flow cytometry in murine cell lines (GL261 glioma and RAW264.7 macrophages). C57BL/6 mice with orthotopically implanted GL261 cells were imaged in vivo over 4 days after intravenous TIM3-800CW injection to assess tumor-specific uptake. Cell-specific uptake was then assessed on histologic sections. RESULTS: The experimental TIM3-800CW, but not its isotype control, bound to RAW264.7 macrophages in vitro. Specificity to RAW264.7 macrophages and not GL261 tumor cells was quantitatively confirmed with the corresponding clone of TIM3 on flow cytometry. In vivo fluorescence imaging of the 800CW signal was localized to the intracranial tumor and significantly higher for the TIM3-800CW cohort, relative to non-targeting isotype control, immediately after tail vein injection and for up to 48 h after injection. Resected organs of tumor bearing mice showed significantly higher uptake in the liver and spleen. TIM3-800CW was seen to co-stain with CD3 (13%), CD11b (29%), and CD206 (26%). CONCLUSIONS: We propose fluorescent imaging of immune cell imaging as a potential strategy for monitoring and localizing immunologically relevant foci in the setting of brain tumors. Alternative markers and target validation will further clarify the temporal relationship of immunosuppressive effector cells throughout glioma resistance.

10.
J Am Heart Assoc ; 10(21): e021723, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34713724

RESUMO

Background Black Americans have more atrial fibrillation risk factors but lower atrial fibrillation risk than White Americans. Left atrial (LA) enlargement and/or dysfunction, frequent atrial tachycardia (AT), and premature atrial contractions (PAC) are associated with increased atrial fibrillation risk. Racial differences in these factors may exist that could explain the difference in atrial fibrillation risk. Methods and Results We included 2133 ARIC (Atherosclerosis Risk in Communities) study participants (aged 74±4.5 years[mean±SD], 59% women, 27% Black participants) who had echocardiograms in 2011 to 2013 and wore the Zio XT Patch (a 2-week continuous heart monitor) in 2016 to 2017. Linear regression was used to analyze (1) differences in AT/day or PAC/hour between Black and White participants, (2) differences in LA measures between Black and White participants, and (3) racial differences in the association of LA measures with AT or PAC frequency. Compared with White participants, Black participants had a higher prevalence of cardiovascular risk factors and disease, lower AT frequency, greater LA size, and lower LA function. After multivariable adjustments, Black participants had 37% (95% CI, 24%-47%) fewer AT runs/day than White participants. No difference in PAC between races was noted. Greater LA size and reduced LA function are associated with more AT and PAC runs; however, no race interaction was present. Conclusions Differences in LA measures are unlikely to explain the difference in atrial fibrillation risk between Black and White individuals. Despite more cardiovascular risk factors and greater atrial remodeling, Black participants have lower AT frequency than White participants. Future research is needed to elucidate the protective mechanisms that confer resilience to atrial arrhythmias in Black individuals.

11.
Oper Neurosurg (Hagerstown) ; 21(6): E559-E560, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34624887

RESUMO

Microsurgical clipping of large paraclinoid aneurysms is challenging because of the complex anatomy of the dural rings, lack of easy proximal control, and wide aneurysm necks. Proximal retrograde suction decompression, or the Dallas technique, can reduce aneurysm turgor and, with aspiration of the trapped cervical and supraclinoid internal carotid arteries (ICAs), can collapse the aneurysm to aid microsurgical clipping.1-5 A woman in her late 30s presented with decreased right-eye visual acuity. Informed written consent was obtained for microsurgical management and publication. Upon cervical exposure of the carotid bifurcation, we performed a standard pterional craniotomy, trans-sylvian exposure, and intradural anterior clinoidectomy. After burst suppression and cross-clamping of the carotid, we inserted an angiocatheter at the common carotid artery (CCA). Distal temporary clips were placed on the posterior communicating artery and C7 ICA. With the cervical ICA unclamped, retrograde suction was continuously applied to deflate the aneurysm. We applied 2 pairs of fenestrated-booster clips to the aneurysm dome and a fifth clip to the aneurysm neck. After restoration of flow, indocyanine green angiography and Doppler assessments were performed. The proximal clip was converted into a curved clip to optimize ICA flow. Postoperative angiography confirmed complete occlusion of the aneurysm. The patient was discharged on postoperative day 3, with stable visual acuity.6 This video demonstrates that retrograde suction decompression via the cervical CCA can be safely performed to facilitate clipping of complex paraclinoid ICA aneurysms. Comprehensive planning of temporary aneurysm trapping for suction decompression and permanent clip construct for aneurysm occlusion are needed for effective aneurysm repair.

12.
Nat Methods ; 18(10): 1223-1232, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34608315

RESUMO

Spatial metabolomics can reveal intercellular heterogeneity and tissue organization. Here we report on the spatial single nuclear metabolomics (SEAM) method, a flexible platform combining high-spatial-resolution imaging mass spectrometry and a set of computational algorithms that can display multiscale and multicolor tissue tomography together with identification and clustering of single nuclei by their in situ metabolic fingerprints. We first applied SEAM to a range of wild-type mouse tissues, then delineated a consistent pattern of metabolic zonation in mouse liver. We further studied the spatial metabolic profile in the human fibrotic liver. We discovered subpopulations of hepatocytes with special metabolic features associated with their proximity to the fibrotic niche, and validated this finding by spatial transcriptomics with Geo-seq. These demonstrations highlighted SEAM's ability to explore the spatial metabolic profile and tissue histology at the single-cell level, leading to a deeper understanding of tissue metabolic organization.


Assuntos
Microambiente Celular , Biologia Computacional/métodos , Cirrose Hepática/metabolismo , Fígado/citologia , Algoritmos , Animais , Hepatócitos/fisiologia , Humanos , Fígado/fisiologia , Metabolômica/métodos , Camundongos , Reprodutibilidade dos Testes , Imagem Individual de Molécula , Transcriptoma
13.
Neuro Oncol ; 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34487172

RESUMO

BACKGROUND: Non-invasive differentiation between schwannomas and neurofibromas is important for appropriate management, preoperative counseling, and surgical planning, but has proven difficult using conventional imaging. The objective of this study was to develop and evaluate machine learning approaches for differentiating peripheral schwannomas from neurofibromas. METHODS: We assembled a cohort of schwannomas and neurofibromas from 3 independent institutions and extracted high-dimensional radiomic features from gadolinium-enhanced, T1-weighted MRI using the PyRadiomics package on Quantitative Imaging Feature Pipeline. Age, sex, neurogenetic syndrome, spontaneous pain, and motor deficit were recorded. We evaluated the performance of 6 radiomics-based classifier models with and without clinical features and compared model performance against human expert evaluators. RESULTS: 107 schwannomas and 59 neurofibroma were included. The primary models included both clinical and imaging data. The accuracy of the human evaluators (0.765) did not significantly exceed the no-information rate (NIR), whereas the Support Vector Machine (0.929), Logistic Regression (0.929), and Random Forest (0.905) classifiers exceeded the NIR. Using the method of DeLong, the AUC for the Logistic Regression (AUC=0.923) and K Nearest Neighbor (AUC=0.923) classifiers was significantly greater than the human evaluators (AUC=0.766; p = 0.041). CONCLUSIONS: The radiomics-based classifiers developed here proved to be more accurate and had a higher AUC on the ROC curve than expert human evaluators. This demonstrates that radiomics using routine MRI sequences and clinical features can aid in differentiation of peripheral schwannomas and neurofibromas.

14.
J Endourol ; 35(S2): S116-S121, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34499542

RESUMO

The gold standard surgical treatment for muscle invasive bladder cancer is radical cystectomy and urinary diversion. This procedure has historically been performed as an open surgery. With the advances of robotic surgery, robotic cystectomy and urinary diversion has gained popularity with the ability to perform intracorporeal urinary diversions in addition to extirpative surgery. Herein, we detail our technique for intracorporeal ileal conduit.


Assuntos
Procedimentos Cirúrgicos Robóticos , Robótica , Neoplasias da Bexiga Urinária , Derivação Urinária , Cistectomia , Humanos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/cirurgia
15.
Cell Rep ; 36(8): 109573, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34433047

RESUMO

MicroRNAs (miRNAs) have been shown to modulate gene expression noise, but less is known about how miRNAs with different properties may regulate noise differently. Here, we investigate the role of competing RNAs and the composition of miRNA response elements (MREs) in modulating noise. We find that weak competing RNAs could introduce lower noise than strong competing RNAs. In comparison with a single MRE, both repetitive and composite MREs can reduce the noise at low expression, but repetitive MREs can elevate the noise remarkably at high expression. We further observed the behavior of a synthetic cell-type classifier with miRNAs as inputs and find that miRNAs and MREs that could introduce higher noise tend to enhance cell state transition. These results provide a systematic and quantitative understanding of the function of miRNAs in controlling gene expression noise and the utilization of miRNAs to modulate the behavior of synthetic gene circuits.

16.
Front Pharmacol ; 12: 723038, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34456733

RESUMO

RPH-120 is a novel fully human anti-PD-L1 IgG1 monoclonal antibody with specifically designed Asn300Ala mutation in Fc fragment. Surface plasmon resonance assay showed that affinity of the RPH-120 to the dimeric form of human PD-L1-Fc fusion protein was much higher than affinity to the monomeric His-tagged PD-L1. Further binding studies demonstrated that RPH-120 is able to bind to human and monkey but not mouse PD-L1. Tissue cross-reactivity study showed good comparability of human and Cynomolgus monkeys tissue staining. Bioactivity was assessed using mixed lymphocyte reaction assay. This study revealed that RPH-120 was able to activate T cells preventing PD1/PD-L1 interaction. Antitumor efficacy was analyzed in HCC-827 lung cancer xenografts in humanized CD34+ mice at three dosage levels: 20, 80, and 200 mg/kg. RPH-120 demonstrated significant tumor growth inhibition, and this inhibition was comparable to that of atezolizumab. In a single dose toxicity, toxicokinetic and dose range finding study performed in Cynomolgus monkeys, RPH-120 was administered via intravenous (IV) bolus or 60-min IV infusion, followed by 8-weeks recovery period. An acceptable toxicokinetic profile was demonstrated and administration at doses of up to 200 mg/kg was well tolerated by all animals. In conclusion, RPH-120 revealed promising in vitro and in vivo activity and safety. RPH-120 is a potent anti-PD-L1 drug candidate for cancer immunotherapy.

17.
Genome Biol ; 22(1): 229, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404448

RESUMO

BACKGROUND: Liquid-liquid phase separation (LLPS) is an important organizing principle for biomolecular condensation and chromosome compartmentalization. However, while many proteins have been reported to undergo LLPS, quantitative and global analysis of chromatin LLPS property remains absent. RESULTS: Here, by combining chromatin-associated protein pull-down, quantitative proteomics and 1,6-hexanediol (1,6-HD) treatment, we develop Hi-MS and define an anti-1,6-HD index of chromatin-associated proteins (AICAP) to quantify 1,6-HD sensitivity of chromatin-associated proteins under physiological conditions. Compared with known physicochemical properties involved in phase separation, we find that proteins with lower AICAP are associated with higher content of disordered regions, higher hydrophobic residue preference, higher mobility and higher predicted LLPS potential. We also construct BL-Hi-C libraries following 1,6-HD treatment to study the sensitivity of chromatin conformation to 1,6-HD treatment. We find that the active chromatin and high-order structures, as well as the proteins enriched in corresponding regions, are more sensitive to 1,6-HD treatment. CONCLUSIONS: Our work provides a global quantitative measurement of LLPS properties of chromatin-associated proteins and higher-order chromatin structure. Hi-MS and AICAP data provide an experimental tool and quantitative resources valuable for future studies of biomolecular condensates.

18.
Ann Plast Surg ; 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34387581

RESUMO

INTRODUCTION: Venous thromboembolism (VTE) is a life-threatening postoperative complication that carries high morbidity and mortality for plastic surgery patients. In 2011, the American Society of Plastic Surgeons recommended the adoption of a VTE risk stratification and mitigation; however, successful implementation of VTE prophylaxis protocols has not been well described. To address and reduce the VTE burden at our academic center, a risk assessment protocol was implemented for patients undergoing outpatient plastic surgery procedures. METHOD: All patients who received outpatient plastic surgery between August 2018 and July 2019 were eligible for the VTE modified Caprini risk assessment screening. Sampling of practice patterns was done by chart review from the first week of each month. The study was divided into 3 phases to assess the relationship of screening compliance rates with each protocol change. Compliance was defined as completion of VTE Caprini screening with documentation in patients' charts. RESULTS: Over the 12-month study period, 277 patients met the inclusion criteria. From August to November 2018 (phase 1), patients were screened at the initial clinic visit with an average compliance rate of 11.1%. In December 2018 (phase 2), patients were screened on the day of surgery, with an average compliance rate of 47.1%. From January to July 2019 (phase 3), surgeons recorded the numerical Caprini score into the patient's electronic medical record with a subsequent compliance rate of 61.3%. The overall compliance during the 12 months was 44.8%. The median calculated Caprini score for this population was 4 (range, 1-7). CONCLUSIONS: Standardization of VTE risk assessment is vital for patient safety and outcomes. Successful implementation and long-term protocol sustainability are not a simple goal. In this study, protocol compliance greatly improved after tailoring the guidelines to the specific institutional needs and workflow. These results reinforce the importance of continuous protocol review and modification to ensure optimal departmental buy-in and sustainability.

19.
Med J Aust ; 215(5): 217-221, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34389995

RESUMO

OBJECTIVES: To examine the epidemiological and clinical characteristics of SARS-CoV-2-positive children in Australia during 2020. DESIGN, SETTING: Multicentre retrospective study in 16 hospitals of the Paediatric Research in Emergency Departments International Collaborative (PREDICT) network; eleven in Victoria, five in four other Australian states. PARTICIPANTS: Children aged 0-17 years who presented to hospital-based COVID-19 testing clinics, hospital wards, or emergency departments during 1 February - 30 September 2020 and who were positive for SARS-CoV-2. MAIN OUTCOME MEASURES: Epidemiological and clinical characteristics of children positive for SARS-CoV-2. RESULTS: A total of 393 SARS-CoV-2-positive children (181 girls, 46%) presented to the participating hospitals (426 presentations, including 131 to emergency departments [31%]), the first on 3 February 2020. Thirty-three children presented more than once (8%), including two who were transferred to participating tertiary centres (0.5%). The median age of the children was 5.3 years (IQR, 1.9-12.0 years; range, 10 days to 17.9 years). Hospital admissions followed 51 of 426 presentations (12%; 44 children), including 17 patients who were managed remotely by hospital in the home. Only 16 of the 426 presentations led to hospital medical interventions (4%). Two children (0.5%) were diagnosed with the paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). CONCLUSION: The clinical course for most SARS-CoV-2-positive children who presented to Australian hospitals was mild, and did not require medical intervention.


Assuntos
Teste para COVID-19/estatística & dados numéricos , COVID-19/diagnóstico , COVID-19/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/epidemiologia , Adolescente , Instituições de Assistência Ambulatorial/estatística & dados numéricos , Austrália , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Avaliação de Sintomas
20.
J Neurooncol ; 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34410576

RESUMO

Over the past two decades, vast improvements in focused ultrasound (FUS) technology have made the therapy an exciting addition to the neurosurgical armamentarium. In this time period, FUS has gained US Food and Drug Administration (FDA) approval for the treatment of two neurological disorders, and ongoing efforts seek to expand the lesion profile that is amenable to ultrasonic intervention. In the following review, we highlight future applications for FUS therapy and compare its potential role against established technologies, including deep brain stimulation and stereotactic radiosurgery. Particular attention is paid to tissue ablation, blood-brain-barrier opening, and gene therapy. We also address technical and infrastructural challenges involved with FUS use and summarize the hurdles that must be overcome before FUS becomes widely accepted in the neurosurgical community.

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