Category: Statistics

Gut Microbes. 2022 Jan-Dec;14(1):2106103. doi: 10.1080/19490976.2022.2106103.

ABSTRACT

How the gut microbiota is organized across space is postulated to influence microbial succession and its mutualistic relationships with the host. The lack of dynamic or perturbed abundance data poses considerable challenges for characterizing the spatial pattern of microbial interactions. We integrate allometric scaling theory, evolutionary game theory, and prey-predator theory into a unified framework under which quasi-dynamic microbial networks can be inferred from static abundance data. We illustrate that such networks can capture the full properties of microbial interactions, including causality, the sign of the causality, strength, and feedback loop, and are dynamically adaptive along spatial gradients, and context-specific, characterizing variability between individuals and within the same individual across time and space. We design and conduct a gut microbiota study to validate the model, characterizing key spatial determinants of the microbial differences between ulcerative colitis and healthy controls. Our model provides a sophisticated means of unraveling a complete atlas of how microbial interactions vary across space and quantifying causal relationships between such spatial variability and change in health state.

PMID:35921525 | DOI:10.1080/19490976.2022.2106103

Hepatology. 2022 Aug 3. doi: 10.1002/hep.32704. Online ahead of print.

ABSTRACT

BACKGROUND & AIMS: Implantation of a transjugular intrahepatic portosystemic shunt (TIPS) improves survival in cirrhotic patients with refractory ascites and portal hypertensive bleeding. However, the indication for TIPS in older adult patients (≥70 years) is debated and a specific prediction model developed in this particular setting is lacking. The aim of this study was to develop and validate a multivariable model for an accurate prediction of mortality in older adults.

APPROACH & RESULTS: We prospectively enrolled 411 consecutive patients observed at 4 referral centers with de novo TIPS implantation for refractory ascites or secondary prophylaxis of variceal bleeding (derivation cohort) and an external cohort of 415 patients with similar indications for TIPS (validation cohort). Older adult patients in the two cohorts were 99 and 76 respectively. A cause-specific Cox competing risks model was used to predict liver-related mortality, with orthotopic liver transplant and death for extrahepatic causes as competing events. Age, alcoholic etiology, creatinine levels and international normalized ratio in the overall cohort, and creatinine and sodium levels in older adults were independent risk factors for liver-related death by multivariable analysis.

CONCLUSIONS: After TIPS implantation, mortality is increased by ageing, but TIPS placement should not be precluded in patients older than 70 years. In older adults, creatinine and sodium levels are useful predictors for decision making. Further efforts to update the prediction model with larger sample size are warranted.

PMID:35921493 | DOI:10.1002/hep.32704

Sci Transl Med. 2022 Aug 3;14(656):eabn7571. doi: 10.1126/scitranslmed.abn7571. Epub 2022 Aug 3.

ABSTRACT

Triple-negative breast cancer (TNBC) is an aggressive subtype associated with early metastatic recurrence and worse patient outcomes. TNBC tumors express molecular markers of the epithelial-mesenchymal transition (EMT), but its requirement during spontaneous TNBC metastasis in vivo remains incompletely understood. We demonstrated that spontaneous TNBC tumors from a genetically engineered mouse model (GEMM), multiple patient-derived xenografts, and archival patient samples exhibited large populations in vivo of hybrid E/M cells that lead invasion ex vivo while expressing both epithelial and mesenchymal characteristics. The mesenchymal marker vimentin promoted invasion and repressed metastatic outgrowth. We next tested the requirement for five EMT transcription factors and observed distinct patterns of utilization during invasion and colony formation. These differences suggested a sequential activation of multiple EMT molecular programs during the metastatic cascade. Consistent with this model, our longitudinal single-cell RNA analysis detected three different EMT-related molecular patterns. We observed cancer cells progressing from epithelial to hybrid E/M and strongly mesenchymal patterns during invasion and from epithelial to a hybrid E/M pattern during colony formation. We next investigated the relative epithelial versus mesenchymal state of cancer cells in both GEMM and patient metastases. In both contexts, we observed heterogeneity between and within metastases in the same individual. We observed a complex spectrum of epithelial, hybrid E/M, and mesenchymal cell states within metastases, suggesting that there are multiple successful molecular strategies for distant organ colonization. Together, our results demonstrate an important and complex role for EMT programs during TNBC metastasis.

PMID:35921474 | DOI:10.1126/scitranslmed.abn7571

Microb Biotechnol. 2022 Aug 3. doi: 10.1111/1751-7915.14124. Online ahead of print.

ABSTRACT

There was inconsistent evidence regarding the use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for microorganism identification with/without antibiotic stewardship team (AST) and the clinical outcome of patients with bloodstream infections (BSI). In a systematic review and meta-analysis, we evaluated the effectiveness of rapid microbial identification by MALDI-TOF MS with and without AST on clinical outcomes. We searched PubMed and EMBASE databases from inception to 1 February 2022 to identify pre-post and parallel comparative studies that evaluated the use of MALDI-TOF MS for microorganism identification. Pooled effect estimates were derived using the random-effects model. Twenty-one studies with 14,515 patients were meta-analysed. Compared with conventional phenotypic methods, MALDI-TOF MS was associated with a 23% reduction in mortality (RR = 0.77; 95% CI: 0.66; 0.90; I² = 35.9%; 13 studies); 5.07-h reduction in time to effective antibiotic therapy (95% CI: -5.83; -4.31; I² = 95.7%); 22.86-h reduction in time to identify microorganisms (95% CI: -23.99; -21.74; I² = 91.6%); 0.73-day reduction in hospital stay (95% CI: -1.30; -0.16; I² = 53.1%); and US$4140 saving in direct hospitalization cost (95% CI: $-8166.75; $-113.60; I² = 66.1%). No significant heterogeneity sources were found, and no statistical evidence for publication bias was found. Rapid pathogen identification by MALDI-TOF MS with or without AST was associated with reduced mortality and improved outcomes of BSI, and may be cost-effective among patients with BSI.

PMID:35921430 | DOI:10.1111/1751-7915.14124

Sci Adv. 2022 Aug 5;8(31):eabp9908. doi: 10.1126/sciadv.abp9908. Epub 2022 Aug 3.

ABSTRACT

Invertebrates constitute the majority of animal species and are critical for ecosystem functioning and services. Nonetheless, global invertebrate biodiversity patterns and their congruences with vertebrates remain largely unknown. We resolve the first high-resolution (~20-km) global diversity map for a major invertebrate clade, ants, using biodiversity informatics, range modeling, and machine learning to synthesize existing knowledge and predict the distribution of undiscovered diversity. We find that ants and different vertebrate groups have distinct features in their patterns of richness and rarity, underscoring the need to consider a diversity of taxa in conservation. However, despite their phylogenetic and physiological divergence, ant distributions are not highly anomalous relative to variation among vertebrate clades. Furthermore, our models predict that rarity centers largely overlap (78%), suggesting that general forces shape endemism patterns across taxa. This raises confidence that conservation of areas important for small-ranged vertebrates will benefit invertebrates while providing a “treasure map” to guide future discovery.

PMID:35921404 | DOI:10.1126/sciadv.abp9908

Vet Med Sci. 2022 Aug 3. doi: 10.1002/vms3.899. Online ahead of print.

ABSTRACT

This study examined whether radiographic images measurements of the calcaneus in cats are determinative of sex and breed. For this purpose, radiographic images of 70 cats (37 male and 33 females) of different ages (from one to 18 years) and different breeds (41 mix-breed, 18 Scottish Fold and 11 British Shorthair cats) without orthopaedic problems were used. Right tarsal joint radiographs of these orthopaedically healthy cats were taken. Four linear measurements and two angle values of the calcaneus were obtained from the radiographic images. The MANOVA result showed that the most determining factor between the three groups was the greatest width (p value = 0.001). Calcaneal body length, calcaneal greatest length and calcaneal shortest depth were higher in mix-breed cats. Calcaneal tuber length was higher in Scottish Fold cats. The only statistically significant difference between Scottish Fold and British Shorthair was in the calcaneal tuber length (p value = 0.04). In the comparison made between the sexes regardless of species, the linear measurements in males were higher than in females. It was determined that these parameters are statistically significant in terms of sex differentiation in cats. Dorsal and plantar calcaneal angles are not sex determinants in cats. The effect of age on other measurements was analysed by correlation test. However, the effect of age on the measurements was not statistically significant. Mix-breed cats were examined in four groups according to their colour (grey, black-white, yellow, tri-colour). No statistically significant difference was found between calcaneal measurements of cats with different skin colour genotypes. In this study, calcaneus measurements were both determinative between breeds and sexes in cats.

PMID:35921402 | DOI:10.1002/vms3.899

PLoS One. 2022 Aug 3;17(8):e0272358. doi: 10.1371/journal.pone.0272358. eCollection 2022.

ABSTRACT

INTRODUCTION: Tuberculosis (TB) is the leading killer of people living with HIV (PLHIV) and almost one-third of deaths in the world are attributed to it and many of these deaths occur in developing countries. Despite these evidences, after the implementation of universal test and treat (UTT) strategy, information regarding the incidence and predictors of tuberculosis among PLHIV is limited in Ethiopia. Therefore, this study aimed to assess the incidence and predictors of tuberculosis among patients enrolled in Anti-Retroviral Therapy (ART) after universal test and treat program at St. Peter hospital and Zewditu Memorial Hospital, Addis Ababa, Ethiopia.

METHODS: Institutional-based retrospective cohort study was conducted from November 1 to 30, 2020. Simple random sampling was used to select a total of 539 adults records which was enrolled on ART. Data was collected and entered into EPI DATA 3.1 and analyzed using STATA version 14.1. Time-to-event distributions were estimated using Kaplan-Meier estimates. Hazards across different categories were compared using log-rank tests. Predictors were identified using the Cox proportional hazards model. The hazard ratio (HR) and 95% confidence interval (CI) were computed. Variables having P-value < 0.05 from the multivariable analysis were considered as a statistically significant.

RESULT: Among 539 records reviewed, 529 (98%) were included in the final analysis. The total follow-up period was 1529 Person-Year (PY). The incidence rate in this cohort was found to be 4.84 per 100-person year (95%CI,3.83-6.11). CD4 count<200 (AHR: 3.14,95% CI:1.64-7.10), poor adherence (AHR:2.16, 95% CI:1.21-3.85), underweight (AHR:2.42, 95% CI: 1.30-4.51), not taking isoniazid prophylaxis therapy (AHR: 2.78,95% CI: 1.06-7.30), being bedridden 3.06; (AHR: 3.06, 95% CI: 1.50-6.24), and baseline WHO stage three or four (AHR:2.33, 95% CI:1.08-5.02) were independent predictors for the incidence of TB among HIV positive patients.

CONCLUSION: In this study, the incidence of tuberculosis is relatively low as compared to studies done before the initiation of test and treat program in Ethiopia. low CD4count, poor level of adherence, low BMI, not taking IPT prophylaxis, bedridden functional status, and being on baseline WHO stage III or IV were found to increase the hazard of tuberculosis. Hence, close follow up, reminders, surveillance, and tracing mechanisms targeting this higher risk group would decrease Tuberculosis among PLHIV.

PMID:35921384 | DOI:10.1371/journal.pone.0272358

PLoS One. 2022 Aug 3;17(8):e0272437. doi: 10.1371/journal.pone.0272437. eCollection 2022.

ABSTRACT

BACKGROUND: The association between insulin resistance and cancer-mortality is not fully explored. We investigated the association between several insulin sensitivity indices (ISIs) and cancer-mortality over 3.5 decades in a cohort of adult men and women. We hypothesized that higher insulin resistance will be associated with greater cancer-mortality risk.

METHODS: A cohort of 1,612 men and women free of diabetes during baseline were followed since 1979 through 2016 according to level of insulin resistance (IR) for cause specific mortality, as part of the Israel study on Glucose Intolerance, Obesity and Hypertension (GOH). IR was defined according to the Mcauley index (MCAi), calculated by fasting insulin and triglycerides, the Homeostatic Model Assessment (HOMA), the Matsuda Insulin Sensitivity Index (MISI), and the Quantitative Insulin Sensitivity Check Index (QUICKI), calculated by plasma glucose and insulin.

RESULTS: Mean age at baseline was 51.5 ± 8.0 years, 804 (49.9%) were males and 871 (54.0%) had prediabetes. Mean follow-up was 36.7±0.2 years and 47,191 person years were accrued. Cox proportional hazard model and competing risks analysis adjusted for age, sex, country of origin, BMI, blood pressure, total cholesterol, smoking and glycemic status, revealed an increased risk for cancer-mortality, HR = 1.5 (95% CI: 1.1-2.0, p = 0.005) for the MCAi Q1 compared with Q2-4. No statistically significant associations were observed between the other ISIs and cancer-mortality.

CONCLUSION: The MCAi was independently associated with an increased risk for cancer-mortality in adult men and women free of diabetes and should be further studied as an early biomarker for cancer risk.

PMID:35921366 | DOI:10.1371/journal.pone.0272437

IEEE Trans Med Imaging. 2022 Aug 3;PP. doi: 10.1109/TMI.2022.3196007. Online ahead of print.

ABSTRACT

How spontaneous brain neural activities emerge from the underlying anatomical architecture, characterized by structural connectivity (SC), has puzzled researchers for a long time. Over the past decades, much effort has been directed toward the graph modeling of SC, in which the brain SC is generally considered as relatively invariant. However, the graph representation of SC is unable to directly describe the connections between anatomically unconnected brain regions and fail to model the negative functional correlations. Here, we extend the static graph model to a spatiotemporal varying hypergraph Laplacian diffusion (STV-HGLD) model to describe the propagation of the spontaneous neural activity in human brain by incorporating the Laplacian of the hypergraph representation of the structural connectome (hSC) into the regular wave equation. Theoretical solution shows that the dynamic functional couplings between brain regions fluctuate in the form of an exponential wave regulated by the spatiotemporal varying Laplacian of hSC. Empirical study suggests that the cortical wave might give rise to resonance with SC during the self-organizing interplay between excitation and inhibition among brain regions, which orchestrates the cortical waves propagating with harmonics emanating from the hSC while being bound by the natural frequencies of SC. Besides, the average statistical dependencies between brain regions, normally defined as the functional connectivity (FC), arises just at the moment before the cortical wave reaches the steady state after the wave spreads across all the brain regions. Comprehensive tests on four extensively studied empirical brain connectome datasets with different resolutions confirm our theory and findings.

PMID:35921340 | DOI:10.1109/TMI.2022.3196007

PLoS One. 2022 Aug 3;17(8):e0271934. doi: 10.1371/journal.pone.0271934. eCollection 2022.

ABSTRACT

OBJECTIVE: To assess sex differences in presentation and management of febrile children with respiratory symptoms attending European Emergency Departments.

DESIGN AND SETTING: An observational study in twelve Emergency Departments in eight European countries.

PATIENTS: Previously healthy children aged 0-<18 years with fever (≥ 38°C) at the Emergency Department or in the consecutive three days before Emergency Department visit and respiratory symptoms were included.

MAIN OUTCOME MEASURES: The main outcomes were patient characteristics and management defined as diagnostic tests, treatment and admission. Descriptive statistics were used for patient characteristics and management stratified by sex. Multivariable logistic regression analyses were performed for the association between sex and management with adjustment for age, disease severity and Emergency Department. Additionally, subgroup analyses were performed in children with upper and lower respiratory tract infections and in children below five years.

RESULTS: We included 19,781 febrile children with respiratory symptoms. The majority were boys (54%), aged 1-5 years (58%) and triaged as low urgent (67%). Girls presented less frequently with tachypnea (15% vs 16%, p = 0.002) and increased work of breathing (8% vs 12%, p<0.001) compared with boys. Girls received less inhalation medication than boys (aOR 0.82, 95% CI 0.74-0.90), but received antibiotic treatment more frequently than boys (aOR 1.09, 95% CI 1.02-1.15), which is associated with a higher prevalence of urinary tract infections. Amongst children with a lower respiratory tract infection and children below five years girls received less inhalation medication than boys (aOR 0.77, 95% CI 0.66-0.89; aOR 0.80, 95% CI 0.72-0.90).

CONCLUSIONS: Sex differences concerning presentation and management are present in previously healthy febrile children with respiratory symptoms presenting to the Emergency Department. Future research should focus on whether these differences are related to clinicians’ attitudes, differences in clinical symptoms at the time of presentation and disease severity.

PMID:35921337 | DOI:10.1371/journal.pone.0271934