bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypervitaminosis D Secondary to a CYP24A1 Loss‐of‐Function Mutation: An Unusual Cause of Hypercalcemia in Two Siblings
Authors: Collins Lucy , Boehm Emma , Luxford Catherine , Clifton‐Bligh Roderick , Grill Vivian 
Published: August 2023

ABSTRACTHypervitaminosis D as a cause of hypercalcemia may be due to vitamin D intoxication, granulomatous diseases, or abnormalities of vitamin D metabolism. The CYP24A1 gene encodes for the 24‐hydroxylase enzyme, which is responsible for the catabolism of 25‐hydroxyvitamin D (25(OH)D) and 1,25‐dihydroxyvitamin D (1,25(OH)2D). Mutations in CYP24A1 can result in elevated 1,25(OH)2D causing parathyroid hormone (PTH)‐independent hypercalcemia, hypercalciuria, nephrolithiasis, and nephrocalcinosis. We present the cases of two siblings exhibiting hypercalcemia secondary to a CYP24A1 loss‐of‐function mutation. Case 1 presented initially with PTH‐dependent hypercalcemia, with localization of a left upper parathyroid adenoma on parathyroid technetium sestamibi (99mTc‐MIBI) uptake study. Despite parathyroidectomy (180 mg adenoma), hypercalcemia, hypercalciuria, and low normal PTH levels persisted. A repeat parathyroid 99mTc‐MIBI uptake study localized a second adenoma and a right inferior parathyroidectomy was performed (170 mg adenoma). PTH subsequently became undetectable, however hypercalcemia and hypercalciuria persisted. A new presentation of PTH‐independent hypercalcemia found to be secondary to a CYP24A1 loss‐of‐function mutation in his sibling, Case 2, signaled the underlying cause. Cascade testing confirmed both siblings were homozygous for the pathogenic variant c.1186C>T, p.Arg396Trp (R396W) of CYP24A1 (NM_000782.5). In clinical practice CYP24A1 loss‐of‐function mutations should be considered in patients presenting with PTH‐independent hypercalcemia, hypercalciuria, and 1,25(OH)2D levels in the upper normal or elevated range. Although in our case assays of 24,25(OH)2D were not available, calculation of the 25(OH)D:24,25(OH)2D ratio can assist in the diagnostic process. Possible treatments to manage the risk of hypercalcemia in patients with a CYP24A1 loss‐of‐function mutation include avoidance of vitamin D oversupplementation and excessive sun exposure. Hydration and bisphosphonate therapy can be useful in managing the hypercalcemia. Although not utilized in our cases, treatment with ketoconazole, fluconazole, and rifampicin have been described as potential therapeutic options. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Effects of Moderate- to High-Impact Exercise Training on Bone Structure Across the Lifespan: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Ng Carrie-Anne , Gandham Anoohya , Mesinovic Jakub , Owen Patrick J , Ebeling Peter R , Scott David 
Published: August 2023

ABSTRACT
Moderate- to high-impact exercise improves bone mineral density (BMD) across the lifespan, but its effects on bone structure, which predicts fracture independent of areal BMD, are unclear. This systematic review and meta-analysis investigated effects of impact exercise on volumetric BMD (vBMD) and bone structure. Four databases (PubMed, Embase, SPORTDiscus, Web of Science) were searched up to March 2022 for randomized controlled trials (RCTs) investigating the effects of impact exercise, with ground reaction forces equal to or greater than running, compared with sham or habitual activity, on bone vBMD and structure. Bone variables were measured by quantitative computed tomography or magnetic resonance imaging at the tibia, radius, lumbar spine, and femur. Percentage changes in bone variables were compared among groups using mean differences (MD) and 95% confidence intervals (CI) calculated via random effects meta-analyses. Subgroup analyses were performed in children/adolescents (&lt;18 years), adults (18–50 years), postmenopausal women, and older men. Twenty-eight RCTs (n = 2985) were included. Across all studies, impact exercise improved trabecular vBMD at the distal tibia (MD = 0.54% [95% CI 0.17, 0.90%]), total vBMD at the proximal femur (3.11% [1.07, 5.14%]), and cortical thickness at the mid/proximal radius (1.78% [0.21, 3.36%]). There was no effect on vBMD and bone structure at the distal radius, femoral shaft, or lumbar spine across all studies or in any subgroup. In adults, impact exercise decreased mid/proximal tibia cortical vBMD (−0.20% [−0.24, −0.15%]). In postmenopausal women, impact exercise improved distal tibia trabecular vBMD (0.79% [0.32, 1.25%]). There was no effect on bone parameters in children/adolescents in overall analyses, and there were insufficient studies in older men to perform meta-analyses. Impact exercise may have beneficial effects on bone structure and vBMD at various skeletal sites, but additional high-quality RCTs in different age and sex subgroups are needed to identify optimal exercise protocols for improving bone health across the lifespan. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
A novel pyrene‐based “off–on” fluorescent probe with high selectivity and sensitivity for Hg2+
Authors: Liang Qingxiang , Zhou Wu , Wu Aibin , Shu Wenming , Yu Weichu 
Published: August 2023

AbstractIn this article, a novel “off–on” fluorescent probe 2‐(pyren‐1‐ylmethylene)‐1H‐indene‐1,3(2H)‐dione (PID) for Hg2+ was designed and synthesized. The selectivity, concentration titration, pH titration, time dependence, limit of detection, and recognition mechanism of PID for Hg2+ in CH3CH2OH/H2O solution were also investigated. The results indicated that PID exhibited high selectivity, sensitivity, and fast response to Hg2+, and the limit of detection was as low as 20.7 nmol/L. In addition, PID could work in a wide pH range, and the determination of Hg2+ in water samples showed that it could be used as a potential detection tool in practical application.
Hepatic stellate cells induce an inflammatory phenotype in Kupffer cells via the release of extracellular vesicles
Authors: Geng Yana , Wang Junyu , Serna‐Salas Sandra Alejandra , Villanueva Alejandra Hernández , Buist‐Homan Manon , Arrese Marco , Olinga Peter , Blokzijl Hans , Moshage Han 
Published: August 2023

AbstractLiver fibrosis is the response of the liver to chronic liver inflammation. The communication between the resident liver macrophages (Kupffer cells [KCs]) and hepatic stellate cells (HSCs) has been mainly viewed as one‐directional: from KCs to HSCs with KCs promoting fibrogenesis. However, recent studies indicated that HSCs may function as a hub of intercellular communications. Therefore, the aim of the present study was to investigate the role of HSCs on the inflammatory phenotype of KCs. Primary rat HSCs and KCs were isolated from male Wistar rats. HSCs‐derived conditioned medium (CM) was harvested from different time intervals (Day 0−2: CM‐D2 and Day 5−7: CM‐D7) during the activation of HSCs. Extracellular vesicles (EVs) were isolated from CM by ultracentrifugation and evaluated by nanoparticle tracking analysis and western blot analysis. M1 and M2 markers of inflammation were measured by quantitative PCR and macrophage function by assessing phagocytic capacity. CM‐D2 significantly induced the inflammatory phenotype in KCs, but not CM‐D7. Neither CM‐D2 nor CM‐D7 affected the phagocytosis of KCs. Importantly, the proinflammatory effect of HSCs‐derived CM is mediated via EVs released from HSCs since EVs isolated from CM mimicked the effect of CM, whereas EV‐depleted CM lost its ability to induce a proinflammatory phenotype in KCs. In addition, when the activation of HSCs was inhibited, HSCs produced less EVs. Furthermore, the proinflammatory effects of CM and EVs are related to activating Toll‐like receptor 4 (TLR4) in KCs. In conclusion, HSCs at an early stage of activation induce a proinflammatory phenotype in KCs via the release of EVs. This effect is absent in CM derived from HSCs at a later stage of activation and is dependent on the activation of TLR4 signaling pathway.
Recovery of pure nickel powder from petroleum refinery sludge via a process consisting of leaching, cementation, precipitation, solvent extraction, and chemical reduction
Authors: Wen Jiangxian , Lee Man Seung 
Published: August 2023

AbstractBACKGROUNDSludge resulting from petroleum refining contains metal oxides such as nickel, copper, aluminum, iron, zinc, calcium, and magnesium. Since the demand for nickel is increasing, a process was proposed to recover pure nickel metal powder from this sludge. In this study, leaching, cementation, precipitation, solvent extraction, and chemical reduction operations were carried out and employed for the recovery of nickel powder from sludge.RESULTSNickel oxide was first completely dissolved using 0.3 mol L−1 H2SO4 solution at a pulp density of 50 g L−1. The leaching solution contained Al(III), Ca(II), Cu(II), Fe(III), Mg(II), Ni(II), and Zn(II). Most of the copper, magnesium, nickel, and zinc were completely dissolved at this step. Copper(II) was removed by cementation with iron powder. After oxidizing Fe(II) to Fe(III) using H2O2, Fe(III) and Al(III) were simultaneously separated by precipitation of their hydroxides at a solution pH of 4. Five stages of cross‐current extraction of Zn(II) with saponified Cyanex 272 led to a raffinate containing only Ni(II), Ca(II), and Mg(II). Nickel metal powders were recovered from this raffinate by chemical reduction with hydrazine.CONCLUSIONThe mass balance of the continuous experiments verified that 99% of the nickel was recovered from the sludge as metal powders with extra high purity. In these separation steps, optimum conditions were obtained and a simple and efficient process was proposed to recover pure nickel metal powders from the sludge. © 2023 Society of Chemical Industry.
Preoperative Discrimination of CDKN2A/B Homozygous Deletion Status in Isocitrate Dehydrogenase‐Mutant Astrocytoma: A Deep Learning‐Based Radiomics Model Using MRI
Authors: Gao Jueni , Liu Zhi , Pan Hongyu , Cao Xu , Kan Yubo , Wen Zhipeng , Chen Shanxiong , Wen Ming , Zhang Liqiang 
Published: August 2023

BackgroundCyclin‐dependent kinase inhibitor 2A/B (CDKN2A/B) homozygous deletion has been verified as an independent and critical biomarker of negative prognosis and short survival in isocitrate dehydrogenase (IDH)‐mutant astrocytoma. Therefore, noninvasive and accurate discrimination of CDKN2A/B homozygous deletion status is essential for the clinical management of IDH‐mutant astrocytoma patients.PurposeTo develop a noninvasive, robust preoperative model based on MR image features for discriminating CDKN2A/B homozygous deletion status of IDH‐mutant astrocytoma.Study TypeRetrospective.PopulationTwo hundred fifty‐one patients: 107 patients with CDKN2A/B homozygous deletion and 144 patients without CDKN2A/B homozygous deletion.Field Strength/Sequence:3.0 T/1.5 TContrast‐enhanced T1‐weighted spin‐echo inversion recovery sequence (CE‐T1WI) and T2‐weighted fluid‐attenuation spin‐echo inversion recovery sequence (T2FLAIR).AssessmentA total of 1106 radiomics and 1000 deep learning features extracted from CE‐T1WI and T2FLAIR were used to develop models to discriminate the CDKN2A/B homozygous deletion status. Radiomics models, deep learning‐based radiomics (DLR) models and the final integrated model combining radiomics features with deep learning features were developed and compared their preoperative discrimination performance.Statistical TestingPearson chi‐square test and Mann Whitney U test were used for assessing the statistical differences in patients' clinical characteristics. The Delong test compared the statistical differences of receiver operating characteristic (ROC) curves and area under the curve (AUC) of different models. The significance threshold is P < 0.05.ResultsThe final combined model (training AUC = 0.966; validation AUC = 0.935; test group: AUC = 0.943) outperformed the optimal models based on only radiomics or DLR features (training: AUC = 0.916 and 0.952; validation: AUC = 0.886 and 0.912; test group: AUC = 0.862 and 0.902).Data ConclusionWhether based on a single sequence or a combination of two sequences, radiomics and DLR models have achieved promising performance in assessing CDKN2A/B homozygous deletion status. However, the final model combining both deep learning and radiomics features from CE‐T1WI and T2FLAIR outperformed the optimal radiomics or DLR model.Evidence Level4Technical EfficacyStage 2
Chatbots in frontline services and customer experience: An anthropomorphism perspective
Authors: Nguyen Mai , Casper Ferm Lars‐Erik , Quach Sara , Pontes Nicolas , Thaichon Park 
Published: August 2023

AbstractThis study measures the effects of chatbot anthropomorphic language on customers' perception of chatbot competence and authenticity on customer engagement while taking into consideration the moderating roles of humanlike appearance and brand credibility. We conducted two experimental studies to examine the conceptual framework. Study 1 tests the moderating effect of a chatbot's anthropomorphic appearance on the relationship between chatbots' language and customer engagement. Study 2 tests the moderating effect of brand credibility on the relationship between a chatbot's anthropomorphic language and customer engagement. The findings confirm that the interaction between humanlike appearance via the use of avatars and anthropomorphic language, such as using emojis, in conversations with customers influences customer engagement, and that this effect is mediated by perceived chatbot competence and authenticity. Further, the positive effect of anthropomorphic language on perceived competence, and subsequently on authenticity and engagement, is only significant when the brand credibility was low (vs. high). This study offers insights into the effect of chatbots' anthropomorphic language and provides suggestions on how to devise efficient strategies for engaging customers using chatbots.
Automated 2‐Dimensional Measurement of Vestibular Schwannoma: Validity and Accuracy of an Artificial Intelligence Algorithm
Authors: Neve Olaf M. , Romeijn Stephan R. , Chen Yunjie , Nagtegaal Larissa , Grootjans Willem , Jansen Jeroen C. , Staring Marius , Verbist Berit M. , Hensen Erik F. 
Published: August 2023

AbstractObjectiveValidation of automated 2‐dimensional (2D) diameter measurements of vestibular schwannomas on magnetic resonance imaging (MRI).Study DesignRetrospective validation study using 2 data sets containing MRIs of vestibular schwannoma patients.SettingUniversity Hospital in The Netherlands.MethodsTwo data sets were used, 1 containing 1 scan per patient (n = 134) and the other containing at least 3 consecutive MRIs of 51 patients, all with contrast‐enhanced T1 or high‐resolution T2 sequences. 2D measurements of the maximal extrameatal diameters in the axial plane were automatically derived from a 3D‐convolutional neural network compared to manual measurements by 2 human observers. Intra‐ and interobserver variabilities were calculated using the intraclass correlation coefficient (ICC), agreement on tumor progression using Cohen's kappa.ResultsThe human intra‐ and interobserver variability showed a high correlation (ICC: 0.98‐0.99) and limits of agreement of 1.7 to 2.1 mm. Comparing the automated to human measurements resulted in ICC of 0.98 (95% confidence interval [CI]: 0.974; 0.987) and 0.97 (95% CI: 0.968; 0.984), with limits of agreement of 2.2 and 2.1 mm for diameters parallel and perpendicular to the posterior side of the temporal bone, respectively. There was satisfactory agreement on tumor progression between automated measurements and human observers (Cohen's κ = 0.77), better than the agreement between the human observers (Cohen's κ = 0.74).ConclusionAutomated 2D diameter measurements and growth detection of vestibular schwannomas are at least as accurate as human 2D measurements. In clinical practice, measurements of the maximal extrameatal tumor (2D) diameters of vestibular schwannomas provide important complementary information to total tumor volume (3D) measurements. Combining both in an automated measurement algorithm facilitates clinical adoption.
The Association of Hearing Loss With Active Music Enjoyment in Hearing Aid Users
Authors: Chern Alexander , Denham Michael W. , Leiderman Alexis S. , Sharma Rahul K. , Su Irene W. , Ucci Amanda J. , Jones Jennifer M. , Mancuso Dean , Cellum Ilana P. , Galatioto Jessica A. , Lalwani Anil K. 
Published: August 2023

AbstractObjectiveHearing aids (HAs) are designed for speech rather than music listening. The impact of HAs on music enjoyment is poorly studied. We examine the effect of HAs on active music enjoyment in individuals with varying levels of hearing loss (HL).Study DesignCross‐sectional study.SettingTertiary medical center and community.MethodsAdult (≥18 years) bilateral HA users and normal hearing (NH) controls actively listened to musical stimuli and rated their enjoyment across 3 measures (pleasantness, musicality, naturalness) with and without HAs using a visual analog scale. Multivariable linear regression was used to assess the association between HL (measured by a pure‐tone average [PTA] and word recognition score [WRS] of the better ear) and music enjoyment with and without HAs, adjusting for covariates. Music enjoyment was compared between HA users and NH controls, and HA users with and without their HAs.ResultsOne hundred bilateral HA users (mean age 66.0 years, 52% female, better ear mean [SD] PTA 50.2 [13.5] dBHL, mean WRS 84.5 [16.5]%) completed the study. Increasing severity of HL (PTA) was independently associated with decreased music enjoyment (pleasantness, musicality, naturalness) with and without HAs (p < .05). HA usage increased music enjoyment (musicality) in those with moderate to moderately severe HL. Music enjoyment in NH controls (n = 20) was significantly greater across all measures compared to HA users.ConclusionIncreased severity of HL is associated with decreased music enjoyment that can be enhanced with HA usage. Thus, HA usage can positively enhance both speech and music appreciation.
Elucidating human–nature connectedness in three EU countries: A pro‐environmental behaviour perspective
Authors: Mikusiński Grzegorz , Elbakidze Marine , Orlikowska Ewa H. , Skaltsa Ioanna G. , Żmihorski Michał , Iwińska Katarzyna 
Published: August 2023

Abstract

Strengthening positive human–nature relationships is seen as a way to more pro‐environmental behaviour and leads to a greater environmental sustainability. Therefore, understanding human–nature relationships has attracted increasing attention among researchers. Nature connectedness is a concept developed to measure such relationships. Since nature connectedness is complex and context dependent phenomenon, more research comparing sociocultural and environmental factors within societies in different countries is needed to understand its determinants.

In this study, we explored how sociodemographic and socioeconomic characteristics and value orientation of respondents and environmental variables affected nature connectedness across different contexts in the European Union. We used 11 sociodemographic, socioeconomic and personal value factors from the computer‐assisted web interview (CAWI) and six environmental variables characterizing the local environments of 1054 respondents as independent variables to explain the nature connectedness of the respondents in Greece, Poland and Sweden. The individual level of nature connectedness (response variable) was expressed by an additive index (NC‐index) based on a 5‐item scale originating from CAWI. The general additive model was applied to link NC‐index to sociodemographic, value orientation and selected environmental variables.

We found that the sociodemographic characteristics of the respondents and their value orientation were substantially more important in explaining the individual level of nature connectedness than environmental variables. The NC‐index was positively correlated with the frequency of visits to the natural environment and biospheric values of the respondents, and was higher for women and the most prosperous respondents. Moreover, we observed several country‐wise differences in associations between explanatory variables and NC‐index. For example, altruistic orientation was positively related to the level of nature connectedness only in Greece, but not in two other countries, and residence during childhood was important to nature connectedness only in Sweden.

Our findings that some sociodemographic, socioeconomic and value orientation variables affect the level of individual nature connectedness across studied countries are encouraging. They indicate that some universally applied educational actions may elevate the level of nature connectedness. We argue that exploration of nature connectedness from a cross‐country perspective may provide significant insights into the environmental debate in national and international contexts.

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DNA methylation‐associated allelic inactivation regulates Keratin 19 gene expression during pancreatic development and carcinogenesis
Authors: Krüger Jana , Fischer Anja , Breunig Markus , Allgöwer Chantal , Schulte Lucas , Merkle Jessica , Mulaw Medhanie A , Okeke Nnamdi , Melzer Michael K , Morgenstern Clara , Azoitei Ninel , Seufferlein Thomas , Barth Thomas FE , Siebert Reiner , Hohwieler Meike , Kleger Alexander 
Published: August 2023

AbstractWithin the pancreas, Keratin 19 (KRT19) labels the ductal lineage and is a determinant of pancreatic ductal adenocarcinoma (PDAC). To investigate KRT19 expression dynamics, we developed a human pluripotent stem cell (PSC)‐based KRT19‐mCherry reporter system in different genetic backgrounds to monitor KRT19 expression from its endogenous gene locus. A differentiation protocol to generate mature pancreatic duct‐like organoids was applied. While KRT19/mCherry expression became evident at the early endoderm stage, mCherry signal was present in nearly all cells at the pancreatic endoderm (PE) and pancreatic progenitor (PP) stages. Interestingly, despite homogenous KRT19 expression, mCherry positivity dropped to 50% after ductal maturation, indicating a permanent switch from biallelic to monoallelic expression. DNA methylation profiling separated the distinct differentiation intermediates, with site‐specific DNA methylation patterns occurring at the KRT19 locus during ductal maturation. Accordingly, the monoallelic switch was partially reverted upon treatment with a DNA‐methyltransferase inhibitor. In human PDAC cohorts, high KRT19 levels correlate with low locus methylation and decreased survival. At the same time, activation of oncogenic KRASG12D signalling in our reporter system reversed monoallelic back to biallelic KRT19 expression in pancreatic duct‐like organoids. Allelic reactivation was also detected in single‐cell transcriptomes of human PDACs, which further revealed a positive correlation between KRT19 and KRAS expression. Accordingly, KRAS mutant PDACs had higher KRT19 mRNA but lower KRT19 gene locus DNA methylation than wildtype counterparts. KRT19 protein was additionally detected in plasma of PDAC patients, with higher concentrations correlating with shorter progression‐free survival in gemcitabine/nabPaclitaxel‐treated and opposing trends in FOLFIRINOX‐treated patients. Apart from being an important pancreatic ductal lineage marker, KRT19 appears tightly controlled via a switch from biallelic to monoallelic expression during ductal lineage entry and is aberrantly expressed after oncogenic KRASG12D expression, indicating a role in PDAC development and malignancy. Soluble KRT19 might serve as a relevant biomarker to stratify treatment. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.