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Nevin Manimala Statistics

Anomaly Detection in Large-Scale Networks With Latent Space Models

Technometrics. 2022;64(2):241-252. doi: 10.1080/00401706.2021.1952900. Epub 2021 Dec 16.

ABSTRACT

We develop a real-time anomaly detection method for directed activity on large, sparse networks. We model the propensity for future activity using a dynamic logistic model with interaction terms for sender- and receiver-specific latent factors in addition to sender- and receiver-specific popularity scores; deviations from this underlying model constitute potential anomalies. Latent nodal attributes are estimated via a variational Bayesian approach and may change over time, representing natural shifts in network activity. Estimation is augmented with a case-control approximation to take advantage of the sparsity of the network and reduces computational complexity from O(N 2) to O(E), where N is the number of nodes and E is the number of observed edges. We run our algorithm on network event records collected from an enterprise network of over 25,000 computers and are able to identify a red team attack with half the detection rate required of the model without latent interaction terms.

PMID:39498474 | PMC:PMC11534301 | DOI:10.1080/00401706.2021.1952900

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Nevin Manimala Statistics

Different minimally invasive surgical methods to hysterectomy for benign gynecological disease: A systematic review and network meta-analysis

Health Sci Rep. 2024 Nov 3;7(11):e70137. doi: 10.1002/hsr2.70137. eCollection 2024 Nov.

ABSTRACT

BACKGROUND AND AIMS: This network meta-analysis aimed to compare the perioperative efficacy of various minimally invasive hysterectomy procedures for treating benign gynecological diseases and to assess whether vaginal natural orifice transluminal endoscopic hysterectomy (VNOTEH), a recently emerging procedure, is inferior to traditional laparoscopy.

METHODS: We searched PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBM), Wanfang Data, and China VIP Database from inception to August 2022 and updated in June 2023. We included randomized controlled trials (RCTs) comparing different minimally invasive hysterectomy techniques in patients with benign gynecological conditions. The intervention measures included nine minimally invasive hysterectomies. The two researchers used the Cochrane risk-of-bias assessment tool for study appraisal. All statistical analyses and drawings were performed using STATA 17.0 and R 4.4.1. A network meta-analysis (NMA) was conducted to compare the effectiveness of minimally invasive hysterectomy and rank its relative impact probabilistically.

RESULTS: A total of 78 RCTs involving 7640 patients and nine minimally invasive hysterectomy methods with 16 intervention combinations were included in this study. Among these, 2, 63, and 13 studies were deemed to have a low, medium, and high risk of bias, respectively. Based on the Surface Under the Cumulative Ranking (SUCRA) probability ranking results of NMA, laparoendoscopic single-site surgery-laparoscopic-assisted vaginal hysterectomy (LESS-LAVH) demonstrated superior outcomes in terms of complications, infections, and 24-h postoperative pain scores. LAVH exhibited better performance in injuries and hospital stays, total laparoscopic hysterectomy showed the least blood loss, and vaginal hysterectomy had the shortest operation time.

CONCLUSION: LESS-LAVH and LAVH are recommended options, if feasible. Meanwhile, VNOTEH can achieve comparable results to traditional laparoscopy but requires careful attention to the risk of injury and infection. Future research should aim to broaden the search scope by including high-quality, large-scale, multicenter RCTs.

PMID:39498464 | PMC:PMC11532236 | DOI:10.1002/hsr2.70137

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Nevin Manimala Statistics

Tumor purity estimated from bulk DNA methylation can be used for adjusting beta values of individual samples to better reflect tumor biology

NAR Genom Bioinform. 2024 Nov 4;6(4):lqae146. doi: 10.1093/nargab/lqae146. eCollection 2024 Sep.

ABSTRACT

Epigenetic deregulation through altered DNA methylation is a fundamental feature of tumorigenesis, but tumor data from bulk tissue samples contain different proportions of malignant and non-malignant cells that may confound the interpretation of DNA methylation values. The adjustment of DNA methylation data based on tumor purity has been proposed to render both genome-wide and gene-specific analyses more precise, but it requires sample purity estimates. Here we present PureBeta, a single-sample statistical framework that uses genome-wide DNA methylation data to first estimate sample purity and then adjust methylation values of individual CpGs to correct for sample impurity. Purity values estimated with the algorithm have high correlation (>0.8) to reference values obtained from DNA sequencing when applied to samples from breast carcinoma, lung adenocarcinoma, and lung squamous cell carcinoma. Methylation beta values adjusted based on purity estimates have a more binary distribution that better reflects theoretical methylation states, thus facilitating improved biological inference as shown for BRCA1 in breast cancer. PureBeta is a versatile tool that can be used for different Illumina DNA methylation arrays and can be applied to individual samples of different cancer types to enhance biological interpretability of methylation data.

PMID:39498434 | PMC:PMC11532792 | DOI:10.1093/nargab/lqae146

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Nevin Manimala Statistics

Faster and more accurate assessment of differential transcript expression with Gibbs sampling and edgeR v4

NAR Genom Bioinform. 2024 Nov 4;6(4):lqae151. doi: 10.1093/nargab/lqae151. eCollection 2024 Sep.

ABSTRACT

This article further develops edgeR’s divided-count approach for differential transcript expression (DTE) analysis of RNA-seq data to produce a faster and more accurate pipeline. The divided-count approach models the precision of transcript quantifications from the kallisto and Salmon software tools and divides the estimated overdispersions out of the transcript read counts, after which the divided-counts can be analysed by statistical tools developed for gene-level counts. This article adds three new refinements to the pipeline that dramatically decrease the computational overhead and storage requirements so that DTE analysis of very large datasets becomes practical. The new pipeline replaces bootstrap with Gibbs resampling and replaces edgeR v3 with v4. Both of these changes improve statistical power and accuracy and provide better resolution for low-count transcripts. The accuracy of overdispersion estimation is shown to depend on the total number of resamples across the whole dataset rather than on individual samples, dramatically reducing the recommended number of technical samples for large datasets. Test data and extensive simulations data show that the new pipeline is more powerful and efficient than previous DTE pipelines while providing correct control of the false discovery rate for any sample size.

PMID:39498433 | PMC:PMC11532793 | DOI:10.1093/nargab/lqae151

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Nevin Manimala Statistics

Long-Term Outcomes of Sleeve Gastrectomy Versus Gastric Bypass

Cureus. 2024 Nov 4;16(11):e72961. doi: 10.7759/cureus.72961. eCollection 2024 Nov.

ABSTRACT

BACKGROUND: Extremely obese patients can benefit greatly from bariatric surgery, a common and successful therapeutic procedure for treating obesity and accompanying medical issues. Although sleeve gastrectomy and gastric bypass have already demonstrated their effectiveness in this demographic, long-term results were not stated in the literature. The purpose of this research is to examine the long-term outcomes of sleeve gastrointestinal surgery and gastric bypass.

METHOD: This retrospective, single-center study compares 100 patients aged 25 years and older who visited the gastrointestinal tract surgical unit at Dar El-Fouad Hospital in Cairo, Egypt, between January 1 and August 31, 2019, according to the inclusion and exclusion criteria. The patients underwent either a Roux-en-Y gastric bypass (RYGB-50%) or sleeve gastrectomy (SG-50%) for severe obesity. Follow-up occurred at one year and up to four years following surgery to collect information from the study subjects. Two tools were used to assess BMI, weight loss, complications after surgery, and incidence outcome of comorbidities after the two surgeries. Qualitative data were presented as number and percentage and frequency distribution tables, and every analysis was done at a significance value < 0.05.

RESULT: The average age of patients within the SG group was 43.02 ± 9.19 years, whereas the average age of patients within the RYGB group was 41.02 ± 11.06 years. In addition, 74% of patients were women in both procedures. The BMI mean of the SG group was 43.90 ± 5.78, the BMI mean of the RYGB group was 42.73 ± 5.12, and the main comorbidity in both techniques was joint pain. The mean BMI at one year was 29.70 kg/m2 after SG compared with 28.64 kg/m2 after RYGB. After four years, BMI was regained within the obese range in both techniques – 30.67 kg/m2 and 30.32, respectively. Fewer postoperative complications occurred in SG than in RYGB. RYGB was superior to SG in managing dyslipidemia (DL), hypertension (HT), type 2 diabetes (T2DM), joint pain, and gastroesophageal reflux disease (GERD).

CONCLUSION: There are no significant differences between the SG and RYGB in long-term outcomes regarding BMI before surgery and at follow-up, after four years, while there were statistically significant differences between them after four years than one year after surgery, and both groups showed a significant decrease in weight. However, RYGB shows improvement to some extent in comorbidities within follow-up period, including BMI, T2DM, HT, DL, HT, DL, GERD, and joint pain than SG, but with a higher rate of minor complications, while greater resolution of OSAS occurred in SG. Finally, at four years, there were no discernible variations in BMI between SG and RYGB because the patients’ mean BMI was within the obese range once more.

PMID:39498430 | PMC:PMC11533043 | DOI:10.7759/cureus.72961

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Prevalence and Risk Factors Associated With Carpal Tunnel Syndrome Among Sudanese Females: A Cross-Sectional Study

Cureus. 2024 Nov 3;16(11):e72943. doi: 10.7759/cureus.72943. eCollection 2024 Nov.

ABSTRACT

BACKGROUND: Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy resulting from compression of the median nerve. This condition is more common in females than in males. The earlier the diagnosis, the better the prognosis and treatment outcomes.

MATERIAL AND METHODS: This is a cross-sectional hospital-based study conducted at Soba Teaching Hospital in obstetrics and gynecology outpatient clinic in Khartoum in the period from February 2022 to March 2022. A simple random sampling was applied, and an interview was conducted using a four-part questionnaire. The first part was based on socio-demographic data, the second was lifestyle, and the third and fourth were based on the Boston Carpal Tunnel Questionnaire (BCTQ). The data were analyzed using the statistical package for social sciences (SPSS) software, version 23 (IBM Corp., Armonk, NY) to find the correlation between the various variables.

RESULTS: A total of 113 women participated in the study (response rate=100%). The prevalence of CTS was found to be 5%. No significant association was found between lifestyle and medical history, e.g., obesity and oral contraceptives and CTS were p=0.167, 0.841 respectively. Conversely, there was a significant association between age and residency, with p=0.005 and 0.049, respectively.

CONCLUSIONS: The prevalence of CTS is increasing in Sudan. Therefore, it is essential to thoroughly assess patients for any symptoms related to hand pain by asking detailed questions during consultations. In addition, further studies covering more states are needed to better understand the regional variation in CTS prevalence.

PMID:39498424 | PMC:PMC11532370 | DOI:10.7759/cureus.72943

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Nevin Manimala Statistics

Evaluating the Clinical Impact of Ureteral Frozen Section Analysis During Radical Cystectomy: A Single-Center Retrospective Study

Cureus. 2024 Nov 3;16(11):e72908. doi: 10.7759/cureus.72908. eCollection 2024 Nov.

ABSTRACT

Introduction The objective of this study is to find out if there are any differences in upper urinary tract recurrence and overall mortality between patients who underwent a frozen section analysis during radical cystectomy and those who did not. Materials and methods In an observational retrospective cohort study, we evaluated data from 164 patients who underwent radical cystectomy in our institution over a five-year period from 2013 to 2018. Fisher’s exact test was applied to find any difference in upper urinary tract recurrence between the two groups. The Kaplan-Meier method and the log-rank (Mantel-Cox) test were used to determine differences or equivalence between treatment groups. Results The sensitivity was 84.6% and the specificity was 95.3% for the frozen section. There was no statistically significant relationship between performing a frozen section and upper urinary tract recurrence, as indicated by Fisher’s exact test (p=0.619). The Kaplan-Meier test showed no statistically significant relationship between performing a frozen section analysis and overall mortality. Discussion The use of ureteric frozen section analysis during radical cystectomy is traditionally taught during surgical training, but the evidence base for this practice is sketchy. Frozen section analysis is thought to reduce the chances of local recurrence and arguably upper urinary tract recurrence. The overall upper urinary tract recurrence after radical cystectomy is reported to be 2-6%, consistent with the 3.3% observed in our study. Conclusion Our study demonstrates that while frozen section analysis is sensitive and specific in detecting dysplasia, it does not significantly impact upper tract recurrence or overall mortality.

PMID:39498422 | PMC:PMC11534417 | DOI:10.7759/cureus.72908

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Nevin Manimala Statistics

Effect of Mutation Type on Ectopic Ossification Among Adult Patients With X-Linked Hypophosphatemia

J Endocr Soc. 2024 Oct 22;8(12):bvae184. doi: 10.1210/jendso/bvae184. eCollection 2024 Oct 29.

ABSTRACT

CONTEXT: Causative factors for ectopic ossifications in X-linked hypophosphatemia (XLH) remain to be elucidated.

OBJECTIVE: This work aimed to investigate the genotype-phenotype correlations between the phosphate-regulating endopeptidase homologue, X-linked gene (PHEX) and ectopic ossifications in XLH.

METHODS: Biochemical data, spinal computed tomography scans, and x-rays of hip/knee joints were retrospectively reviewed. Genetic analysis and the measurement of plasma inorganic pyrophosphate (PPi)-a potent inhibitor of tissue calcification-were performed. The effect of PHEX mutations on protein function was predicted using nonsense-mediated decay (NMD) and 3-dimensional structure modeling. The index of ossification of the anterior/posterior longitudinal ligament and yellow ligament (OA/OP/OY index) and the sum of the OA/OP/OY index (OS index) were used to quantify the severity of spinal ligament ossification. The severity of the hip/knee osteoarthritis was evaluated by the Kellgren-Lawrence classification.

RESULTS: We examined 24 distinct pathogenic PHEX variants in 28 patients from a study population of 33 individuals in 27 unrelated, nonconsanguineous families. Among the 31 patients whose plasma samples were analyzed for PPi, 14 patients (45%) showed decreased plasma PPi concentrations; however, PPi concentrations did not correlate with mutation type or ectopic ossification. Fibroblast growth factor 23 levels in women with NMD-insensitive mutations trended lower than in men with NMD-sensitive mutations but failed to reach statistical significance. Both models revealed no correlations between PHEX pathogenic variant and ectopic ossification.

CONCLUSION: Neither modeling found correlates between PHEX pathogenic variants and ectopic ossification. The effects of PPi on ectopic ossifications in adults with XLH revealed trends that should be investigated with a large sample size.

PMID:39498416 | PMC:PMC11532897 | DOI:10.1210/jendso/bvae184

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Nevin Manimala Statistics

Metabolic biomarkers of neonatal sepsis: identification using metabolomics combined with machine learning

Front Cell Dev Biol. 2024 Oct 21;12:1491065. doi: 10.3389/fcell.2024.1491065. eCollection 2024.

ABSTRACT

BACKGROUND: Sepsis is a common disease associated with neonatal and infant mortality, and for diagnosis, blood culture is currently the gold standard method, but it has a low positivity rate and requires more than 2 days to develop. Meanwhile, unfortunately, the specific biomarkers for the early and timely diagnosis of sepsis in infants and for the determination of the severity of this disease are lacking in clinical practice.

METHODS: Samples from 18 sepsis infants with comorbidities, 25 sepsis infants without comorbidities, and 25 infants with noninfectious diseases were evaluated using a serum metabolomics approach based on liquid chromatography‒mass spectrometry (LC‒MS) technology. Differentially abundant metabolites were screened via multivariate statistical analysis. In addition, least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) analyses were conducted to identify the key metabolites in infants with sepsis and without infections. The random forest algorithm was applied to determine key differentially abundant metabolites between sepsis infants with and without comorbidities. Receiver operating characteristic (ROC) curves were generated for biomarker value testing. Finally, a metabolic pathway analysis was conducted to explore the metabolic and signaling pathways associated with the identified differentially abundant metabolites.

RESULTS: A total of 189 metabolites exhibited significant differences between infectious infants and noninfectious infants, while 137 distinct metabolites exhibited differences between septic infants with and without comorbidities. After screening for the key differentially abundant metabolites using LASSO and SVM-RFE analyses, hexylamine, psychosine sulfate, LysoPC (18:1 (9Z)/0:0), 2,4,6-tribromophenol, and 25-cinnamoyl-vulgaroside were retained for the diagnosis of infant sepsis. ROC curve analysis revealed that the area under the curve (AUC) was 0.9200 for hexylamine, 0.9749 for psychosine sulfate, 0.9684 for LysoPC (18:1 (9Z)/0:0), 0.7405 for 2,4,6-tribromophenol, 0.8893 for 25-cinnamoyl-vulgaroside, and 1.000 for the combination of all metabolites. When the septic infants with comorbidities were compared to those without comorbidities, four endogenous metabolites with the greatest importance were identified using the random forest algorithm, namely, 12-oxo-20-trihydroxy-leukotriene B4, dihydrovaltrate, PA (8:0/12:0), and 2-heptanethiol. The ROC curve analysis of these four key differentially abundant metabolites revealed that the AUC was 1 for all four metabolites. Pathway analysis indicated that phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, and porphyrin metabolism play important roles in infant sepsis.

CONCLUSION: Serum metabolite profiles were identified, and machine learning was applied to identify the key differentially abundant metabolites in septic infants with comorbidities, septic infants without comorbidities, and infants without infectious diseases. The findings obtained are expected to facilitate the early diagnosis of sepsis in infants and determine the severity of the disease.

PMID:39498415 | PMC:PMC11532037 | DOI:10.3389/fcell.2024.1491065

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Correlation between hyperlipidemia and serum vitamin D levels in an adult Chinese cohort

Front Nutr. 2024 Oct 21;11:1302260. doi: 10.3389/fnut.2024.1302260. eCollection 2024.

ABSTRACT

Vitamin D deficiency has emerged as a significant concern in public health due to its potential association with various metabolic disorders. This study aimed to investigate the relationship between serum vitamin D levels and the susceptibility to hyperlipidemia among adults. Using a multi-stage sampling approach, we recruited a cohort of 2072 eligible individuals aged over 18 years. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured alongside glucolipid metabolic markers, and comprehensive demographic and physical data were collected. The cohort exhibited a hyperlipidemia prevalence of 42.18%, with 19.88% demonstrating vitamin D deficiency. Notably, 23.68% of individuals with vitamin D deficiency also presented hyperlipidemia. Statistical analysis revealed a significantly higher prevalence of hyperlipidemia among those with vitamin D deficiency compared to those with sufficient levels (23.68% vs. 17.11%, P < 0.05). After adjusting for various factors including age, geographical region, exercise status, BMI, fasting glucose level, and blood pressure, lower serum 25(OH)D concentrations were found to significantly increase the risk of hyperlipidemia (Odds Ratio [OR] = 1.41; 95% CI: 1.057, 1.885; P < 0.05). Further stratification of the hyperlipidemic cohort revealed that vitamin D deficiency was associated with 1.459- and 1.578-times higher risks for total cholesterol and triglyceride abnormalities, respectively, compared to those with sufficient vitamin D levels. Moreover, each 10 ng/mL decrease in serum vitamin D level corresponded to an increased risk of total cholesterol (OR = 0.82; 95% CI: 0.728, 0.974; P < 0.05) and triglyceride abnormalities (OR = 0.79; 95% CI: 0.678, 0.927; P < 0.05). However, there were no significant differences observed between vitamin D-sufficient and-deficient groups regarding Low-Density Lipoprotein (LDL) and High-Density Lipoprotein (HDL) abnormalities. These findings underscore the potential role of serum vitamin D deficiency as an independent risk factor contributing to the elevated prevalence of hyperlipidemia in the adult population.

PMID:39498411 | PMC:PMC11532166 | DOI:10.3389/fnut.2024.1302260