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1.
Bull Math Biol ; 86(8): 103, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38980452

ABSTRACT

Phylogenetic diversity indices are commonly used to rank the elements in a collection of species or populations for conservation purposes. The derivation of these indices is typically based on some quantitative description of the evolutionary history of the species in question, which is often given in terms of a phylogenetic tree. Both rooted and unrooted phylogenetic trees can be employed, and there are close connections between the indices that are derived in these two different ways. In this paper, we introduce more general phylogenetic diversity indices that can be derived from collections of subsets (clusters) and collections of bipartitions (splits) of the given set of species. Such indices could be useful, for example, in case there is some uncertainty in the topology of the tree being used to derive a phylogenetic diversity index. As well as characterizing some of the indices that we introduce in terms of their special properties, we provide a link between cluster-based and split-based phylogenetic diversity indices that uses a discrete analogue of the classical link between affine and projective geometry. This provides a unified framework for many of the various phylogenetic diversity indices used in the literature based on rooted and unrooted phylogenetic trees, generalizations and new proofs for previous results concerning tree-based indices, and a way to define some new phylogenetic diversity indices that naturally arise as affine or projective variants of each other or as generalizations of tree-based indices.


Subject(s)
Biodiversity , Phylogeny , Models, Genetic , Mathematical Concepts , Biological Evolution , Animals
2.
Mol Biol Rep ; 51(1): 845, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39042259

ABSTRACT

BACKGROUND: This study examines genetic variations in CYP2E1 (rs6413432, rs3813867), GCKR (rs780094, rs1260326), and PNPLA3 (rs738409) among Turkish patients to assess their influence on nonalcoholic steatohepatitis. METHODS: Allele and genotype frequencies were compared between 245 NASH patients and 120 healthy controls using SNP genotyping via polymerase chain reaction-restriction fragment length polymorphism. Additionally, the deviation of the observed genotype frequencies from Hardy-Weinberg proportion was examined. RESULTS: No significant differences were found in the allelic and genotypic distributions of rs6413432, rs3813867, and rs780094 between NASH patients and healthy controls. However, significant disparities were noted for rs1260326 and rs738409. Gender and age-specific distributions showed no notable differences. The only observed deviation from Hardy-Weinberg proportion was in the genotype frequency of rs738409. CONCLUSIONS: Variants in GCKR (rs1260326) and PNPLA3 (rs738409) are significantly associated with increased NASH risk in the Turkish population, with the rs738409 variant potentially playing a more prominent role in NASH development.


Subject(s)
Adaptor Proteins, Signal Transducing , Cytochrome P-450 CYP2E1 , Gene Frequency , Genetic Predisposition to Disease , Genotype , Lipase , Membrane Proteins , Non-alcoholic Fatty Liver Disease , Polymorphism, Single Nucleotide , Humans , Male , Female , Turkey , Lipase/genetics , Polymorphism, Single Nucleotide/genetics , Non-alcoholic Fatty Liver Disease/genetics , Middle Aged , Adult , Membrane Proteins/genetics , Gene Frequency/genetics , Cytochrome P-450 CYP2E1/genetics , Adaptor Proteins, Signal Transducing/genetics , Alleles , Case-Control Studies , Aged , Acyltransferases , Phospholipases A2, Calcium-Independent
3.
Infect Dis Model ; 9(4): 1147-1162, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39027017

ABSTRACT

Background: Under-reporting and, thus, uncertainty around the true incidence of health events is common in all public health reporting systems. While the problem of under-reporting is acknowledged in epidemiology, the guidance and methods available for assessing and correcting the resulting bias are obscure. Objective: We aim to design a simple modification to the Susceptible - Infected - Removed (SIR) model for estimating the fraction or proportion of reported infection cases. Methods: The suggested modification involves rescaling of the classical SIR model producing its mathematically equivalent version with explicit dependence on the reporting parameter (true proportion of cases reported). We justify the rescaling using the phase plane analysis of the SIR model system and show how this rescaling parameter can be estimated from the data along with the other model parameters. Results: We demonstrate how the proposed method is cross-validated using simulated data with known disease cases and then apply it to two empirical reported data sets to estimate the fraction of reported cases in Missoula County, Montana, USA, using: (1) flu data for 2016-2017 and (2) COVID-19 data for fall of 2020. Conclusions: We establish with the simulated and COVID-19 data that when most of the disease cases are presumed reported, the value of the additional reporting parameter in the modified SIR model is close or equal to one, so that the original SIR model is appropriate for data analysis. Conversely, the flu example shows that when the reporting parameter is close to zero, the original SIR model is not accurately estimating the usual rate parameters, and the re-scaled SIR model should be used. This research demonstrates the role of under-reporting of disease data and the importance of accounting for under-reporting when modeling simulated, endemic, and pandemic disease data. Correctly reporting the "true" number of disease cases will have downstream impacts on predictions of disease dynamics. A simple parameter adjustment to the SIR modeling framework can help alleviate bias and uncertainty around crucial epidemiological metrics (e.g.: basic disease reproduction number) and public health decision making.

4.
Clin Exp Dent Res ; 10(4): e923, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38970240

ABSTRACT

OBJECTIVES: To evaluate the validity of the Golden Proportion, Golden Percentage, and Recurring Esthetic Dental (RED) Proportion among Kenyans of African descent with naturally well-aligned teeth. MATERIALS AND METHODS: Standardized frontal photographic images of the smiles of 175 participants aged 18-35 years were obtained, and Adobe Photoshop was used to analyze and measure the frontal widths of the maxillary central and lateral incisors and canines in triplicate. The average teeth widths were calculated to determine the existence of the Golden Proportion, Golden Percentage, and RED Proportion, and their validity using independent sample t-tests to compare the differences in the mean teeth widths at α < 0.05. RESULTS: The number of male and female participants was 107 (61.1%) and 68 (38.9%), respectively. The Golden Proportion between the maxillary central and lateral incisors was found in 4.0% on the right and 2.8% on the left of all the participants, but between the maxillary lateral incisors and canines was found in only 0.6% on the right of male participants (p < 0.0001). The RED Proportion between the maxillary lateral and central incisors was in the range of 67%-70%, and between the canines and lateral incisors was 82%-84% (p < 0.0001). The proportion of RED was not constant, and gradually increased distally. The Golden Percentage of 15% was observed in the lateral incisors bilaterally; however, in the central incisors and the canines, the Golden Percentage was 22% and 12%, respectively. CONCLUSION: The Golden and RED Proportions were invalid determinants of anterior teeth proportions. The Golden Percentage existed only in the lateral incisors. The Golden Proportion, RED Proportion, and Golden Percentage theories may not be applicable to all populations when designing smiles. Racial and ethnic backgrounds are important considerations to establish objective quantifiable values of anterior tooth proportions that are beneficial for esthetic restorations.


Subject(s)
Black People , Cuspid , Esthetics, Dental , Incisor , Odontometry , Humans , Male , Female , Adult , Adolescent , Incisor/anatomy & histology , Black People/statistics & numerical data , Young Adult , Cuspid/anatomy & histology , Odontometry/methods , Kenya , Smiling , Maxilla/anatomy & histology , Photography, Dental
5.
Endocrine ; 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38970759

ABSTRACT

PURPOSE: Hobnail features may enhance the clinical aggressiveness of papillary thyroid carcinoma (PTC). However, whether a low proportion (<30%) of these features contributes to increased PTC aggressiveness remains unclear. This study investigated whether PTC cases with a low proportion hobnail features (<30%) exhibit clinical invasiveness and pathological features of aggressiveness. METHODS: Pathological specimens from patients with postoperatively diagnosed PTC were retrospectively analyzed. Among them, 29 PTC cases with a low proportion of hobnail features (<30%) were compared with 173 consecutive classical PTC (cPTC) cases. Data regarding age at presentation, sex, tumor size, number of tumors, and histological characteristics were obtained by reviewing electronic medical records. Postoperative information was obtained during follow-up visits and telephone interviews. RESULTS: Twenty-nine patients with PTC with a low proportion of hobnail features (<30%) were identified, exhibiting a median age of 34 years. At a median follow-up of 31 (IQR, 23-37) months, two patients had recurrent disease in the PTC with a low proportion of hobnail features (<30%) group, whereas there was no recurrence in the cPTC group. No distant metastasis and postoperative mortality were observed in either group. Compared with the cPTC group, patients with PTC and a low proportion of hobnail features exhibited larger tumor volumes and higher susceptibility to capsular invasion and lymph node metastasis. Tumor size and hobnail features emerged as independent risk factors for lymph node metastasis. CONCLUSION: PTC with a low proportion hobnail features (<30%) and larger tumor volumes are associated with the occurrence of lymph node metastasis. A low proportion of hobnail features (<30%) in PTC may heighten invasiveness, elevating the risk of recurrence.

6.
Hum Genomics ; 18(1): 81, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39030631

ABSTRACT

BACKGROUND: Maternal genetic risk of type 2 diabetes (T2D) has been associated with fetal growth, but the influence of genetic ancestry is not yet fully understood. We aimed to investigate the influence of genetic distance (GD) and genetic ancestry proportion (GAP) on the association of maternal genetic risk score of T2D (GRST2D) with fetal weight and birthweight. METHODS: Multi-ancestral pregnant women (n = 1,837) from the NICHD Fetal Growth Studies - Singletons cohort were included in the current analyses. Fetal weight (in grams, g) was estimated from ultrasound measurements of fetal biometry, and birthweight (g) was measured at delivery. GRST2D was calculated using T2D-associated variants identified in the latest trans-ancestral genome-wide association study and was categorized into quartiles. GD and GAP were estimated using genotype data of four reference populations. GD was categorized into closest, middle, and farthest tertiles, and GAP was categorized as highest, medium, and lowest. Linear regression analyses were performed to test the association of GRST2D with fetal weight and birthweight, adjusted for covariates, in each GD and GAP category. RESULTS: Among women with the closest GD from African and Amerindigenous ancestries, the fourth and third GRST2D quartile was significantly associated with 5.18 to 7.48 g (weeks 17-20) and 6.83 to 25.44 g (weeks 19-27) larger fetal weight compared to the first quartile, respectively. Among women with middle GD from European ancestry, the fourth GRST2D quartile was significantly associated with 5.73 to 21.21 g (weeks 18-26) larger fetal weight. Furthermore, among women with middle GD from European and African ancestries, the fourth and second GRST2D quartiles were significantly associated with 117.04 g (95% CI = 23.88-210.20, p = 0.014) and 95.05 g (95% CI = 4.73-185.36, p = 0.039) larger birthweight compared to the first quartile, respectively. The absence of significant association among women with the closest GD from East Asian ancestry was complemented by a positive significant association among women with the highest East Asian GAP. CONCLUSIONS: The association between maternal GRST2D and fetal growth began in early-second trimester and was influenced by GD and GAP. The results suggest the use of genetic GD and GAP could improve the generalizability of GRS.


Subject(s)
Birth Weight , Diabetes Mellitus, Type 2 , Fetal Development , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Female , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/epidemiology , Pregnancy , Fetal Development/genetics , Birth Weight/genetics , Adult , Fetal Weight/genetics , Risk Factors , Polymorphism, Single Nucleotide/genetics , Genetic Risk Score
7.
Plants (Basel) ; 13(13)2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38999598

ABSTRACT

Stand basal area (SBA) is an important variable in the prediction of forest growth and harvest yield. However, achieving the additivity of SBA models for multiple tree species in the complex structure of broad-leaved mixed forests is an urgent scientific issue in the study of accurately predicting the SBA of mixed forests. This study used data from 58 sample plots (30 m × 30 m) for Populus davidiana × Betula platyphylla broad-leaved mixed forests to construct the SBA basic model based on nonlinear least squares regression (NLS). Adjustment in proportion (AP) and nonlinear seemingly unrelated regression (NSUR) were used to construct a multi-species additive basal area prediction model. The results identified the Richards model (M6) and Korf model (M1) as optimal for predicting the SBA of P. davidiana and B. platyphylla, respectively. The SBA models incorporate site quality, stand density index, and age at 1.3 m above ground level, which improves the prediction accuracy of basal area. Compared to AP, NSUR is an effective method for addressing the additivity of basal area in multi-species mixed forests. The results of this study can provide a scientific basis for optimizing stand structure and accurately predicting SBA in multi-species mixed forests.

8.
Mar Pollut Bull ; 206: 116677, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39018823

ABSTRACT

The relative importance of each sediment physicochemical property to sediment heavy-metal (HM) contents has not yet been quantitatively evaluated. Differences in the HM contents of mangrove surface sediments among the high, middle, and low intertidal zones, and their quantitative relationships to sediment physicochemical properties, were investigated in Dongzhaigang and Qinglan Harbor reserves, Hainan, China. In both reserves, the Cu and Ni concentrations increased significantly from the low to high intertidal zones; the patterns of change in the Mn and Pb contents were opposite in the two reserves. The Cr concentration was significantly lower and the Pb concentration was significantly higher in the dry season than in the wet season. Ecological risks of HM were higher in Dongzhaigang than in Qinglan Harbor. Regression and redundancy (hierarchical partitioning) analyses showed that the sediment total sulfur, nitrogen and potassium contents and pH were key factors affecting the HM contents of mangrove surface sediments.

9.
Farm Hosp ; 2024 Jul 01.
Article in English, Spanish | MEDLINE | ID: mdl-38955664

ABSTRACT

OBJECTIVE: Improving understanding of actual pulmonary hypertension (PH) treatment adherence patterns is crucial to properly treating these patients. We aimed to primarily assess adherence to treatments used for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) specific therapies, identify potential factors related to it and secondly describe its treatment patterns. METHODS: A 6-month observational cross-sectional study in a tertiary care hospital was conducted. Patients with PH-targeted therapy who picked it up in the ambulatory hospital pharmacy and who had been on treatment with the same drug for at least 1 year were included. Adherence was assessed as: 1) Proportion of days covered (PDC); and 2) Simplified Medication Adherence Questionnaire (SMAQ). PDC ≥80% was considered adherent. Statistical analyses were performed to evaluate the study outcomes. Logistic regressions were estimated to identify the association between baseline characteristics and factors associated with adherence. P < 0.05 indicated statistical significance. RESULTS: A total of 63 patients with 127 different treatments were included, 71.4% were females with a mean age (SD) of 59 (15) years. PAH was the most common diagnosis (74.6%). Double therapy was used in 39.7% of patients, being the combination of Macitentan + Tadalafil and Ambrisentan + Tadalafil the most prescribed. Endothelin receptor antagonists were the most used treatment (40.2%). Adherence according to PDC was 93.7%, showing no great differences depending on the targeted drug used, and according to SMAQ 61.9%. The agreement degree of both methods was slight (65.1%; Kappa 0.12). Only female sex (OR: 0.23, 95% CI: 0.06-0.90; p = 0.035) was associated with worse adherence in the SMAQ method but not in the PDC. Adverse events were reported by a 55.6% of participants and the perception of effective treatment was high (95.2%). CONCLUSIONS: Adherence to PH therapy differs depending on the assessment method; PDC showed greater adherence rate than SMAQ. According to SMAQ, female sex may have a negative impact on adherence in this cohort, but PDC revealed no factors influencing it. No notable differences in adherence between treatment types were found and generally patients felt the treatments were effective in controlling their disease.

10.
Exp Brain Res ; 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38963561

ABSTRACT

In the flanker task, the behavioral performance for incompatible stimuli is worse in the mostly compatible (rare) condition than in the equiprobable condition. Furthermore, incompatible stimuli evoke visual mismatch negativity (VMMN) when comparing the rare and equiprobable conditions. Compatible and incompatible stimuli differ in terms of their shape and type. This study aimed to examine whether VMMN evoked by rare incompatible stimuli were associated with the shape or type of the stimulus. In a modified version of the flanker task, stimuli were manipulated by two shapes (typical or peculiar) and two types (compatible or incompatible): typical compatible stimuli (< < < < < and > > > > >), typical incompatible stimuli (> > < > > and < < > < <), peculiar compatible stimuli (+ < < < + and + > > > +), and peculiar incompatible stimuli (+ > < > + and + < > < +). In the rare condition, typical incompatible, peculiar compatible, and peculiar incompatible stimuli were presented with a probability of 10%, whereas all the stimuli were presented equally in the equiprobable condition. Right posterior negativity from 200 to 250 ms was significantly more negative in the rare condition than in the equiprobable condition for typical and peculiar incompatible stimuli; however, this difference was not observed for peculiar compatible stimuli. VMMN was significantly more negative for typical and peculiar incompatible stimuli than for peculiar compatible stimuli, and was not significantly different between typical and peculiar incompatible stimuli. These findings suggest that VMMN for incompatible stimuli is associated with the type rather than the shape of the stimulus.

11.
Influenza Other Respir Viruses ; 18(7): e13348, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38949103

ABSTRACT

Understanding the clinical spectrum of SARS-CoV-2 infection, including the asymptomatic fraction, is important as asymptomatic individuals are still able to infect other individuals and contribute to ongoing transmission. The WHO Unity Household transmission investigation (HHTI) protocol provides a platform for the prospective and systematic collection of high-quality clinical, epidemiological, serological and virological data from SARS-CoV-2 confirmed cases and their household contacts. These data can be used to understand key severity and transmissibility parameters-including the asymptomatic proportion-in relation to local epidemic context and help inform public health response. We aimed to estimate the asymptomatic proportion of SARS-CoV-2 Omicron variant infections in Unity-aligned HHTIs. We conducted a systematic review and meta-analysis in alignment with the PRISMA 2020 guidelines and registered our systematic review on PROSPERO (CRD42022378648). We searched EMBASE, Web of Science, MEDLINE and bioRxiv and medRxiv from 1 November 2021 to 22 August 2023. We identified 8368 records, of which 98 underwent full text review. We identified only three studies for data extraction, with substantial variation in study design and corresponding estimates of the asymptomatic proportion. As a result, we did not generate a pooled estimate or I2 metric. The limited number of quality studies that we identified highlights the need for improved preparedness and response capabilities to facilitate robust HHTI implementation, analysis and reporting, to better inform national, regional and global risk assessments and policymaking.


Subject(s)
Asymptomatic Infections , COVID-19 , Family Characteristics , SARS-CoV-2 , Humans , Asymptomatic Infections/epidemiology , COVID-19/epidemiology , COVID-19/transmission , COVID-19/virology , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification
12.
Biom J ; 66(5): e202300075, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38953670

ABSTRACT

Closed testing has recently been shown to be optimal for simultaneous true discovery proportion control. It is, however, challenging to construct true discovery guarantee procedures in such a way that it focuses power on some feature sets chosen by users based on their specific interest or expertise. We propose a procedure that allows users to target power on prespecified feature sets, that is, "focus sets." Still, the method also allows inference for feature sets chosen post hoc, that is, "nonfocus sets," for which we deduce a true discovery lower confidence bound by interpolation. Our procedure is built from partial true discovery guarantee procedures combined with Holm's procedure and is a conservative shortcut to the closed testing procedure. A simulation study confirms that the statistical power of our method is relatively high for focus sets, at the cost of power for nonfocus sets, as desired. In addition, we investigate its power property for sets with specific structures, for example, trees and directed acyclic graphs. We also compare our method with AdaFilter in the context of replicability analysis. The application of our method is illustrated with a gene ontology analysis in gene expression data.


Subject(s)
Biometry , Biometry/methods , Gene Expression Profiling/methods , Gene Ontology , Humans
13.
Clin Rheumatol ; 43(8): 2435-2444, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38853227

ABSTRACT

INTRODUCTION: Optimal adherence thresholds can vary across medications and disease states. The objective of the study was to determine the optimal threshold of the proportion of days covered (PDC) for tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA). METHODS: Patients with RA initiating self-administered TNF inhibitors were identified using 2012-18 Medicare fee-for-service claims. Time-varying PDC was calculated every day for the preceding 90 days during follow-up. Oral and injected glucocorticoid use, hospitalizations, emergency room (ER) visits, serious infections, and a composite of these were measured as outcomes. Time to first occurrence of each outcome as a function of time-varying PDC for TNF inhibitors was evaluated using Cox regression. Incident/dynamic time-dependent receiver operating characteristic curves and Youden's J index were used to obtain the optimal PDC threshold for outcomes at 365 days. RESULTS: Of the 1190 patients who met the study inclusion criteria, almost 75% (865 patients) experienced at least one of the outcomes. Increasing PDC by 10% was significantly associated with decreased risks of the composite outcome (HR 0.98, 95% CI 0.96-1.00), oral glucocorticoid use (HR 0.93, 95% CI 0.91-0.96), and hospitalization (HR 0.96, 95% CI 0.94-0.99) but an increased risk of ER visits (HR 1.04, 95% 1.01-1.07). Optimal PDC thresholds for the composite outcome, oral glucocorticoid use, and hospitalization were 0.64, 0.59, and 0.56, respectively. CONCLUSIONS: Increased PDC was associated with a decreased risk of adverse outcomes, except ER visits. The optimal PDC for TNF inhibitors in Medicare patients with RA based on clinical outcomes was about 60%. Key Points • The optimal proportion of days covered threshold for tumor necrosis factor inhibitors at 365 days based on clinical outcomes was found to be about 60%, which is lower than the traditional 80% used to define adherence. • Increased adherence was associated with decreased risks of oral glucocorticoid use, hospitalization, and the composite outcome. However, it was also associated with an increased risk of emergency room visits. • The mean time-varying 90-day proportion of days covered decreased throughout the study starting 92% at day 1 of follow-up to 62% at day 365.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Medication Adherence , Tumor Necrosis Factor-alpha , Humans , Arthritis, Rheumatoid/drug therapy , Female , Male , Aged , Medication Adherence/statistics & numerical data , Antirheumatic Agents/therapeutic use , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Glucocorticoids/therapeutic use , Glucocorticoids/administration & dosage , Hospitalization/statistics & numerical data , United States , Middle Aged , Medicare , Aged, 80 and over , Proportional Hazards Models , Retrospective Studies , Tumor Necrosis Factor Inhibitors/therapeutic use
14.
Sci Rep ; 14(1): 12619, 2024 06 01.
Article in English | MEDLINE | ID: mdl-38824173

ABSTRACT

Subgroup analysis aims to identify subgroups (usually defined by baseline/demographic characteristics), who would (or not) benefit from an intervention under specific conditions. Often performed post hoc (not pre-specified in the protocol), subgroup analyses are prone to elevated type I error due to multiple testing, inadequate power, and inappropriate statistical interpretation. Aside from the well-known Bonferroni correction, subgroup treatment interaction tests can provide useful information to support the hypothesis. Using data from a previously published randomized trial where a p value of 0.015 was found for the comparison between standard and Hemopatch® groups in (the subgroup of) 135 patients who had hand-sewn pancreatic stump closure we first sought to determine whether there was interaction between the number and proportion of the dependent event of interest (POPF) among the subgroup population (patients with hand-sewn stump closure and use of Hemopatch®), Next, we calculated the relative excess risk due to interaction (RERI) and the "attributable proportion" (AP). The p value of the interaction was p = 0.034, the RERI was - 0.77 (p = 0.0204) (the probability of POPF was 0.77 because of the interaction), the RERI was 13% (patients are 13% less likely to sustain POPF because of the interaction), and the AP was - 0.616 (61.6% of patients who did not develop POPF did so because of the interaction). Although no causality can be implied, Hemopatch® may potentially decrease the POPF after distal pancreatectomy when the stump is closed hand-sewn. The hypothesis generated by our subgroup analysis requires confirmation by a specific, randomized trial, including only patients undergoing hand-sewn closure of the pancreatic stump after distal pancreatectomy.Trial registration: INS-621000-0760.


Subject(s)
Randomized Controlled Trials as Topic , Humans , Pancreatectomy , Female , Male , Pancreas/surgery
15.
Trials ; 25(1): 353, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38822392

ABSTRACT

BACKGROUND: The SAVVY project aims to improve the analyses of adverse events (AEs) in clinical trials through the use of survival techniques appropriately dealing with varying follow-up times and competing events (CEs). This paper summarizes key features and conclusions from the various SAVVY papers. METHODS: Summarizing several papers reporting theoretical investigations using simulations and an empirical study including randomized clinical trials from several sponsor organizations, biases from ignoring varying follow-up times or CEs are investigated. The bias of commonly used estimators of the absolute (incidence proportion and one minus Kaplan-Meier) and relative (risk and hazard ratio) AE risk is quantified. Furthermore, we provide a cursory assessment of how pertinent guidelines for the analysis of safety data deal with the features of varying follow-up time and CEs. RESULTS: SAVVY finds that for both, avoiding bias and categorization of evidence with respect to treatment effect on AE risk into categories, the choice of the estimator is key and more important than features of the underlying data such as percentage of censoring, CEs, amount of follow-up, or value of the gold-standard. CONCLUSIONS: The choice of the estimator of the cumulative AE probability and the definition of CEs are crucial. Whenever varying follow-up times and/or CEs are present in the assessment of AEs, SAVVY recommends using the Aalen-Johansen estimator (AJE) with an appropriate definition of CEs to quantify AE risk. There is an urgent need to improve pertinent clinical trial reporting guidelines for reporting AEs so that incidence proportions or one minus Kaplan-Meier estimators are finally replaced by the AJE with appropriate definition of CEs.


Subject(s)
Randomized Controlled Trials as Topic , Humans , Time Factors , Randomized Controlled Trials as Topic/standards , Practice Guidelines as Topic , Data Interpretation, Statistical , Risk Assessment , Research Design/standards , Risk Factors , Drug-Related Side Effects and Adverse Reactions , Bias , Survival Analysis , Follow-Up Studies , Treatment Outcome , Computer Simulation , Kaplan-Meier Estimate
16.
Cancers (Basel) ; 16(11)2024 May 31.
Article in English | MEDLINE | ID: mdl-38893222

ABSTRACT

For practical reasons, in many studies PD-L1 expression is measured by combined positive score (CPS) from a single tumor sample. This does not reflect the heterogeneity of PD-L1 expression in head and neck squamous cell carcinoma (HNSCC). We investigated the extent and relevance of PD-L1 expression heterogeneity in HNSCC analyzing primary tumors and recurrences (LRs), as well as metastases. Tumor tissue from 200 HNSCC patients was immunohistochemically stained for PD-L1 and analyzed using image-analysis software QuPath v3.4 with multiple specimens per patient. CPS was ≥20 in 25.6% of primary tumors. Intra-tumoral heterogeneity led to a therapeutically relevant underestimation of PD-L1 expression in 28.7% of patients, when only one specimen per patient was analyzed. Inter-tumoral differences in PD-L1 expression between primary tumors and lymph node metastasis (LNM) or LR occurred in 44.4% and 61.5% (CPS) and in 40.6% and 50% of cases (TPS). Overall survival was increased in patients with CPS ≥ 1 vs. CPS < 1 in primary tumors and LNM (hazard ratio: 0.46 and 0.35; p < 0.005); CPS in LR was not prognostic. Our analysis shows clinically relevant intra- and inter-sample heterogeneity of PD-L1 expression in HNSCC. To account for heterogeneity and improve patient selection for immunotherapy, multiple sample analyses should be performed, particularly in patients with CPS/TPS < 1.

17.
Int J Biol Macromol ; 273(Pt 2): 133173, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38880441

ABSTRACT

Sodium alginate (SA) and chito oligosaccharide (COS) are widely used food additives in the food industry, and exploring their interaction to form polyelectrolyte complexes (PECs) may provide insights into food development. In the present study, the effects of viscosity-average molecular weight (Mv) and relative amounts of SA on the formation of sodium alginate/chito oligosaccharide polyelectrolyte (SCP) complexes were investigated. The results showed that the electrostatic interaction between -COOH and -NH2 and the hydrogen bonding between OH, were attributed to the formation of the SCP complexes. Then the formation and properties of SCP complexes were greatly dependent on the Mv and the relative amount of SA. SA with Mv of ≥2.16 × 106 Da could form spherical SCP complexes, while the SA/COS ratio (w/w) ≥ 0.8 was not conducive to the formation of SCP complexes. Moreover, the SCP complexes were more stable in the gastric environment than in the intestinal condition. In addition, 1.73 × 107 Da was the optimal Mv of SA for SCP complexes formation. This study contributed to a comprehensive understanding of the interaction between SA and COS, and shed light on the potential application of SA and COS formulation to develop new food products.


Subject(s)
Alginates , Molecular Weight , Oligosaccharides , Polyelectrolytes , Alginates/chemistry , Oligosaccharides/chemistry , Polyelectrolytes/chemistry , Viscosity , Chitosan/chemistry , Static Electricity , Hydrogen Bonding
18.
J Appl Stat ; 51(9): 1729-1755, 2024.
Article in English | MEDLINE | ID: mdl-38933136

ABSTRACT

We introduce the bivariate unit-log-symmetric model based on the bivariate log-symmetric distribution (BLS) defined in Vila et al. [25] as a flexible family of bivariate distributions over the unit square. We then study its mathematical properties such as stochastic representations, quantiles, conditional distributions, independence of the marginal distributions and marginal moments. Maximum likelihood estimation method is discussed and examined through Monte Carlo simulation. Finally, the proposed model is used to analyze some soccer data sets.

19.
Biosens Bioelectron ; 261: 116475, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-38852324

ABSTRACT

Rapid and accurate identification of tumor boundaries is critical for the cure of glioma, but it is difficult due to the invasive nature of glioma cells. This paper aimed to explore a rapid diagnostic strategy based on a label-free surface-enhanced Raman scattering (SERS) technique for the quantitative detection of glioma cell proportion intraoperatively. With silver nanoparticles as substrate, an in-depth SERS analysis was performed on simulated clinical samples containing normal brain tissue and different concentrations of patient-derived glioma cells. The results revealed two universal characteristic peaks of 655 and 717 cm-1, which strongly correlated with glioma cell proportion regardless of individual differences. Based on the intensity ratio of the two peaks, a ratiometric SERS strategy for the quantification of glioma cells was established by employing an artificial neuron network model and a polynomial regression model. Such a strategy accurately estimated the proportion of glioma cells in simulated clinical samples (R2 = 0.98) and frozen samples (R2 = 0.85). More importantly, it accurately facilitated the delineation of tumor margins in freshly obtained samples. Taken together, this SERS-based method ensured a rapid and more detailed identification of tumor margins during surgical resection, which could be beneficial for intraoperative decision-making and pathological evaluation.


Subject(s)
Brain Neoplasms , Glioma , Metal Nanoparticles , Silver , Spectrum Analysis, Raman , Glioma/surgery , Glioma/pathology , Glioma/diagnostic imaging , Humans , Spectrum Analysis, Raman/methods , Metal Nanoparticles/chemistry , Brain Neoplasms/surgery , Brain Neoplasms/pathology , Brain Neoplasms/diagnostic imaging , Silver/chemistry , Biosensing Techniques/methods
20.
Article in English | MEDLINE | ID: mdl-38934223

ABSTRACT

This study aimed to predict the index of effectiveness (IE) and positive impulse proportion (PIP) to assess the cyclist's pedalling technique from lower limb kinematic variables. Several wrapped feature selection techniques were applied to select the best predictors. To predict IE and PIP two multiple linear regressions (MLR) composed of 11 predictors (R² = 0.81 ± 0.12, R² = 0.81 ± 0.05) and two artificial neural networks (ANN) composed of 21 and 28 predictors (R² = 0.95 ± 0.01, R² = 0.92 ± 0.02) were developed. The ANN predicts with accuracy, and the MLR shows the influence of each predictor.

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