Tag: statistics

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

Epilepsia. 2022 Jun 27. doi: 10.1111/epi.17348. Online ahead of print.

ABSTRACT

OBJECTIVE: Hormonal therapy is a standard treatment for children with infantile spasms. However, the high doses given, and long treatment duration expose patients to the risk of adrenal insufficiency (AI). This study aims to quantify the cumulative incidence of AI among children with infantile spasms treated with high-dose corticosteroids and/or adrenocorticotropic hormone.

METHODS: A retrospective chart review of patients treated for infantile spasms was performed between January 2009 and March 2020 in one pediatric specialized hospital. Variables collected include patient and treatment characteristics, risk factors of AI, and adrenal function testing. Analysis included descriptive statistics such as incidence and bivariate analysis.

RESULTS: Thirty-one patients were included and received a total of 33 courses of treatment (17 corticosteroids [prednisone/prednisolone], 12 adrenocorticotropic hormone and four combined). Physiologic hydrocortisone replacement therapy with stress supplementation was received after 32/33 (97%) courses of treatment. Adrenal function was assessed in 32/33 (97%) and AI occurred in 25/33 (76% [95CI 58-89]). No predictive factor of AI was identified after hormonal treatment. No drug regimen was found to be safe. The two patients who developed an acute adrenal crisis presented to the emergency room within the days (between two and seven) following weaning off of hormonal treatment. They were the youngest children of the cohort, and both received prednisolone.

SIGNIFICANCE: Adrenal insufficiency is frequent and can potentially lead to an adrenal crisis in this population. This study highlights the necessity of hydrocortisone replacement therapy until AI has been excluded in a patient who received hormonal therapy to treat infantile spasms. As such, routine laboratory assessment of adrenal function should be done in all patients.

PMID:35759339 | DOI:10.1111/epi.17348

Commun Med (Lond). 2022 Jun 20;2:70. doi: 10.1038/s43856-022-00133-4. eCollection 2022.

ABSTRACT

BACKGROUND: Alzheimer’s disease, the most common cause of dementia, causes a progressive and irreversible deterioration of cognition that can sometimes be difficult to diagnose, leading to suboptimal patient care.

METHODS: We developed a predictive model that computes multi-regional statistical morpho-functional mesoscopic traits from T1-weighted MRI scans, with or without cognitive scores. For each patient, a biomarker called “Alzheimer’s Predictive Vector” (ApV) was derived using a two-stage least absolute shrinkage and selection operator (LASSO).

RESULTS: The ApV reliably discriminates between people with (ADrp) and without (nADrp) Alzheimer’s related pathologies (98% and 81% accuracy between ADrp – including the early form, mild cognitive impairment – and nADrp in internal and external hold-out test sets, respectively), without any a priori assumptions or need for neuroradiology reads. The new test is superior to standard hippocampal atrophy (26% accuracy) and cerebrospinal fluid beta amyloid measure (62% accuracy). A multiparametric analysis compared DTI-MRI derived fractional anisotropy, whose readout of neuronal loss agrees with ADrp phenotype, and SNPrs2075650 is significantly altered in patients with ADrp-like phenotype.

CONCLUSIONS: This new data analytic method demonstrates potential for increasing accuracy of Alzheimer diagnosis.

PMID:35759330 | PMC:PMC9209493 | DOI:10.1038/s43856-022-00133-4

JMIR Mhealth Uhealth. 2022 Jun 27;10(6):e34273. doi: 10.2196/34273.

ABSTRACT

BACKGROUND: Tobacco addiction is the leading cause of preventable morbidity and mortality worldwide, but only 1 in 20 cessation attempts is supervised by a health professional. The potential advantages of mobile health (mHealth) can circumvent this problem and facilitate tobacco cessation interventions for public health systems. Given its easy scalability to large populations and great potential, chatbots are a potentially useful complement to usual treatment.

OBJECTIVE: This study aims to assess the effectiveness of an evidence-based intervention to quit smoking via a chatbot in smartphones compared with usual clinical practice in primary care.

METHODS: This is a pragmatic, multicenter, controlled, and randomized clinical trial involving 34 primary health care centers within the Madrid Health Service (Spain). Smokers over the age of 18 years who attended on-site consultation and accepted help to quit tobacco were recruited by their doctor or nurse and randomly allocated to receive usual care (control group [CG]) or an evidence-based chatbot intervention (intervention group [IG]). The interventions in both arms were based on the 5A’s (ie, Ask, Advise, Assess, Assist, and Arrange) in the US Clinical Practice Guideline, which combines behavioral and pharmacological treatments and is structured in several follow-up appointments. The primary outcome was continuous abstinence from smoking that was biochemically validated after 6 months by the collaborators. The outcome analysis was blinded to allocation of patients, although participants were unblinded to group assignment. An intention-to-treat analysis, using the baseline-observation-carried-forward approach for missing data, and logistic regression models with robust estimators were employed for assessing the primary outcomes.

RESULTS: The trial was conducted between October 1, 2018, and March 31, 2019. The sample included 513 patients (242 in the IG and 271 in the CG), with an average age of 49.8 (SD 10.82) years and gender ratio of 59.3% (304/513) women and 40.7% (209/513) men. Of them, 232 patients (45.2%) completed the follow-up, 104/242 (42.9%) in the IG and 128/271 (47.2%) in the CG. In the intention-to-treat analysis, the biochemically validated abstinence rate at 6 months was higher in the IG (63/242, 26%) compared with that in the CG (51/271, 18.8%; odds ratio 1.52, 95% CI 1.00-2.31; P=.05). After adjusting for basal CO-oximetry and bupropion intake, no substantial changes were observed (odds ratio 1.52, 95% CI 0.99-2.33; P=.05; pseudo-R²=0.045). In the IG, 61.2% (148/242) of users accessed the chatbot, average chatbot-patient interaction time was 121 (95% CI 121.1-140.0) minutes, and average number of contacts was 45.56 (SD 36.32).

CONCLUSIONS: A treatment including a chatbot for helping with tobacco cessation was more effective than usual clinical practice in primary care. However, this outcome was at the limit of statistical significance, and therefore these promising results must be interpreted with caution.

TRIAL REGISTRATION: Clinicaltrials.gov NCT03445507; https://tinyurl.com/mrnfcmtd.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12911-019-0972-z.

PMID:35759328 | DOI:10.2196/34273