bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and cost-effectiveness of ‘Live Well with Parkinson’s’ self-management intervention versus treatment as usual for improving quality of life for people with Parkinson’s: study protocol for a randomised controlled trial
Authors: Walters Kate , Armstrong Megan , Gardner Benjamin , Ambler Gareth , Hunter Rachael , Maydon Bev , Davies Nathan , Atkinson Catherine , Brown Richard , Rookes Tasmin , Davis Daniel , Schrag Anette 
Published: December 2023

Abstract
Background
The Live Well with Parkinson’s Self-Management Toolkit is designed for use in the NHS to support people with Parkinson’s, their carers and health professionals in managing motor and non-motor symptoms and promoting well-being. The Toolkit was developed based on theory-based behaviour change and self-management techniques in consultation with people living with Parkinson’s and health and social care practitioners. There are digital (e-Toolkit) and paper (manual) versions.

Methods
Single-blind two-arm randomised controlled trial RCT of clinical effectiveness and cost-effectiveness of the Toolkit, facilitated by up to six sessions with a trained non-specialist supporter, in improving quality of life. People with Parkinson’s will be assessed at baseline, 6 and 12 months. Assessors will be blind to the treatment group. The primary outcome measure is the Parkinson’s Disease Questionnaire (PDQ-39, Parkinson’s related quality of life) score at 12 months. Secondary outcome measures include the MDS Unified Parkinson’s Disease Rating Scale (Part I, II, III, IV), EQ-5D, and a Client Service Receipt Inventory shortened, adapted for Parkinson’s. Carer outcomes include the Zarit Carer Burden Inventory and Carer Quality of Life Questionnaire for Parkinsonism. A total of 338 people with Parkinson’s, and their carers if appropriate, will be recruited from diverse settings across England. Those with advanced dementia, at end-of-life or with atypical Parkinsonism will be excluded. A parallel mixed methods process evaluation will explore the factors promoting or inhibiting implementation, uptake, use, effectiveness and cost-effectiveness of the Toolkit and sessions.

Discussion
If successful, the Live Well with Parkinson’s Toolkit could be used as a model for other complex long-term disorders, including dementia. This would bridge existing gaps in the NHS (as shown by the national Parkinson’s audit data), by enabling patients and carers to access personalised information, advice and support on symptom management and ‘living well’ with Parkinson’s.

Trial registration
ISRCTN92831552. Registered on 26th Oct 2021.
A small stretch of poor codon usage at the beginning of dengue virus open reading frame may act as a translational checkpoint
Authors: Yimyaem Maneenop , Jitobaom Kunlakanya , Auewarakul Prasert 
Published: December 2023

Abstract
Objective
Rare codons were previously shown to be enriched at the beginning of the dengue virus (DENV) open reading frame. However, the role of rare codons in regulating translation efficiency and replication of DENV remains unclear. The present study aims to clarify the significance of rare codon usage at the beginning of DENV transcripts using the codon adaptation index (CAI).

Methodology
CAIs of the whole starting regions of DENV transcripts as well as 18-codon sliding windows of the regions were analyzed.

Results
One of the intriguing findings is that those rare codons do not typically result in uniformly low CAI in the starting region with rare codons. However, it shows a notable local drop in CAI around the 50th codon in all dengue serotypes. This suggests that there may be a translational checkpoint at this site and that the rare codon usage upstream to this checkpoint may not be related to translational control.
Successful use of dupilumab for egg-induced eosinophilic gastroenteritis with duodenal ulcer: a pediatric case report and review of literature
Authors: Tsuge Mitsuru , Shigehara Kenji , Uda Kazuhiro , Kawano Seiji , Iwamuro Masaya , Saito Yukie , Yashiro Masato , Ikeda Masanori , Tsukahara Hirokazu 
Published: December 2023

Abstract
Background
Non-esophageal eosinophilic gastrointestinal disorder (non-EoE-EGID) is a rare disease in which eosinophils infiltrate parts of the gastrointestinal tract other than the esophagus; however, the number of patients with non-EoE-EGID has been increasing in recent years. Owing to its chronic course with repeated relapses, it can lead to developmental delays due to malnutrition, especially in pediatric patients. No established treatment exists for non-EoE-EGID, necessitating long-term systemic corticosteroid administration. Although the efficacy of dupilumab, an anti-IL-4/13 receptor monoclonal antibody, for eosinophilic esophagitis, has been reported, only few reports have demonstrated its efficacy in non-EoE EGIDs.

Case presentation
A 13-year-old boy developed non-EoE-EGID with duodenal ulcers, with chicken eggs as the trigger. He was successfully treated with an egg-free diet, proton pump inhibitors, and leukotriene receptor antagonists. However, at age 15, he developed worsening upper abdominal pain and difficulty eating. Blood analysis revealed eosinophilia; elevated erythrocyte sedimentation rate; and elevated levels of C-reactive protein, total immunoglobulin E, and thymic and activation-regulated chemokines. Upper gastrointestinal endoscopy revealed a duodenal ulcer with marked mucosal eosinophilic infiltration. Gastrointestinal symptoms persisted even after starting systemic steroids, making it difficult to reduce the steroid dose. Subcutaneous injection of dupilumab was initiated because of comorbid atopic dermatitis exacerbation. After 3 months, the gastrointestinal symptoms disappeared, and after 5 months, the duodenal ulcer disappeared and the eosinophil count decreased in the mucosa. Six months later, systemic steroids were discontinued, and the duodenal ulcer remained recurrence-free. The egg challenge test result was negative; therefore, the egg-free diet was discontinued. Blood eosinophil count and serum IL-5, IL-13, and eotaxin-3 levels decreased after dupilumab treatment. The serum levels of IL-5 and eotaxin-3 remained within normal ranges, although the blood eosinophil counts increased again after discontinuation of oral prednisolone.

Conclusions
Suppression of IL-4R/IL-13R-mediated signaling by dupilumab may improve abdominal symptoms and endoscopic and histologic findings in patients with non-EoE-EGID, leading to the discontinuation of systemic steroid administration and tolerance of causative foods.
Clinicopathological and prognostic value of calcification morphology descriptors in ductal carcinoma in situ of the breast: a systematic review and meta-analysis
Authors: van Leeuwen Merle M. , Doyle Shannon , van den Belt–Dusebout Alexandra W. , van der Mierden Stevie , Loo Claudette E. , Mann Ritse M. , Teuwen Jonas , Wesseling Jelle 
Published: December 2023

Abstract
Background
Calcifications on mammography can be indicative of breast cancer, but the prognostic value of their appearance remains unclear. This systematic review and meta-analysis aimed to evaluate the association between mammographic calcification morphology descriptors (CMDs) and clinicopathological factors.

Methods
A comprehensive literature search in Medline via Ovid, Embase.com, and Web of Science was conducted for articles published between 2000 and January 2022 that assessed the relationship between CMDs and clinicopathological factors, excluding case reports and review articles. The risk of bias and overall quality of evidence were evaluated using the QUIPS tool and GRADE. A random-effects model was used to synthesize the extracted data. This systematic review is reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA).

Results
Among the 4715 articles reviewed, 29 met the inclusion criteria, reporting on 17 different clinicopathological factors in relation to CMDs. Heterogeneity between studies was present and the overall risk of bias was high, primarily due to small, inadequately described study populations. Meta-analysis demonstrated significant associations between fine linear calcifications and high-grade DCIS [pooled odds ratio (pOR), 4.92; 95% confidence interval (CI), 2.64–9.17], (comedo)necrosis (pOR, 3.46; 95% CI, 1.29–9.30), (micro)invasion (pOR, 1.53; 95% CI, 1.03–2.27), and a negative association with estrogen receptor positivity (pOR, 0.33; 95% CI, 0.12–0.89).

Conclusions
CMDs detected on mammography have prognostic value, but there is a high level of bias and variability between current studies. In order for CMDs to achieve clinical utility, standardization in reporting of CMDs is necessary.

Critical relevance statement
Mammographic calcification morphology descriptors (CMDs) have prognostic value, but in order for CMDs to achieve clinical utility, standardization in reporting of CMDs is necessary.

Systematic review registration
CRD42022341599

Key points
• Mammographic calcifications can be indicative of breast cancer.
• The prognostic value of mammographic calcifications is still unclear.
• Specific mammographic calcification morphologies are related to lesion aggressiveness.
• Variability between studies necessitates standardization in calcification evaluation to achieve clinical utility.

Graphical Abstract
Emerging role of mesenchymal stromal cells in gynecologic cancer therapy
Authors: Song Yizuo , Liu Hejing , Pan Shuya , Xiang Xinli , Ye Miaomiao , Zhu Xueqiong 
Published: December 2023

AbstractMesenchymal stromal cells (MSCs) show considerable promise in regenerative medicine with superior anti-fibrotic, immunomodulatory, and angiogenic functions. More recently, discovered with the tumor tropism, MSCs have been exploited as the basis of targeted cancer therapy. In this scenario, MSCs can directly home to tumor tissues and play anti-tumor properties. In addition, MSCs, MSC-derived exosomes and MSC-derived membranes are often developed as carriers for precisely delivering cytotoxic agents to cancer sites, including chemotherapeutic drugs, therapeutic genes, or oncolytic viruses. However, it has revealed the tumorigenic risk of MSCs as an important component within the tumor microenvironment, hampering the translation of MSC-based cancer therapies into clinical settings. Therefore, in this review, we introduce the specific tumor-tropic ability of MSCs and underlying mechanisms. We also summarize the current application of MSC-based therapeutic approaches in treating gynecologic cancers, mainly including cervical, ovarian, and endometrial cancers. Moreover, we discuss the main challenges that the current MSC-based cancer therapies are facing.
Gene editing and cardiac disease modelling for the interpretation of genetic variants of uncertain significance in congenital heart disease
Authors: Fear Vanessa S. , Forbes Catherine A. , Shaw Nicole C. , Farley Kathryn O. , Mantegna Jessica L. , Htun Jasmin P. , Syn Genevieve , Viola Helena , Cserne Szappanos Henrietta , Hool Livia , Ward Michelle , Baynam Gareth , Lassmann Timo 
Published: December 2023

Abstract
Background
Genomic sequencing in congenital heart disease (CHD) patients often discovers novel genetic variants, which are classified as variants of uncertain significance (VUS). Functional analysis of each VUS is required in specialised laboratories, to determine whether the VUS is disease causative or not, leading to lengthy diagnostic delays. We investigated stem cell cardiac disease modelling and transcriptomics for the purpose of genetic variant classification using a GATA4 (p.Arg283Cys) VUS in a patient with CHD.

Methods
We performed high efficiency CRISPR gene editing with homology directed repair in induced pluripotent stem cells (iPSCs), followed by rapid clonal selection with amplicon sequencing. Genetic variant and healthy matched control cells were compared using cardiomyocyte disease modelling and transcriptomics.

Results
Genetic variant and healthy cardiomyocytes similarly expressed Troponin T (cTNNT), and GATA4. Transcriptomics analysis of cardiomyocyte differentiation identified changes consistent with the patient’s clinical human phenotype ontology terms. Further, transcriptomics revealed changes in calcium signalling, and cardiomyocyte adrenergic signalling in the variant cells. Functional testing demonstrated, altered action potentials in GATA4 genetic variant cardiomyocytes were consistent with patient cardiac abnormalities.

Conclusions
This work provides in vivo functional studies supportive of a damaging effect on the gene or gene product. Furthermore, we demonstrate the utility of iPSCs, CRISPR gene editing and cardiac disease modelling for genetic variant interpretation. The method can readily be applied to other genetic variants in GATA4 or other genes in cardiac disease, providing a centralised assessment pathway for patient genetic variant interpretation.
Association between body mass index and myopia in the United States population in the National Health and Nutrition Examination Surveys 1999 to 2008: a cross-sectional study
Authors: Qu Yaohui , Huang Huamin , Zhang Hongxing 
Published: December 2023

Abstract
Background
This study investigated the association between body mass index (BMI) and myopia in the United States.

Methods
This cross-sectional study included 8,000 participants from the 1999 to 2008 National Health and Nutrition Examination Survey (NHANES). BMI was classified into four groups: < 18.5, 18.5 – 24.9, 25–29.9, and > 29.9. Three diagnostic thresholds were used for myopia A\B\C: spherical equivalent ≤ −0.5\−0.75\−1 diopters in the right eye. Multivariate logistic regression analysis and smooth curve fitting were performed to evaluate the association between BMI and myopia.

Results
The incidence of myopia was 39.4%. BMI was correlated with myopia, with each 1 kg/m2 increase in BMI associated with a 1% increase in the risk of myopia (OR, 1.01; 95% CI 1.01 1.02; p < 0.05). In myopia B, after adjusting for confounding factors, compared with the reference group (BMI 18.5–24.9), participants with a BMI of 25–29.9 and greater than 29.9 had a 14% and 25% increased risk of myopia, respectively (OR 1.14; 95% CI 1.01 1.29; p = 0.037, OR 1.25; 95% CI 1.08 1.44; p = 0.003), which was similar to the results for myopic A (OR, 1.15; 95% CI 1.02 1.3; p = 0.027, OR 1.19; 95% CI 1.03 1.37; p = 0.018) and myopia C (OR 1.15; 95% CI 1.01 1.31; p = 0.035, OR 1.18; 95% CI 1.01 1.37; p = 0.032). Moreover, there was a linear relationship between myopia and BMI (p for nonlinearity = 0.767).

Conclusions
Myopia using all three diagnostic thresholds was positively associated with higher BMI. This suggests a potential association between myopia and higher BMI in the American population, warranting further investigations.
Role of the CASZ1 transcription factor in tissue development and disease
Authors: Liu Tiantian , Li Tao , Ke Shaorui 
Published: December 2023

AbstractThe zinc finger transcription factor gene, CASZ1/Castor (Castor zinc finger 1), initially identified in Drosophila, plays a critical role in neural, cardiac, and cardiovascular development, exerting a complex, multifaceted influence on cell fate and tissue morphogenesis. During neurogenesis, CASZ1 exhibits dynamic expression from early embryonic development to the perinatal period, constituting a key regulator in this process. Additionally, CASZ1 controls the transition between neurogenesis and gliomagenesis. During human cardiovascular system development, CASZ1 is essential for cardiomyocyte differentiation, cardiac morphogenesis, and vascular morphology homeostasis and formation. The deletion or inactivation of CASZ1 mutations can lead to human developmental diseases or tumors, including congenital heart disease, cardiovascular disease, and neuroblastoma. CASZ1 can be used as a biomarker for disease prevention and diagnosis as well as a prognostic indicator for cancer. This review explores the unique functions of CASZ1 in tissue morphogenesis and associated diseases, offering new insights for elucidating the molecular mechanisms underlying diseases and identifying potential therapeutic targets for disease prevention and treatment.
The economic fitness of nations in value added. 2000–2014
Authors: Cervantes-Martínez Rosario , Villaseñor–Becerra Jorge 
Published: December 2023

AbstractIn this paper, we explore the Economic Fitness (EF) indicator from the World Bank Database that measures the nations level of international competitiveness. At the same time, using input–output tables, we present our estimations of this new metric, replacing the revealed comparative advantages (RCA) from exports in gross value with an estimate of RCA from exports in domestic value-added (DVA). We find that between 1995 and 2015, there is a positive relationship between Economic Fitness and per capita GDP for low and middle-income countries. Besides, we also show that the estimations of the EF using the domestic value-added content of exports changed significantly from 2000 to 2014 since there has been a widening gap between global exports in gross value and exports in value-added. The latter suggests that, given the increasing levels of productive links at the international level, the competitiveness of nations is also conditioned by how they participate in global production networks.
Umbilical cord blood and cord tissue banking as somatic stem cell resources to support medical cell modalities
Authors: Nagamura-Inoue Tokiko , Nagamura Fumitaka 
Published: December 2023

AbstractHuman umbilical cord blood (CB) and umbilical cord tissue (UC) are attractive sources of somatic stem cells for gene and cell therapies. CB and UC can be obtained noninvasively from donors. CB, a known source of hematopoietic stem cells for transplantation, has attracted attention as a new source of immune cells, including universal chimeric antigen receptor-T cell therapy (CAR-T) and, more recently, universal CAR-natural killer cells. UC-derived mesenchymal stromal cells (UC-MSCs) have a higher proliferation potency than those derived from adult tissues and can be used anon-HLA restrictively. UC-MSCs meet the MSC criteria outlined by the International Society of Gene and Cellular Therapy. UC-MSCs are negative for HLA-DR, CD80, and CD86 and have an immunosuppressive ability that mitigates the proliferation of activated lymphocytes through secreting indoleamine 2,3-dioxygenase 1 and prostaglandin E2, and the expression of PD-L2 and PD-L1. We established the off-the-shelf cord blood/cord bank IMSUT CORD to support novel cell therapy modalities, including the CB-derived immune cells, MSCs, MSCs-derived extracellular vesicles, biological carriers loaded with chemotherapy drugs, prodrug, oncolytic viruses, nanoparticles, human artificial chromosome, combinational products with a scaffold, bio3D printing, and so on.
Evaluation of MR-safe bioptomes for MR-guided endomyocardial biopsy in minipigs: a potential radiation-free clinical approach
Authors: Svetlove Angelika , Ritter Christian O. , Dullin Christian , Schmid Michael , Schauer Senta , Uihlein Johannes , Uecker Martin , Mietsch Matthias , Stadelmann Christine , Lotz Joachim , Unterberg-Buchwald Christina 
Published: December 2023

Abstract
Background
Diagnostic accuracy of endomyocardial biopsy could improve if clinically safe magnetic resonance (MR)-compatible bioptomes were available. We explored two novel MR-compatible cardiac bioptomes for performance, safety, and clinical viability, employing in vivo minipig trials and phase-contrast synchrotron radiation computed microtomography (SRµCT).

Methods
Analysis of ex vivo obtained pig endomyocardial biopsies was performed using phase-contrast SRµCT and conventional two-dimensional histology. The technical performance was evaluated by measuring volume, inner and outer integrities, compression, and histological diagnostic value in 3 sets (6 per set) of biopsies for each experimental bioptome. The bioptomes were tested in vivo in 3 healthy minipigs per bioptome. The clinical feasibility was evaluated by procedural and cutting success as well as histological diagnostic value.

Results
The bioptome with the ‘grind-grind’ design achieved similar values to control in compression (p = 0.822), inner (p = 0.628), and outer (p = 0.507), integrities ex vivo. It showed a better performance in the in vivo real-time MRI setting demonstrating a higher cutting success (91.7%) than the ‘grind-anvil’ (86.2%) design. In both ex vivo and in vivo evaluations, the ‘grind-grind’ design displayed sufficient diagnostic value (83% and 95%). The ‘grind-anvil’ design showed adequate diagnostic value both ex vivo and in vivo (78% and 87.5%) but was not comparable to control according to the three-dimensional (3D) analysis.

Conclusion
A novel MR-compatible bioptome was identified as plausible in a clinical setting. Additionally, SRµCT and subsequent 3D structural analysis could be valuable in the label-free investigation of myocardial tissue at a micrometer level.

Relevance statement
Implementation of MR-guided biopsy can improve animal studies on structural myocardial changes at any point in an experimental setup. With further improvements in guiding catheters, MR-guided biopsy, using the new bioptome, has a potential to increase quality and diagnostic accuracy in patients both with structural and inflammatory cardiomyopathies.

Key points
• Novel MR-compatible bioptomes show promise for a clinical application.
• SRµCT enabled detailed analysis of endomyocardial biopsies.
• The bioptomes showed adequate in vivo performance without major complications.

Graphical Abstract
Interactive Association Between Gut Microbiota and Thyroid Cancer
Authors: Hou Tianzhichao , Wang Qi , Dai Huajie , Hou Yanan , Zheng Jie , Wang Tiange , Lin Hong , Wang Shuangyuan , Li Mian , Zhao Zhiyun , Chen Yuhong , Xu Yu , Lu Jieli , Liu Ruixin , Ning Guang , Wang Weiqing , Xu Min , Bi Yufang 
Published: December 2023

Abstract

Context
The association between the gut microbiota and thyroid cancer remains controversial.

Objective
We aimed to systematically investigate the interactive causal relationships between the abundance and metabolism pathways of gut microbiota and thyroid cancer.

Methods
We leveraged genome-wide association studies for the abundance of 211 microbiota taxa from the MiBioGen study (N = 18 340), 205 microbiota metabolism pathways from the Dutch Microbiome Project (N = 7738), and thyroid cancer from the Global Biobank Meta-analysis Initiative (N cases = 6699 and N participants = 1 620 354). We performed a bidirectional Mendelian randomization (MR) to investigate the causality from microbiota taxa and metabolism pathways to thyroid cancer and vice versa. We performed a systematic review of previous observational studies and compared MR results with observational findings.

Results
Eight taxa and 12 metabolism pathways had causal effects on thyroid cancer, where RuminococcaceaeUCG004 genus (P = .001), Streptococcaceae family (P = .016), Olsenella genus (P = .029), ketogluconate metabolism pathway (P = .003), pentose phosphate pathway (P = .016), and L-arginine degradation II in the AST pathway (P = .0007) were supported by sensitivity analyses. Conversely, thyroid cancer had causal effects on 3 taxa and 2 metabolism pathways, where the Holdemanella genus (P = .015) was supported by sensitivity analyses. The Proteobacteria phylum, Streptococcaceae family, Ruminococcus2 genus, and Holdemanella genus were significantly associated with thyroid cancer in both the systematic review and MR, whereas the other 121 significant taxa in observational results were not supported by MR.

Discussions
These findings implicated the potential role of host-microbiota crosstalk in thyroid cancer, while the discrepancy among observational studies calls for further investigations.