bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inter-observer variation in two-dimensional and three-dimensional ultrasound measurement of papillary thyroid microcarcinoma
Authors: Yan Lin , Ren Ling , Li Yingying , Luo Yukun 
Published: October 2023

Abstract
Backgrounds
The reliable ultrasound (US) measurements of papillary thyroid microcarcinoma (PTMC) are very important during active surveillance. This prospective study was design to investigate the inter-observer reliability and agreement of two- dimensional ultrasound(2DUS) and three-dimensional ultrasound(3DUS) in the measurement of maximum diameter and volume for PTMC.

Methods
This prospective study included 51 consecutive patients with solitary PTMC confirmed by biopsy. Two independent observers performed measurements of each tumor using a standardized measurement protocol. The maximum diameter was the largest one of the three diameters measured on the largest transverse and longitudinal 2DUS images. 2DUS volume was calculated using ellipsoid formula method. The virtual organ computer aided analysis(VOCAL) was used to determine 3DUS volume. The inter-observer reliability was assessed using intraclass correlation coefficient(ICC) with 95% confidence intervals(CIs). Bland-Altman analysis was used to evaluate agreement, and expressed as a bias with 95% limits of agreement(LOA).

Results
The maximum diameter was 0.78 ± 0.14 cm. Volume measured by 3DUS was significantly smaller than that by 2DUS(0.163 ± 0.074 cm3 vs. 0.175 ± 0.078 cm3, P = 0.005). The ICCs of inter-observer reliability of maximum diameter, 2DUS volume and 3DUS volume was 0.922(0.864–0.955), 0.928(0.874–0.959), and 0.974(0.955–0.985), respectively. The ICCs of 2DUS and 3DUS volume was 0.955(0.909–0.976). The inter-observer agreement of maximum diameter, 2DUS volume and 3DUS volume was 1.096(0.7322 to 1.459), 1.008(0.5802–1.435), and 1.011(0.7576–1.265), respectively. The inter-observer agreement of 2DUS and 3DUS volume was 1.096(0.7322 to 1.459).

Conclusion
Maximum diameter had the lowest degree of observer variation among all the measurements. Volume measured by 3DUS had lower variability and higher repeatability than that by 2DUS, which might be helpful to provide more reliable estimates of tumor size for PTMC.
Using the kidney failure risk equation to predict end-stage kidney disease in CKD patients of South Asian ethnicity: an external validation study
Authors: Maher Francesca , Teece Lucy , Major Rupert W. , Bradbury Naomi , Medcalf James F. , Brunskill Nigel J. , Booth Sarah , Gray Laura J. 
Published: October 2023

Abstract
Background
The kidney failure risk equation (KFRE) predicts the 2- and 5-year risk of needing kidney replacement therapy (KRT) using four risk factors — age, sex, urine albumin-to-creatinine ratio (ACR) and creatinine-based estimated glomerular filtration rate (eGFR). Although the KFRE has been recalibrated in a UK cohort, this did not consider minority ethnic groups. Further validation of the KFRE in different ethnicities is a research priority. The KFRE also does not consider the competing risk of death, which may lead to overestimation of KRT risk. This study externally validates the KFRE for patients of South Asian ethnicity and compares methods for accounting for ethnicity and the competing event of death.

Methods
Data were gathered from an established UK cohort containing 35,539 individuals diagnosed with chronic kidney disease. The KFRE was externally validated and updated in several ways taking into account ethnicity, using recognised methods for time-to-event data, including the competing risk of death. A clinical impact assessment compared the updated models through consideration of referrals made to secondary care.

Results
The external validation showed the risk of KRT differed by ethnicity. Model validation performance improved when incorporating ethnicity and its interactions with ACR and eGFR as additional risk factors. Furthermore, accounting for the competing risk of death improved prediction. Using criteria of 5 years ≥ 5% predicted KRT risk, the competing risks model resulted in an extra 3 unnecessary referrals (0.59% increase) but identified an extra 1 KRT case (1.92% decrease) compared to the previous best model. Hybrid criteria of predicted risk using the competing risks model and ACR ≥ 70 mg/mmol should be used in referrals to secondary care.

Conclusions
The accuracy of KFRE prediction improves when updated to consider South Asian ethnicity and to account for the competing risk of death. This may reduce unnecessary referrals whilst identifying risks of KRT and could further individualise the KFRE and improve its clinical utility. Further research should consider other ethnicities.
An efficient permutation approach for SbPN-based symmetric block ciphers
Authors: Nazish Mir , Banday M. Tariq , Syed Insha , Banday Sheena 
Published: October 2023

AbstractIt is challenging to devise lightweight cryptographic primitives efficient in both hardware and software that can provide an optimum level of security to diverse Internet of Things applications running on low-end constrained devices. Therefore, an efficient hardware design approach that requires some specific hardware resource may not be efficient if implemented in software. Substitution bit Permutation Network based ciphers such as PRESENT and GIFT are efficient, lightweight cryptographic hardware design approaches. These ciphers introduce confusion and diffusion by employing a 4 × 4 static substitution box and bit permutations. The bit-wise permutation is realised by simple rerouting, which is most cost-effective to implement in hardware, resulting in negligible power consumption. However, this method is highly resource-consuming in software, particularly for large block-sized ciphers, with each single-bit permutation requiring multiple sub-operations. This paper proposes a novel software-based design approach for permutation operation in Substitution bit Permutation Network based ciphers using a bit-banding feature. The conventional permutation using bit rotation and the proposed approach have been implemented, analysed and compared for GIFT and PRESENT ciphers on ARM Cortex-M3-based LPC1768 development platform with KEIL MDK used as an Integrated Development Environment. The real-time performance comparison between conventional and the proposed approaches in terms of memory (RAM/ROM) footprint, power, energy and execution time has been carried out using ULINKpro and ULINKplus debug adapters for various code and speed optimisation scenarios. The proposed approach substantially reduces execution time, energy and power consumption for both PRESENT and GIFT ciphers, thus demonstrating the efficiency of the proposed method for Substitution bit Permutation Network based symmetric block ciphers.
Independent external validation of a stroke recurrence score in patients with embolic stroke of undetermined source
Authors: Ingwersen Thies , Olma Manuel C. , Schlemm Eckhard , Mayer Carola , Cheng Bastian , Tütüncü Serdar , Kirchhof Paulus , Veltkamp Roland , Röther Joachim , Laufs Ulrich , Nabavi Darius G. , Ntaios George , Endres Matthias , Haeusler Karl Georg , Thomalla Götz 
Published: October 2023

Abstract
Background
Embolic stroke of undetermined source (ESUS) accounts for a substantial proportion of ischaemic strokes. A stroke recurrence score has been shown to predict the risk of recurrent stroke in patients with ESUS based on a combination of clinical and imaging features. This study aimed to externally validate the performance of the ESUS recurrence score using data from a randomized controlled trial.

Methods
The validation dataset consisted of eligible stroke patients with available magnetic resonance imaging (MRI) data enrolled in the PreDAFIS sub-study of the MonDAFIS study. The score was calculated using three variables: age (1 point per decade after 35 years), presence of white matter hyperintensities (2 points), and multiterritorial ischaemic stroke (3 points). Patients were assigned to risk groups as described in the original publication. The model was evaluated using standard discrimination and calibration methods.

Results
Of the 1054 patients, 241 (22.9%) were classified as ESUS. Owing to insufficient MRI quality, three patients were excluded, leaving 238 patients (median age 65.5 years [IQR 20.75], 39% female) for analysis. Of these, 30 (13%) patients experienced recurrent ischaemic stroke or transient ischemic attack (TIA) during a follow-up period of 383 patient-years, corresponding to an incidence rate of 7.8 per 100 patient-years (95% CI 5.3–11.2). Patients with an ESUS recurrence score value of ≥ 7 had a 2.46 (hazard ratio (HR), 95% CI 1.02–5.93) times higher risk of stroke recurrence than patients with a score of 0–4. The cumulative probability of stroke recurrence in the low-(0–4), intermediate-(5–6), and high-risk group (≥ 7) was 9%, 13%, and 23%, respectively (log-rank test, χ2 = 4.2, p = 0.1).

Conclusions
This external validation of a published scoring system supports a threshold of ≥ 7 for identifying ESUS patients at high-risk of stroke recurrence. However, further adjustments may be required to improve the model’s performance in independent cohorts. The use of risk scores may be helpful in guiding extended diagnostics and further trials on secondary prevention in patients with ESUS.
Trial registration: Clinical Trials, NCT02204267. Registered 30 July 2014, https://clinicaltrials.gov/ct2/show/NCT02204267.
The AnimalAssociatedMetagenomeDB reveals a bias towards livestock and developed countries and blind spots in functional-potential studies of animal-associated microbiomes
Authors: Avila Santos Anderson Paulo , Kabiru Nata’ala Muhammad , Kasmanas Jonas Coelho , Bartholomäus Alexander , Keller-Costa Tina , Jurburg Stephanie D. , Tal Tamara , Camarinha-Silva Amélia , Saraiva João Pedro , Ponce de Leon Ferreira de Carvalho André Carlos , Stadler Peter F. , Sipoli Sanches Danilo , Rocha Ulisses 
Published: October 2023

AbstractBackgroundMetagenomic data can shed light on animal-microbiome relationships and the functional potential of these communities. Over the past years, the generation of metagenomics data has increased exponentially, and so has the availability and reusability of data present in public repositories. However, identifying which datasets and associated metadata are available is not straightforward. We created the Animal-Associated Metagenome Metadata Database (AnimalAssociatedMetagenomeDB - AAMDB) to facilitate the identification and reuse of publicly available non-human, animal-associated metagenomic data, and metadata. Further, we used the AAMDB to (i) annotate common and scientific names of the species; (ii) determine the fraction of vertebrates and invertebrates; (iii) study their biogeography; and (iv) specify whether the animals were wild, pets, livestock or used for medical research.ResultsWe manually selected metagenomes associated with non-human animals from SRA and MG-RAST. Next, we standardized and curated 51 metadata attributes (e.g., host, compartment, geographic coordinates, and country). The AAMDB version 1.0 contains 10,885 metagenomes associated with 165 different species from 65 different countries. From the collected metagenomes, 51.1% were recovered from animals associated with medical research or grown for human consumption (i.e., mice, rats, cattle, pigs, and poultry). Further, we observed an over-representation of animals collected in temperate regions (89.2%) and a lower representation of samples from the polar zones, with only 11 samples in total. The most common genus among invertebrate animals was Trichocerca (rotifers).ConclusionOur work may guide host species selection in novel animal-associated metagenome research, especially in biodiversity and conservation studies. The data available in our database will allow scientists to perform meta-analyses and test new hypotheses (e.g., host-specificity, strain heterogeneity, and biogeography of animal-associated metagenomes), leveraging existing data. The AAMDB WebApp is a user-friendly interface that is publicly available athttps://webapp.ufz.de/aamdb/.
MRI features for predicting the pathological grade of HCC in patients undergoing liver transplantation
Authors: Altan Kus Aylin , Keceoglu Selim , Ozer Ali 
Published: October 2023

Abstract
Background
Contrast-enhanced magnetic resonance imaging (MRI) plays a crucial role in the diagnosis of hepatocellular carcinoma (HCC). This study aims to assess the performance of MRI features for evaluating hepatocellular carcinoma (HCC) aggressiveness in living liver transplantation in patients.

Material and methods
This retrospective study included patients who underwent liver transplantation in our hospital between 2015 and 2020. Abdominal contrast-enhanced MRIs of these patients were reviewed, and clinical, radiological, and histopathological findings of HCCs were recorded. The prognostic features of HCCs as determined by MRI were compared with Edmondson-Steiner (E-S) grades. Liver parenchyma fibrosis based on an apparent diffusion coefficient (ADC) map was correlated with histological subclassification of cirrhosis using the Laennec staging system.

Results
The study subjects included 37 men and 8 women with a mean age of 59.56 ± 7.81 (range: 25–72). The mean tumour size was 37.33 ± 22.27 mm (range: 10–118 mm), and nine tumours (23.1%) involved portal vein tumour thrombosis. There was a significant correlation between tumour grade and size (p = 0.007) and intratumoral fat (p = 0.014) even though no significant correlations between grade and mean ADC value, capsule appearance, presence of satellite lesions, smooth margin, imaging of the tumour feeding artery, and corona enhancement of HCC (p > 0.05) were found. There was a statistically significant correlation between mild (stage 4A) and moderate (stage 4B) fibrosis of non-tumorous liver parenchyma and ADC value (p < 0.001).

Conclusion
Our study found that ADC values can be used to distinguish mild cirrhotic livers from moderate cirrhotic livers. Diffusion MRI might be used to diagnose the degree of liver fibrosis without histopathological analysis. According to our results, only intralesional fat and tumour size correlated with tumour grade, and as such, these parameters could be used as prognostic MRI biomarkers for HCC.
Baseline and recurrent exposure to the standard dose of artemisinin-based combination therapies (ACTs) induces oxidative stress and liver damage in mice (BALB/c)
Authors: Audu David , Patel Vinood B. , Idowu Olufunmilayo A. , Mshelbwala Fakilahyel M. , Idowu Adewumi B. 
Published: October 2023

Abstract
Background
In malaria-endemic countries, repeated intake of artemisinin-based combination therapies (ACTs) is rampant and driven by drug resistance, improper usage, and easy accessibility. Stress effects and potential liver toxicity due to the frequent therapeutic use of ACTs have not been extensively studied. Here, we investigated the effects of repeated treatment with standard doses of the commonly used ACTs artemether/lumefantrine (A/L) and artesunate-amodiaquine (A/A) on oxidative stress and liver function markers in male mice (BALB/c).

Methods
Forty Five mice were divided into three groups: control, A/L, and A/A. The drugs were administered three days in a row per week, and the regimen was repeated every two weeks for a total of six cycles. The levels of oxidative stress and liver function markers were measured in both plasma and liver tissue after initial (baseline) and repeated exposures for the second, third, and sixth cycles.

Results
Exposure to A/L or A/A caused a significant (p < 0.001) increase in plasma malondialdehyde (MDA) levels after the first and repeated exposure periods. However, Hepatic MDA levels increased significantly (p < 0.01) only after the sixth exposure to A/A. Following either single or repeated exposure to A/L or A/A, plasma and liver glutathione peroxidase (GPx) and catalase (CAT) activities, plasma aspartate and alanine transaminase, alkaline phosphatase activity, and bilirubin levels increased, whereas total plasma protein levels decreased significantly (p < 0.001). Varying degrees of hepatocyte degeneration and blood vessel congestion were observed in liver tissues after a single or repeated treatment period.

Conclusion
Irrespective of single or repeated exposure to therapeutic doses of A/L or A/A, plasma oxidative stress and liver damage were observed. However, long-term repeated A/A exposure can led to hepatic stress. Compensatory processes involving GPx and CAT activities may help reduce the observed stress.
Association Between Concurrent Use of Benzodiazepines and Opioids and Health Care Utilization Among Patients With Cancer in Puerto Rico
Authors: Fuentes Payán Wilmarie , González Lorenzo Keyla , Gelabert Martínez Frankie , Conte Schmidt Nelly , Tortolero-Luna Guillermo , Ramos-Fernández María R. , Gierbolini-Bérmudez Axel , Melin Kyle , Ortiz-Ortiz Karen J. 
Published: October 2023

PURPOSE To evaluate the association between concurrent use of opioids and benzodiazepines (BZDs) and emergency room (ER) visits and hospital admissions in patients with cancer. METHODS Data were obtained from the Puerto Rico Central Cancer Registry-Health Insurance Linkage. Odds ratios (ORs) with 95% CIs and incidence rate ratio (IRR) were estimated using logistic and negative binomial regression analyses to assess the association between concurrent use of opioids and BZDs (overlap of at least 7 days) and ER visits and hospital admissions. RESULTS A total of 9,259 patients were included in the main analysis. The logistic regression results showed a significant association between concurrent use of opioids and BZDs and at least one ER visit (OR, 1.28 [95% CI, 1.07 to 1.54]) or hospital admission (OR, 1.42 [95% CI, 1.18 to 1.71]) compared with individuals with BZDs alone, after adjusting for age, sex, comorbidity index, cancer stage, health insurance, and health region. Compared with individuals with opioid use alone, the association did not reach significance. In the negative binomial regression, a significant association was observed for ER visits (IRR, 1.52 [95% CI, 1.31 to 1.76]) and hospitalizations (IRR, 1.34 [95% CI, 1.20 to 1.50]) when compared with individuals with BZDs alone. Compared with individuals with opioids alone, it only reached significance for ER visits (IRR, 1.39 [95% CI, 1.20 to 1.61]). CONCLUSION Careful evaluation must be done before prescribing concurrent opioids and BZDs in patients with cancer, as the results suggest that coprescribing may increase the odds of ER visits and hospitalizations.
Skewness in Body fat Distribution Pattern Links to Specific Cardiometabolic Disease Risk Profiles
Authors: Linge Jennifer , Cariou Bertrand , Neeland Ian J , Petersson Mikael , Rodríguez Ángel , Dahlqvist Leinhard Olof 
Published: October 2023

Abstract

Objective
Fat distribution pattern could help determine cardiometabolic risk profile. This study aimed to evaluate the association of balance/imbalance between visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (aSAT), and liver fat (LF) with incident type 2 diabetes (T2D) and cardiovascular disease (CVD) in the UK Biobank prospective cohort study.

Methods
Magnetic resonance images of 40 174 participants were analyzed for VAT, aSAT, and LF using AMRA® Researcher. To assess fat distribution patterns independent of body mass index (BMI), fat z-scores (z-VAT, z-aSAT, z-LF) were calculated. Participants without prevalent T2D/CVD (N = 35 138) were partitioned based on balance between (1) z-VAT and z-LF (z-scores = 0 as cut-points for high/low), (2) z-VAT and z-aSAT, and (3) z-LF and z-aSAT. Associations with T2D/CVD were investigated using Cox regression (crude and adjusted for sex, age, BMI, lifestyle, arterial hypertension, statin treatment).

Results
T2D was significantly associated with z-LF (hazard ratio, [95% CI] 1.74 [1.52-1.98], P &lt; .001) and z-VAT (1.70 [1.49-1.95], P &lt; .001). Both remained significant after full adjustment. For z-scores balance, strongest associations with T2D were z-VAT &gt; 0 and z-LF &gt; 0 (4.61 [2.98-7.12]), z-VAT &gt; 0 and z-aSAT &lt; 0 (4.48 [2.85-7.06]), and z-LF &gt; 0 and z-aSAT &lt; 0 (2.69 [1.76-4.12]), all P &lt; .001. CVD was most strongly associated with z-VAT (1.22 [1.16-1.28], P &lt; .001) which remained significant after adjustment for sex, age, BMI, and lifestyle. For z-scores balance, strongest associations with CVD were z-VAT &gt; 0 and z-LF &lt; 0 (1.53 [1.34-1.76], P &lt; .001) and z-VAT &gt; 0 and z-aSAT &lt; 0 (1.54 [1.34-1.76], P &lt; .001). When adjusted for sex, age, and BMI, only z-VAT &gt; 0 and z-LF &lt; 0 remained significant.

Conclusion
High VAT in relation to BMI (z-VAT &gt; 0) was consistently linked to both T2D and CVD; z-LF &gt; 0 was linked to T2D only. Skewed fat distribution patterns showed elevated risk for CVD (z-VAT &gt; 0 and z-LF &lt; 0 and z-VAT &gt; 0 and z-aSAT &lt; 0) and T2D (z-VAT &gt; 0 and z-aSAT &lt; 0).
THU128 Transcription Factor ETV5 In POMC Neurons Regulate Energy And Glucose Homeostasis
Authors: Gahlot Surbhi , Caron Alexandre , Lee Syann , Elmquist Joel K 
Published: October 2023

Abstract
Disclosure: S. Gahlot: None. A. Caron: None. S. Lee: None. J.K. Elmquist: None.
Pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARH) are critical for the regulation of energy balance and glucose homeostasis. Pomc gene transcription is regulated by the Erythrocyte Transformation Specific (ETS)-domain transcription factors, including Etv1, Etv2, Etv4, and Etv5. Large-scale genome-wide association studies have identified ETV5 genetic variants linked with human obesity and body mass index. Histological studies in adult mouse pituitaries also show the co-localization of ETV5 with POMC and POMC-derived peptides: adrenocorticotropic hormone (ACTH) and alpha-melanocyte stimulating hormone (α-MSH). Furthermore, whole-body Etv5 knockout mice are lean, severely glucose intolerant and hypoinsulinaemic. While these findings suggest a potential role for Etv5 in the control of energy and glucose balance, the role of Etv5 remains unknown. This study aims to determine whether ETV5 binds to the Pomc promoter to alter its expression and regulate energy balance and glucose homeostasis. To assess whether ETV5 binds to the Pomc promoter, we performed chromatin immunoprecipitation with quantitative real-time PCR (ChIP-qPCR) in C57BL/6J mice. ChIP-qPCR determined that Etv5 directly binds to the Pomc promoter. We further performed luciferase reporter assay in mouse neuroblastoma N2a cell lysates to measure the Pomc promoter activity after Etv5 knockdown or overexpression. Luciferase assay revealed that Etv5 knockdown increased, while Etv5 overexpression reduced the Pomc promoter activity in N2a cells. Also, Etv5 overexpression blocked the leptin-induced POMC activation. Further, to determine the role of Etv5 in POMC neurons to regulate energy balance and glucose homeostasis, we used the Cre/loxP system to selectively delete Etv5 from POMC neurons both prenatally and postnatally. Mice were fed either a standard chow or a 60% high-fat diet (HFD), followed by serial body weight, food intake, body composition, metabolic assessment, glucose tolerance and insulin tolerance test measurements. We found that mice with a prenatal deletion of Etv5 in POMC neurons had reduced body weight, reduced lean mass, and were protected from HFD-induced insulin resistance. Similarly, postnatal deletion of Etv5 in POMC neurons resulted in reduced body weight, lean mass and fat mass, and increased insulin sensitivity and energy expenditure in mice of 8 weeks age. We also performed electrophysiological recordings in hypothalamic slices from these mice to assess POMC neuron excitability. We found that loss of Etv5 increased the activity and electrical excitability of POMC neurons. These findings highlight a previously unrecognized role of Etv5 in POMC neurons in the regulation of energy balance and glucose homeostasis. These results also point to the potential therapeutic applications for Etv5 against obesity.
Presentation: Thursday, June 15, 2023