Category: Statistics

Ann Surg Oncol. 2022 Jul 9. doi: 10.1245/s10434-022-12038-6. Online ahead of print.

ABSTRACT

BACKGROUND: The extent of residual disease after neoadjuvant chemotherapy (NAC) can be quantified by the Residual Cancer Burden (RCB), a prognostic tool used to estimate survival outcomes in breast cancer. This study investigated the association between RCB and locoregional recurrence (LRR).

METHODS: The study reviewed 532 women with breast cancer who underwent NAC between 2010 and 2016. Relapse in the ipsilateral breast, skin/subcutis at the surgical site, chest wall, pectoralis, or regional lymph nodes defined an LRR. The LRR cumulative incidence (LRCI) was estimated using the Fine and Gray competing-risks model, with death and distant recurrence defined as competing events. The association of LRCI with prognostic variables was evaluated.

RESULTS: Overall, 5.5% of the patients experienced an LRR after a median follow-up period of 65 months. The 5-year LRCI rates by RCB were as follows: RCB-0 (0.9%), RCB-1 (3.2%), RCB-2 (6.0%), and RCB-3 (12.9%). In the univariable analysis, LRCI varied significantly by RCB (p = 0.010). The multivariable analysis showed a significant association of LRCI with increasing RCB, and the patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) phenotype were at lower risk for LRR than those with HER2+ and triple-negative cancers (p < 0.032). The patients with RCB-3 were at a higher risk for local relapse than those with RCB-0 (hazard ratio, 13.78; confidence interval, 2.25-84.45; p = 0.04). Type of operation (p = 0.04) and use of adjuvant radiation (p = 0.046) were statistically significant in the multivariable model.

CONCLUSIONS: The study results demonstrate a significant association between LRCI and increasing RCB, although distant recurrence is a substantial driver of disease outcomes. Future prospective studies should examine the role of RCB in clinical decisions regarding indications for adjuvant therapy.

PMID:35810226 | DOI:10.1245/s10434-022-12038-6

Lab Invest. 2022 Jul 9. doi: 10.1038/s41374-022-00801-y. Online ahead of print.

ABSTRACT

Great advances in deep learning have provided effective solutions for prediction tasks in the biomedical field. However, accurate prognosis prediction using cancer genomics data remains challenging due to the severe overfitting problem caused by curse of dimensionality inherent to high-throughput sequencing data. Moreover, there are unique challenges to perform survival analysis, arising from the difficulty in utilizing censored samples whose events of interest are not observed. Convolutional neural network (CNN) models provide us the opportunity to extract meaningful hierarchical features to characterize cancer subtype and prognosis outcomes. On the other hand, feature selection can mitigate overfitting and reduce subsequent model training computation burden by screening out significant genes from redundant genes. To accomplish model simplification, we developed a concise and efficient survival analysis model, named CNN-Cox model, which combines a special CNN framework with prognosis-related feature selection cascaded Wx, with the advantage of less computation demand utilizing light training parameters. Experiment results show that CNN-Cox model achieved consistent higher C-index values and better survival prediction performance across seven cancer type datasets in The Cancer Genome Atlas cohort, including bladder carcinoma, head and neck squamous cell carcinoma, kidney renal cell carcinoma, brain low-grade glioma, lung adenocarcinoma (LUAD), lung squamous cell carcinoma, and skin cutaneous melanoma, compared with the existing state-of-the-art survival analysis methods. As an illustration of model interpretation, we examined potential prognostic gene signatures of LUAD dataset using the proposed CNN-Cox model. We conducted protein-protein interaction network analysis to identify potential prognostic genes and further analyzed the biological function of 13 hub genes, including ANLN, RACGAP1, KIF4A, KIF20A, KIF14, ASPM, CDK1, SPC25, NCAPG, MKI67, HJURP, EXO1, HMMR, whose high expression is significantly associated with poor survival of LUAD patients. These findings confirmed that CNN-Cox model is effective in extracting not only prognosis factors but also biologically meaningful gene features. The codes are available at the GitHub website: https://github.com/wangwangCCChen/CNN-Cox .

PMID:35810236 | DOI:10.1038/s41374-022-00801-y

World J Surg. 2022 Jul 9. doi: 10.1007/s00268-022-06648-0. Online ahead of print.

ABSTRACT

BACKGROUND: Although laparoscopic hepatectomy (LH) is associated with improved short-term outcomes compared to open hepatectomy (OH), it is unknown whether frail patients also benefit from LH. The aim of this study was to evaluate the impact of frailty on post-operative outcomes after LH and OH.

PATIENTS AND METHODS: Consecutive patients who underwent LH and OH between January 2011 and December 2018 were identified from a prospective database. Frailty was assessed using the modified Frailty Index (mFI), with patients scoring mFI ≥ 1 deemed to be frail.

RESULTS: Of 1826 patients, 34.7% (N = 634) were frail and 18.6% (N = 340) were elderly (≥ 75 years). Frail patients had significantly higher 90-day mortality (6.6% vs. 2.9%, p < 0.001) and post-operative complications (36.3% vs. 26.1%, p < 0.001) than those who were not frail, effects that were independent of patient age on multivariate analysis. For those undergoing minor resections, the benefits of LH vs. OH were similar for frail and non-frail patients. Length of hospital stay was 53% longer in OH (vs. LH) in frail patients, compared to 58% longer in the subgroup of non-frail patients.

CONCLUSIONS: Frailty is independently associated with inferior post-operative outcomes in patients undergoing hepatectomy. However, the benefits of laparoscopic (compared to open) hepatectomy are similar for frail and non-frail patients. Frailty should not be a contraindication to laparoscopic minor hepatectomy in carefully selected patients.

PMID:35810214 | DOI:10.1007/s00268-022-06648-0

Sci Rep. 2022 Jul 9;12(1):11707. doi: 10.1038/s41598-022-15585-w.

ABSTRACT

The functional relationship between bone and cartilage is modulated by mechanical factors. Scarce data exist on the relationship between bone shape and the spatial distribution of cartilage thickness. The aim of the study was to characterise the coupled variation in knee bone morphology and cartilage thickness distributions in knees with healthy cartilage and investigate this relationship as a function of sex, height, body mass, and age. MR images of 51 knees from young adults (28.4 ± 4.1 years) were obtained from a previous study and used to train a statistical shape model of the femur, tibia, and patella and their cartilages. Five multiple linear regression models were fitted to characterise morphology as a function of sex, height, body mass, and age. A logistic regression classifier was fitted to characterise morphological differences between males and females, and tenfold cross-validation was performed to evaluate the models’ performance. Our results showed that cartilage thickness and its distribution were coupled to bone morphology. The first five shape modes captured over 90% of the variance and described coupled changes to the bone and spatial distribution of cartilage thickness. Mode 1 (size) was correlated to sex (p < 0.001) and height (p < 0.0001). Mode 2 (aspect ratio) was also correlated to sex (p = 0.006) and height (p = 0.017). Mode 4 (condylar depth) was correlated to sex only (p = 0.024). A logistic regression model trained on modes 1, 2, and 4 could classify sex with an accuracy of 92.2% (95% CI [81.1%, 97.8%]). No other modes were influenced by sex, height, body mass, or age. This study demonstrated the coupled relationship between bone and cartilage, showing that cartilage is thicker with increased bone size, diaphysis size, and decreased femoral skew. Our results show that sex and height influence bone shape and the spatial distribution of cartilage thickness in a healthy young adult population, but body mass and age do not.

PMID:35810204 | DOI:10.1038/s41598-022-15585-w

Sci Rep. 2022 Jul 9;12(1):11716. doi: 10.1038/s41598-022-16069-7.

ABSTRACT

The common cold is a leading cause of morbidity and contributes significantly to the health costs in Bhutan. The study utilized multivariate Zero-inflated Poisson regression in a Bayesian framework to identify climatic variability and spatial and temporal patterns of the common cold in Bhutan. There were 2,480,509 notifications of common cold between 2010 and 2018. Children aged < 15 years were twice (95% credible interval [CrI] 2.2, 2.5) as likely to get common cold than adults, and males were 12.4% (95 CrI 5.5%, 18.7%) less likely to get common cold than females. A 10 mm increase in rainfall lagged one month, and each 1 °C increase of maximum temperature was associated with a 5.1% (95% CrI 4.2%, 6.1%) and 2.6% (95% CrI 2.3%, 2.8%) increase in the risk of cold respectively. An increase in elevation of 100 m and 1% increase in relative humidity lagged three months were associated with a decrease in risk of common cold by 0.1% (95% CrI 0.1%, 0.2%) and 0.3% (95% CrI 0.2%, 0.3%) respectively. Seasonality and spatial heterogeneity can partly be explained by the association of common cold to climatic variables. There was statistically significant residual clustering after accounting for covariates. The finding highlights the influence of climatic variables on common cold and suggests that prioritizing control strategies for acute respiratory infection program to subdistricts and times of the year when climatic variables are associated with common cold may be an effective strategy.

PMID:35810192 | DOI:10.1038/s41598-022-16069-7

Transl Psychiatry. 2022 Jul 9;12(1):270. doi: 10.1038/s41398-022-01992-0.

ABSTRACT

Alterations in tryptophan and serotonin have been implicated in various mental disorders; but studies are limited on child neurodevelopmental disabilities such as autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). This prospective cohort study examined the associations between levels of tryptophan and select metabolites (5-methoxytryptophol (5-MTX), 5-hydroxytryptophan (5-HTP), serotonin, N-acetyltrytophan) in cord plasma (collected at birth) and physician-diagnosed ASD, ADHD and other developmental disabilities (DD) in childhood. The study sample (n = 996) derived from the Boston Birth Cohort, which included 326 neurotypical children, 87 ASD, 269 ADHD, and 314 other DD children (mutually exclusive). These participants were enrolled at birth and followed-up prospectively (from October 1, 1998 to June 30, 2018) at the Boston Medical Center. Higher levels of cord 5-MTX was associated with a lower risk of ASD (aOR: 0.56, 95% CI: 0.41, 0.77) and ADHD (aOR: 0.79, 95% CI: 0.65, 0.96) per Z-score increase, after adjusting for potential confounders. Similarly, children with cord 5-MTX ≥ 25th percentile (vs. <25th percentile) had a reduction in ASD (aOR: 0.27, 95% CI: 0.14, 0.49) and ADHD risks (aOR: 0.45, 95% CI: 0.29, 0.70). In contrast, higher levels of cord tryptophan, 5-HTP and N-acetyltryptophan were associated with higher risk of ADHD, with aOR: 1.25, 95% CI: 1.03, 1.51; aOR: 1.32, 95% CI: 1.08, 1.61; and aOR: 1.27, 95% CI: 1.05, 1.53, respectively, but not with ASD and other DD. Cord serotonin was not associated with ASD, ADHD, and other DD. Most findings remained statistically significant in the sensitivity and subgroup analyses.

PMID:35810183 | DOI:10.1038/s41398-022-01992-0

Sci Rep. 2022 Jul 9;12(1):11698. doi: 10.1038/s41598-022-14760-3.

ABSTRACT

In this study,the water samples were collected from 31 sites of Tawang, Arunachal Pradesh, India (North-Eastern Himalaya), during the winter season to check the suitability of water for drinking and irrigation purposes.The study scientifically demonstrates the estimation of Water quality index (WQI) andhydrogeochemical characteristics of surface water samples by utilizing multivariate statistical methods. The main water quality parameters considered for this study were TDS, conductivity, salinity, pH, hardness, cations and anions. WQI was calculated in order to find out the deviation in the water quality parameters particularly with respect to BIS permissible limits.The major influencing factors responsible for the variation in these parameters were derived by using Principal component analysis (PCA) and Correlation matrix.To check the suitability of water for drinking purpose, hydrogeochemical facies and rock water interaction was derived by using well established methods such as Piper Plot (determine water type), WQI (Quality monitoring), and saturation index (for mineral dissolution). The results revealed that the silicate weathering was the main ionic source in comparison to carbonate weathering which is due to the higher dissolution capacity of silicate minerals.The results of the scattered plot between (Ca²⁺ + Mg²⁺)-(HCO₃– + SO₄²-) versus (Na⁺ + K⁺)-Cl- (meq/L) highlighted thation exchange occurs between Mg²⁺ and Ca²⁺ofsurface water with Na⁺ and K⁺of rock /soil. This means that calcium ion was getting adsorbed, and sodium ion was getting released. The Ca²⁺-Mg²⁺-HCO₃-, Na⁺-HCO₃-and Na⁺-Cl- type of surface water suggested permanent and temporary hardness respectively in the studied region. The dominant cations of this study were Na⁺ and Ca²⁺ while the dominant anions were HCO₃– and SO₄²-. In order to check the suitability of water sources for irrigation, parameters like, Magnesium hazard (MH), Total hardness (TH), Permeability Index (PI), Kelly Index (KI), Sodium adsorption rate (SAR), Sodium percentage (Na%), and Residual sodium carbonate (RSC) were determined. The results showed that 93% of the samples had PI score < 75, which indicates the suitability of the water for irrigation. Also the WQI calculation showed an average WQI value of 82.49, amongst which 61% samples were in the range of 0-50 being considered as good for drinking, while 39% were catageorised as unsuitable for drinking showing a value of > 50. Hence the above findings reveal that geogenic activities play a major role in influencing the water quality of Tawang region. Hence suitable water treatment technologies or methods might be used to eliminate thenon desirable elements and minerals present in surface water.

PMID:35810170 | DOI:10.1038/s41598-022-14760-3

Nat Commun. 2022 Jul 9;13(1):3993. doi: 10.1038/s41467-022-31625-5.

ABSTRACT

Gene-environment interactions represent the modification of genetic effects by environmental exposures and are critical for understanding disease and informing personalized medicine. These often induce differential phenotypic variance across genotypes; these variance-quantitative trait loci can be prioritized in a two-stage interaction detection strategy to greatly reduce the computational and statistical burden and enable testing of a broader range of exposures. We perform genome-wide variance-quantitative trait locus analysis for 20 serum cardiometabolic biomarkers by multi-ancestry meta-analysis of 350,016 unrelated participants in the UK Biobank, identifying 182 independent locus-biomarker pairs (p < 4.5×10^-9). Most are concentrated in a small subset (4%) of loci with genome-wide significant main effects, and 44% replicate (p < 0.05) in the Women’s Genome Health Study (N = 23,294). Next, we test each locus-biomarker pair for interaction across 2380 exposures, identifying 847 significant interactions (p < 2.4×10^-7), of which 132 are independent (p < 0.05) after accounting for correlation between exposures. Specific examples demonstrate interaction of triglyceride-associated variants with distinct body mass- versus body fat-related exposures as well as genotype-specific associations between alcohol consumption and liver stress at the ADH1B gene. Our catalog of variance-quantitative trait loci and gene-environment interactions is publicly available in an online portal.

PMID:35810165 | DOI:10.1038/s41467-022-31625-5

Foot Ankle Surg. 2022 Jun 25:S1268-7731(22)00116-3. doi: 10.1016/j.fas.2022.06.012. Online ahead of print.

ABSTRACT

BACKGROUND: Trimalleolar fractures are generally considered to have inferior outcomes among ankle injuries. Historically, emphasis was placed on the size of the posterior malleolar fracture (PMF) to guide surgical decision-making and predict outcomes. Recent studies have suggested that the morphology of the PMF fragment is more important than its size. The aim of this systematic review was to determine if the outcomes of trimalleolar fractures depend on the morphology of the PMF as per the Haraguchi classification system after surgical fixation.

METHODS: A systematic literature search was conducted in the electronic databases of PubMed, Embase, Scopus, and Ovid. Title and abstracts were screened, and data from eligible studies were extracted. Meta-regression and pooled analysis was performed using appropriate computer software.

RESULTS: 11 studies with 597 patients were included in the final analysis. Pooled mean AOFAS score was 87.43 (95% CI 84.24-90.62) after a mean follow-up of 31.6 months. Univariate and multivariate meta-regression analysis demonstrated that as the percentage of Haraguchi type 1 patients increased, there was a statistically significant improvement in outcome scores. A similar trend was noted for Haraguchi type 3 fractures, and a reverse trend was observed for Haraguchi type 2 injuries, although neither were statistically significant.

CONCLUSION: Our review suggests that the outcomes of trimalleolar fractures after surgical fixation may depend on the morphology of the PMF, with Haraguchi type 1 fractures having overall superior functional outcomes than Haraguchi type 2 and 3 injuries. Future studies need to done to conclusively prove or refute these findings.

PMID:35810125 | DOI:10.1016/j.fas.2022.06.012

Cell Mol Biol (Noisy-le-grand). 2022 May 22;68(1):67-74. doi: 10.14715/cmb/2022.68.1.10.

ABSTRACT

This experiment was designed to explore the relationship and effect of miR-1-3p expression and BDNF level in patients with primary hypertension complicated with depression. The subjects of the study were 145 patients with hypertension with a small fluctuation range of blood pressure in recent three months. Within 48 hours after admission, patients were evaluated with the Hospital Anxiety and Depression Scale (HADS) and Hamilton Depression Rating Scale (HAMD). After fasting for 12 hours, enrolled subjects were subject to blood collection (5 ml) in the morning for detecting blood lipid levels, miR-1-3p expression and BDNF by using an automatic biochemical analyzer, real-time fluorescence quantitative PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Results showed that compared with the normal control group, while miR-1-3p expression increased obviously in patients with hypertension, while the level of BDNF decreased significantly; and compared with patients with simple hypertension, the expression of miR-1-3p in hypertension patients with depression was significantly increased, while BDNF level was decreased evidently (All P < 0.05). miR-1-3p expression in patients with hypertension complicated with depression was negatively correlated with serum BDNF level (r=-0.302, P < 0.05). In relative to the normal control population, the area under the curve (AUC) of ROC produced by serum miR-1-3p and BDNF in patients with primary hypertension complicated with depression was 0.971 (95% CI = 0.945-0.998, P < 0.0001) and 0.875 (95% CI = 0.808-0.942, P < 0.0001); and in relative to primary hypertension patients without depression, the AUC of ROC produced by serum miR-1-3p and BDNF in patients with primary hypertension with depression was 0.957 (95% CI = 0.925-0.989, P < 0.0001) and 0.883 (95% CI = 0.821-0.944, P < 0.0001), respectively. HADS-D score, HAMD score, course of the disease, miR-1-3p expression and BDNF level showed statistical differences in primary hypertension patients with and without depression (All P < 0.05). It was concluded that there are high miR-1-3p expression and low serum BDNF levels in patients with primary hypertension complicated with depression. miR-1-3p has a negative correlation with BDNF, and it may play a role by negatively regulating the expression of BDNF. Detecting miR-1-3p and BDNF in patients with primary hypertension can indicate the occurrence of depression to some extent.

PMID:35809326 | DOI:10.14715/cmb/2022.68.1.10