Category: Statistics

Brief Bioinform. 2023 Feb 8:bbad042. doi: 10.1093/bib/bbad042. Online ahead of print.

ABSTRACT

Feature gene selection has significant impact on the performance of cell clustering in single-cell RNA sequencing (scRNA-seq) analysis. A well-rounded feature selection (FS) method should consider relevance, redundancy and complementarity of the features. Yet most existing FS methods focus on gene relevance to the cell types but neglect redundancy and complementarity, which undermines the cell clustering performance. We develop a novel computational method GeneClust to select feature genes for scRNA-seq cell clustering. GeneClust groups genes based on their expression profiles, then selects genes with the aim of maximizing relevance, minimizing redundancy and preserving complementarity. It can work as a plug-in tool for FS with any existing cell clustering method. Extensive benchmark results demonstrate that GeneClust significantly improve the clustering performance. Moreover, GeneClust can group cofunctional genes in biological process and pathway into clusters, thus providing a means of investigating gene interactions and identifying potential genes relevant to biological characteristics of the dataset. GeneClust is freely available at https://github.com/ToryDeng/scGeneClust.

PMID:36754847 | DOI:10.1093/bib/bbad042

J Chem Phys. 2023 Feb 7;158(5):054113. doi: 10.1063/5.0135249.

ABSTRACT

The transport of particles through channels is of paramount importance in physics, chemistry, and surface science due to its broad real world applications. Much insight can be gained by observing the transition paths of a particle through a channel and collecting statistics on the lifetimes in the channel or the escape probabilities from the channel. In this paper, we consider the diffusive transport through a narrow conical channel of a Brownian particle subject to intermittent dynamics, namely, stochastic resetting. As such, resetting brings the particle back to a desired location from where it resumes its diffusive phase. To this end, we extend the Fick-Jacobs theory of channel-facilitated diffusive transport to resetting-induced transport. Exact expressions for the conditional mean first passage times, escape probabilities, and the total average lifetime in the channel are obtained, and their behavior as a function of the resetting rate is highlighted. It is shown that resetting can expedite the transport through the channel-rigorous constraints for such conditions are then illustrated. Furthermore, we observe that a carefully chosen resetting rate can render the average lifetime of the particle inside the channel minimal. Interestingly, the optimal rate undergoes continuous and discontinuous transitions as some relevant system parameters are varied. The validity of our one-dimensional analysis and the corresponding theoretical predictions is supported by three-dimensional Brownian dynamics simulations. We thus believe that resetting can be useful to facilitate particle transport across biological membranes-a phenomenon that can spearhead further theoretical and experimental studies.

PMID:36754825 | DOI:10.1063/5.0135249

J Chem Phys. 2023 Feb 7;158(5):054903. doi: 10.1063/5.0123431.

ABSTRACT

We present a computationally efficient multiscale method for preparing equilibrated, isotropic long-chain model polymer melts. As an application, we generate Kremer-Grest melts of 1000 chains with 200 entanglements and 25 000-2000 beads/chain, which cover the experimentally relevant bending rigidities up to and beyond the limit of the isotropic-nematic transition. In the first step, we employ Monte Carlo simulations of a lattice model to equilibrate the large-scale chain structure above the tube scale while ensuring a spatially homogeneous density distribution. We then use theoretical insight from a constrained mode tube model to introduce the bead degrees of freedom together with random walk conformational statistics all the way down to the Kuhn scale of the chains. This is followed by a sequence of simulations with carefully parameterized force-capped bead-spring models, which slowly introduce the local bead packing while reproducing the larger-scale chain statistics of the target Kremer-Grest system at all levels of force-capping. Finally, we can switch to the full Kremer-Grest model without perturbing the structure. The resulting chain statistics is in excellent agreement with literature results on all length scales accessible in brute-force simulations of shorter chains.

PMID:36754791 | DOI:10.1063/5.0123431

J Chem Theory Comput. 2023 Feb 8. doi: 10.1021/acs.jctc.2c01094. Online ahead of print.

ABSTRACT

Polarizabilities play significant roles in describing dispersive and inductive interactions of the atom and molecular systems. However, an accurate prediction of molecular polarizabilities from first principles is computationally prohibitive. Although physical models or statistical machine learning models have been proposed, either a lack of accurate description of local chemical environments or demanding a large number of samples for training has limited their practical applications. In this study, we combine a physically inspired dipole interaction model and an accurate neural network method for predicting the polarizability tensors of molecules. With the local chemical environment precisely described and the requirement of rotational covariance naturally fulfilled, this hybrid model is proven to give an accurate molecular polarizability prediction, essentially reducing the number of training samples. The atomic polarizabilities are physically interpretable and transferable to larger molecules unseen in the training set. This promising method may find its wide range of applications, such as spectroscopic simulations and the construction of polarizable force fields.

PMID:36753749 | DOI:10.1021/acs.jctc.2c01094

J Cardiovasc Med (Hagerstown). 2023 Mar 1;24(3):191-199. doi: 10.2459/JCM.0000000000001446.

ABSTRACT

AIMS: To assess the characteristics of left atrial appendage (LAA) stump and left atrial (LA) volume after standalone totally thoracoscopic LAA exclusion in 40 patients with nonvalvular atrial fibrillation (NVAF) and contraindications to oral anticoagulation (OAC), using cardiac computed tomography (CCT) and transoesophageal echocardiography (TOE).

METHODS: Using CCT and TOE, we evaluated correct AtriClip Pro II positioning, the presence and characteristics of the LAA stump and the postprocedural LA volume, at 3 months’ follow-up. Stump depth was measured with both CCT and TOE using a new method, based on left circumflex artery (LCX) course.

RESULTS: After placement of AtriClip, all 40 patients discontinued OAC, and no stroke occurred. LAA exclusion was achieved in 40/40 patients at 3 months’ follow-up. LAA stump (depth <10 mm in 12/18 stump, 67%) was observed in 18 patients. The overall (LA + LAA) volume and isolated LA volume were statistically different when comparing cases with and without LAA stump (P < 0.02). LAA ostium dimensions (perimeter and area) and LAA volume correlate with stump depth (P < 0.02). There was a high correlation between CCT and TOE in stump identification and depth measurement (P < 0.02). Compared with the baseline, CCT LA volume increased (P < 0.01) at 3 months’ follow-up.

CONCLUSION: Preprocedural and postprocedural CCT and TOE are useful and comparable in patients undergoing standalone totally thoracoscopic exclusion of LAA, because these imaging methods can identify anatomical LAA and LA characteristics predisposing for a postprocedural residual stump.

PMID:36753726 | DOI:10.2459/JCM.0000000000001446

J Cardiovasc Med (Hagerstown). 2023 Mar 1;24(3):172-183. doi: 10.2459/JCM.0000000000001441.

ABSTRACT

AIMS: This large cohort study aimed to assess the role of chronic statin use on COVID-19 disease severity.

METHODS: An observational retrospective study from electronic medical records of hospitalized patients (n = 43 950) with COVID-19 between January and September 2020 in 185 hospitals in the United States. A total of 38 875 patients met inclusion criteria; 23 066 were included in the propensity-matched sampling with replacement cohort; 11 533 were prehospital statin users. The primary outcome was all-cause death; secondary outcomes were death from COVID-19 and serious complications. Mean, standard deviation, chi-square test, Student’s t-test, linear regression, and binary and multinomial logistic regressions were used for statistical analysis.

RESULTS: Among 38 875 patients, 30% were chronic statin users [mean age, 70.82 (±12.25); 47.1% women] and 70% were statin nonusers [mean age, 58.44 (±18.27); 48.5% women]. Key propensity-matched outcomes among 11 533 chronic statin users showed 20% lower risk of all-cause mortality (OR 0.80, 95% CI 0.74-0.86, P < 0.001), 23% lower risk of mortality from COVID-19 (OR 0.77, 95% CI 0.71-0.84, P < 0.001), 16% lower risk of ICU admission (OR 0.84, 95% CI 0.79-0.89, P < 0.001), 24% lower risk of critical acute respiratory distress syndrome with COVID-19 (OR 0.76, 95% CI 0.70-0.83, P < 0.001), 23% lower risk of mechanical ventilation (OR 0.77, 95% CI 0.71-0.82, P < 0.001), 20% lower risk of severe sepsis with septic shock (OR 0.80, 95% CI 0.67-0.93, P = 0.004), shorter hospital length of stay [9.87 (±8.94), P < 0.001] and brief duration of mechanical ventilation [8.90 (±8.94), P < 0.001].

CONCLUSION: Chronic use of statins is associated with reduced mortality and improved clinical outcomes in patients hospitalized for COVID-19.

PMID:36753725 | DOI:10.2459/JCM.0000000000001441

J Spec Oper Med. 2023 Feb 8:KCZS-41KZ. doi: 10.55460/KCZS-41KZ. Online ahead of print.

ABSTRACT

BACKGROUND: Transfusion of blood products is life-saving and time-sensitive in the setting of acute blood-loss anemia, and is increasingly common in the emergency medical services (EMS) setting. Prehospital blood products are generally “cold-stored” at 4°C, then warmed with a portable fluid-warming system for the purpose of preventing the “lethal triad” of hypothermia, acidosis, and coagulopathy. This study aims to evaluate body temperature changes of EMS patients receiving packed red blood cells (PRBC) and/or fresh frozen plasma (FFP) when using the LifeWarmer Quantum Blood & Fluid Warming System (LifeWarmer, https://www.lifewarmer.com/).

METHODS: From 1 January 2020 to 31 August 2021, patients who qualified for and received PRBC and/or FFP were retrospectively reviewed. Body-temperature homeostasis pre- and post-transfusion were evaluated with attention given to those who arrived to the emergency department (ED) hypothermic (<36°C).

RESULTS: For all 69 patients analyzed, the mean initial prehospital temperature (°C) was 36.5 ± 1.0, and the mean initial ED temperature was 36.7 ± 0.6, demonstrating no statically significant change in value pre- or post-transfusion (0.2 ± 0.8, p = .09). Shock index showed a statistically significant decrease following transfusion: 1.5 ± 0.5 to 0.9 ± 0.4 (p < .001).

CONCLUSION: Use of the Quantum prevents the previously identified risk of hypothermia with respect to unwarmed prehospital transfusions. The data is favorable in that body temperature did not decrease in critically ill patients receiving cold-stored blood warmed during administration with the Quantum.

PMID:36753715 | DOI:10.55460/KCZS-41KZ

J Clin Oncol. 2023 Feb 8:JCO2201726. doi: 10.1200/JCO.22.01726. Online ahead of print.

ABSTRACT

PURPOSE: To assess the efficacy and safety of darolutamide maintenance after successful taxane chemotherapy in patients with metastatic castration-resistant prostate cancer (mCRPC).

PATIENTS AND METHODS: Swiss Group for Clinical Cancer Research (SAKK) 08/16 is a randomized phase II study. Patients with mCRPC who received prior androgen-receptor pathway inhibitors (ARPIs) and subsequently had nonprogressive disease on a taxane were randomly assigned to darolutamide 600 mg twice a day or placebo twice a day. The primary end point was radiographic progression-free survival (rPFS) at 12 weeks. Secondary end points were rPFS, event-free survival, overall survival (OS), prostate-specific antigen (PSA) 50% response rate, and adverse events.

RESULTS: Overall, 92 patients were recruited by 26 centers. Prior taxane was docetaxel in 93% and cabazitaxel in 7%. Prior ARPI was abiraterone in 60%, enzalutamide in 31%, and both in 9%. rPFS at 12 weeks was significantly improved with darolutamide (64.7% v 52.2%; P = .127). Median rPFS on darolutamide was 5.5 versus 4.5 months on placebo (hazard ratio [HR], 0.54; 95% CI, 0.32 to 0.91; P = .017), and median event-free survival was 5.4 versus 2.9 months (HR, 0.46; 95% CI, 0.29 to 0.73; P = .001). PSA 50% response rate was improved (22% v 4%; P = .014). Median OS for darolutamide was 24 versus 21.3 months for placebo (HR, 0.62; 95% CI, 0.3 to 1.26; P = .181). Treatment-related adverse events were similar in both arms.

CONCLUSION: SAKK 08/16 met its primary end point, showing that switch maintenance with darolutamide after prior taxane chemotherapy and at least one ARPI resulted in a statistically significant but clinically modest rPFS prolongation with good tolerability. The median OS with darolutamide maintenance appears promising. Should these findings be confirmed in a larger trial, maintenance treatment could be a novel strategy in managing patients with mCRPC, especially those who responded well to prior ARPI.

PMID:36753698 | DOI:10.1200/JCO.22.01726

Perfusion. 2023 Feb 8:2676591231156487. doi: 10.1177/02676591231156487. Online ahead of print.

ABSTRACT

Introduction: Obesity is associated with a worse prognosis in COVID-19 patients with acute respiratory distress syndrome (ARDS). Veno-venous (V-V) Extracorporeal Membrane Oxygenation (ECMO) can be a rescue option, however, the direct impact of morbid obesity in this select group of patients remains unclear.Methods: This is an observational study of critically ill adults with COVID-19 and ARDS supported by V-V ECMO. Data are from 82 institutions participating in the COVID-19 Critical Care Consortium international registry. Patients were admitted between 12 January 2020 to 27 April 2021. They were stratified based on Body Mass Index (BMI) at 40 kg/m². The endpoint was survival to hospital discharge.Results: Complete data available on 354 of 401 patients supported on V-V ECMO. The characteristics of the high BMI (>40 kg/m²) and lower BMI (≤40 kg/m²) groups were statistically similar. However, the ‘high BMI’ group were comparatively younger and had a lower APACHE II score. Using survival analysis, older age (Hazard Ratio, HR 1.49 per-10-years, CI 1.25-1.79) and higher BMI (HR 1.15 per-5 kg/m² increase, CI 1.03–1.28) were associated with a decreased patient survival. A safe BMI threshold above which V-V ECMO would be prohibitive was not apparent and instead, the risk of an adverse outcome increased linearly with BMI.Conclusion: In COVID-19 patients with severe ARDS who require V-V ECMO, there is an increased risk of death associated with age and BMI. The risk is linear and there is no BMI threshold beyond which the risk for death greatly increases.

PMID:36753684 | DOI:10.1177/02676591231156487