bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating individualized treatment effects from randomized controlled trials: a simulation study to compare risk-based approaches
Authors: Rekkas Alexandros , Rijnbeek Peter R. , Kent David M. , Steyerberg Ewout W. , van Klaveren David 
Published: March 2023

Abstract
Background
Baseline outcome risk can be an important determinant of absolute treatment benefit and has been used in guidelines for “personalizing” medical decisions. We compared easily applicable risk-based methods for optimal prediction of individualized treatment effects.

Methods
We simulated RCT data using diverse assumptions for the average treatment effect, a baseline prognostic index of risk, the shape of its interaction with treatment (none, linear, quadratic or non-monotonic), and the magnitude of treatment-related harms (none or constant independent of the prognostic index). We predicted absolute benefit using: models with a constant relative treatment effect; stratification in quarters of the prognostic index; models including a linear interaction of treatment with the prognostic index; models including an interaction of treatment with a restricted cubic spline transformation of the prognostic index; an adaptive approach using Akaike’s Information Criterion. We evaluated predictive performance using root mean squared error and measures of discrimination and calibration for benefit.

Results
The linear-interaction model displayed optimal or close-to-optimal performance across many simulation scenarios with moderate sample size (N = 4,250; ~ 785 events). The restricted cubic splines model was optimal for strong non-linear deviations from a constant treatment effect, particularly when sample size was larger (N = 17,000). The adaptive approach also required larger sample sizes. These findings were illustrated in the GUSTO-I trial.

Conclusions
An interaction between baseline risk and treatment assignment should be considered to improve treatment effect predictions.
Real-world management and outcomes of older patients with locally advanced esophageal squamous cell carcinoma: a multicenter retrospective study
Authors: Saito Yuki , Hamamoto Yasuo , Hirata Kenro , Yamasaki Makoto , Watanabe Masaya , Abe Tetsuya , Tsubosa Yasuhiro , Hamai Yoichi , Murakami Kentaro , Bamba Takeo , Yoshii Takako , Tsuda Masahiro , Watanabe Masayuki , Ueno Masaki , Kitagawa Yuko 
Published: March 2023

Abstract
Background
Neoadjuvant chemotherapy (NAC) followed by surgery is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). Chemoradiotherapy (CRT) is an alternative treatment approach. However, both treatments are associated with toxicity, and the optimal treatment for older patients with ESCC is unknown. This study aimed to evaluate the treatment strategies and prognosis of older patients with locally advanced ESCC in a real-world setting.

Methods
We retrospectively evaluated 381 older patients (≥ 65 years) with locally advanced ESCC (stage IB/II/III, excluding T4) who received anticancer therapy at 22 medical centers in Japan. Based on age, performance status (PS), and organ function, the patients were classified into two groups: clinical trial eligible and ineligible groups. Patients aged ≤ 75 years with adequate organ function and a PS of 0–1 were categorized into the eligible group. We compared the treatments and prognoses between the two groups.

Results
The ineligible group had significantly shorter overall survival (OS) than the eligible group (hazard ratio [HR] for death, 1.65; 95% confidence interval [CI], 1.22–2.25; P = 0.001). The proportion of patients receiving NAC followed by surgery was significantly higher in the eligible group than in the ineligible group (P = 1.07 × 10–11), whereas the proportion of patients receiving CRT was higher in the ineligible group than in the eligible group (P = 3.09 × 10–3). Patients receiving NAC followed by surgery in the ineligible group had comparable OS to those receiving the same treatment in the eligible group (HR, 1.02; 95% CI, 0.57–1.82; P = 0.939). In contrast, patients receiving CRT in the ineligible group had significantly shorter OS than those receiving CRT in the eligible group (HR, 1.85; 95% CI, 1.02–3.37; P = 0.044). In the ineligible group, patients receiving radiation alone had comparable OS to those receiving CRT (HR, 1.13; 95% CI, 0.58–2.22; P = 0.717).

Conclusions
NAC followed by surgery is justified for select older patients who can tolerate radical treatment, even if they are old or vulnerable to enrollment in clinical trials. CRT did not provide survival benefits over radiation alone in patients ineligible for clinical trials, suggesting the need to develop less-toxic CRT.
Machine learning integrations develop an antigen-presenting-cells and T-Cells-Infiltration derived LncRNA signature for improving clinical outcomes in hepatocellular carcinoma
Authors: Wang Xiaodong , Chen Ji , Lin Lifan , Li Yifei , Tao Qiqi , Lang Zhichao , Zheng Jianjian , Yu Zhengping 
Published: March 2023

AbstractAs a highly heterogeneous cancer, the prognostic stratification and personalized management of hepatocellular carcinoma (HCC) are still challenging. Recently, Antigen-presenting-cells (APCs) and T-cells-infiltration (TCI) have been reported to be implicated in modifying immunology in HCC. Nevertheless, the clinical value of APCs and TCI-related long non-coding RNAs (LncRNAs) in the clinical outcomes and precision treatment of HCC is still obscure. In this study, a total of 805 HCC patients were enrolled from three public datasets and an external clinical cohort. 5 machine learning (ML) algorithms were transformed into 15 kinds of ML integrations, which was used to construct the preliminary APC-TCI related LncRNA signature (ATLS). According to the criterion with the largest average C-index in the validation sets, the optimal ML integration was selected to construct the optimal ATLS. By incorporating several vital clinical characteristics and molecular features for comparison, ATLS was demonstrated to have a relatively more significantly superior predictive capacity. Additionally, it was found that the patients with high ATLS score had dismal prognosis, relatively high frequency of tumor mutation, remarkable immune activation, high expression levels of T cell proliferation regulators and anti-PD-L1 response as well as extraordinary sensitivity to Oxaliplatin/Fluorouracil/Lenvatinib. In conclusion, ATLS may serve as a robust and powerful biomarker for improving the clinical outcomes and precision treatment of HCC.
Indications and outcomes of intraocular Lens Exchange among pseudophakic eyes in a Tertiary Referral Center
Authors: Jafarinasab Mohammadreza , Kalantarion Masomeh , Hooshmandi Sadid , Hassanpour Kiana , Najdi Danial , Kheiri Bahareh , Sabbaghi Hamideh 
Published: March 2023

Abstract
Purpose
To determine the indications and surgical outcomes of intraocular lens (IOL) exchange in pseudophakic patients at Labbafinejad Tertiary Referral Center between 2014 and 2019.

Methods
In this retrospective interventional case series, the medical records of 193 patients with a history of IOL exchange were reviewed. Preoperative data, including clinical characteristics, indications of the first and second IOL implantation, intra- and postoperative complications due to IOL exchange, and the pre-and postoperative refractive error and best-corrected visual acuity (BCVA) were considered the outcome measures in this study. All postoperative data were analyzed at least six months after follow-up.

Results
The mean age of our participants was 59.13 ± 20.97 years old at the time of the IOL exchange, with a male percentage of 63.2%. The mean follow-up after the IOL exchange was 15.72 ± 16.28 months. The main indications of IOL exchange were IOL decentration (50.3%), corneal decompensation (30.6%), and residual refractive errors (8.3%). 57.10% of patients with the postoperative spherical equivalent at -2.00 diopter (D) to + 2.00D. The mean best-corrected visual acuity was 0.82 ± 0.76 LogMAR before the IOL exchange and was improved to 0.73 ± 0.79 LogMAR after the surgery. Corneal decompensation (6.2%), glaucoma (4.7%), retinal detachment (4.1%), cystoid macular edema (2.1%), and uveitis (1%) were found as the postoperative complications. There was only one case with suprachoroidal hemorrhage during IOL exchange.

Conclusions
IOL decentration followed by corneal decompensation was the most common indication of IOL exchange. After IOL exchange, the most complications during follow-up were corneal decompensation, glaucoma, retinal detachment, and cystoid macular edema.
The subjective controllability of exotropia and its effect on surgical outcomes in patients with intermittent exotropia
Authors: Kim Mirae , Kim Hong Kyun , Kim Won Jae 
Published: March 2023

Abstract
Background/aims
We evaluate the clinical characteristics of intermittent exotropia with controllability and compare surgical outcomes between patients with and without controllability.

Methods
We reviewed the medical records of patients aged 6–18 years with intermittent exotropia who underwent surgery between September 2015 and September 2021. Controllability was defined as the patient’s subjective awareness of exotropia or diplopia associated with the presence of exotropia and ability to instinctively correct the ocular exodeviation. Surgical outcomes were compared between patients with and without controllability, with a favorable surgical outcome defined as an ocular deviation between ≤ 10 PD of exotropia and ≤ 4 PD of esotropia at distance and near.

Results
Among 521 patients, 130 (25%, 130/521) had controllability. The mean age of onset (7.7 years) and surgery (9.9 years) were higher in patients with controllability than in those without controllability (p < 0.001). The mean control scores of patients with controllability (distance: 1.9, near: 1.5) were lower compared with patients without controllability (distance: 3.0, near: 2.2), reflecting a better level of control. Patients with controllability had a better surgical outcome than those without controllability, as analyzed by log-rank test (p < 0.001). Larger preoperative ocular exodeviation at distance (hazard ratio [HR] = 1.083, confidence interval [CI] = 1.018–1.151, p = 0.012) and near (HR = 1.102, CI = 1.037–1.172, p = 0.002) were significantly related to recurrence in patients with controllability.

Conclusions
Patients with controllability showed better surgical outcomes, later exotropia onset, and better level of control than patients without controllability. Preoperative ocular exodeviation was a significant factor influencing favorable outcomes in patients with controllable exotropia.
Factors associated with public awareness of the relationship between alcohol use and breast cancer risk
Authors: Doyle Anne , O’Dwyer Claire , Mongan Deirdre , Millar Seán R. , Galvin Brian 
Published: March 2023

Abstract
Background
Public awareness of the carcinogenic effects of alcohol is low, particularly the association between alcohol use and the risk of developing breast cancer. Breast cancer is the third most common cancer in Ireland and alcohol use remains high. This study examined factors related to awareness of the association between alcohol use and breast cancer risk.

Methods
Using data from Wave 2 of the national Healthy Ireland Survey, a representative sample of 7,498 Irish adults aged 15 + years, descriptive and logistic regression analyses were conducted to investigate relationships between demographic characteristics, type of drinker and awareness of breast cancer risk.

Results
A low level of awareness of the risk of alcohol use (drinking more than the recommended low–risk limit) associated with breast cancer was found, with just 21% of respondents correctly identifying the relationship. Multivariable regression analyses found that factors most strongly associated with awareness were sex (female), middle age (45—54 years) and higher educational levels.

Conclusion
As breast cancer is a prevalent disease among women in Ireland, it is essential that the public, in particular women who drink, are made aware of this association. Public health messages that highlight the health risks associated with alcohol use, and which target individuals with lower educational levels, are warranted.
Implementation fidelity to a behavioral diabetes prevention intervention in two New York City safety net primary care practices
Authors: Gupta Avni , Hu Jiyuan , Huang Shengnan , Diaz Laura , Gore Radhika , Levy Natalie , Bergman Michael , Tanner Michael , Sherman Scott E. , Islam Nadia , Schwartz Mark D. 
Published: March 2023

Abstract
Background
It is critical to assess implementation fidelity of evidence-based interventions and factors moderating fidelity, to understand the reasons for their success or failure. However, fidelity and fidelity moderators are seldom systematically reported. The study objective was to conduct a concurrent implementation fidelity evaluation and examine fidelity moderators of CHORD (Community Health Outreach to Reduce Diabetes), a pragmatic, cluster-randomized, controlled trial to test the impact of a Community Health Workers (CHW)-led health coaching intervention to prevent incident type 2 Diabetes Mellitus in New York (NY).

Methods
We applied the Conceptual Framework for Implementation Fidelity to assess implementation fidelity and factors moderating it across the four core intervention components: patient goal setting, education topic coaching, primary care (PC) visits, and referrals to address social determinants of health (SDH), using descriptive statistics and regression models. PC patients with prediabetes receiving care from safety-net patient-centered medical homes (PCMHs) at either, VA NY Harbor or at Bellevue Hospital (BH) were eligible to be randomized into the CHW-led CHORD intervention or usual care. Among 559 patients randomized and enrolled in the intervention group, 79.4% completed the intake survey and were included in the analytic sample for fidelity assessment. Fidelity was measured as coverage, content adherence and frequency of each core component, and the moderators assessed were implementation site and patient activation measure.

Results
Content adherence was high for three components with nearly 80.0% of patients setting ≥ 1 goal, having ≥ 1 PC visit and receiving ≥ 1 education session. Only 45.0% patients received ≥ 1 SDH referral. After adjusting for patient gender, language, race, ethnicity, and age, the implementation site moderated adherence to goal setting (77.4% BH vs. 87.7% VA), educational coaching (78.9% BH vs. 88.3% VA), number of successful CHW-patient encounters (6 BH vs 4 VA) and percent of patients receiving all four components (41.1% BH vs. 25.7% VA).

Conclusions
The fidelity to the four CHORD intervention components differed between the two implementation sites, demonstrating the challenges in implementing complex evidence-based interventions in different settings. Our findings underscore the importance of measuring implementation fidelity in contextualizing the outcomes of randomized trials of complex multi-site behavioral interventions.

Trial registration
The trial was registered with ClinicalTrials.gov on 30/12/2016 and the registration number is NCT03006666.
Effect of preoperative dynamic cervical sagittal alignment on the loss of cervical lordosis after laminoplasty
Authors: Liu Chengxin , Shi Bin , Wang Wei , Li Xiangyu , Lu Shibao 
Published: March 2023

Abstract
Purpose
Cervical laminoplasty (CLP) is a developed surgical procedure for the treatment of cervical spondylotic myelopathy (CSM), but only a few of those studies focus on preoperative dynamic cervical sagittal alignment and the study of different degrees of loss of cervical lordosis (LCL) is lacking. This study aimed to analyze patients who underwent CLP to investigate the effect of cervical extension and flexion function on different degrees of LCL.

Methods
In this retrospective case–control study, we analyzed 79 patients who underwent CLP for CSM between January 2019 and December 2020. We measured the cervical sagittal alignment parameters on lateral radiographs (neutral, flexion, and extension positions) and used Japanese Orthopedic Association (JOA) score to assess clinical outcomes. We defined the extension ratio (EXR) as 100 × Ext ROM (cervical range of extension)/ROM (cervical range of motion). We observed the relationships between collected variables (demographic and radiological variables) and LCL. Patients were classified into the following three groups according to the LCL: stability group: (LCL ≤ 5°); mild loss group (5° < LCL ≤ 10°); and severe loss group (LCL > 10°). We compared the differences of collected variables (demographic, surgical and radiological variables) among the three groups.

Results
Seventy-nine patients were enrolled (mean age 62.92 years; 51 men, 28 women) in the study. Among the three groups, cervical Ext ROM was the best in the stability group (p < 0.01). Compared with the stability group, range of flexion (Flex ROM) was significantly higher (p < 0.05) and EXR was significantly lower (p < 0.01) in the severe loss group. Compared with the severe loss group, JOA recovery rates were better (p < 0.01) in the stability group. Receiver-operating characteristic curve (ROC) analysis to predict LCL > 10° (area under the curve = 0.808, p < 0.001). The cutoff value for EXR was 16.80%, with sensitivity and specificity of 72.5% and 82.4%, respectively.

Conclusion
CLP should be carefully considered for patients with a preoperative low Ext ROM and high Flex ROM, as a significant kyphotic change is likely to develop after surgery. EXR is a useful and simple index to predict significant kyphotic changes.
Drivers for low-value imaging: a qualitative study of stakeholders’ perspectives in Norway
Authors: Brandsæter Ingrid Øfsti , Andersen Eivind Richter , Hofmann Bjørn Morten , Kjelle Elin 
Published: March 2023

Abstract
Background
One kind of overutilization of diagnostic imaging is low-value imaging, i.e., imaging that does not lead to altered clinical pathways or improved health outcomes. Despite having well-documented extension and consequences, low-value imaging is still widespread. The objective of this study was to identify the drivers for the use of low-value imaging in the Norwegian healthcare services.

Methods
We conducted individual, semi-structured interviews among representatives from the health authorities, general practitioners, specialists working in hospitals, radiologists, radiographers, and managers of imaging departments. Data analysis was carried out in line with framework analysis consisting of five steps: Familiarization, indexing, charting, mapping, and interpretation.

Results
The analysis included 27 participants and resulted in two themes. The stakeholders identified drivers in the healthcare system and in the interaction between radiologists, referrers, and patients. The identified drivers were categorized in sub-themes, such as organization, communication, competence, expectations, defensive medicine, roles and responsibilities, and referral quality and time constraints. The drivers interact with each other and may strengthen the effect of other drivers.

Conclusions
Several drivers for low-value imaging in Norway were identified at all levels of the healthcare system. The drivers work simultaneously and synergistically. To free resources for high-value imaging, drivers should be targeted by appropriate measures at several levels to reduce low-value imaging.
Identifying potential biomarkers for the diagnosis and treatment of IgA nephropathy based on bioinformatics analysis
Authors: Li Xiaohui , Zeng Mengru , Liu Jialu , Zhang Shumin , Liu Yifei , Zhao Yuee , Wei Cong , Yang Kexin , Huang Ying , Zhang Lei , Xiao Li 
Published: March 2023

Abstract
Background
IgA nephropathy (IgAN) has become the leading cause of end-stage renal disease in young adults. Nevertheless, the current diagnosis exclusively relies on invasive renal biopsy, and specific treatment is deficient. Thus, our study aims to identify potential crucial genes, thereby providing novel biomarkers for the diagnosis and therapy of IgAN.

Methods
Three microarray datasets were downloaded from GEO official website. Differentially expressed genes (DEGs) were identified by limma package. GO and KEGG analysis were conducted. Tissue/organ-specific DEGs were distinguished via BioGPS. GSEA was utilized to elucidate the predominant enrichment pathways. The PPI network of DEGs was established, and hub genes were mined through Cytoscape. The CTD database was employed to determine the association between hub genes and IgAN. Infiltrating immune cells and their relationship to hub genes were evaluated based on CIBERSORT. Furthermore, the diagnostic effectiveness of hub markers was subsequently predicted using the ROC curves. The CMap database was applied to investigate potential therapeutic drugs. The expression level and diagnostic accuracy of TYROBP was validated in the cell model of IgAN and different renal pathologies.

Results
A total of 113 DEGs were screened, which were mostly enriched in peptidase regulator activity, regulation of cytokine production, and collagen-containing extracellular matrix. Among these DEGs, 67 genes manifested pronounced tissue and organ specificity. GSEA analysis revealed that the most significant enriched gene sets were involved in proteasome pathway. Ten hub genes (KNG1, FN1, ALB, PLG, IGF1, EGF, HRG, TYROBP, CSF1R, and ITGB2) were recognized. CTD showed a close connection between ALB, IGF, FN1 and IgAN. Immune infiltration analysis elucidated that IGF1, EGF, HRG, FN1, ITGB2, and TYROBP were closely associated with infiltrating immune cells. ROC curves reflected that all hub genes, especially TYROBP, exhibited a good diagnostic value for IgAN. Verteporfin, moxonidine, and procaine were the most significant three therapeutic drugs. Further exploration proved that TYROBP was not only highly expressed in IgAN, but exhibited high specificity for the diagnosis of IgAN.

Conclusions
This study may offer novel insights into the mechanisms involved in IgAN occurrence and progression and the selection of diagnostic markers and therapeutic targets for IgAN.