bluuebunny/crossref_metadata_2025_split huggingface dataset:
A retrospective head‐to‐head comparison of the Lugano classification and PERCIST for FDG‐PET/CT response assessment in diffuse large B‐cell lymphoma
Authors: Nielsen Nicklas B. , Gerke Oke , Nielsen Anne L. , Juul‐Jensen Karen , Larsen Thomas S. , Møller Michael B. , Hildebrandt Malene G. 
Published: July 2023

AbstractBackgroundDiffuse large B‐cell lymphoma (DLBCL) is the most common form of lymphoma. European guidelines recommend FDG‐PET/CT for staging and end of treatment (EOT) response assessment, mid‐treatment response assessment is optional. We compared the Lugano classification and PET Response Criteria In Solid Tumours (PERCIST) for FDG‐PET/CT response assessment in DLBCL head‐to‐head.MethodsWe retrospectively included patients with DLBCL who underwent first‐line R‐CHOP(‐like) therapy (2013−2020). Interim and EOT FDG‐PET/CT response were reevaluated using the Lugano classification and PERCIST. Response was dichotomized into complete metabolic response (CMR) versus non‐CMR (interim and EOT) and responders versus nonresponders (interim only). The cutoff for nonresponse at interim was a Deauville score of 5 (DS5) with the Lugano classification and a partial metabolic response with ≤66% reduction in SULpeak using PERCIST (PERCIST66).ResultsIn multivariable Cox regression (N = 170), DS5 at interim, PERCIST66 at interim, non‐CMR at EOT with the Lugano classification and non‐CMR at EOT with PERCIST were predictive of progression‐free survival (PFS). The Lugano classification and PERCIST agreed perfectly at interim and EOT and with 98.4% for the identification of nonresponders at interim. The accuracy for predicting events within 2 years of diagnosis was 84.2% for DS‐5 at interim, 87.6% for PERCIST66 at interim, 86% for non‐CMR with the Lugano classification at EOT and 83.3% for non‐CMR with PERCIST at EOT.ConclusionThe Lugano classification and PERCIST were equally predictive of PFS. Nonresponse at interim and non‐CMR at EOT were predictive of poor PFS with comparable accuracy for predicting events within 2 years.
Relationship between the strain measures of left atrial function and heart failure worsening
Authors: Diomede Davide , Terazzi Erica , Diomede Nicolangelo , Alcidi Gianmarco , Pugliese Rosanna , Ioannoni Sara , Romano Matteo , Granatiero Michele , Di Terlizzi Vito , Correale Michele , Di Biase Matteo , Brunetti Natale Daniele , Iacoviello Massimo 
Published: July 2023

AbstractBackgroundTwo‐dimensional speckle tracking evaluation (2D‐STE) is a useful tool to evaluate the complexity of atrial function by the analysis of the different phases of atrial deformation and by the combination with Doppler measurements of diastolic function.Aim of the studyTo evaluate the role of the left atrial (LA) strain parameters to predict worsening chronic heart failure (CHF).MethodsWe enrolled outpatients affected by CHF referred to our heart failure unit. Each patient underwent a medical visit, an electrocardiogram (ECG), and an echocardiographic examination. LA function was assessed by 2D‐STE. The three phases of LA strain, that is, the reservoir (LAr), the conduit (LAcd), and the contraction (LAct)—were evaluated. Moreover, the ratio between E and LAr (E/LAr) and those between LAr and septal (LAr/Ees), lateral (LAr/Eel), and septal‐lateral (LAr/Eem) E/e’ were measured. During follow‐up, the events related to worsening of heart failure were evaluated.ResultsTwo hundred eleven patients were enrolled. During a mean follow‐up of 14 ± 7 months, 37 patients showed at least one event related to heart failure worsening. At univariate Cox regression analysis, LAr, LAcd, LAct, E/LAr, LAr/Ees, LAr/Eel, and LAr/Eem were all associated with events related to heart failure worsening, but at multivariate regression analyses, only LAr (Hazard Ratio, HR: .95; 95% Confidence Interval, CI: .92–.99; p: .031), LAct (HR: 1.06; 95% CI: 1.01–1.12; p: .027), E/LAr (HR: 1.10; 95%CI: 1.0–1.16; p < .001), LAr/Ees (HR: .57; 95% CI: .37–.87; p: .010), and LAr/Eem (HR: .71; 95% CI: .53–.96; p: .026) remained significantly associated with the events. Finally, in a predictive model including the other relevant echocardiographic parameters LAr < 18%, LAct > −10.0%, LAr/Ees < 1.28, and E/LAr > 3.70 were associated with a statistically significant overall net reclassification improvement.ConclusionsIn CHF patients, the measure of the LA reservoir and contraction by 2D‐STE is independently associated with heart failure worsening, but the accuracy in predicting the events is even greater when the reservoir is combined with the Doppler measures of diastolic function.
Subclones with variants of uncertain clinical significance might contribute to ineffective hemopoiesis and leukemia predisposition
Authors: Giudice Valentina , Serio Bianca , Errichiello Santa , Ferrara Idalucia , Galdiero Alessandra , Bertolini Angela , Visconti Roberta , De Novellis Danilo , Guariglia Roberto , Luponio Serena , Morini Denise , Della Corte Anna Maria , Sessa Anna Maria , Verdesca Francesco , Langella Maddalena , Izzo Barbara , Selleri Carmine 
Published: July 2023

AbstractBackgroundSplicing modifications, genomic instability, and hypomethylation are central mechanisms promoting myelodysplasia and acute myeloid leukemia (AML). In this real‐life retrospective study, to elucidate pathophysiology of clonal hemopoiesis in hematological malignancies, we investigated clinical significance of mutations in leukemia‐related genes of known pathogenetic significance and of variants of uncertain clinical significance (VUS) in a cohort of patients with MDS and AML.MethodsA total of 59 consecutive subjects diagnosed with MDS, 48 with AML, and 17 with clonal cytopenia with unknown significance were screened for somatic mutations in AML‐related genes by next‐generation sequencing.ResultsWe showed that TET2, SETBP1, ASXL1, EZH2, RUNX1, SRSF2, DNMT3A, and IDH1/2 were commonly mutated. MDS patients also showed a high genetic complexity, especially for SETBP1. Moreover, the presence of SETBP1 wild‐type or two or more simultaneous VUS variants identified a subgroup of AML and MDS patients with better outcome, while the presence of single SETBP1 VUS variant was related to a worse prognosis, regardless TET2 mutational status.ConclusionsIn conclusions, we linked both pathogenic and VUS variants in AML‐related genes to clonal hematopoiesis; therefore, we proposed to consider those variants as prognostic markers in leukemia and myelodysplasia. However, further studies in larger prospective cohorts are required to validate our results.
Is the cingulate island sign a marker for early dementia conversion in Parkinson's disease?
Authors: Chung Seok Jong , Kim Su Hong , Park Chan Wook , Lee Hye Sun , Kim Yun Joong , Lee Phil Hyu , Jeong Yong , Sohn Young H. 
Published: July 2023

AbstractBackgroundTo investigate whether the cingulate island sign (CIS) ratio (i.e., the ratio of regional uptake in the posterior cingulate cortex relative to the precuneus and cuneus on cerebral perfusion scans) is associated with early dementia conversion in Parkinson's disease (PD).MethodsWe enrolled 226 patients with newly diagnosed PD and 48 healthy controls who underwent dual‐phase 18F‐FP‐CIT PET scans. Patients with PD were classified into three groups according to the CIS ratio on early‐phase 18F‐FP‐CIT PET images: a PD group with CIS or high CIS ratios (PD‐CIS; n = 96), a PD group with inverse CIS or low CIS ratios (PD‐iCIS; n = 40), and a PD group consisting of the remaining patients with normal CIS ratios (PD‐nCIS; n = 90). We compared the risk of dementia conversion within a 5‐year time point between the groups.ResultsThere were no significant differences in age, sex, education, or baseline cognitive function between the PD groups. The PD‐CIS group had higher Unified Parkinson's Disease Rating Scale (UPDRS) motor scores and more severely decreased dopamine transporter availability in the putamen. The PD‐iCIS group had a smaller hippocampal volume compared with the other groups. The risk of dementia conversion in the PD‐CIS group did not differ from that in the PD‐iCIS and PD‐nCIS groups. Meanwhile, the PD‐iCIS group had a higher risk of dementia conversion than the PD‐nCIS group.ConclusionThe results of this study suggest that inverse CIS, rather than CIS, is relevant to early dementia conversion in patients with PD.
Impact on carbamazepine usage and cutaneous adverse reactions before and after the reimbursement of HLA‐B*1502 genotyping in Taiwan, 2000–2017: A nationwide longitudinal study
Authors: Chang Bao‐Luen , Liu Jia‐Rou , Chang Shu‐Hao , See Lai‐Chu 
Published: July 2023

AbstractObjectiveThe HLA‐B*1502 allele is strongly associated with carbamazepine (CBZ)‐induced Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in the Han Chinese population. This study investigated the impact of HLA‐B*1502 screening on CBZ utilization and rates of severe cutaneous allergic reactions (SCARs) and SJS/TEN over time in Taiwan, where screening for HLA‐B*1502 genotyping before prescribing CBZ was reimbursed in June 2010.MethodsUsing the Taiwan National Health Insurance Research Database, we analyzed 13 277 457 episodes of seeking treatment for epilepsy or neuralgia between 2000 and 2017. Episodes were categorized into quarters based on treatment time. Propensity score‐based stabilized weighting (PSSW) ensured well‐balanced covariates. The difference in 3‐month SCAR and SJS/TEN rates between phase 2 (2011–2017) and phase 1 (2000–2009) was examined using a one‐sample Z‐test. Pearson correlation coefficients assessed the association between screening rate, the number of CBZ users and nonusers, and SCAR and SJS/TEN rates after HLA‐B*1502 genotyping.ResultsCBZ prescriptions reduced from 7% (2000–2003) to 6% (2004–2010) and 4% (2011–2017). The screening rates of CBZ nonusers and CBZ users increased from 0%, .5% in 2011 to .8%, 16% in 2017, respectively. After PSSW, the mean 3‐month SCAR incidence rates (per 10 000 episodes) significantly decreased from phase 1 to phase 2 for CBZ users (6.91 vs. 3.09, p < .0001) and nonusers (1.96 vs. 1.65, p < .0001). SJS/TEN incidence rates (per 10 000 episodes) significantly decreased from phase 1 to phase 2 for CBZ users (2.94 vs. 1.93, p < .0001) but not for nonusers (.71 vs. .74, p = .1492). In phase 2, SCAR incidence rates were significantly and negatively correlated with the screening rate for both CBZ users (r = −.38, p = .0342) and nonusers (r = −.80, p < .001). No significant correlation was found between SJS/TEN incidence rates and screening rates.SignificanceRecognizing HLA‐B*1502 allele and avoiding CBZ therapy in HLA‐B*1502‐positive patients is critical for preventing CBZ‐induced severe adverse events.
Rafoxanide, a salicylanilide anthelmintic, interacts with human plasma protein transthyretin
Authors: Yokoyama Takeshi , Mizuguchi Mineyuki , Nabeshima Yuko , Nakagawa Yusuke , Okada Takuya , Toyooka Naoki , Kusaka Katsuhiro 
Published: July 2023

Transthyretin (TTR) is a carrier protein for thyroid hormone thyroxine (T4) in plasma, placental cytosol, and cerebrospinal fluid. While the potential toxicity of small molecules that compete with T4 for binding to TTR should be carefully studied, these small molecules can also serve as anti‐ATTR amyloidosis drugs by stabilizing the TTR structure. Here, we demonstrated that rafoxanide, an EU‐approved anthelmintic drug for domesticated animals, binds to the T4‐binding site of TTR. An intrinsic fluorescence quenching assay showed that rafoxanide also binds to the thyroid hormone‐related proteins, including serum albumin and thyroid hormone receptor β. Rafoxanide strongly inhibited TTR amyloidogenesis in fibrillization assay, but the binding of rafoxanide to TTR was interfered with in human plasma, probably due to interactions with thyroid hormone‐related proteins. Protein crystallography provided clues for the optimization of binding affinity and selectivity. Our findings emphasize the importance of considering rafoxanide as both a possible thyroid‐disrupting chemical and a lead compound for the development of new ATTR amyloidosis inhibitors.
An equivalent cohesive zone model for a wide range of ductile and brittle adhesives
Authors: Noruzi Mohammad , Khoramishad Hadi 
Published: July 2023

AbstractThis paper aims to propose an equivalent trapezoidal traction–separation law (ET‐TSL) of the cohesive zone model applicable to a wide range of ductile and brittle adhesives using equivalent and fictitious material concepts. The ET‐TSL can reduce the analysis time and cost of complex problems without degrading the prediction accuracy. To experimentally validate the proposed ET‐TSL, double‐cantilever beam (DCB) samples were fabricated with glass fiber‐reinforced polymer substrates and a highly ductile adhesive and then tested. The fracture behavior of the specimens was modeled using the proposed ET‐TSL. Moreover, the accuracy and comprehensiveness of the proposed model were verified by employing the proposed ET‐TSL for different adhesive joints made of different adhesives ranging from brittle to ductile adhesives and different substrates found in the literature. It was found that the proposed ET‐TSL can provide reasonable accuracy in simulating the fracture response of different types of adhesive joints with brittle and ductile adhesives.
Dried blood spot‐based host genome analysis technique targeting pathological associations with hepatitis B: Development and clinical application in the Cambodian population
Authors: Setoyama Hiroko , Nishida Nao , Nagashima Shintaro , Ko Ko , Yamazoe Taiji , Tanaka Yasuhito , Mizokami Masashi , Tanaka Junko , Kanto Tatsuya 
Published: July 2023

AbstractAimReports of patients with hepatitis B have highlighted associations between polymorphisms in the human leukocyte antigen (HLA)‐DPB1, CXCL13, and CXCR5 genes and disease pathology. Owing to its potential to contribute to the development of new diagnostic and therapeutic methods, we aimed to establish a reliable host genome analysis technique that can be used in countries with inadequate infrastructure.MethodWe compared multiple commercially available kits for dried blood spot (DBS)‐based sample collection to develop a basic DBS‐based host genome analysis technique. We then collected blood samples from Cambodian patients with hepatitis B and performed single‐nucleotide polymorphism genotyping and HLA allele typing by the DBS system.ResultWe were able to perform single‐nucleotide polymorphism genotyping and HLA allele typing with host DNA samples obtained using a combination of a HemaSpot™ filter paper‐based device and a SMITEST® EX‐R&D DNA extraction kit. The accuracy of genotyping using samples obtained by this method was not inferior to one using samples obtained by venipuncture. In the Cambodian population, significant associations of HLA‐DPB1*04:01 with protection against chronic hepatitis B virus (HBV) infection, and HLA‐DPB1*05:01 and HLA‐DPB1*13:01 with susceptibility to chronic HBV infection were identified.ConclusionBased on the DBS system, we clarified the associations of HLA‐DPB1 alleles with chronic HBV infection in the Cambodian population for the first time. Because the DBS is a low‐cost, durable, transportable, and easy‐to‐handle modality, genetic analysis based on the DBS system is a feasible strategy for obtaining a deeper understanding of HBV epidemiology, especially in middle‐ or low‐income countries.
Predictions based on phylogeography and climatic niche modelling depict an uncertain future scenario for giant blister beetles (Berberomeloe, Meloidae) facing intensive greenhouse expansion and global warming
Authors: Sánchez‐Vialas Alberto , Calatayud‐Mascarell Arnau , Recuero Ernesto , Ruiz José L. , García‐París Mario 
Published: July 2023

Abstract
Large‐scale agricultural and tourism development are the main threats to biodiversity in south‐eastern Spain. Species with low dispersal abilities, such as some endemic insects from this region, are particularly vulnerable to fragmentation and loss of genetic and morphological diversity. Here, we studied the current and future threat of climate and land‐use change on the intraspecific diversity of one such group of endemics, the giant blister beetles of the Berberomeloe insignis species group.
Using a phylogeographic approach and morphometrics, we identified intraspecific variation within the B. insignis species group. These data were coupled with ecological niche modelling (ENM) to determine the effect of agricultural and climate change on the connectivity across phylogroups.
We identified a marked geographic structure within B. insignis, with the time to the most recent common ancestor (TMRCA) of the two main mtDNA clades dating back to 2.1 Ma. Cyto‐nuclear discordances found across parapatric populations suggest past events of genetic introgression. B. insignis presents a head pattern that is geographically structured and mostly congruent with the four mitochondrial lineages. In contrast, diversification within Berberomeloe tenebrosus is more recent, dating back to less than 1 Ma. Future ENMs highlight the role of mountains as potential refugia under a climate warming scenario but predict extinctions in the lowlands.
Based on our analyses, two lineages of B. insignis are threatened and should be urgently considered as independent conservation units, and their current geographic distribution areas protected to conserve, at the very least, a portion of the species' evolutionary heritage.
Government Expenditure on the Public Education System
Authors: Fu Chao , Ishimaru Shoya , Kennan John 
Published: July 2023

AbstractWe investigate equilibrium impacts of federal policies such as free‐college proposals, taking into account that human capital is cumulative and that state governments have resource constraints. In our model, a state government cares about household welfare and aggregate educational attainment. The government chooses income tax rates, per‐student expenditures on K‐12 and college education, college tuition, and the provision of other public goods. We estimate the model using U.S. data. Our simulations suggest that free‐college policies would decrease state expenditure on education. More students would obtain college degrees. Most households would “pay” for the free‐college policies through negative welfare effects.
Speaking anxiety and task complexity effects on second language speech
Authors: Mora Joan C. , Mora‐Plaza Ingrid , Bermejo Miranda Gonzalo 
Published: July 2023

AbstractThe association between speaking anxiety and L2 speech production, including L2 pronunciation, remains largely under‐researched, especially in relation to task complexity. The present study investigates the effect of task complexity on speaking anxiety and their impact on specific dimensions of L2 speech production: speaking fluency (speed, breakdown, and repair) and accuracy (grammar, lexis and pronunciation); and global assessments of L2 speaking performance: accentedness and comprehensibility. Forty‐two Spanish learners of English performed simple and complex versions of a monologic oral narrative task. The results indicated that task complexity affected learners’ anxiety levels and was detrimental to their L2 speaking fluency, pronunciation accuracy, and accentedness. Moreover, higher self‐perceived anxiety was associated with lower breakdown fluency and less lexico‐grammatical accuracy. Last, once the contributions of L2 proficiency and working memory were controlled for, anxiety accounted for a significant 13%–15% of variance in breakdown fluency.
Comparison of nutritional and trace element concentrations in some Sri Lankan traditional rice varieties
Authors: Kodikara Chamali , Vidanarachchi Janak K. , Nissanka Sarath P. , Bergquist Jonas , Pettersson Jean , Ubhayasekera Sarojini Jayantha Kumari A. 
Published: July 2023

SummaryRecently, traditional rice cultivars have become more popular than new, enhanced rice varieties, with the main focus being on their health benefits. Few rice cultivars have been thoroughly studied to understand their nutritional and health benefits. Inductively coupled plasma atomic emission/mass spectroscopy methods were used to determine the concentrations of 24 key nutrients and trace elements in 104 traditional rice types (Oryza sativa L.) grown in Sri Lanka. Compared to the Codex Alimentarius provisional tolerable daily intake for 24 different elements, the concentrations of toxic elements such as As, Cd, Pb and Cr were significantly lower (P < 0.05), and most of the nutritional elemental concentrations were substantially higher (P < 0.05) in evaluated traditional rice varieties. Furthermore, Pb, Bi, B, K, Mg, S, Zn and Fe concentrations among traditional rice varieties were not substantially different (P > 0.05). Notably, several traditional rice varieties (i.e. Rathu Heenati, Pragathi Wee, Weda Heenati, etc.) contained significantly high levels of selenium (≈250 μg L−1 DM, P < 0.05), an important trace element that is deficient in the diets of 1 billion people globally.
Bone‐modifying agents are protective for symptomatic skeletal events in Radium‐223 treatment
Authors: Blas Leandro , Shiota Masaki , Matsumoto Takashi , Hori Yoshifumi , Nakamura Motonobu , Seki Narihito , Kuroiwa Kentaro , Yokomizo Akira , Morokuma Futoshi , Kiyoshima Keijiro , Eto Masatoshi 
Published: July 2023

IntroductionRadium‐223 (Ra‐223) dichloride therapy increases overall survival and delays time to the first symptomatic skeletal event (SSE) in patients with castration‐resistant prostate cancer (CRPC) and bone metastases. Bone‐modifying agents (BMA) reduce SSE in patients with bone metastasis, but there is little information on their use with Ra‐223. This study aimed to investigate the effect of BMA on SSE in patients with bone metastatic CRPC treated with Ra‐223 in real‐world practice.MethodsWe included 73 patients treated with Ra‐223 from 10 institutions in Japan. Time to the first SSE was estimated using the Kaplan–Meier method and compared between groups using the log‐rank test. We used univariate analysis to ascertain the association between variables and SSE.ResultsDuring a median follow‐up of 12.7 months (interquartile range, 7–21.7), 12 (16.4%) patients presented SSE. Age and BMA use were different between men with and without SSE. The 1‐year SSE‐free survival rate from Ra‐223 treatment initiation was 82.4% (95% CI, 69.4%–90.2%). BMA use was associated with favorable SSE‐free survival (hazard risk, 0.23; 95% confidence interval, 0.061–0.85; p = 0.027). Two (4.7%) and seven (23.3%) patients presented symptomatic pathological bone fracture in groups with and without BMA use, respectively (p = 0.017).ConclusionThis study stresses the importance of BMA use in patients with CRPC and bone metastases in Ra‐223 treatment.