Category: Statistics

BMC Genomics. 2022 Aug 25;23(1):617. doi: 10.1186/s12864-022-08766-4.

ABSTRACT

Individuals with schizophrenia (SCZ) have, on average, a 10- to 20-year shorter expected life span than the rest of the population, primarily due to cardiovascular disease comorbidity. Genome-wide association studies (GWAS) have previously been used to separately identify common variants in SCZ and cardiometabolic traits. However, genetic variants jointly influencing both traits remain to be fully characterised. To assess overlaps (if any) between the genetic architecture of SCZ and cardiometabolic traits, we used conditional false discovery rate (FDR) and local genetic correlation statistical framework analyses. A conjunctional FDR was used to identify shared genetic traits between SCZ and cardiometabolic risk factors. We identified 144 genetic variants which were shared between SCZ and body mass index (BMI), and 15 variants shared between SCZ and triglycerides (TG). Furthermore, we discovered four novel single nucleotide polymorphisms (SNPs) (rs3865350, rs9860913, rs13307 and rs9614186) and four proximate genes (DERL2, SNX4, LY75 and EFCAB6) which were shared by SCZ and BMI. We observed that the novel genetic variant rs13307 and the most proximate gene LY75 exerted potential effects on SCZ and BMI comorbidity. Also, we observed a mixture of concordant and opposite direction associations with shared genetic variants. We demonstrated a moderate to high genetic overlap between SCZ and cardiometabolic traits associated with a pattern of bidirectional associations. Our data suggested a complex interplay between metabolism-related gene pathways in SCZ pathophysiology.

PMID:36008755 | DOI:10.1186/s12864-022-08766-4

BMC Genomics. 2022 Aug 25;23(Suppl 6):616. doi: 10.1186/s12864-022-08828-7.

ABSTRACT

BACKGROUND: The reduction of the chromosome number from 48 in the Great Apes to 46 in modern humans is thought to result from the end-to-end fusion of two ancestral non-human primate chromosomes forming the human chromosome 2 (HSA2). Genomic signatures of this event are the presence of inverted telomeric repeats at the HSA2 fusion site and a block of degenerate satellite sequences that mark the remnants of the ancestral centromere. It has been estimated that this fusion arose up to 4.5 million years ago (Mya).

RESULTS: We have developed an enhanced algorithm for the detection and efficient counting of the locally over-represented weak-to-strong (AT to GC) substitutions. By analyzing the enrichment of these substitutions around the fusion site of HSA2 we estimated its formation time at 0.9 Mya with a 95% confidence interval of 0.4-1.5 Mya. Additionally, based on the statistics derived from our algorithm, we have reconstructed the evolutionary distances among the Great Apes (Hominoidea).

CONCLUSIONS: Our results shed light on the HSA2 fusion formation and provide a novel computational alternative for the estimation of the speciation chronology.

PMID:36008753 | DOI:10.1186/s12864-022-08828-7

Br J Cancer. 2022 Aug 25. doi: 10.1038/s41416-022-01926-z. Online ahead of print.

ABSTRACT

BACKGROUND: Adverse event (AE) reporting in early-phase clinical trials is essential in determining the tolerability of experimental anticancer therapies. The patient-reported outcome version of the CTCAE (PRO-CTCAE) evaluates AE components such as severity and interference in daily life. The aim of this study was to correlate the grade of clinician-reported AEs with patients’ reported experience of these toxicities using PRO-CTCAE.

METHODS: Patients with advanced solid tumours enrolled on Phase I clinical trials were surveyed using the PRO-CTCAE. Symptomatic AEs were recorded by physicians using the CTCAE. A logistic regression model was used to assess associations between CTCAE grade and PRO responses.

RESULTS: Of 219 evaluable patients, 81 experienced a high-grade (3/4) clinician-reported symptom, and of these, only 32 (40%) and 26 (32%) patients concordantly reported these as either severe or very severe, and interfering with daily life either ‘quite a bit’ or ‘very much’, respectively. Of the 137 patients who experienced a low-grade (1/2) clinician-reported AE as their worst symptom, 98 (72%) and 118 (86%) patients concordantly reported these as either mild-moderate severity and minimally interfering with daily life, respectively. There was a statistically significant association between clinician-reported AE grade and interference. Interference scores were also associated with dose reductions.

CONCLUSION: This is the first study to explore patient-reported severity and interference from symptomatic toxicities and compare clinician grading of the same toxicities. The study provided further evidence to support the added value of the PRO-CTCAE in Phase I oncology trials, which would make AE reporting patient-centred. Further work is needed to determine how this would affect the assessment of tolerability.

PMID:36008705 | DOI:10.1038/s41416-022-01926-z

Biol Trace Elem Res. 2022 Aug 26. doi: 10.1007/s12011-022-03391-4. Online ahead of print.

ABSTRACT

Serum magnesium is involved in the process of blood coagulation, and low serum magnesium is associated with haemorrhagic diseases. No studies have explored the relationship between serum magnesium and gastrointestinal bleeding (GIB). This study aimed to explore the association between serum magnesium and GIB in peritoneal dialysis (PD) patients. This was a multicentre retrospective cohort study. The primary endpoint was GIB. According to the baseline serum magnesium level of 0.7 mmol/L, patients were divided into two groups: the hypomagnesaemia group and the nonhypomagnesaemia group. A multivariate Cox regression model was used to investigate the association between hypomagnesaemia and GIB. A total of 654 PD patients from four Chinese peritoneal dialysis centres were recruited from February 1, 2010 to January 31, 2020. During the follow-up, 47 patients experienced GIB. Kaplan-Meier curves showed that there was a significant difference in the risk of GIB between the two groups (log-rank = 11.82, P < 0.001). The multivariable Cox regression model showed that the risk of GIB was higher in the hypomagnesaemia group than the nonhypomagnesaemia group after adjustment for demographic variables and laboratory indicators (HR = 3.007, 95% CI 1.488-6.079, P = 0.002). A baseline lower serum magnesium level was associated with a higher risk of GIB in PD patients.

PMID:36008701 | DOI:10.1007/s12011-022-03391-4

Int Urol Nephrol. 2022 Aug 25. doi: 10.1007/s11255-022-03346-7. Online ahead of print.

ABSTRACT

PURPOSE: We aim to evaluate the impact of preoperative thrombocytosis on oncological outcomes in patients with bladder cancer (BC) who undergo radical cystectomy (RC).

METHODS: Retrospective data collection of 1092 patients managed by RC for BC from 2 tertiary-care centers was performed. Elevated platelet count (PLT) was defined as > 450 × 10⁹/L. Univariable and multivariable logistic regression analyses were used to investigate the impact of thrombocytosis on oncological outcomes. These outcomes were also compared using Kaplan-Meier survival analysis.

RESULTS: The median follow-up was 50 months (32-64 months). Thrombocytosis was detected in 18.6% of the patients. The 3-year cancer-specific survival (CSS) for patients with normal PLT count was 92% which was higher than those with elevated PLT count (55%, P < 0.001). Similar results were found for the 6-year CSS with 82% for the no thrombocytosis group and 27% for the thrombocytosis group. Thrombocytosis was still significantly associated with poor prognosis for overall survival and recurrence-free survival (P < 0.001). In the multivariate analysis, CSS was significantly lower in patients with thrombocytosis (HR = 1.71, 95% CI = 1.22-2.39, P = 0.002). Patients with elevated PLT counts were also significantly more likely to receive adjuvant chemotherapy, to have a T stage > pT2b (P = 0.024), to have a positive lymph node, to have variant histology and positive resection margins, and to have concomitant carcinoma in situ (CIS) on final pathology (all P < 0.001).

CONCLUSIONS: Preoperative thrombocytosis was valuable for predicting the oncological outcomes of patients undergoing RC for BC.

PMID:36008697 | DOI:10.1007/s11255-022-03346-7

Environ Monit Assess. 2022 Aug 25;194(10):709. doi: 10.1007/s10661-022-10342-y.

ABSTRACT

The growth of the world population has led to the expansion of agricultural areas to produce food that meets world demand, making it necessary to increase productivity and maintain environmental sustainability in these areas. Seeking sustainable food production, the agricultural use of soil must be assessed in view of optimal use or land as natural resource, as well as minimize the effects of global warming related to land use and land cover (LULC). We hypothesize that different LULC affects Amazonian soil attributes. In this study, the effect of different LULC in the southern Brazilian Amazon, namely, native forest, pasture, and rice and soybean crops, on the spatial variability of soil fertility and texture was assessed, seeking to obtain information that will guide farmers in the near future to better exploit their areas and contribute to a more sustainable agriculture. Descriptive statistical analysis was performed for the pH, H + Al, Al, Ca, Mg, P, K, Cu, Fe, Mn, Zn, V, m, organic matter, clay, silt, and sand values from soil samples under different LULC. To verify the data normality, the Shapiro-Wilk test at 5% significance was performed. Outlier analysis using boxplot graphics, principal component analysis (PCA), and cluster analysis was performed. Data were submitted to geostatistical analysis to verify the spatial dependence degree of the variables through semivariograms for interpolated kriging maps. Except for silt, all variables were well represented in the factor map. PCA revealed that the data variability can be explained mainly by pH, V, Ca, K, and Zn values, which are inversely proportional to m, P, and sand. Through geostatistical analysis, spatial dependence ranging from moderate to strong was observed, generating reliability in the prediction of most attributes in pasture, rice, and soybean areas. Yet, a spatial dependence ranging from moderate to strong was found, generating reliability in the prediction of most attributes in pasture, rice, and soybean areas. Our findings reveal a lower fertility and higher acidity in forest areas, whereas crop areas presented the opposite result.

PMID:36008644 | DOI:10.1007/s10661-022-10342-y

Bull Math Biol. 2022 Aug 25;84(10):107. doi: 10.1007/s11538-022-01066-8.

ABSTRACT

The spiking activity of mitral cells (MC) in the olfactory bulb is a key attribute in olfactory sensory information processing to downstream cortical areas. A more detailed understanding of the modulation of MC spike statistics could shed light on mechanistic studies of olfactory bulb circuits and olfactory coding. We study the spike response of a recently developed single-compartment biophysical MC model containing seven known ionic currents and calcium dynamics subject to constant current input with background white noise. We observe rich spiking dynamics even with constant current input, including multimodal peaks in the interspike interval distribution (ISI). Although weak-to-moderate background noise for a fixed current input does not change the firing rate much, the spike dynamics can change dramatically, exhibiting non-monotonic spike variability not commonly observed in standard neuron models. We explain these dynamics with a phenomenological model of the ISI probability density function. Our study clarifies some of the complexities of MC spiking dynamics.

PMID:36008641 | DOI:10.1007/s11538-022-01066-8

Psychon Bull Rev. 2022 Aug 25. doi: 10.3758/s13423-022-02161-6. Online ahead of print.

ABSTRACT

Dyadic interactions require dynamic correspondence between one’s own movements and those of the other agent. This mapping is largely viewed as imitative, with the behavioural hallmark being a reaction-time cost for mismatched actions. Yet the complex motor patterns humans enact together extend beyond direct-matching, varying adaptively between imitation, complementary movements, and counter-imitation. Optimal behaviour requires an agent to predict not only what is likely to be observed but also how that observed action will relate to their own motor planning. In 28 healthy adults, we examined imitation and counter-imitation in a task that varied the likelihood of stimulus-response congruence from highly predictable, to moderately predictable, to unpredictable. To gain mechanistic insights into the statistical learning of stimulus-response compatibility, we compared two computational models of behaviour: (1) a classic fixed learning-rate model (Rescorla-Wagner reinforcement [RW]) and (2) a hierarchical model of perceptual-behavioural processes in which the learning rate adapts to the inferred environmental volatility (hierarchical Gaussian filter [HGF]). Though more complex and hence penalized by model selection, the HGF provided a more likely model of the participants’ behaviour. Matching motor responses were only primed (faster) in the most experimentally volatile context. This bias was reversed so that mismatched actions were primed when beliefs about volatility were lower. Inferential statistics indicated that matching responses were only primed in unpredictable contexts when stimuli-response congruence was at 50:50 chance. Outside of these unpredictable blocks the classic stimulus-response compatibility effect was reversed: Incongruent responses were faster than congruent ones. We show that hierarchical Bayesian learning of environmental statistics may underlie response priming during dyadic interactions.

PMID:36008626 | DOI:10.3758/s13423-022-02161-6

Ophthalmol Ther. 2022 Aug 25. doi: 10.1007/s40123-022-00560-5. Online ahead of print.

ABSTRACT

INTRODUCTION: Recent studies indicate that short-term monocular deprivation increases the deprived eye’s contribution to binocular fusion in both adults with normal vision and amblyopia. In this study, we investigated whether the changes in visual plasticity depended on the duration of deprivation in normal and amblyopic adults.

METHODS: Twelve anisometropia amblyopic observers (aged 24.8 ± 2.3 years) and 12 age-matched normal observers (aged 23.9 ± 1.2 years) participated in the study. The non-dominant eye of normal observers or amblyopic eye of amblyopic observers was deprived for 30, 120, and 300 min in a randomized order. Their eye balance was measured with a phase combination task, which is a psychophysical test, before and after the deprivation. This design enabled us to measure changes induced in binocular balance as an index visual plasticity due to monocular deprivations.

RESULTS: By comparing the ocular dominance changes as a result of monocular deprivation with different deprivation durations, we found evidence that the ocular dominance changes are slightly larger after longer deprivations in both normal and amblyopic observers, albeit with a statistical significance. The changes from 120-min were significantly greater than those from 30-min deprivation in both groups. The magnitude of changes in sensory eye balance was significantly larger in normal observers than that in the amblyopic observers; however, the longevity of changes in visual plasticity was found to be more long-lasting in amblyopic observers than the normal counterparts.

CONCLUSIONS: The duration of deprivation matters in both normal and amblyopic observers. Ocular dominance imbalance that is typically observed in amblyopia can be more ameliorated with a longer duration of deprivation.

PMID:36008603 | DOI:10.1007/s40123-022-00560-5

Pediatr Res. 2022 Aug 25. doi: 10.1038/s41390-022-02270-x. Online ahead of print.

ABSTRACT

BACKGROUND: Maintaining of remission early in the disease course of Crohn’s disease (CD) is essential and has major impact on the future prognosis. This study aimed to identify baseline predictors to develop model allowing stratification of patients who will not benefit from long-term azathioprine (AZA) treatment and will require more intensive therapy.

METHODS: This study was designed to develop clinical prediction rule using retrospective data analysis of pediatric CD patients included in prospective inception cohort. Clinical relapse was defined as necessity of re-induction of remission. Sequence of Cox models was fitted to predict risk of relapse.

RESULTS: Out of 1190 CD patients from 13 European centers, 441 were included, 50.3% patients did not experience clinical relapse within 2 years of AZA treatment initiation. Median time to relapse was 2.11 (CI 1.59-2.46) years. Of all the tested parameters available at diagnosis, six were significant in multivariate analyses: C-reactive protein (p = 0.038), body mass index Z-score >0.8 SD (p = 0.002), abnormal sigmoid imaging (p = 0.039), abnormal esophageal endoscopy (p = 0.005), ileocolonic localization (p = 0.023), AZA dose in specific age category (p = 0.031).

CONCLUSIONS: Although the possibility of predicting relapse on AZA treatment appears limited, we developed predictive model based on six baseline parameters potentially helpful in clinical decision.

IMPACT: The possibility of predicting relapse on AZA treatment appears to be possible but limited. We identified six independent predictors available at diagnosis of early AZA/6-MP treatment failure in pediatric CD patients. Using combination of these factors, a model applicable to clinical practice was created. A web-based tool, allowing estimation of individual relapse risk in pediatric CD patients on a particular therapeutic regimen, has been developed.

PMID:36008595 | DOI:10.1038/s41390-022-02270-x