bluuebunny/crossref_metadata_2025_split huggingface dataset:
Containing costs in the Italian local healthcare market
Authors: Riganti Andrea 
Published: February 2021

AbstractWe aim to investigate the cost containment effects of the creation in 2005 of agencies specifically responsible for all technical and administrative services within the regional healthcare system of the Tuscany region of Italy. We seek to contribute to the existing literature on the centralization and decentralization of purchases and technical services by assessing the amount of savings produced by these agencies at the intermediate level between local authorities and hospitals and the regional administration. We use the balances of all Italian local health authorities and hospital trusts combined with the synthetic control procedure to create from a donor pool of untreated units a weighted average of observations resembling the exposed units before and after the policy change in 2005. The magnitude of the effect is significant as the creation of these agencies is estimated to have reduced expenditures on auxiliary goods and contracted services by 6% in the period from 2006–2014. Moreover, we find that the cost reduction is not associated with a decrease in the provision of healthcare services and procedures to the general population or in the quality or efficiency of the regional healthcare system itself.
Liver‐Specific Deletion of Mouse Tm6sf2 Promotes Steatosis, Fibrosis, and Hepatocellular Cancer
Authors: Newberry Elizabeth P. , Hall Zoe , Xie Yan , Molitor Elizabeth A. , Bayguinov Peter O. , Strout Gregory W. , Fitzpatrick James A.J. , Brunt Elizabeth M. , Griffin Julian L. , Davidson Nicholas O. 
Published: February 2021

Background and Aims
Human transmembrane 6 superfamily 2 (TM6SF2) variant rs58542926 is associated with NAFLD and HCC. However, conflicting reports in germline Tm6sf2 knockout mice suggest no change or decreased very low density lipoprotein (VLDL) secretion and either unchanged or increased hepatic steatosis, with no increased fibrosis. We generated liver‐specific Tm6Sf2 knockout mice (Tm6 LKO) to study VLDL secretion and the impact on development and progression of NAFLD.

Approach and Results
Two independent lines of Tm6 LKO mice exhibited spontaneous hepatic steatosis. Targeted lipidomic analyses showed increased triglyceride species whose distribution and abundance phenocopied findings in mice with liver‐specific deletion of microsomal triglyceride transfer protein. The VLDL triglyceride secretion was reduced with small, underlipidated particles and unchanged or increased apolipoprotein B. Liver‐specific adeno‐associated viral, serotype 8 (AAV8) rescue using either wild‐type or mutant E167K‐Tm6 reduced hepatic steatosis and improved VLDL secretion. The Tm6 LKO mice fed a high milk‐fat diet for 3 weeks exhibited increased steatosis and fibrosis, and those phenotypes were further exacerbated when mice were fed fibrogenic, high fat/fructose diets for 20 weeks. In two models of HCC, either neonatal mice injected with streptozotocin (NASH/STAM) and high‐fat fed or with diethylnitrosamine injection plus fibrogenic diet feeding, Tm6 LKO mice exhibited increased steatosis, greater tumor burden, and increased tumor area versus Tm6 flox controls. Additionally, diethylnitrosamine‐injected and fibrogenic diet–fed Tm6 LKO mice administered wild‐type Tm6 or E167K‐mutant Tm6 AAV8 revealed significant tumor attenuation, with tumor burden inversely correlated with Tm6 protein levels.

Conclusions
Liver‐specific Tm6sf2 deletion impairs VLDL secretion, promoting hepatic steatosis, fibrosis, and accelerated development of HCC, which was mitigated with AAV8‐ mediated rescue.
Hepatic Steatosis and Ectopic Fat Are Associated With Differences in Subcutaneous Adipose Tissue Gene Expression in People With HIV
Authors: Gabriel Curtis L. , Ye Fei , Fan Run , Nair Sangeeta , Terry James G. , Carr John Jeffrey , Silver Heidi , Baker Paxton , Hannah LaToya , Wanjalla Celestine , Mashayekhi Mona , Bailin Sam , Lima Morgan , Woodward Beverly , Izzy Manhal , Ferguson Jane F. , Koethe John R. 
Published: February 2021

Persons with human immunodeficiency virus (PWH) have subcutaneous adipose tissue (SAT) dysfunction related to antiretroviral therapy and direct viral effects, which may contribute to a higher risk of nonalcoholic fatty liver disease compared with human immunodeficiency virus–negative individuals. We assessed relationships between SAT expression of major adipocyte regulatory and lipid storage genes with hepatic and other ectopic lipid deposits in PWH. We enrolled 97 PWH on long‐term antiretroviral therapy with suppressed plasma viremia and performed computed tomography measurements of liver attenuation, a measure of hepatic steatosis, skeletal muscle (SM) attenuation, and the volume of abdominal subcutaneous, visceral, and pericardial adipose tissue. Whole SAT gene expression was measured using the Nanostring platform, and relationships with computed tomography imaging and fasting lipids were assessed using multivariable linear regression and network mapping. The cohort had a mean age of 47 years, body mass index of 33.4 kg/m2, and CD4 count of 492 cells/mm3. Lower liver attenuation, a marker of greater steatosis, was associated with differences in SAT gene expression, including lower lipoprotein lipase and acyl‐CoA dehydrogenase, and higher phospholipid transfer protein. Lower liver attenuation clustered with lower visceral adipose tissue (VAT) attenuation and greater VAT volume, pericardial fat volume and triglycerides, but no relationship was observed between liver attenuation and SAT volume, SM attenuation, or low‐density lipoprotein. Conclusion: Liver attenuation was associated with altered SAT expression of genes regulating lipid metabolism and storage, suggesting that SAT dysfunction may contribute to nonalcoholic fatty liver disease in PWH. SAT gene‐expression relationships were similar for VAT volume and attenuation, but not SM, indicating that ectopic lipid deposition may involve multiple pathways.
Mentees and their mothers: The association between maternal relationship difficulties and targeted outcomes of mentoring
Authors: Williamson Supriya , Lyons Michael D. , Deutsch Nancy L. , Lawrence Edith 
Published: February 2021

AbstractMaternal relationship characteristics have been found to impact academic and behavioral outcomes for youth. However, less is known about how and through what mechanisms these characteristics impact outcomes for mentored youth. In this study, we examined if mentoring relationship quality mediated the relations between maternal relationship characteristics and academic and behavioral outcomes targeted by mentoring programs. Data were drawn from 205 participants who participated in a mentoring program that pairs adolescent girls with college women mentors for 1 year of mentoring. Mentoring relationship quality was the hypothesized mechanism of change and was included in the analysis as a mediator. Results revealed that maternal relationship characteristics (i.e., maternal quality communication/trust and maternal alienation) were directly related to academic and behavioral outcomes of mentoring. The relationship between maternal relationship characteristics and behavioral outcomes was mediated by mentoring relationship quality. Results suggested that girls with stronger maternal quality communication and trust as well as girls who felt more alienated from their mothers may benefit more from mentoring. Results can be used to inform mentor training to include a focus on relationship development with girls experiencing a variety of relational difficulties with their mothers to help improve targeted mentoring outcomes.
Role of magnifying endoscopy with narrow‐band imaging in the diagnosis of noninvasive gastric neoplasia
Authors: Tanaka Keisuke , Maekawa Shinya , Yoshida Takashi , Yamaguchi Tatsuya , Takano Shinichi , Matsuda Shuya , Hayakawa Hiroshi , Ishida Yasuaki , Muraoka Masaru , Kawakami Satoshi , Fukasawa Yoshimitsu , Kuno Toru , Iwamoto Fumihiko , Tsukui Yuya , Kobayashi Shoji , Asakawa Yukiko , Shindo Hiroko , Fukasawa Mitsuharu , Nakayama Yasuhiro , Inoue Taisuke , Uetake Tomoyoshi , Ohtaka Masahiko , Sato Tadashi , Mochizuki Kunio , Enomoto Nobuyuki 
Published: February 2021

AbstractBackground and AimThere are no globally approved, distinguishing criteria enabling the classification of gastric adenomas and intramucosal carcinomas for differential diagnosis of noninvasive neoplasia (NIN).MethodsNext‐generation sequencing of 50 cancer‐related genes was undertaken on 68 pathologically diagnosed microdissected gastric neoplasms (25 adenomas, 27 intramucosal carcinomas, and 16 submucosal carcinomas) obtained during endoscopic submucosal dissection. Findings from magnifying endoscopy with narrow‐band imaging (M‐NBI) of 52 NINs (the 25 adenomas and 27 intramucosal carcinomas) were compared with these data.ResultsAmong all 68 neoplasms, the most frequently mutated genes were APC (76% in adenoma, 11.1% in intramucosal carcinoma, and 0% in submucosal carcinoma; P < 0.001) and TP53 in intramucosal and submucosal carcinomas (8% in adenoma, 48.1% in intramucosal carcinoma, and 75% in submucosal carcinoma; P < 0.001). Dividing the NIN neoplasms into five groups according to their mutational status (A1: APC mutation, A2: APC + α mutation, B: APC + TP53 mutation, C: TP53 mutation, D: no mutation in either APC or TP53) resulted in almost identical diagnoses by pathology and M‐NBI for groups A1 (12/13, 92%), C (12/13, 92%), and D (16/17, 94%) but not for groups A2 (3/7, 43%) or B (0/2, 0%). This finding implies that NINs with the APC + α mutation have carcinoma‐like endoscopic features despite most being judged as adenomas by pathology.ConclusionA diagnosis of NINs by pathology or M‐NBI in the subset of gastric tumors classified by cancer‐related mutations is not completely identical, suggesting the possible additional role of M‐NBI in diagnosing NINs. Further studies are needed to confirm this.
The spectrum of peripheral neuropathy in disorders of the mitochondrial trifunctional protein
Authors: Grünert Sarah C. , Eckenweiler Matthias , Haas Dorothea , Lindner Martin , Tsiakas Konstantinos , Santer René , Tucci Sara , Spiekerkoetter Ute 
Published: February 2021

AbstractPeripheral neuropathy is a known irreversible long‐term complication of long‐chain 3‐hydroxyacyl‐CoA dehydrogenase deficiency (LCHADD) and mitochondrial trifunctional protein deficiency (MTPD), two inherited disorders of mitochondrial long‐chain fatty acid oxidation. The underlying pathophysiology of neuropathy is still not fully understood. We report electrophysiological studies and neurological findings in a series of 8 LCHAD‐deficient and 11 MTP‐deficient patients. The median age at time of the study was 8.0 years (0.5‐25 years). The overall prevalence of neuropathy was 58% with neuropathic symptoms being slightly more common in MTPD compared to LCHADD (70% vs 50%, respectively). Onset of neuropathy was significantly earlier in MTPD patients compared to LCHADD patients (median age at onset 4.7 vs 15.3 years, respectively, P = .047). In four patients, isolated peripheral neuropathy was the first and only presenting symptom, and in all four the diagnosis was missed by newborn screening. About half of the patients (45.5%) had a sensorimotor neuropathy, while 27.3% showed a pure motor form and another 27.3% an isolated sensory form. Despite early diagnosis by newborn screening and early initiation of therapy, peripheral neuropathy cannot be prevented in all patients with LCHADD/MTPD and has severe impact on the life of affected patients. Electrophysiology classifies LCHADD/MTPD neuropathy as axonal with secondary demyelination. A novel observation is that in patients with acute, fulminant onset of neuropathy, symptoms can be partly reversible. Further studies are needed to elucidate the underlying pathophysiology of axonal damage and possible therapeutic targets.
MultiparametricMRI‐Based Radiomics Approaches for Preoperative Prediction ofEGFRMutation Status in Spinal Bone Metastases in Patients with Lung Adenocarcinoma
Authors: Jiang Xiran , Ren Meihong , Shuang Xue , Yang Huazhe , Shi Dabao , Lai Qingyuan , Dong Yue 
Published: February 2021

BackgroundPreoperative prediction of epidermal growth factor receptor (EGFR) mutation status in patients with spinal bone metastases (SBM) from primary lung adenocarcinoma is potentially important for treatment decisions.PurposeTo develop and validate multiparametric magnetic resonance imaging (MRI)‐based radiomics methods for preoperative prediction of EGFR mutation based on MRI of SBM.Study TypeRetrospective.PopulationA total of 97 preoperative patients with lumbar SBM from lung adenocarcinoma (77 in training set and 20 in validation set).Field Strength/SequenceT1‐weighted, T2‐weighted, and T2‐weighted fat‐suppressed fast spin echo sequences at 3.0 T.AssessmentRadiomics handcrafted and deep learning‐based features were extracted and selected from each MRI sequence. The abilities of the features to predict EGFR mutation status were analyzed and compared. A radiomics nomogram was constructed integrating the selected features.Statistical TestsThe Mann‐WhitneyUtest and χ2test were employed for evaluating associations between clinical characteristics and EGFR mutation status for continuous and discrete variables, respectively. Least absolute shrinkage and selection operator was used for selection of predictive features. Sensitivity (SEN), specificity (SPE), and area under the receiver operating characteristic curve (AUC) were used to evaluate the ability of radiomics models to predict the EGFR mutation. Calibration and decision curve analysis (DCA) were performed to assess and validate nomogram results.ResultsThe radiomics signature comprised five handcrafted and one deep learning‐based features and achieved good performance for predicting EGFR mutation status, with AUCs of 0.891 (95% confidence interval [CI], 0.820–0.962, SEN = 0.913, SPE = 0.710) in the training group and 0.771 (95% CI, 0.551–0.991, SEN = 0.750, SPE = 0.875) in the validation group. DCA confirmed the potential clinical usefulness of the radiomics models.Data ConclusionMultiparametric MRI‐based radiomics is potentially clinical valuable for predicting EGFR mutation status in patients with SBM from lung adenocarcinoma.Level of Evidence3Technical Efficacy2
Gamification via mobile applications: A longitudinal examination of its impact on attitudinal loyalty and behavior toward a core service
Authors: Kunkel Thilo , Lock Daniel , Doyle Jason P. 
Published: February 2021

AbstractOrganizations increasingly use gamification to engage with, and influence, consumers’ attitudes and behaviors. In this article, we present findings from a longitudinal, mixed‐method research design that (1) examined the extent to which game design elements created by a third‐party app lead to increased attitudinal loyalty toward core service providers and (2) sought to explain the underlying processes that invoke attitudinal change. Behavioral data collected from app users indicated that knowledge‐focused affordances positively influenced consumer loyalty and explained 11.3% of the variance in attitudinal change. Follow‐up interviews revealed that Rewards, Competition, Sense of Achievement, and Gaining Knowledge were representative of consumers’ motives for using the app, and Engagement and Identity explained how using the gamified application influenced users’ attitudinal loyalty toward the core service. Overall, we contribute to knowledge about how gamified affordances can be used to add value to consumer experiences, both in relation to the gamified consumption experiences, and the focal brand that is serviced by a third‐party app.
Competitors' envy, gamers' pride: An exploration of gamers' divergent behavior
Authors: Sharma Rashmini , Singh Gurmeet , Sharma Shavneet 
Published: February 2021

AbstractCheating in games has existed since the beginning of video games. The landscape of gaming and cheating has changed profoundly with its migration to the online environment. This study aims to investigate the unethical behavioral intention of online gamers. The Theory of Planned Behavior and Social Comparison Theory is used to develop a comprehensive framework to understand gamers' cheating intention. This study employs a quantitative approach to collect data from 404 gamers using a random sampling technique. Results show that attitude, subjective norms, perceived behavioral control, hedonic motivation, and benign envy influences gamers' online cheating intention. Online cheating intention was found to influence online cheating behavior positively. Looking at the moderating effect of ethical judgment, this study revealed that ethical judgment dampens the positive relationship between attitude, benign envy, and perceived behavioral control on gamers' online cheating intention. This study is the first to explore the impact of different types of envy on divergent gaming behavior. It contributes to the literature by generating insights into an under‐researched area of divergent online gaming behavior.
QSM reconstruction challenge 2.0: A realistic in silico head phantom for MRI data simulation and evaluation of susceptibility mapping procedures
Authors: Marques José P. , Meineke Jakob , Milovic Carlos , Bilgic Berkin , Chan Kwok‐Shing , Hedouin Renaud , van der Zwaag Wietske , Langkammer Christian , Schweser Ferdinand 
Published: February 2021

PurposeTo create a realistic in silico head phantom for the second QSM reconstruction challenge and for future evaluations of processing algorithms for QSM.MethodsWe created a digital whole‐head tissue property phantom by segmenting and postprocessing high‐resolution (0.64 mm isotropic), multiparametric MRI data acquired at 7 T from a healthy volunteer. We simulated the steady‐state magnetization at 7 T using a Bloch simulator and mimicked a Cartesian sampling scheme through Fourier‐based processing. Computer code for generating the phantom and performing the MR simulation was designed to facilitate flexible modifications of the phantom in the future, such as the inclusion of pathologies as well as the simulation of a wide range of acquisition protocols. Specifically, the following parameters and effects were implemented: TR and TE, voxel size, background fields, and RF phase biases. Diffusion‐weighted imaging phantom data are provided, allowing future investigations of tissue‐microstructure effects in phase and QSM algorithms.ResultsThe brain part of the phantom featured realistic morphology with spatial variations in relaxation and susceptibility values similar to the in vivo setting. We demonstrated some of the phantom’s properties, including the possibility of generating phase data with nonlinear evolution over TE due to partial‐volume effects or complex distributions of frequency shifts within the voxel.ConclusionThe presented phantom and computer programs are publicly available and may serve as a ground truth in future assessments of the faithfulness of quantitative susceptibility reconstruction algorithms.
Feeling responsible but unsupported: How relatives of out‐of‐hospital cardiac arrest survivors experience the transition from hospital to daily life – A focus group study
Authors: Dichman Camilla , Wagner Mette Kirstine , Joshi Vicky L. , Bernild Camilla 
Published: February 2021

AbstractAimTo generate knowledge about how relatives of out‐of‐hospital cardiac arrest survivors experience the transition between hospital and daily life. The research question was “how do relatives of out‐of‐hospital cardiac arrest survivors experience collaboration and communication with healthcare professionals, and what is emphasized as important in the transition from hospital to daily life”.DesignQualitative design.MethodsSix semi‐structured focus group interviews were conducted with 23 relatives of out‐of‐hospital cardiac arrest survivors who participated in a residential rehabilitation course. Data was collected between November 2018 and March 2019. Transcripts were analysed using a phenomenological hermeneutic approach.ResultsThe analysis generated three themes “a necessary presence,” “communication with healthcare professionals on the cardiac ward” and “the abrupt disappearance of the system.” Relatives of out‐of‐hospital cardiac arrest survivors feel a great responsibility when coping and adjusting to their new life. In the transition to daily life, a focus on systematic involvement and collaboration with relatives should be an essential part of the post‐cardiac arrest pathway.
Nurses' Experiences and Perceptions of two Early Warning Score systems to Identify Patient Deterioration—A Focus Group Study
Authors: Langkjaer Caroline S. , Bove Dorthe G. , Nielsen Pernille B. , Iversen Kasper K. , Bestle Morten H. , Bunkenborg Gitte 
Published: February 2021

AbstractAimsTo explore Registered Nurses' experiences and perceptions with National Early Warning Score and Individual Early Warning Score to identify patient deterioration.DesignA qualitative exploratory design.MethodsSix focus groups were conducted at six Danish hospitals from February to June 2019. Registered Nurses from both medical, surgical and emergency departments participated. The focus groups were analysed using content analysis.ResultsOne theme and four categories were identified. Theme: Meaningful in identifying patient deterioration but causing frustration due to lack of flexibility. Categories: (a) Inter‐professional collaboration strengthened through the use of Early Warning Score systems, (b) Enhanced professional development and communication among nurses when using Early Warning Score systems, (c) Detecting patient deterioration by integrating nurses' clinical gaze with Early Warning Score systems and (d) Modification and fear of making mistakes when using Early Warning Score systems.
The foggy world(s) of p63 isoform regulation in normal cells and cancer
Authors: Pokorná Zuzana , Vysloužil Jan , Hrabal Václav , Vojtěšek Borˇivoj , Coates Philip J 
Published: February 2021

AbstractThe p53 family member p63 exists as two major protein variants (TAp63 and ΔNp63) with distinct expression patterns and functional properties. Whilst downstream target genes of p63 have been studied intensively, how p63 variants are themselves controlled has been relatively neglected. Here, we review advances in understanding ΔNp63 and TAp63 regulation, highlighting their distinct pathways. TAp63 has roles in senescence and metabolism, and in germ cell genome maintenance, where it is activated post‐transcriptionally by phosphorylation cascades after DNA damage. The function and regulation of TAp63 in mesenchymal and haematopoietic cells is less clear but may involve epigenetic control through DNA methylation. ΔNp63 functions to maintain stem/progenitor cells in various epithelia and is overexpressed in squamous and certain other cancers. ΔNp63 is transcriptionally regulated through multiple enhancers in concert with chromatin modifying proteins. Many signalling pathways including growth factors, morphogens, inflammation, and the extracellular matrix influence ΔNp63 levels, with inconsistent results reported. There is also evidence for reciprocal regulation, including ΔNp63 activating its own transcription. ΔNp63 is downregulated during cell differentiation through transcriptional regulation, while post‐transcriptional events cause proteasomal degradation. Throughout the review, we identify knowledge gaps and highlight discordances, providing potential explanations including cell‐context and cell–matrix interactions. Identifying individual p63 variants has roles in differential diagnosis and prognosis, and understanding their regulation suggests clinically approved agents for targeting p63 that may be useful combination therapies for selected cancer patients. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.