bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting the risk of variceal rehemorrhage in cirrhotic patients with portal vein thrombosis: A two‐center retrospective study
Authors: Zhang Shuo , Zhong Xuan , Zhong Hui , Zhong Lan , Li Jing , Zhu Feng Shang , Xia Lu , Yang Chang Qing 
Published: November 2023

ObjectivesAlthough portal vein thrombosis (PVT) was thought to deteriorate portal hypertension and contribute to poor prognosis, risk stratification remains unclear. This study aimed to evaluate its effect on the risk of variceal rehemorrhage and to develop a competitive risk model in cirrhotic patients with PVT.MethodsCirrhotic patients with and without PVT admitted for acute variceal hemorrhage were retrospectively included after matching (1:1) for age, gender and etiology of cirrhosis from two tertiary centers with 1‐year follow‐up. Those with PVT were subsequently divided into the training and validation cohorts. Cox regression analysis was performed to identify risk factors and develop a competitive risk model, of which the predictive performance and optimal decision threshold were evaluated by C‐index, competitive risk curves, calibration curves and decision curve analysis.ResultsAmong 398 patients, PVT significantly increased the variceal rehemorrhage risk. Multivariate Cox regression analysis identified that the Child–Turcotte–Pugh score (P = 0.013), chronic PVT (P = 0.025), C‐reactive protein (P < 0.001), and aspartate aminotransferase (P = 0.039) were independently associated with variceal rehemorrhage, which were incorporated into the competitive risk model, with high C‐index (0.804 and 0.742 of the training and validation cohorts, respectively), risk stratification ability, and consistency. The optimal decision range of the threshold probability was 0.2–1.0.ConclusionWe confirmed the adverse effect of PVT on variceal rehemorrhage and developed a competitive risk model for variceal rehemorrhage in cirrhotic patients with PVT, which might be conveniently used for clinical decision‐making.
DARS2 promotes the occurrence of lung adenocarcinoma via the ERK/c‐Myc signaling pathway
Authors: Fang Tao , Jiang Jin , Yu Wenhao , Li Rongyang , Tian Hui 
Published: November 2023

AbstractBackgroundDARS2 expression is upregulated in lung adenocarcinoma (LUAD) which correlates with tumor patient stage and prognosis. The mechanism of DARS2 involvement in LUAD still needs to be further explored.MethodsIn this study, we found that DARS2 expression in LUAD tissue was significantly higher than that in normal tissue. At the same time, the Kaplan–Meier curve showed that the survival prognosis of LUAD patients with high expression of DARS2 was significantly worse than low expression of DARS2. The expression of DARS2 was detected in LUAD and adjacent normal tissues by IHC staining, histochemical scoring and a survival curve was generated. In addition, we demonstrated that the knockdown and overexpression of DARS2 significantly affected the proliferation, invasion, and migration of LUAD cells in vitro and in vivo. Finally, western blot and rescue assay were performed on LUAD cells to further explore and verify the signaling pathway.ResultsDARS2 expression was significantly upregulated in LUAD tissues and cell lines. What is more, the increased expression of DARS2 was closely related to proliferation, invasion and metastasis. The tumorigenic assay in nude mice further showed that the tumorigenic ability of nude mice was significantly improved with the increase in DARS2 expression. Finally, we determined that DARS2 plays its role in LUAD by targeting the ERK/c‐Myc signaling pathway.ConclusionOur data revealed the oncogenic role of DARS2 in LUAD, indicating that DARS2 may be a predictive biomarker and novel therapeutic target for LUAD.
Programme for prevention of foot dermatoses in patients with work‐related skin diseases: Follow‐up data of a prospective cohort study (OCCUPES)
Authors: Hübner Anja , John Swen Malte , Wilke Annika , Brans Richard 
Published: November 2023

AbstractBackgroundA programme based on health education has been developed to prevent foot dermatoses (FD) in patients with work‐related skin diseases (WRSD).ObjectiveTo evaluate the effectiveness of the programme in a prospective cohort study (OCCUPES).MethodsSix and 12 months after completing the programme, follow‐up questionnaires were sent to 231 patients with WRSD and FD. Assessments included occupational footwear and foot care, self‐reported disease course, and health‐related quality of life.ResultsResponse to follow‐ups was >70%. Wearing functional socks and changing footwear and socks during one work shift increased (all p < 0.001). Complaints about occupational footwear decreased, including sweating and exposure to moisture/wetness. More than 60% reported improved FD while quality of life significantly increased. After 12 months, all foot symptoms were less frequent, including itch (p = 0.009), pain when walking (p = 0.005), pain in rest (p = 0.015) and smell (p = 0.001). The programme received very good ratings by the participants.ConclusionsThe intervention was effective in improving occupational footwear, foot care and preventive behaviour. It resulted in a reduced burden of FD and should be implemented in the general care of patients with WRSD.
Design Thinking and AI: A New Frontier for Designing Human‐Centered AI Solutions
Authors: Böckle Martin , Kouris Iana 
Published: November 2023

AbstractIn recent years, design thinking (DT) has become a pervasive innovation approach in the managerial community as a structured way of solving challenging problems through a human‐centered perspective. The approach fosters lateral thinking and has a huge impact on the organizational culture and the core elements of the innovation process. At the same time, the number of organizations trying to solve problems through the application of artificial intelligence (AI) is constantly growing, although more than 80% of AI projects never reach deployment due to the wrong strategic approach, poor data quality, or a lack of AI awareness among employees—and those that do remain below profitability expectations. The aim of this paper is therefore to connect the AI and DT communities by proposing a first framework supporting the development of AI solutions in a human‐centered way. The contribution of this paper is thus twofold: First, we investigate ways in which design thinking adds real value along the design process of intelligent solutions, thereby enriching the present body of design management literature. Second, we propose a first framework by linking core elements of both worlds to support strategic designers and data engineers in designing such applications. Finally, we propose a research agenda that can serve as a basis for future research directions in order to advance contributions at the intersection of the two fields.
Implementing Evidence‐Based Design to Improve Adherence in Self‐Administered Treatment Technology
Authors: Elmansy Rafiq , English Stuart 
Published: November 2023

A low level of treatment adherence is one of the challenges facing the UK's healthcare system. An estimated 30% to 50% of patients with chronic diseases fail to adhere to prescribed medical interventions. While medical technology provides an opportunity to overcome existing challenges, poor adherence blurs this opportunity by reducing the intervention's positive impact. The spread of the Covid pandemic dramatically increased the pressure on healthcare systems and highlighted the urgency to address the low adherence problem. Various studies have investigated the underlying factors behind low adherence. However, two main gaps were identified: 1) lack of adherence frameworks that consider self‐administered treatment technology, and 2) lack of a practical mechanism to help companies consider adherence factors during the design and development of the technology.This paper introduces the development of an Adherence Framework for self‐administered treatment technology and a design‐focused adherence canvas used as a practical resource for companies to consider during the design process. Adherence factor data from literature and case studies were triangulated to an eDelphi study used to develop the adherence framework. The presented adherence canvas and Adherence Framework allow companies to consider adherence during the design of self‐administered treatment technology.
AI Enabled Airline Cabin Services: AI Augmented Services for Emotional Values. Service Design for High‐Touch Solutions and Service Quality
Authors: Rjsé Vássil , Jylkäs Titta , Miettinen Satu 
Published: November 2023

AbstractThis paper highlights the significance of emotional values within digital services during the airline cabin experience. Currently, emotional engagement with front‐line AI interactions, such as AI assistants, lacks trust. Thus, the role of AI must be reimagined to better integrate the human factor into the service experience through things like high‐touch in order to create trust and improve the perception of cabin service quality. Service design is a human‐centric approach to service creation in which the user is typically made the main subject of the service research; the service process (service interaction) then co‐creates values alongside the service provider. The major concept discussed here is AI Augmented Services (AIAS), which turn high‐tech capabilities into high‐touch “human centric” services that can offer access, control, and well‐being to the user, all of which are key components in the establishment of trust. Airline future services can then implement this study for the purpose of detecting human emotions, co‐creating emotional values, and promoting emotional intelligence through the AIAS interactive communication channels, thereby transforming high‐tech capabilities into high‐touch opportunities. The methodological approach began by determining a benchmark for the state‐of‐the‐art AI technology in transport and conducting a set of expert interviews. Notably, the possible materialisation and challenges of AIAS high‐touch cabin services are also discussed here. This article can be considered to be a first step toward a service design in which opportunities are discussed with the goal of “discovering” possible AI solutions. Consecutive stages will be presented in future articles in which the concepts introduced here will be further defined and developed.
DNMTs‐mediated SOCS3 methylation promotes the occurrence and development of AML
Authors: Zhang Xiaohui , Zhang Kai , Zhang Jing , Chang Wei , Zhao Yunguo , Suo Xiaohui 
Published: November 2023

AbstractObjectivesAs a tumor suppressor gene, SOCS3 inhibits the growth of tumor cells by regulating JAK/STAT signaling pathway through negative feedback. This study aimed to investigate the biological function and mechanism of SOCS3 methylation mediated by DNMTs in the development of AML.MethodsBone marrow samples were collected from 70 AML patients and 20 healthy volunteers. The expression and methylation status of each gene were detected by RT‐qPCR, western blot and MS‐PCR, and the growth and apoptosis rate of leukemia cell lines were detected by CCK‐8 and flow cytometry. The effects of changes in SOCS3 gene expression and methylation status of AML cell lines were observed by gene transfection and gene knockdown.ResultsThe methylation rate of SOCS3 in AML initial treatment group was significantly higher than that in the remission group and the normal control group (60% vs. 0%, 0%). The expression of SOCS3 in the SOCS3 methylation group was significantly lower than that in the non‐methylated group and control group, while the expression of DNMT1, DNMT3a, p‐JAK2, p‐STAT3 and p‐STAT5 were significantly higher than those in the non‐methylated group and control group. Demethylation treatment, SOCS3 transfection and DNMT3a knockdown could up‐regulate the expression of SOCS3, which decreased the proliferation and increased the apoptosis of leukemia cell lines.ConclusionSOCS3 methylation mediated by DNMTs promotes the occurrence and development of AML and can be used as a potential biomarker for the diagnosis and efficacy evaluation of AML.
Long‐term treatment with ganaxolone for seizures associated with cyclin‐dependent kinase‐like 5 deficiency disorder: Two‐year open‐label extension follow‐up
Authors: Olson Heather E. , Amin Sam , Bahi‐Buisson Nadia , Devinsky Orrin , Marsh Eric D. , Pestana‐Knight Elia , Rajaraman Rajsekar R. , Aimetti Alex A. , Rybak Eva , Kong Fanhui , Miller Ian , Hulihan Joseph , Demarest Scott 
Published: November 2023

AbstractObjectiveIn the placebo‐controlled, double‐blind phase of the Marigold study (NCT03572933), ganaxolone significantly reduced major motor seizure frequency (MMSF) in patients with cyclin‐dependent kinase‐like 5 deficiency disorder (CDD). We report 2‐year safety and clinical outcomes data from the open‐label extension (OLE) phase of Marigold.MethodsPatients with CDD who completed the double‐blind phase were eligible to continue in the OLE. Efficacy assessments included MMSF reduction from prerandomization baseline, responder rates, and Clinical Global Impression–Improvement scores, including assessment of seizure intensity and duration (CGI‐CSID). Safety assessments included treatment‐emergent adverse events (TEAEs) and TEAEs leading to discontinuation.ResultsOf 101 patients who enrolled in Marigold, 88 (87.1%) entered the OLE (median age = 5 years, 79.5% female). Median 28‐day MMSF at baseline was 50.6. At 2 years in the OLE (months 22–24), MMSF was reduced by a median of 48.2% (n = 50); when missing data were imputed, median reduction in MMSF was 43.8% using a mixed effects model and 27.4% using a last observation carried forward model. During months 22–24, 23 of 50 (46.0%) patients experienced reductions in MMSF of ≥50%; 12 of 50 (24.0%) patients experienced MMSF reductions of ≥75%. During months 22–24, 40 of 49 (81.6%) patients were rated by caregivers as having improvement in seizure‐related outcomes based on CGI‐CSID scores. Thirty‐seven patients discontinued ganaxolone due to lack of efficacy (n = 13), withdrawal by caregiver (n = 12), adverse event (n = 10), physician decision (n = 1), or death (n = 1; unrelated to study drug). The most common treatment‐related TEAEs were somnolence (17.0%), seizure (11.4%), and decreased appetite (5.7%). Patients reported serious TEAEs (n = 28, 31.8%); those reported in ≥3% of patients were seizure (n = 6), pneumonia (n = 5), acute respiratory failure (n = 3), aspiration pneumonia (n = 3), and dehydration (n = 3).SignificanceSustained reductions in MMSF at 2 years in the OLE support the efficacy of ganaxolone in seizures associated with CDD. Safety findings in the OLE were consistent with the double‐blind phase.
Galectin‐3 in biliary atresia and other pediatric cholestatic liver diseases
Authors: Yoeli Dor , Mack Cara L. , Luo Yuhuan , Chaidez Alexander , De La Rosa Nathaly Limon , Wang Zhaohui , Cervantes‐Alvarez Eduardo , Huang Christene A. , Navarro‐Alvarez Nalu 
Published: November 2023

AbstractAimsBiliary atresia (BA) is characterized by intrahepatic inflammation and rapid progression of liver fibrosis. Galectin‐3, a beta‐galactoside binding protein, is a key regulator of inflammation and fibrosis. The aim of this study was to characterize circulating and hepatic Galectin‐3 levels in children with BA.MethodsPlasma and liver samples were obtained from children with early BA at time of Kasai hepatoportoenterostomy, late BA at time of transplant, early and late other cholestatic liver diseases (CLD), and controls. Plasma Galectin‐3 was measured using standard enzyme‐linked immunoassay. Liver tissue was analyzed with multiplex immunohistochemistry and quantified using whole slide analysis. Statistical comparisons were made using nonparametric testing.ResultsPlasma Galectin‐3 in late BA was significantly higher than in early BA (20.82 [12.45–30.46] vs. 11.30 [8.74–16.83] ng/mL, p = 0.0096). Galectin‐3 levels correlated with markers of disease severity and interleukin‐6. There were significantly more Galectin‐3+ M2 macrophages in late BA in comparison to late other CLD (162 [157–233] vs. 49 [33–59] cells/mm2, p = 0.03). The number of Galectin‐3+ M2 macrophages correlated with the number of activated hepatic stellate cells and bile duct proliferation.ConclusionsPlasma Galectin‐3 is higher in late BA at time of transplant in comparison to early BA at time of Kasai. The number of Galectin‐3 expressing M2 macrophages in late BA is elevated relative to late other CLD and was associated with other prognostic histological findings. Galectin‐3 targeted therapy may be beneficial in slowing disease progression to cirrhosis in children with BA.
Potential involvement of oncostatin M in the immunosuppressive tumor immune microenvironment in hepatocellular carcinoma with vessels encapsulating tumor clusters
Authors: Shigematsu Yasuyuki , Tanaka Kazuhito , Amori Gulanbar , Kanda Hiroaki , Takahashi Yu , Takazawa Yutaka , Takeuchi Kengo , Inamura Kentaro 
Published: November 2023

AbstractAimVessels encapsulating tumor clusters (VETC) represents an adverse prognostic morphological feature of hepatocellular carcinoma (HCC), which is associated with an immunosuppressive tumor immune microenvironment (TIM). However, the underlying factors characterizing the TIM in HCC with a VETC pattern (VETC‐positive HCC) remain uncertain. Oncostatin M (OSM), a pleiotropic cytokine of the interleukin‐6 family, regulates various biological processes, including inflammation, proliferation, and invasiveness of tumor cells. We aimed to test a hypothesis that OSM is associated with the immunosuppressive TIM of VETC‐positive HCC.MethodsA total of 397 consecutive HCC patients with curative‐intent hepatectomy were included. OSM‐positive cells and inflammatory cells including CD4‐, CD8‐, CD163‐, and FOXP3‐positive cells were immunohistochemically evaluated. We compared VETC‐positive and VETC‐negative HCCs in terms of the number of these cells.ResultsWe found the VETC pattern in 62 patients (15.6%). Our analysis revealed a significant decrease in the expression of arginase‐1, a marker associated with mature hepatocyte differentiation, in VETC‐positive HCC (p = 0.046). The number of tumor‐infiltrating OSM‐positive cells was significantly low in VETC‐positive HCC (p = 0.0057). Notably, in VETC‐positive HCC, the number of OSM‐positive cells was not associated with vascular invasion, whereas in VETC‐negative HCC, an increase in the number of OSM‐positive cells was associated with vascular invasion (p = 0.042).ConclusionsWe identified an association between a decrease in OSM‐positive cells and the VETC pattern. Additionally, our findings indicate that VETC‐positive HCC is characterized by low hepatocyte differentiation and OSM‐independent vascular invasion. These findings highlight the potential interaction between VETC‐positive HCC cells and their TIM through the reduction of OSM‐expressing cells.
Australian data on the utilisation and duration on treatment of ibrutinib with a proton pump inhibitor in patients with relapsed or refractory chronic lymphocytic leukaemia
Authors: Salvaris Ross , Mulligan Stephen , Puig Andrea , McGeachie Marija , Opat Stephen 
Published: November 2023

AbstractIn Australia, over half of patients with relapsed/refractory chronic lymphocytic leukaemia treated with ibrutinib use concomitant proton pump inhibitors (PPIs). High gastric pH reduces the bioavailability of some Bruton tyrosine kinase inhibitors. There was no difference in duration on ibrutinib with or without concomitant PPI (unadjusted P = 0.61; adjusted hazard ratio: 1.23, 95% confidence interval: 0.75–2.02, P = 0.411). PPI use does not affect ibrutinib treatment persistence.
Look before you reach: Fixation‐reach latencies predict reaching kinematics in toddlers
Authors: Abney Drew H. , Jerry Christian M. , Smith Linda B. , Yu Chen 
Published: November 2023

AbstractResearch on infant and toddler reaching has shown evidence for motor planning after the initiation of the reaching action. However, the reach action sequence does not begin after the initiation of a reach but rather includes the initial visual fixations onto the target object occurring before the reach. We developed a paradigm that synchronizes head‐mounted eye‐tracking and motion capture to determine whether the latency between the first visual fixation on a target object and the first reaching movement toward the object predicts subsequent reaching behavior in toddlers. In a corpus of over one hundred reach sequences produced by 17 toddlers, we found that longer fixation‐reach latencies during the pre‐reach phase predicted slower reaches. If the slowness of an executed reach indicates reach difficulty, then the duration of pre‐reach planning would be correlated with reach difficulty. However, no relation was found with pre‐reach planning duration when reach difficulty was measured by usual factors and independent of reach duration. The findings raise important questions about the measurement of reach difficulty, models of motor control, and possible developmental changes in the relations between pre‐planning and continuously unfolding motor plans throughout an action sequence.
Improving post‐acute stroke follow‐up care by adopting telecare consultations in a nurse‐led clinic: Study protocol of a hybrid implementation‐effectiveness trial
Authors: Wong Arkers Kwan Ching , Kwok Vivian Wai Yan , Wong Frances Kam Yuet , Tong Danny Wah Kun , Yuen Bernard Man Kam , Fong Ching Sing , Chan Shun Tim , Li Wah Chun , Zhou Shiyi , Lee Athena Yin Lam 
Published: November 2023

AbstractAimTo evaluate the clinical effectiveness and implementation strategies of telecare consultations in post‐stroke nurse‐led clinics.BackgroundTelecare consultations could be an alternative to conventional in‐person consultations and improve continuity of care for stroke survivors following their discharge from hospital. Previous studies utilizing telecare consultations only focused on testing their clinical effectiveness on stroke survivors; the appropriateness and feasibility of adopting this new delivery modality in a real‐world setting were not examined.DesignA Type II hybrid effectiveness‐implementation design will be adopted.MethodsEligible stroke survivor participants will be randomly assigned to the intervention group (telecare consultation) or control group (usual in‐person clinic consultation). Both groups will receive the same nursing intervention but delivered through different channels. The Reach, Effectiveness, Adoption, Implementation, Maintenance framework will be used to evaluate the clinical effectiveness and implementation outcomes. The primary outcome is the non‐inferiority of the degree of disability between the two groups at 3 months into the intervention and at 3 months post‐intervention. The paper complies with the SPIRIT guidelines for study protocols adapted for designing and reporting parallel group randomized trials.ConclusionThe findings of this study will provide key insights into the processes for implementing and adopting telecare consultations into long‐term services for post‐stroke patients.ImpactThis study contributes to the translation of telecare consultations for stroke survivors into real‐life settings. If effective, this program may provide guidance for expanding telecare consultations to other post‐stroke nurse‐led clinics or to patients with other chronic diseases.Trial RegistrationThis study has been registered at clinicaltrials.gov (identifier: NCT05183672). Registered on 10 January 2022.