Tag: statistics

Environ Sci Technol. 2022 Jun 27. doi: 10.1021/acs.est.1c08673. Online ahead of print.

ABSTRACT

Wastewater-based surveillance (WBS) for disease monitoring is highly promising but requires consistent methodologies that incorporate predetermined objectives, targets, and metrics. Herein, we describe a comprehensive metagenomics-based approach for global surveillance of antibiotic resistance in sewage that enables assessment of 1) which antibiotic resistance genes (ARGs) are shared across regions/communities; 2) which ARGs are discriminatory; and 3) factors associated with overall trends in ARGs, such as antibiotic concentrations. Across an internationally sourced transect of sewage samples collected using a centralized, standardized protocol, ARG relative abundances (16S rRNA gene-normalized) were highest in Hong Kong and India and lowest in Sweden and Switzerland, reflecting national policy, measured antibiotic concentrations, and metal resistance genes. Asian versus European/US resistomes were distinct, with macrolide-lincosamide-streptogramin, phenicol, quinolone, and tetracycline versus multidrug resistance ARGs being discriminatory, respectively. Regional trends in measured antibiotic concentrations differed from trends expected from public sales data. This could reflect unaccounted uses, captured only by the WBS approach. If properly benchmarked, antibiotic WBS might complement public sales and consumption statistics in the future. The WBS approach defined herein demonstrates multisite comparability and sensitivity to local/regional factors.

PMID:35759608 | DOI:10.1021/acs.est.1c08673

Zh Nevrol Psikhiatr Im S S Korsakova. 2022;122(5. Vyp. 2):52-57. doi: 10.17116/jnevro202212205252.

ABSTRACT

OBJECTIVE: To evaluate a relative telomere length in patients with obstructive sleep apnea (OSA) before and after a 6-month course of continuous positive airway pressure (CPAP) therapy.

MATERIAL AND METHODS: Seventy-five men participated in the study, including 50 men with OSA (the main group 1) and 25 men without OSA (the control group). The average age in the total group was 53.4±3.6 years. Thirty-five men completed the study (the main group 2). According to the design, night polysomnography (PSG) was performed for all the subjects, blood sampling to assess the length of telomeres was carried out in the morning according to the standard method. The values of the relative telomere length were obtained using the difference between the values of the threshold cycles for telomeric DNA and the reference gene albumin (∆CCt). After clarifying the diagnosis, CPAP was applied for 6 months.

RESULTS: Statistically significant indicators of PSG were revealed: a decrease in NREM 3 in patients with OSA compared to controls (89.3±15.8 versus 150±23.4 minutes), an increase in NREM1-2 in OSA (296.2±31.1 and 170.1±24.5, respectively), REM was 84.6±15.4 in the main group and 118.5±19.5 in the control group. CPAP therapy conducted for 6 months (at least 4-5 nights a week, lasting at least 5-6 hours of night sleep) demonstrated a significant improvement in the qualitative and quantitative parameters of sleep. In patients of the main group 1, there is a shortening of the telomere length compared with the control group (p<0.001). With the elimination of hypoxia and improvement of the structure of sleep after CPAP, there was an increase in the telomere lengths in the main group 1 from 0.28 [0.24-0.29] to 0.32 [0.30-0.34] in the main group 2 (p=0.03). The telomers length in the control group was 0.53 [0.50-0.55].

CONCLUSION: Intermittent hypoxia and fragmentation of sleep in OSA leads to shortening of telomeres. CPAP, by eliminating the pathophysiological triggers of OSA, contributes to an increase in telomeres lengths and can slow down the premature aging in OSA.

PMID:35759567 | DOI:10.17116/jnevro202212205252

PLoS Comput Biol. 2022 Jun 27;18(6):e1010271. doi: 10.1371/journal.pcbi.1010271. Online ahead of print.

ABSTRACT

While deep learning models have seen increasing applications in protein science, few have been implemented for protein backbone generation-an important task in structure-based problems such as active site and interface design. We present a new approach to building class-specific backbones, using a variational auto-encoder to directly generate the 3D coordinates of immunoglobulins. Our model is torsion- and distance-aware, learns a high-resolution embedding of the dataset, and generates novel, high-quality structures compatible with existing design tools. We show that the Ig-VAE can be used with Rosetta to create a computational model of a SARS-CoV2-RBD binder via latent space sampling. We further demonstrate that the model’s generative prior is a powerful tool for guiding computational protein design, motivating a new paradigm under which backbone design is solved as constrained optimization problem in the latent space of a generative model.

PMID:35759518 | DOI:10.1371/journal.pcbi.1010271

PLoS Comput Biol. 2022 Jun 27;18(6):e1010281. doi: 10.1371/journal.pcbi.1010281. Online ahead of print.

ABSTRACT

In the context of infectious disease transmission, high heterogeneity in individual infectiousness indicates that a few index cases can generate large numbers of secondary cases, a phenomenon commonly known as superspreading. The potential of disease superspreading can be characterized by describing the distribution of secondary cases (of each seed case) as a negative binomial (NB) distribution with the dispersion parameter, k. Based on the feature of NB distribution, there must be a proportion of individuals with individual reproduction number of almost 0, which appears restricted and unrealistic. To overcome this limitation, we generalized the compound structure of a Poisson rate and included an additional parameter, and divided the reproduction number into independent and additive fixed and variable components. Then, the secondary cases followed a Delaporte distribution. We demonstrated that the Delaporte distribution was important for understanding the characteristics of disease transmission, which generated new insights distinct from the NB model. By using real-world dataset, the Delaporte distribution provides improvements in describing the distributions of COVID-19 and SARS cases compared to the NB distribution. The model selection yielded increasing statistical power with larger sample sizes as well as conservative type I error in detecting the improvement in fitting with the likelihood ratio (LR) test. Numerical simulation revealed that the control strategy-making process may benefit from monitoring the transmission characteristics under the Delaporte framework. Our findings highlighted that for the COVID-19 pandemic, population-wide interventions may control disease transmission on a general scale before recommending the high-risk-specific control strategies.

PMID:35759509 | DOI:10.1371/journal.pcbi.1010281

PLoS Comput Biol. 2022 Jun 27;18(6):e1010203. doi: 10.1371/journal.pcbi.1010203. Online ahead of print.

ABSTRACT

The topology of metabolic networks is recognisably modular with modules weakly connected apart from sharing a pool of currency metabolites. Here, we defined modules as sets of reversible reactions isolated from the rest of metabolism by irreversible reactions except for the exchange of currency metabolites. Our approach identifies topologically independent modules under specific conditions associated with different metabolic functions. As case studies, the E.coli iJO1366 and Human Recon 2.2 genome-scale metabolic models were split in 103 and 321 modules respectively, displaying significant correlation patterns in expression data. Finally, we addressed a fundamental question about the metabolic flexibility conferred by reversible reactions: “Of all Directed Topologies (DTs) defined by fixing directions to all reversible reactions, how many are capable of carrying flux through all reactions?”. Enumeration of the DTs for iJO1366 model was performed using an efficient depth-first search algorithm, rejecting infeasible DTs based on mass-imbalanced and loopy flux patterns. We found the direction of 79% of reversible reactions must be defined before all directions in the network can be fixed, granting a high degree of flexibility.

PMID:35759507 | DOI:10.1371/journal.pcbi.1010203

PLoS One. 2022 Jun 27;17(6):e0270554. doi: 10.1371/journal.pone.0270554. eCollection 2022.

ABSTRACT

BACKGROUND: Stroke incidence and case-fatality in Mainland China, Hong Kong, and Macao vary by geographic region and rates often differ across and within regions. This systematic review and meta-analysis (SR) estimated the pooled incidence and short-term case-fatality of acute first ever stroke in mainland China, Hong Kong, and Macao.

METHODS: Longitudinal studies published in English or Chinese after 1990 were searched in PubMed/Medline, EMBASE, CINAHL, Web of Science, SinoMed and CQVIP. The incidence was expressed as Poisson means estimated as the number of events divided by time at risk. Random effect models calculated the pooled incidence and pooled case-fatality. Chi-squared trend tests evaluated change in the estimates over time. When possible, age standardised rates were calculated. Percent of variation across studies that was due to heterogeneity rather than chance was tested using the I2 statistic.The effect of covariates on heterogeneity was investigated using meta-regressions. Publication bias was tested using funnel plots and Egger’s tests.

RESULTS: Overall, 72 studies were included. The pooled incidences of total stroke (TS), ischaemic stroke (IS) and haemorrhagic stroke (HS) were 468.9 (95% confidence interval (CI): 163.33-1346.11), 366.79 (95% CI: 129.66-1037.64) and 106.67 (95% CI: 55.96-203.33) per 100,000 person-years, respectively, varied according to the four economic regions (East Coast, Central China, Northeast and Western China) with the lowest rates detected in the East Coast. Increased trends over time in the incidence of TS and IS were observed (p<0.001 in both). One-month and three-to-twelve-month case-fatalities were 0.11 (95% CI: 0.04-0.18) and 0.15 (95% CI: 0.12-0.17), respectively for IS; and 0.36 (95% CI: 0.26-0.45) and 0.25 (95% CI: 0.18-0.32), respectively for HS. One-month case-fatality of IS and HS decreased over time for both (p<0.001). Three-to-twelve-month fatalities following IS increased over time (p<0.001). Publication bias was not found.

CONCLUSIONS: Regional differences in stroke incidence were observed with the highest rates detected in less developed regions. Although 1-month fatality following IS is decreasing, the increased trends in 3-12-month fatality may suggest an inappropriate long-term management following index hospital discharge.

REGISTRATION: Registration-URL: https://www.crd.york.ac.uk/prospero/; Reference code: CRD42020170724.

PMID:35759497 | DOI:10.1371/journal.pone.0270554

PLoS One. 2022 Jun 27;17(6):e0266754. doi: 10.1371/journal.pone.0266754. eCollection 2022.

ABSTRACT

OBJECTIVE: This study aims to evaluate the efficacy and safety of oxycodone hydrochloride (OxyContin) rectal administration in cancer pain patients. This is geared towards providing the research evidence for a novel route of OxyContin administration.

METHODS: Relevant randomized controlled trials (RCTs) were searched in electronic databases, including PubMed, Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP database), Wanfang Data Knowledge Service Platform, and Chinese Biomedical Literature Database (CBM). Moreover, unpublished academic data were obtained by contacting the colleague, professor, or Institute of Traditional Chinese Medicine. The RCTs of transrectal Oxycodone administration of sustained-release tablets for moderate and severe pain patients were searched in the databases from inception to December 2020.

RESULTS: According to the inclusion criteria, a total of 8 RCTs were included, with a total of 648 patients. Meta analysis results showed that there was no statistically significant difference in the efficacy of moderate to severe pain control between the rectal administration group and the oral administration group (RR = 1.04, 95%CI: 0.99-1.10, p = 0.13>0.05). At the same time, the incidence of adverse reactions in the rectal administration group was low. In terms of constipation, the rectal administration group was less than the oral administration group, with a statistically significant difference (RR = 0.43, 95%CI: 0.31-0.58, p< 0.00001). In terms of nausea and vomiting, the rectal administration group was less than the oral administration group, and the difference was statistically significant(RR = 0.30, 95%CI: 0.21-0.42, p<0.00001). In terms of sleepiness, there was no significant difference between the two groups(RR = 0.54, 95%CI: 0.26-1.15, p = 0.11>0.05). In terms of dizziness, there was no statistically significant difference between the two groups (RR = 0.43, 95%CI:0.27-0.68, p = 0.31>0.05). In terms of dyuria, there was no statistically significant difference between the two groups (RR = 0.37, 95%CI: 0.02-7.02, p = 0.51>0.05). In terms of KPS scores there was no significant difference was noted between the rectal and oral administration groups (RR = 1.04, 95%CI: 0.89-1.21, p = 0.63>0.05).

CONCLUSION: In summary, we found no significant differences in efficacy between rectal administration of OxyContin and oral administration. Thus, rectal administration should be considered in managing cancer pain among patients with difficulty in oral OxyContin administration.

PROSPERO REGISTRATION NUMBER: CRD42021209660.

PMID:35759471 | DOI:10.1371/journal.pone.0266754

Chem Rev. 2022 Jun 27. doi: 10.1021/acs.chemrev.2c00141. Online ahead of print.

ABSTRACT

Artificial intelligence and specifically machine learning applications are nowadays used in a variety of scientific applications and cutting-edge technologies, where they have a transformative impact. Such an assembly of statistical and linear algebra methods making use of large data sets is becoming more and more integrated into chemistry and crystallization research workflows. This review aims to present, for the first time, a holistic overview of machine learning and cheminformatics applications as a novel, powerful means to accelerate the discovery of new crystal structures, predict key properties of organic crystalline materials, simulate, understand, and control the dynamics of complex crystallization process systems, as well as contribute to high throughput automation of chemical process development involving crystalline materials. We critically review the advances in these new, rapidly emerging research areas, raising awareness in issues such as the bridging of machine learning models with first-principles mechanistic models, data set size, structure, and quality, as well as the selection of appropriate descriptors. At the same time, we propose future research at the interface of applied mathematics, chemistry, and crystallography. Overall, this review aims to increase the adoption of such methods and tools by chemists and scientists across industry and academia.

PMID:35759465 | DOI:10.1021/acs.chemrev.2c00141

PLoS Comput Biol. 2022 Jun 27;18(6):e1010266. doi: 10.1371/journal.pcbi.1010266. Online ahead of print.

ABSTRACT

Cells sense their surrounding by employing intracellular signaling pathways that transmit hormonal signals from the cell membrane to the nucleus. TGF-β/SMAD signaling encodes various cell fates, controls tissue homeostasis and is deregulated in diseases such as cancer. The pathway shows strong heterogeneity at the single-cell level, but quantitative insights into mechanisms underlying fluctuations at various time scales are still missing, partly due to inefficiency in the calibration of stochastic models that mechanistically describe signaling processes. In this work we analyze single-cell TGF-β/SMAD signaling and show that it exhibits temporal stochastic bursts which are dose-dependent and whose number and magnitude correlate with cell migration. We propose a stochastic modeling approach to mechanistically describe these pathway fluctuations with high computational efficiency. Employing high-order numerical integration and fitting to burst statistics we enable efficient quantitative parameter estimation and discriminate models that assume noise in different reactions at the receptor level. This modeling approach suggests that stochasticity in the internalization of TGF-β receptors into endosomes plays a key role in the observed temporal bursting. Further, the model predicts the single-cell dynamics of TGF-β/SMAD signaling in untested conditions, e.g., successfully reflects memory effects of signaling noise and cellular sensitivity towards repeated stimulation. Taken together, our computational framework based on burst analysis, noise modeling and path computation scheme is a suitable tool for the data-based modeling of complex signaling pathways, capable of identifying the source of temporal noise.

PMID:35759468 | DOI:10.1371/journal.pcbi.1010266

Rev Med Inst Mex Seguro Soc. 2022 Mar 1;60(2):164-170.

ABSTRACT

BACKGROUND: Despite the fact that the Papanicolaou technique is the most effective method of prevention and detection of cervical cancer, the precision of this tool remains controversial; Because of this, there are medical and scientific efforts to improve the quality of the procedure.

OBJECTIVE: Compare the quality of sampling between the conventional and modified technique.

MATERIAL AND METHODS: Descriptive and comparative observational study in 150 cervical cytology samples (75 conventional technique samples and 75 in modified technique) in women aged 25 to 64 years. Demographic variables, characteristics of the cervix and quality of the sample were analyzed. Descriptive statistics and association measures were performed. Study with risk greater than the minimum. All participants signed an informed consent.

RESULTS: The quality of the sample was satisfactory in 92.0% for the conventional technique vs 89.3% for the modified technique. The main cause of unsatisfactory samples was insufficient cellularity 6.7% in conventional technique vs 12% of the modified technique, with no significant difference between both techniques p = 0.575 (1.37; 0.45-4.1), findings that reject the working hypothesis.

CONCLUSIONS: There was no significant difference when using both tests, the samples with satisfactory quality were similar between both techniques.

PMID:35759446