bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic accuracy of apparent diffusion coefficient (ADC) value in differentiating malignant from benign solid liver lesions: a systematic review and meta-analysis
Authors: Nalaini Farhad , Shahbazi Fatemeh , Mousavinezhad Seyedeh Maryam , Ansari Ali , Salehi Mohammadgharib 
Published: June 2021

Objectives:
We undertook a systematic review and meta-analysis of the diagnostic performance of mean apparent diffusion coefficient (ADC) values derived by diffusion-weighted (DW)-MRI in the characterization of solid benign and malignant liver lesions, and to assess their value in discriminating these lesions in daily routine practice.

Methods:
A systematic review of PubMed, Embase, Scopus, and Web of Science was conducted to retrieve studies that used ADC values for differentiating solid benign/dysplastic nodules and malignant liver lesions. A bivariate random-effects model with pooled sensitivity and specificity values with 95% CI (confidence interval) was used. This meta-analysis was performed on the per-lesion basis. Summary receiver operating characteristic (SROC) plot and area under curve (AUC) were created.

Results:
A total of 14 original articles were retrieved. The combined (95% CI) sensitivity and specificity of mean ADC values for differentiating solid benign from malignant lesions were 78% (67–86%) and 74% (64–81%), respectively. The pooled (95% CI) positive and negative LRs were respectively 3 (2.3–3.8) and 0.3 (0.21–0.43). The DOR (95% CI) was 10 (7–15). The AUC (95% CI) of the SROC plot was 82% (78–85%). Reporting bias was negligible (p value of regression test = 0.36). Mean size of malignant lesions and breathing pattern of MRI were found to be sources of heterogeneity of pooled sensitivity.

Conclusion:
ADC measurement independently may not be an optimal diagnostic imaging method for differentiating solid malignant from solid benign hepatic lesions. The meta-analysis showed that ADC measurement had moderate diagnostic accuracy for characterizing solid liver lesions. Further prospective and comparative studies with pre-specified ADC thresholds could be performed to investigate the best MRI protocol and ADC threshold for characterizing solid liver lesions.

Advances in knowledge:
ADC measurement by DW-MRI does not have a good diagnostic performance to differentiate solid malignant from solid benign lesions. Therefore, we suggest not using ADC values in clinical practice to evaluate solid liver lesions.
Metformin improves FOXP3 mRNA expression through suppression of interferon gamma levels in pristane-induced murine models of lupus
Authors: Sumantri Stevent , Hatta Mochammad , Natzir Rosdiana , Rasyid Haerani , Rengganis Iris , Massi Muhammad Nasrum , Islam Andi Asadul , Lawrence Gatot , Patellongi Ilhamjaya , Benyamin Andi Fachruddin 
Published: June 2021

Background: A recent study has indicated the potential of metformin therapy for lupus in animal models, but there has been no study evaluating the effect on pristane-induced lupus. This study aims to evaluate the effect of intraperitoneal versus oral metformin on interferon (IFN)-γ levels and FOXP3 mRNA expression on pristane-induced female BALB/c mice. Methods: In total, 31 female BALB/c mice, aged 6 weeks, were intraperitoneally induced with 0.5 ml of pristane (2,6,10,14-tetramethylpentadecane). After 120 days, the mice were grouped and treated with various treatments: normal saline 100 MCL, oral metformin 100mg/kg-BW, or intraperitoneal metformin 100mg/kg-BW. After 60 days of treatment, all treatment groups were sacrificed, and kidney specimens prepared and stained using hematoxylin and eosin. Results: IFNγ levels of saline controls vs. oral metformin group was 309.39 vs. 292.83 pg/mL (mean difference 16.56 pg/mL; 95% CI 0.74-32.37; p=0.042), and saline control vs. intraperitoneal metformin group was 309.39 vs. 266.90 pg/mL (mean difference 42.49 pg/mL; 95% CI 29.24-55.73 pg/mL; p<0.001). FOXP3 mRNA expression changes in saline controls vs. oral metformin group was 6.90 vs. 7.79-fold change (mean difference -0.89-fold change; 95% CI -1.68-(-0.11); p=0.03) and in saline controls vs. intraperitoneal metformin group was 6.90 vs. 9.02-fold change (mean difference -2.12-fold change; 95% CI -2.99-(-1.25); p=<0.001). Correlation analysis of FOXP3 mRNA expression and IFNγ level changes revealed a Pearson correlation of -0.785 (p=0.001) and R2 value of 0.616 (p=0.001). Conclusion: Metformin is a potential new therapy to reduce the levels of IFNγ and increase FOXP3 mRNA expression in mice models of systemic lupus erythematosus.
Clustering of noncommunicable disease risk factors among adolescents attending higher secondary schools in Kasaragod District, Kerala, India
Authors: Sreena Thekke Veedu , Mathews Elezebeth , Kodali Prakash Babu , Thankappan Kavumpurathu Raman 
Published: June 2021

Background: Limited evidence exists on the presence of collective non-communicable disease (NCD) risk factors among adolescents in Kerala, India. We aimed to assess the prevalence and factors associated with multiple NCD risk factors and clustering of these risk factors among adolescents in Kasaragod District, Kerala.Methods: We selected 470 adolescents (mean age 16.6 years, male 53.8%) through multi-stage cluster sampling from higher secondary schools of Kasaragod district. Self-administered questionnaires were used, and anthropometric measurements were taken using standard techniques and protocols. Tobacco use, alcohol consumption, low fruits and vegetable consumption, inadequate physical activity, extra salt intake, overweight, consumption of soft drinks and packed foods were the eight NCD risk factors included. Multinomial logistic regression analysis was done to find out the factors associated with one, two and three or more NCD risk factors.Results: Risk factor clusters with two risk factors (dyads) and three risk factors (triads) were observed in 163 (34.7%) and 102 (21.7%) of the sample, respectively. Adolescents residing in urban areas (odds ratio (OR) = 3.55; 95% confidence interval (CI) = 1.45-8.73), whose father’s education level was lower (OR = 3.54; 95% CI = 1.24-10.10), whose mother’s education was lower (OR= 4.13; 95% CI = 1.27-13.51), who had restrictions on physical activity (OR = 5.41; 95% CI = 1.20-24.30) and who did not have a kitchen garden (an area where fruits and vegetables are grown for domestic use) (OR=4.51;95% CI = 1.44-14.12) were more likely to have three or more NCD risk factors compared to their counterparts. Conclusions: Clustering of NCD risk factors was prevalent in more than half of the adolescents. Efforts are warranted to reduce multiple risk factors, focussing on children of low educated parents and urban residents. Parents of adolescents may be encouraged to have kitchen gardens and not to restrict adolescent’s physical activity.
Short-term metabolic resistance inductive effect of different agrochemical groups on Anopheles gambiae mosquitoes
Authors: Sadia Christabelle G. , Kouadio France-Paraudie A. , Fodjo Behi K. , Oyou Sebastien K. , Beatrice Adepo-Gourene A. , Koudou Benjamin G. , Mouhamadou Chouaïbou S. 
Published: June 2021

Background: In order to assess the impact of the different groups of agricultural pesticides used in Côte d'Ivoire on the increase of mosquitoes resistance to insecticides, the expression profiles of 7 P450 cytochromes and one GSTE2 of Anopheles gambiae involved in mosquito resistance to insecticides were studied. The goal of this study was to determine the effect of short exposure of mosquito larvae to different groups of agricultural pesticides on mosquito resistance. Methods: Three groups of pesticides were selected: (i) agricultural insecticide solutions, (ii) none-insecticide pesticide solutions (a mixture of herbicides and fungicides), and (iii) a mixture of the first two. A fourth non-pesticide solution was used as a control. Four groups of each stage 2 larvae (strain Kisumu, male and female) were exposed to 20% concentrated solution for 24 hours. Susceptibility tests for dichlorodiphenyltrichloroethane (DDT) and Deltamethrin were carried out on adults aged 2-5 days. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was performed to quantify the expression of eight metabolic genes involved in mosquito resistance to insecticides. Results: Susceptibility to DDT showed a similar increase in the time required to knock down 50% of mosquitoes (kdt50) in l colonies exposed to insecticides and none-insecticides compared to the control colony. As for deltamethrin, kdt50 was higher in the colonies exposed to insecticides and the pesticide mixture compared to the colony exposed to none-insecticides. Of all the genes studied in all colonies, except for CYP6P1 induced only in the colony consisting of the pesticide mixture, no genes were induced. Conclusions: This study confirmed that induction is influenced by the duration, the concentration of the solution and the type of xenobiotic used as an inducer. The overexpression of CYP6P1 confirmed the inductive effect that a short exposure of mosquito larvae to agricultural pesticides could have.
Broadband ultraviolet-visible frequency combs from cascaded high-harmonic generation in quasi-phase-matched waveguides
Authors: Rutledge Jay , Catanese Anthony , Hickstein Daniel D. , Diddams Scott A. , Allison Thomas K. , Kowligy Abijith S. 
Published: June 2021

High-harmonic generation (HHG) provides short-wavelength light that is useful for precision spectroscopy and probing ultrafast dynamics. We report efficient, phase-coherent harmonic generation up to the ninth order (333 nm) in chirped periodically poled lithium niobate waveguides driven by phase-stable

≤

12

n
J

, 100 fs pulses at 3 µm with 100 MHz repetition rate. A mid-infrared to ultraviolet-visible conversion efficiency as high as 10% is observed, among an overall 23% conversion of the fundamental to all harmonics. We verify the coherence of the harmonic frequency combs despite the complex highly nonlinear process. Accommodating the extreme spectral bandwidth, numerical simulations based on a single broadband envelope equation with only quadratic nonlinearity give estimates for the conversion efficiency within approximately 1 order of magnitude over a wide range of experimental parameters. From this comparison between theory and experiment, we identify a dimensionless parameter capturing the competition between three-wave mixing and group-velocity walk-off of the harmonics that governs the cascaded HHG physics. We also gain insights into spectral optimization via tuning the waveguide poling profile and pump pulse parameters. These results can inform cascaded HHG in a range of different platforms.
General health of patients with diabetic macular edema—The LIPSIA study
Authors: Busch Catharina , Katzmann Julius L. , Jochmann Claudia , Unterlauft Jan Darius , Vollhardt Daniela , Wiedemann Peter , Laufs Ulrich , Rehak Matus 
Published: June 2021

Purpose
Cardiovascular risk factors such as hypertension or dyslipidemia can influence the incidence and progression of diabetic retinopathy (DR) and diabetic macular edema (DME). The aim of this study is to describe the comorbidities in patients with DME.

Methods
Prospective, monocentric observational study. Patients presenting for the treatment of DME received laboratory and clinical examinations including 24-hour blood pressure measurement.

Results
Seventy-five consecutive patients were included in the study. The mean age was 61.0 ± 14.5 years, and 83% had type 2 diabetes. The mean body mass index (BMI) was 32.8 ± 6.0 kg/m2. Overweight (BMI ≥ 25 kg/m2) was present in 92% of all patients. HbA1c values were > 7.0% in 57%. Although 87% of the patients already received antihypertensive therapy, the blood pressure (BP) of 82% was still above the recommended target values of systolic < 140 mmHg and diastolic < 80 mmHg. An insufficient nocturnal fall of the systolic BP (< 10%, non-dipping or reverse dipping) was observed in 62%. In 83% of the patients the glomerular filtration rate was ≤ 90 ml/min/1.73m2. Despite 65% of the cohort already receiving lipid-lowering therapy, LDL cholesterol was above the target value of 1.4 mmol/l in 93%. All patients had at least one cardiovascular risk factor in addition to diabetes (overweight, hypertension, insufficient nocturnal BP fall, dyslipidemia, or renal dysfunction) and 86% had ≥ 3 risk factors.

Conclusion
DME patients are characterized by highly prevalent cardiovascular risk factors that are poorly controlled. These comorbidities reduce the prognosis and negatively influence existing DR and DME. The data reveal an important opportunity for improving patient care by interaction of the ophthalmologist with the general practitioner and internal specialists for the detection and treatment of these conditions.
Hybrid 2-[18F] FDG PET/MRI in premanifest Huntington’s disease gene-expansion carriers: The significance of partial volume correction
Authors: Hellem Marie N. N. , Vinther-Jensen Tua , Anderberg Lasse , Budtz-Jørgensen Esben , Hjermind Lena E. , Larsen Vibeke Andrée , Nielsen Jørgen E. , Law Ian 
Published: June 2021

Background
Huntington’s disease (HD) is an inherited, progressive neurodegenerative disease that has no cure. Striatal atrophy and hypometabolism has been described in HD as far as 15 years before clinical onset and therefore structural and functional imaging biomarkers are the most applied biomarker modalities which call for these to be exact; however, most studies are not considering the partial volume effect and thereby tend to overestimate metabolic reductions, which may bias imaging outcome measures of interventions.

Objective
Evaluation of partial volume effects in a cohort of premanifest HD gene-expansion carriers (HDGECs).

Methods
21 HDGECs and 17 controls had a hybrid 2-[18F]FDG PET/MRI scan performed. Volume measurements and striatal metabolism, both corrected and uncorrected for partial volume effect were correlated to an estimate of disease burden, the CAG age product scaled (CAPS).

Results
We found significantly reduced striatal metabolism in HDGECs, but not in striatal volume. There was a negative correlation between the CAPS and striatal metabolism, both corrected and uncorrected for the partial volume effect. The partial volume effect was largest in the smallest structures and increased the difference in metabolism between the HDGEC with high and low CAPS scores. Statistical parametric mapping confirmed the results.

Conclusions
A hybrid 2-[18F]FDG PET/MRI scan provides simultaneous information on structure and metabolism. Using this approach for the first time on HDGECs, we highlight the importance of partial volume effect correction in order not to underestimate the standardized uptake value and thereby the risk of overestimating the metabolic effect on the striatal structures, which potentially could bias studies determining imaging outcome measures of interventions in HDGECs and probably also symptomatic HD.
Evaluation of liver enzyme elevations and hepatotoxicity in patients treated with checkpoint inhibitor immunotherapy
Authors: Cunningham Morven , Iafolla Marco , Kanjanapan Yada , Cerocchi Orlando , Butler Marcus , Siu Lillian L. , Bedard Philippe L. , Ross Kendra , Hansen Bettina , Spreafico Anna , Feld Jordan J. 
Published: June 2021

Background and aims
Immune checkpoint inhibitors (ICI) are increasingly used in cancer therapy. Elevated liver enzymes frequently occur in patients treated with ICI but evaluation is poorly described. We sought to better understand causes of liver enzyme elevation, investigation and management.

Methods
Patients treated with anti-PD-1, PDL-1 or CTLA-4 therapy in Phase I/II clinical trials between August 2012 and December 2018 were included. Clinical records of patients with significant liver enzyme elevations were retrospectively reviewed.

Results
Of 470 ICI-treated patients, liver enzyme elevation occurred in 102 (21.6%), attributed to disease progression (56; 54.9%), other drugs/toxins (7; 6.9%), other causes (22; 21.6%) and ICI immunotoxicity (17; 16.7%; 3.6% of total cohort). Immunotoxicity was associated with higher peak ALT than other causes of enzyme elevation (N = 17; M = 217, 95% CI 145–324 for immunotoxicity, N = 103; M = 74, 95% CI 59–92 for other causes; ratio of means 0.34, 95% CI 0.19–0.60, p = <0.001) and higher ALT:AST ratio (M = 1.27, 95% CI 0.78–2.06 for immunotoxicity, M = 0.69, 95% CI 0.59–0.80 for other causes, ratio of means 0.54, 95% CI 0.36–0.82, p = 0.004). Immunotoxicity was more often seen in patients with prior CPI exposure (41.2% of immunotoxicity vs 15.9% of patients without, p = 0.01), anti-CTLA-4 –containing ICI treatments (29.4% of immunotoxicity vs 6.8% of patients without, p = <0.001) and other organ immunotoxicity (76.5% of immunotoxicity vs 19.2% of patients without, p = <0.001). Cause for enzyme elevation was established in most patients after non-invasive investigation. Liver biopsy was reserved for four patients with atypical treatment response.

Conclusions
Liver enzyme elevation is common in patients receiving ICI, but often has a cause other than immunotoxicity. A biochemical signature with higher ALT and ALT/AST ratio, a history of prior ICI exposure and other organ immunotoxicities may help to identify patients at a higher likelihood of immunotoxicity. Liver biopsy can be safely deferred in most patients. We propose an approach to diagnostic evaluation in patients with liver enzyme elevations following ICI exposure.
Sickle-trait hemoglobin reduces adhesion to both CD36 and EPCR by Plasmodium falciparum-infected erythrocytes
Authors: Petersen Jens E. V. , Saelens Joseph W. , Freedman Elizabeth , Turner Louise , Lavstsen Thomas , Fairhurst Rick M. , Diakité Mahamadou , Taylor Steve M. 
Published: June 2021

Sickle-trait hemoglobin protects against severe Plasmodium falciparum malaria. Severe malaria is governed in part by the expression of the Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) that are encoded by var genes, specifically those variants that bind Endothelial Protein C Receptor (EPCR). In this study, we investigate the effect of sickle-trait on parasite var gene expression and function in vitro and in field-collected parasites. We mapped var gene reads generated from RNA sequencing in parasite cultures in normal and sickle-cell trait blood throughout the asexual lifecycle. We investigated sickle-trait effect on PfEMP1 interactions with host receptors CD36 and EPCR using static adhesion assays and flow cytometry. Var expression in vivo was compared by assembling var domains sequenced from total RNA in parasites infecting Malian children with HbAA and HbAS. Sickle-trait did not alter the abundance or type of var gene transcripts in vitro, nor the abundance of overall transcripts or of var functional domains in vivo. In adhesion assays using recombinant host receptors, sickle-trait reduced adhesion by 73–86% to CD36 and 83% to EPCR. Similarly, sickle-trait reduced the surface expression of EPCR-binding PfEMP1. In conclusion, Sickle-cell trait does not directly affect var gene transcription but does reduce the surface expression and function of PfEMP1. This provides a direct mechanism for protection against severe malaria conferred by sickle-trait hemoglobin.
Trial Registration: ClinicalTrials.gov Identifier: NCT02645604.
Students' preference for the use of gamification in virtual learning environments
Authors: Acosta-Medina Julieth Katherin , Torres-Barreto Martha Liliana , Cárdenas-Parga Andrés Felipe 
Published: June 2021

Virtual education faces tremendous challenges such as lack of motivation and high dropout rates. However, one solution to this problem is the incorporation of digital pedagogical strategies based on gamification, which promote interest, facilitate the learning process, and contribute to reducing dropout. In this sense, we evaluated the student's preference for using the gamified tool Didactic City, by using a quantitative methodology and structural equation models. This preference included fundamental factors such as utility, knowledge, engagement, enjoyment, motivation, and ease of use. The results are expected to contribute to create a more informed decision-making process not only for video game designers but also for pedagogues, and educational managers who could perform game improvements, redesigns, inclusion, or exclusion of individual elements that would make students prefer to use gamification tools in the future. The results indicate that the students' utility, the enjoyment generated by the tool, and the improvement of knowledge are the critical factors in terms of preference for using gamified tools in virtual learning environments.

Implications for policy and practice:

In virtual learning environments, higher education institutions and instructors can include gamified tools to create pleasant environments that increase students' motivation and facilitate learning.
Designers and developers of gamified educational tools should measure their acceptance, as this factor is decisive for fulfilling the purposes of these pedagogical tools.
Researchers could evidence more factors that influence the preference for the use of gamified educational tools.
Obligations de travail dans les économies palatiales du Bronze récent
Authors: Rougemont Françoise , Vita Juan-Pablo 
Published: June 2021

AbstractPalatial economic archives from various regions — from the Aegean world to Mesopotamia — and from various periods of the Bronze Age, attest to the use by palatial administrations of procedures in which workers were obliged to perform a task, whether craft or agricultural, on behalf of the palace. This article examines the possibility that such a procedure existed also in Ugarit, since a group of administrative texts relating to metals appear comparable to these systems of work-assignments. The material from Ugarit and the conclusions reached allow, then, a comparison with the system of work-assignment attested in the Mycenaean texts and calledta-ra-si-ja. Mycenaean and Ugaritic documentations present typological, structural and chronological analogies, which add to the interest of the comparison.
“Both my Cleansed Hands”
Authors: Wagensonner Klaus 
Published: June 2021

AbstractThis short contribution edits for the first time a small fragment housed in the Horn Archaeological Museum at St Andrews University, Berrien Springs, Michigan. This fragment contains the meagre remains of what once was a letter addressed to the goddess Ištar sent by a woman named Abī-tukultī. Literary letters of the Old Babylonian period are fairly scarce, and the present text is the first known letter to Ištar and hence a welcome addition to the corpus.
Self-Control Preferences and Status-Quo Bias
Authors: Barokas Guy 
Published: June 2021

Abstract
In a setting of choice with an observable status quo, we model an agent who struggles with temptation by exercising (costly) self-control, and who views the status quo as a commitment opportunity that allows him to avoid the self-control costs incurred when making an active choice. Our model is rational in that the agent always maximizes the same ex-post utility function; hence, when the standard indirect utility property holds, the model reduces to classic rational choice model. However, when we allow for costly self-control, our theory provides a rationale for three well-documented phenomena that cannot be captured by the standard model: the status-quo bias, the compromise effect, and the satisficing choice procedure (when ignoring the information on the status quo). A notable feature of our theory is that while it relaxes the indirect utility property, it still allows for a complete identification of an agent’s preference relation over menus. This is found to be important in many practical situations.