bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimated glucose disposal rate and risk of cardiovascular disease: evidence from the China Health and Retirement Longitudinal Study
Authors: Ren Xiao , Jiang Minglan , Han Longyang , Zheng Xiaowei 
Published: December 2022

Abstract
Objectives
Previous studies had reported that insulin resistance (assessed by estimated glucose disposal rate; eGDR) was associated with higher risk of cardiovascular events (CVD) in diabetes patients. The aim of present study was to investigate the potential association between eGDR and CVD in general population.

Methods
The China Health and Retirement Longitudinal Study with 8,267 individuals were included in analysis. Participants were divided into four subgroups according to eGDR quartile. Cox proportional hazards regression models were used to examine the associations of eGDR with CVD (stroke or cardiac events).

Results
During 6 years of follow-up, a total of 1,476 respondents experienced a CVD (494 stroke and 1,110 cardiac events). In multivariable-adjusted analyses, the corresponding hazard ratio (95% confidence intervals) for the highest eGDR versus lowest quartile of eGDR was 0.58(0.49–0.67) for CVD. Each 1-SD increase of eGDR was associated with 16% (HRs = 0.84; 0.79–0.88) decreased risk of CVD. There was also a significant linear association between eGDR and CVD (P for linearity < 0.001). Similar associations were also found between eGDR and stroke and cardiac events.

Conclusion
A higher eGDR (a measure of insulin resistance) was associated with a decreased risk of CVD, stroke and cardiac events in general Chinese population, suggesting that eGDR could be considered as a preferential predictor and treatment target of CVD. Future well-designed prospective clinical studies are needed to verify our findings and to assess the effect of eGDR interventions in CVD prevention and therapy.
A case report of neuromyelitis optica spectrum disorder induced by pembrolizumab treatment for lung adenocarcinoma: a clinical and immunohistochemical study
Authors: Hirano Shigeki , Kojima Akira , Nakayama Yoko , Takeda Takahiro , Kishimoto Takashi , Takahashi Toshiyuki , Kuwabara Satoshi , Mori Masahiro 
Published: December 2022

Abstract
Background
We report a case of neuromyelitis optica spectrum disorders (NMOSD), who developed after the pembrolizumab treatment, an immune checkpoint inhibitor, against lung adenocarcinoma. The present case is discussed with the lung adenocarcinoma specimen which was stained by aquaporin-4 (AQP4) and with literature review of NMOSD linked to immune checkpoint inhibitors.

Case presentation
A 62-year-old Japanese man presented with acute diencephalic syndrome, left optic neuritis, and myelitis 5 months after initiation of pembrolizumab treatment for lung adenocarcinoma. He was diagnosed with NMOSD based on serum anti-aquaporin-4 (AQP4) antibody positivity. Immunohistochemistry of lung biopsy samples showed AQP4 expression on CD68+ cells. This is the fifth reported case of AQP4+ NMOSD triggered by an immune checkpoint inhibitor and the first with a brain lesion. Four out of five NMOSD cases, including the present case and one case with lung metastasis, had lung cancer.

Conclusions
Immune checkpoint inhibitors may trigger AQP4+ NMOSD owing to their molecular similarity to AQP4 expressed in lung and glial tissues. Prompt brain/spinal cord imaging and anti-AQP4 antibody testing may facilitate early diagnosis of immune-mediated adverse event in central nervous system associated with immune checkpoint inhibitors.
Rationale and protocol design of a phase II study of first-line osimertinib treatment for patients with poor performance status and EGFR mutation-positive non-small cell lung cancer (OPEN/TORG2040)
Authors: Fukui Tomoya , Sasaki Jiichiro , Igawa Satoshi , Kada Akiko , Saito Toshiki I. , Kogure Yoshihito , Okamoto Hiroaki , Naoki Katsuhiko 
Published: December 2022

Abstract
Background
Cancer chemotherapy indications for patients with poor performance status and advanced lung cancer are limited. Molecular targeted drugs, including epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors, can be used in patients with poor performance status owing to their high efficacy and safety. The third-generation EGFR-tyrosine kinase inhibitor osimertinib has demonstrated effectiveness in the initial treatment of advanced EGFR mutation-positive non-small cell lung cancer in patients with good performance status; however, no evidence exists of the drug’s effectiveness in patients with poor performance status in a prospective study. We designed a study that aims to investigate the efficacy and safety of first-line osimertinib treatment in patients with advanced non-small cell lung cancer harboring sensitive EGFR mutations and with poor performance status.

Methods
The OPEN/TORG2040 study is a multicenter, single-arm, phase II trial for patients with unresectable, advanced EGFR mutation-positive non-small cell lung cancer with a poor performance status (≥ 2). Eligible patients will receive osimertinib until disease progression or unacceptable toxicity. The primary endpoint is the objective response rate of the first-line osimertinib treatment. Considering a threshold value of 45%, expected value of 70% for objective response rate, one-sided significance level of 5%, statistical power of 80%, and ineligible patients, the sample size was set to 30. The secondary endpoints are disease control rate, performance status improvement rate, and safety and patient-reported outcomes using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core Quality of Life Questionnaire and Lung Cancer 13. Time to treatment failure, progression-free survival, and overall survival will also be assessed.

Discussion
Our study can determine the clinical benefits of osimertinib treatment in patients with poor performance status, since the clinical outcomes of patients with EGFR mutation-positive non-small cell lung cancer with poor performance status treated with this drug as a first-line treatment have not been sufficiently evaluated.

Trial registration
Japan Registry of Clinical Trials: jRCTs041200100 (registration date: February 12, 2021).
Study on the efficacy and safety of foldable capsular vitreous body in the severe retinal detachment eyes
Authors: Ma Shengnan , Zhao Suzhen , Zhang Chunxiao , Tang Xia , Zhou Weiyan 
Published: December 2022

AbstractBackgroundThis study was to evaluate the efficacy and safety of the implantation of foldable capsular vitreous body (FCVB) in severe retinal detachment eyes.MethodsA retrospective study in retinal detachment eyes was performed at Shandong Provincial Hospital Affiliated to Shandong First Medical University. A standard three-port pars plana vitrectomy was performed, and the FCVB was triple folded and implanted into the vitreous cavity. The silicone oil (SO) was then injected into the capsule of the FCVB to support the retina and eye. During the follow-up period, The treated eyes were examined by ophthalmoscopy, fundus photography, and tonometry. B-scan ultrasonography, optical coherence tomography (OCT), and computed tomography (CT), were also performed.ResultsFrom May 2020 to November 2021, 31 cases with severe retinal detachment were enrolled in the study. The postoperative follow-up time gradient ranged from 1 to 72 weeks, At various observation time points during the 72 weeks after surgery, The postoperative IOP was maintained at around 10 mmhg at various time points, with a slight decrease compared to the preoperative IOP (14.2 ± 4.6 mmHgn = 18), and was statistically significant. 9 of 31 patients had clear refractive media, both fundus and OCT showed retinal reattachment, OCT showed the 200 μm thick FCVB capsule support retina. The remaining 22 patients with unclear refractive media, B-scan showed arcuate hyperechoes in front of the retina. There was also no significant difference in visual acuity compared to preoperative. The FCVB was well positioned in the vitreous cavity, and no serious complications such as endophthalmitis, glaucoma, silicone oil emulsification, product exposure, or sympathetic uveitis were found.ConclusionsFCVB has retinal support with certain ability to maintain IOP and eye morphology and avoid eye removal in patients with severe retinal detachment during the 72-week observation period.
Skeletal and dentoalveolar characteristics of maxillary lateral incisor agenesis patients: a comparative cross-sectional study
Authors: Tageldin Mostafa A. , Yacout Yomna M. , Marzouk Eiman S. 
Published: December 2022

Abstract
Background
The aim of the study was to evaluate the cephalometric and dentoalveolar characteristics of maxillary lateral incisor agenesis patients, and to compare the findings to a matched control group without tooth agenesis, excluding third molars, from the same population.

Methods
The pre-orthodontic records of 72 non-growing patients, who were treated at the Orthodontic Department, Faculty of Dentistry, Alexandria University, were used to address the aim of this retrospective study. Patients having unilateral or bilateral maxillary lateral incisor agenesis, with no history of previous orthodontic treatment, congenital craniofacial malformations, facial trauma, or surgeries were divided into two test groups based on the pattern of maxillary lateral incisors agenesis (group I: unilateral (UMLIA), group II: bilateral (BMLIA)). A control group (group III (CTRL)) having a complete set of permanent dentition (excluding third molars), and having no dental anomalies was age-matched with the test groups. Measurements were performed on the pre-orthodontic lateral cephalometric radiographs and the pre-orthodontic digital dental casts. The measured variables were compared between the groups using one-way ANOVA and Kruskal Wallis tests according to the normality of the variable. In case of significant results, both tests were followed by multiple pairwise comparisons using Bonferroni adjusted significance level. Significance level was set at P < 0.05.

Results
BMLIA group showed a smaller SNA angle and maxillary length, a more negative ANB angle and Wits appraisal, and a larger Maxillo-mandibular differential than UMLIA and/or CTRL group. The dental and soft tissue cephalometric measurements did not show any significant differences between the groups. Dentoalveolar cast measurements showed that BMLIA patients presented with significantly smaller maxillary inter-canine width than UMLIA and CTRL patients.

Conclusions
Cephalometric analysis has shown that subjects with BMLIA have a statistically significant reduced ANB and maxillary length. Tooth eruption may play a role in the development of the maxillary arch.
Development and pilot testing of a decision aid for navigating breast cancer survivorship care
Authors: Ke Yu , Cheng Ivy , Tan Gretchen Ser Hua , Fok Rose Wai Yee , Chan Jack Junjie , Loh Kiley Wei-Jen , Chan Alexandre 
Published: December 2022

Abstract
Background
The predominant oncologist-led model in many countries is unsustainable to meet the needs of a growing cohort of breast cancer survivors (BCS). Despite available alternative models, adoption rates have been poor. To help BCS navigate survivorship care, we aimed to systematically develop a decision aid (DA) to guide their choice of follow-up care model and evaluate its acceptability and usability among BCS and health care providers (HCPs).

Methods
We recruited BCS aged ≥ 21 years who have completed primary treatment and understand English. BCS receiving palliative care or with cognitive impairment were excluded. HCPs who routinely discussed post-treatment care with BCS were purposively sampled based on disciplines. Each participant reviewed the DA during a semi-structured interview using the ‘think aloud’ approach and completed an acceptability questionnaire. Descriptive statistics and directed content analysis were used.

Results
We conducted three rounds of alpha testing with 15 BCS and 8 HCPs. All BCS found the final DA prototype easy to navigate with sufficient interactivity. The information imbalance favouring the shared care option perceived by 60% of BCS in early rounds was rectified. The length of DA was optimized to be ‘just right’. Key revisions made included (1) presenting care options side-by-side to improve perceived information balance, (2) creating dedicated sections explaining HCPs’ care roles to address gaps in health system contextual knowledge, and (3) employing a multicriteria decision analysis method for preference clarification exercise to reflect the user’s openness towards shared care. Most BCS (73%) found the DA useful for decision-making, and 93% were willing to discuss the DA with their HCPs. Most HCPs (88%) agreed that the DA was a reliable tool and would be easily integrated into routine care.

Conclusions
Our experience highlighted the need to provide contextual information on the health care system for decisions related to care delivery. Developers should address potential variability within the care model and clarify inherent biases, such as low confidence levels in primary care. Future work could expand on the developed DA’s informational structure to apply to other care models and leverage artificial intelligence to optimize information delivery.
Clinicopathologic features and abnormal signaling pathways in plasmablastic lymphoma: a multicenter study in China
Authors: Shi Di , Gao Lin , Wan Xiao-Chun , Li Jin , Tian Tian , Hu Jue , Zhang Qun-Ling , Su Yi-Fan , Zeng Yu-Peng , Hu Zi-Juan , Yu Bao-Hua , Li Xiao-Qiu , Wei Ping , Li Ji-Wei , Zhou Xiao-Yan 
Published: December 2022

Abstract

Background
Plasmablastic lymphoma (PBL) is a rare but aggressive B-cell lymphoma subtype with poor prognosis. Knowledge about the etiology, clinicopathologic and molecular features, and outcomes of PBL is limited. This study aimed to examine the clinicopathologic characteristics, therapeutic approaches, and clinical outcomes of PBL patients in a Chinese population.

Methods
A total of 102 PBL patients were recruited from three cancer centers. The pathologic features and clinical outcomes of 56 patients with available treatment details and follow-up data were reviewed and analyzed. RNA sequencing was performed in 6 PBL and 11 diffuse large B-cell lymphoma (DLBCL) patients.

Results
Most patients in our cohort were male (n = 36, 64.3%), and 35 patients presented with Ann Arbor stage I/II disease at diagnosis. All these patients showed negative findings for human immunodeficiency virus, and the vast majority of patients in our cohort were immunocompetent. Lymph nodes (n = 13, 23.2%) and gastrointestinal tract (n = 10, 17.9%) were the most commonly involved site at presentation. Post-treatment complete remission (CR) was the only prognostic factor affecting overall survival (OS) and progression-free survival (PFS) in the multivariate analysis. RNA-seq demonstrated that B-cell receptor (BCR), T-cell receptor (TCR), P53, calcium signaling, and Wnt signaling pathways were significantly downregulated in PBLs compared with GCB (or non-GCB) DLBCLs.

Conclusions
In this multicenter study in the Chinese population, PBL mainly occurred in immunocompetent individuals and most patients present with early-stage disease at diagnosis. Post-treatment CR was an important prognostic factor affecting OS and PFS. RNA-seq showed that the B-cell receptor (BCR), P53, calcium signaling, cell adhesion molecules, and Wnt signaling pathways significantly differed between PBL and GCB (or non-GCB) DLBCL, which provided theoretical basis for its pathogenesis and future treatment.
Systematic analysis of relationships between plasma branched-chain amino acid concentrations and cardiometabolic parameters: an association and Mendelian randomization study
Authors: Doestzada Marwah , Zhernakova Daria V. , C. L. van den Munckhof Inge , Wang Daoming , Kurilshikov Alexander , Chen Lianmin , Bloks Vincent W. , van Faassen Martijn , Rutten Joost H. W. , Joosten Leo A. B. , Netea Mihai G. , Wijmenga Cisca , Riksen Niels P. , Zhernakova Alexandra , Kuipers Folkert , Fu Jingyuan 
Published: December 2022

Abstract
Background
Branched-chain
amino acids (BCAAs; valine, leucine, and isoleucine) are essential amino acids that are associated with an increased risk of cardiometabolic diseases (CMD). However, there are still only limited insights into potential direct associations between BCAAs and a wide range of CMD parameters, especially those remaining after correcting for covariates and underlying causal relationships.

Methods
To shed light on these relationships, we systematically characterized the associations between plasma BCAA concentrations and a large panel of 537 CMD parameters (including atherosclerosis-related parameters, fat distribution, plasma cytokine concentrations and cell counts, circulating concentrations of cardiovascular-related proteins and plasma metabolites) in 1400 individuals from the Dutch population cohort LifeLines DEEP and 294 overweight individuals from the 300OB cohort. After correcting for age, sex, and BMI, we assessed associations between individual BCAAs and CMD parameters. We further assessed the underlying causality using Mendelian randomization.

Results
A total of 838 significant associations were detected for 409 CMD parameters. BCAAs showed both common and specific associations, with the most specific associations being detected for isoleucine. Further, we found that obesity status substantially affected the strength and direction of associations for valine, which cannot be corrected for using BMI as a covariate. Subsequent univariable Mendelian randomization (UVMR), after removing BMI-associated SNPs, identified seven significant causal relationships from four CMD traits to BCAA levels, mostly for diabetes-related parameters. However, no causal effects of BCAAs on CMD parameters were supported.

Conclusions
Our cross-sectional association study reports a large number of associations between BCAAs and CMD parameters. Our results highlight some specific associations for isoleucine, as well as obesity-specific effects for valine. MR-based causality analysis suggests that altered BCAA levels can be a consequence of diabetes and alteration in lipid metabolism. We found no MR evidence to support a causal role for BCAAs in CMD. These findings provide evidence to (re)evaluate the clinical importance of individual BCAAs in CMD diagnosis, prevention, and treatment.
Patients with type 1 and type 2 diabetes hospitalized with COVID-19 in comparison with influenza: mortality and cardiorenal complications assessed by nationwide Swedish registry data
Authors: Kristófi Robin , Bodegard Johan , Ritsinger Viveca , Thuresson Marcus , Nathanson David , Nyström Thomas , Norhammar Anna , Eriksson Jan W. 
Published: December 2022

Abstract
Background
The risk of severe coronavirus disease 2019 (COVID-19) is increased in people with diabetes, but effects of diabetes type and other risk factors remain incompletely characterized. We studied this in a Swedish cohort of hospitalized patients with type 1 and type 2 diabetes (T1D and T2D), also including comparisons with influenza epidemics of recent years.

Methods
Nationwide healthcare registries were used to identify patients. A total of 11,005 adult patients with diabetes (T1D, n = 373; T2D, n = 10,632) were hospitalized due to COVID-19 from January 1, 2020 to September 1, 2021. Moreover, 5111 patients with diabetes (304 T1D, 4807 T2D) were hospitalized due to influenza from January 1, 2015 to December 31, 2019. Main outcomes were death within 28 days after admission and new hospitalizations for heart failure (HF), chronic kidney disease (CKD), cardiorenal disease (CRD; composite of HF and CKD), myocardial infarction (MI) and stroke during 1 year of follow-up.

Results
Number of deaths and CRD events were 2025 and 442 with COVID-19 and 259 and 525 with influenza, respectively. Age- and sex-adjusted Cox regression models in COVID-19 showed higher risk of death and HF in T1D vs. T2D, hazard ratio (HR) 1.77 (95% confidence interval 1.41–2.22) and 2.57 (1.31–5.05). With influenza, T1D was associated with higher risk of death compared with T2D, HR 1.80 (1.26–2.57). Older age and previous CRD were associated with higher risks of death and hospitalization for CRD. After adjustment for prior comorbidities, mortality differences were still significant, but there were no significant differences in cardiovascular and renal outcomes. COVID-19 relative to influenza was associated with higher risk of death in both T1D and T2D, HR 2.44 (1.60–3.72) and 2.81 (2.59–3.06), respectively.

Conclusions
In Sweden, patients with T1D as compared to T2D had a higher age- and sex-adjusted risk of death within 28 days and HF within one year after COVID-19 hospitalization, whereas the risks of other non-fatal cardiovascular and renal disease events were similar. Patients with T1D as well as T2D have a greater mortality rate when hospitalized due to COVID-19 compared to influenza, underscoring the importance of vaccination and other preventive measures against COVID-19 for diabetes patients.
Assessing the health risk of living near composting facilities on lung health, fungal and bacterial disease in cystic fibrosis: a UK CF Registry study
Authors: Khan Muhammad Saleem , Douglas Philippa , Hansell Anna L. , Simmonds Nicholas J. , Piel Frédéric B. 
Published: December 2022

Abstract
Aim
To explore the health risk of living near permitted composting sites (PCSs) on disease severity in children and adults with cystic fibrosis (CF) across the UK.

Methods
A semi-individual cross-sectional study was used to examine the risk of disease severity in people with CF (pwCF) within and beyond 4 km of PCSs in the UK in 2016. All pwCF registered in the UK CF Registry were eligible for this study. Linear and Poisson regressions, adjusted for age, gender, genotype, BMI, Pseudomonas aeruginosa and deprivation, were used to quantify associations between distance to a PCS and percent predicted forced expiratory volume in one second (ppFEV1), pulmonary exacerbations (#IVdays), and fungal and bacterial infections.

Results
The mean age of the 9,361 pwCF (3,931 children and 5,430 adults) studied was 20.1 (SD = 14.1) years; 53.3% were male; and 49.2% were homozygous F508del. Over 10% of pwCF (n = 1,015) lived within 4 km of a PCS. We found no statistically significant difference in ppFEV1 and #IVdays/year in children. However, in adults, ppFEV1 was -1.07% lower (95% confidence interval (CI): -2.29%, 0.16%) and #IVdays/year were 1.02 day higher (95%CI: 1.01, 1.04) within 4 km of a PCS. Furthermore, there were statistically significant differences in mean ppFEV1 in CF adults with Aspergillus fumigatus (58.2.% vs 62.0%, p = 0.005) and Candida spp. (56.9% vs 59.9%, p = 0.029) residing within 4 km of a PCS. No associations were identified for allergic bronchopulmonary aspergillosis, P. aeruginosa or Staphylococcus aureus.

Conclusions
This novel national study provides evidence that adults with CF living near a PCS may experience small reductions in lung function, an increased risk of pulmonary exacerbations, and more frequent fungal infections. If confirmed by studies using refined exposure assessment methods accounting for bioaerosol dispersion, these results could have important implications for the living environment of pwCF.