bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Indirect Impact of COVID-19 on Major Clinical Outcomes of People With Parkinson's Disease or Parkinsonism: A Cohort Study
Authors: Vignatelli Luca , Baccari Flavia , Belotti Laura Maria Beatrice , Zenesini Corrado , Baldin Elisa , Calandra-Buonaura Giovanna , Cortelli Pietro , Descovich Carlo , Giannini Giulia , Guarino Maria , Loddo Giuseppe , Nassetti Stefania Alessandra , Sambati Luisa , Scaglione Cesa , Trombetti Susanna , D'Alessandro Roberto , Nonino Francesco 
Published: May 2022

BackgroundThe indirect impact of the COVID-19 epidemic on major clinical outcomes of people with Parkinson's disease (PD) or other parkinsonism is unknown.ObjectivesThe study aimed to (1) describe changes in healthcare services during the first epidemic bout in people with PD or parkinsonism; (2) compare the occurrence of hospitalization for any PD-related major clinical outcomes in 2020 with 2019; (3) investigate the factors, including changes in healthcare services, associated with major clinical outcomes and death.MethodsAll healthcare services of the province of Bologna and major clinical outcomes were assessed through a record linkage study (ParkLink Bologna) using clinical data and health databases. Same analyses were performed in a random cohort of controls matched for age, sex, district of residence, and comorbidities with the ParkLink cohort (ratio of 1:10).ResultsA cohort of subjects with PD (759) or other parkinsonism (192) was included together with a cohort of controls (9,226). All indicators of healthcare services dropped at least below 50% during the lockdown period in all cohorts, mostly impacting physiotherapy in people with PD (−93%, 95% CI 88–96%). In 2020, compared to 2019, a three-fold risk of major injuries (RR 3.0, 95% CI 1.5–6.2) and infections (RR 3.3, 95% CI 1.5–7.2), excluding COVID-19, was observed only in people with PD, and neither in people with parkinsonism nor in controls. Decreased physiotherapy was associated with the occurrence of at least one major clinical outcome (OR 3.3, 95% CI 1.1–9.8) in people with PD. Experiencing at least one major clinical outcome was the strongest risk factor for death (OR 30.4, 95% CI 11.1–83.4) in people with PD.ConclusionsDuring the first COVID-19 epidemic peak, healthcare services were drastically reduced in a province of northern Italy, regardless of the disease condition. However, compared to 2019, in 2020, only people with PD had a higher risk of major clinical outcomes, that were associated with higher mortality. Strategies to maintain physical activity in people with PD should be implemented in possible future health emergencies.
Correlations Between Structural Brain Abnormalities, Cognition and Electroclinical Characteristics in Patients With Juvenile Myoclonic Epilepsy
Authors: Zhang Jun , Wu Dan , Yang Haoran , Lu Hongjuan , Ji Yichen , Liu Huixin , Zang Zhenxiang , Lu Jie , Sun Wei 
Published: May 2022

ObjectiveTo explore the structural brain abnormality and its relationship with neuropsychological disorders and electroclinical characteristics in juvenile myoclonic epilepsy (JME) patients.MethodsSixty-seven patients diagnosed with JME and 56 healthy controls were enrolled. All subjects underwent MRI using T1-weighted 3D brain structural images with 1 mm thickness. Voxel-based morphometry (VBM) and surface-based morphometry (SBM) analyses were performed. They also underwent a series of neuropsychological tests to assess cognitive function. The correlation analyses were conducted between structural changes, neuropsychological outcomes, and electroclinical features.ResultsThe gray matter concentration (GMC) was decreased in the bilateral pre-central and post-central gyrus, right anterior cingulate gyrus, left posterior orbital region, bilateral occipital regions, bilateral hippocampus and bilateral caudate nucleus in the JME groups (corrected P &lt; 0.05). The evaluation of gray matter volume (GMV) showed significant decrease respectively in bilateral pre-central and post-central gyrus, left paracentral lobule, left orbital gyrus, left amygdala, left basal ganglia and left thalamus of JME patients (P &lt; 0.05). The cortex thicknesses of the right inferior temporal gyrus, right insular gyrus, and right cingulate gyrus had negative correlations with the disease duration significantly. At the same time, the whole-brain white matter volume was positively associated with the course of the disease (P &lt; 0.05). Patients with persistent abnormal EEG discharges had significantly less whole-brain gray matter volume than JME patients with normal EEG (P = 0.03). Correlation analyses and linear regression analyses showed that, in addition to the gray matter volumes of frontal and parietal lobe, the temporal lobe, as well as the basal ganglia and thalamus, were also significantly correlated with neuropsychological tests' results (P &lt; 0.05).ConclusionThe JME patients showed subtle structural abnormalities in multiple brain regions that were not only limited to the frontal lobe but also included the thalamus, basal ganglia, parietal lobe, temporal lobe and some occipital cortex, with significant involvement of the primary somatosensory cortex and primary motor cortex. And we significantly demonstrated a correlation between structural abnormalities and cognitive impairment. In addition, the course of disease and abnormal discharges had a specific negative correlation with the structural changes.
Association Between Dietary Fatty Acid Pattern and Risk of Oral Cancer
Authors: Fan Yi , Qiu Yu , Wang Jing , Chen Qing , Wang Sijie , Wang Yaping , Li Yanni , Weng Yanfeng , Qian Jiawen , Chen Fa , Wang Jing , Shi Bin , Pan Lizhen , Lin Lisong , He Baochang , Liu Fengqiong 
Published: May 2022

ObjectiveTo investigate the association between dietary fatty acid (FA) patterns and the risk of oral cancer.MethodA case-control study which included 446 patients with oral cancer and 448 controls subjects was conducted in Southeast China. A structured food frequency questionnaire was used to assess the dietary FA consumption before cancer diagnosis. FA patterns were identified using the principal component analysis, and the relationship between the dietary FA patterns and oral cancer was analyzed by logistic regression.ResultsGeneral differences in FA intake were observed between the patient and control groups. The intakes of saturated FAs (SFAs) C14:0, C16:0, C18:0, and monounsaturated FA C18:1 were higher in the patient group than the control group (p &lt; 0.001). Four FA patterns were derived by principal component analysis. The “SFA” pattern, “Polyunsaturated FA” pattern, “Monounsaturated FA” pattern, and “Medium- and long-chain FA” pattern, which could explain 75.7% of the variance of the dietary FA intake, were submitted to logistic regression analysis. A positive association was observed between the “SFA” pattern and oral cancer risk. Compared with the lowest quartile score, the OR of the highest quartile score was 3.71 (95%CI: 2.31, 5.94, Ptrend &lt; 0.001) in the multivariate logistic regression model. No significant association was found among the other three patterns and oral cancer risk.ConclusionsGeneral differences in dietary FA intake were observed between patients with oral cancer and controls. A positive association between the “SFA” pattern and risk of oral cancer was observed after adjusting for potential confounders.
Pan-Cancer Analysis of the Oncogenic and Immunological Role of RCN3: A Potential Biomarker for Prognosis and Immunotherapy
Authors: Ding Jian , Meng Yan , Han Zelong , Luo Xiaobei , Guo Xuxue , Li Yiwen , Liu Side , Zhuang Kangmin 
Published: May 2022

Despite emerging publications have elucidated a functional association between RCN3 and tumors, no evidence about a pan-cancer analysis of RCN3 is available. Our study first conducted a comprehensive assessment of its expression profiles, prognosis value, immune infiltration, and relevant cellular pathways via bioinformatics techniques based on the public database of TCGA (The Cancer Genome Atlas). RCN3 is highly expressed in most tumors, and it is associated with poor prognosis. Kaplan-Meier analysis and Cox regression analysis suggested that the high expression of RCN3 was associated with poor overall survival (OS) in pan-cancer, Cox regression analysis also indicated high RCN3 expression was correlated with disease-specific survival (DSS) and progression-free interval (PFI) in most tumors. We observed a regulation function of RCN3 at genetic and epigenetic levels through CNA and DNA methylation using cBioPortal database. Based on Gene Set Enrichment Analysis, we first identified related pathways of RCN3 and its potential biological functions in pan-cancer, RCN3 was implicated in oncogenic pathways, and was related to extracellular matrix and immune regulation. We found that RCN3 positively correlated with the levels of infiltrating cells such as TAMs and CAFs, but negatively correlated with CD8+ T-cells by analyzing immune cell infiltration data we downloaded from published work and online databases, further investigation of the correlation between immunosuppressive genes, chemokines, chemokines receptors, and high RCN3 expression showed a significant positive association in the vast majority of TCGA cancer types. These results indicated its role as an immune regulatory in cancers and suggested that RCN3 is a potential biomarker for immunotherapy. Also, we found that expression of RCN3 was much higher in CRC tissues than in normal tissues with a higher expression level of RCN3 closely correlating to advanced American Joint Committee on Cancer (AJCC) stage, poor differentiation, increased tumor size, and poor prognosis of CRC. Biological function experiments showed that RCN3 regulated CRC cells’ proliferation and metastasis ability. Upregulation of RCN3 in CRC cells increased the expression of immune related factor, including TGFβ1, IL-10, and IL-6. Thus, our pan-cancer analysis offers a deep understanding of potential oncogenic roles of RCN3 in different cancers.
Elaboration and Validation of a Nomogram Based on Axillary Ultrasound and Tumor Clinicopathological Features to Predict Axillary Lymph Node Metastasis in Patients With Breast Cancer
Authors: Liu Yubo , Ye Feng , Wang Yun , Zheng Xueyi , Huang Yini , Zhou Jianhua 
Published: May 2022

BackgroundThis study aimed at constructing a nomogram to predict axillary lymph node metastasis (ALNM) based on axillary ultrasound and tumor clinicopathological features.MethodsA retrospective analysis of 281 patients with pathologically confirmed breast cancer was performed between January 2015 and March 2018. All patients were randomly divided into a training cohort (n = 197) and a validation cohort (n = 84). Univariate and multivariable logistic regression analyses were performed to identify the clinically important predictors of ALNM when developin1 g the nomogram. The area under the curve (AUC), calibration plots, and decision curve analysis (DCA) were used to assess the discrimination, calibration, and clinical utility of the nomogram.ResultsIn univariate and multivariate analyses, lymphovascular invasion (LVI), axillary lymph node (ALN) cortex thickness, and an obliterated ALN fatty hilum were identified as independent predictors and integrated to develop a nomogram for predicting ALNM. The nomogram showed favorable sensitivity for ALNM with AUCs of 0.87 (95% confidence interval (CI), 0.81–0.92) and 0.84 (95% CI, 0.73–0.92) in the training and validation cohorts, respectively. The calibration plots of the nomogram showed good agreement between the nomogram prediction and actual ALNM diagnosis (P &gt; 0.05). Decision curve analysis (DCA) revealed the net benefit of the nomogram.ConclusionsThis study developed a nomogram based on three daily available clinical parameters, with good accuracy and clinical utility, which may help the radiologist in decision-making for ultrasound-guided fine needle aspiration cytology/biopsy (US-FNAC/B) according to the nomogram score.
Tumor Size Is an Independent Prognostic Factor for Stage I Ovarian Clear Cell Carcinoma: A Large Retrospective Cohort Study of 1,000 Patients
Authors: Wu Liangcai , Shi Shuo , Sun Hong , Zhang Haiyan 
Published: May 2022

ObjectiveThe aim of this study was to investigate the prognostic value and stratification cutoff point for tumor size in stage I ovarian clear cell carcinoma (OCCC).MethodsThis was a retrospective cohort study using the Surveillance, Epidemiology, and End Results database (version: SEER 8.3.9). Patients diagnosed with stage I OCCC from 1988 to 2018 were included for further analysis. X-Tile software was used to identify the potential cutoff point for tumor size. Stratification analysis, propensity score matching, and inverse probability weighting analysis were used to balance the potential confounding factors.ResultsA total of 1,000 stage I OCCC patients were included. Of these 1,000 patients, median follow-up was 106 months (95% confidence interval [CI]: 89–112 months). Multivariate analysis showed that tumor size, age at diagnosis, and stage IC were significantly associated with stage I OCCC patients. Eight centimeters is a promising cutoff point that can divide stage I OCCC patients into a good or a poor prognosis group. After controlling potential confounding factors with propensity score matching and inverse probability weighting, we demonstrated that stage I OCCC patients with tumor size ≤ 8 cm enjoyed a significantly better 5-year overall survival (OS, 89.8% vs. 81%, p &lt; 0.0001). Tumor size ≤ 8 cm was an independent prognostic factor of stage I OCCC patients (hazard ratio [HR] 0.5608, 95% CI: 0.4126–0.7622, p = 0.0002).ConclusionsTumor size is an independent prognostic factor for stage I OCCC, and 8 cm is a promising cutoff point for tumor size for risk stratification. However, using tumor size in the stratification management of stage I OCCC patients warrants further investigation.
A Clinical-Radiomics Nomogram Based on the Apparent Diffusion Coefficient (ADC) for Individualized Prediction of the Risk of Early Relapse in Advanced Sinonasal Squamous Cell Carcinoma: A 2-Year Follow-Up Study
Authors: Lin Naier , Yu Sihui , Lin Mengyan , Shi Yiqian , Chen Wei , Xia Zhipeng , Cheng Yushu , Sha Yan 
Published: May 2022

PurposeTo develop and validate a nomogram model combining radiomic features and clinical characteristics to preoperatively predict the risk of early relapse (ER) in advanced sinonasal squamous cell carcinomas (SNSCCs).MethodsA total of 152 SNSCC patients (clinical stage III-IV) who underwent diffusion-weighted imaging (DWI) were included in this study. The training cohort included 106 patients assessed at the headquarters of our hospital using MR scanner 1. The testing cohort included 46 patients assessed at the branch of our hospital using MR scanner 2. Least absolute shrinkage and selection operator (LASSO) regression was applied for feature selection and radiomic signature (radscore) construction. Multivariable logistic regression analysis was applied to identify independent predictors. The performance of the model was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curve and decision curve analysis (DCA). Furthermore, the patients were classified into high- or low-risk ER subgroups according to the optimal cutoff value of the nomogram using X-tile. The recurrence-free survival probability (RFS) of each subgroup was assessed.ResultsER was noted in 69 patients. The radscore included 8 selected radiomic features. The radscore, T stage and surgical margin were independent predictors. The nomogram showed better performance (AUC = 0.92) than either the radscore or the clinical factors in the training cohort (P &lt; 0.050). In the testing cohort, the nomogram showed better performance (AUC = 0.92) than the clinical factors (P = 0.016) and tended to show better performance than the radscore (P = 0.177). The nomogram demonstrated good calibration and clinical utility. Kaplan-Meier analysis showed that the 2-year RFS rate for low-risk patients was significantly greater than that for high-risk patients in both the training and testing cohorts (P &lt; 0.001).ConclusionsThe ADC-based radiomic nomogram model is potentially useful in predicting the risk of ER in advanced SNSCCs.
Targeted Training for Subspecialist Care in Children With Medical Complexity
Authors: Eibensteiner Fabian , Ritschl Valentin , Valent Isabella , Schaup Rebecca Michaela , Hellmann Axana , Kaltenegger Lukas , Daniel-Fischer Lisa , Oviedo Flores Krystell , Brandstaetter Stefan , Stamm Tanja , Schaden Eva , Aufricht Christoph , Boehm Michael 
Published: May 2022

BackgroundChildren with medical complexity (CMC) are prone to medical errors and longer hospital stays, while residents do not feel prepared to provide adequate medical care for this vulnerable population. No educational guidance for the training of future pediatric tertiary care specialists outside their field of expertise involving the multidisciplinary care of CMC exists. We investigated pediatric residents past educational needs and challenges to identify key learning content for future training involving care for CMC.MethodsThis was a prospective mixed-methods study at a single pediatric tertiary care center. Qualitative semi-structured interviews with residents were conducted, submitted to thematic content analysis, linked to the American Board of Pediatrics (ABP) general pediatrics content outline, and analyzed with importance performance analysis (IPA). Quantitative validation was focused on key themes of pediatric nephrology within the scope of an online survey among pediatric residents and specialists.ResultsA total of 16 interviews, median duration 69 min [interquartile range IQR 35], were conducted. The 280 listed themes of the ABP general pediatrics content outline were reduced to 165 themes, with 86% (theoretical) knowledge, 12% practical skills, and 2% soft skills. IPA identified 23 knowledge themes to be of high importance where improvement is necessary and deemed fruitful. Quantitative validation among 84 residents and specialists (response rate 55%) of key themes in nephrology yielded high agreement among specialists in pediatric nephrology but low interrater agreement among trainees and “trained” non-nephrologists. The occurrence of themes in the qualitative interviews and their calculated importance in the quantitative survey were highly correlated (tau = 0.57, p = 0.001). Two clusters of high importance for other pediatric specialties emerged together with a contextual cluster of frequent encounters in both in- and outpatient care.ConclusionRegarding patient safety, this study revealed the heterogeneous aspects and the importance of training future pediatric tertiary care specialists outside their field of expertise involving the multidisciplinary care of CMC. Our results may lay the groundwork for future detailed analysis and development of training boot camps that might be able to aid the improvement of patient safety by decreasing preventable harm by medical errors, especially for vulnerable patient groups, such as CMC in tertiary care pediatrics.
Orphan Drug Use in Patients With Rare Diseases: A Population-Based Cohort Study
Authors: Gorini Francesca , Santoro Michele , Pierini Anna , Mezzasalma Lorena , Baldacci Silvia , Bargagli Elena , Boncristiano Alessandra , Brunetto Maurizia Rossana , Cameli Paolo , Cappelli Francesco , Castaman Giancarlo , Coco Barbara , Donati Maria Alice , Guerrini Renzo , Linari Silvia , Murro Vittoria , Olivotto Iacopo , Parronchi Paola , Pochiero Francesca , Rossi Oliviero , Scappini Barbara , Sodi Andrea , Vannucchi Alessandro Maria , Coi Alessio 
Published: May 2022

Background: Orphan drugs are used for the diagnosis, prevention and treatment of rare diseases that, in the European Union, are defined as disorders affecting no more than 5 persons in 10,000. So far, a total of around 800 orphan medicinal products have been approved by the European Medicines Agency, however the utilization profile of orphan drugs has yet to be explored. This study aimed at assessing the utilization profile of orphan drugs authorized for marketing by the Italian Medicines Agency using population-based data.Methods: A total of 21 orphan drugs used in outpatient settings, approved in the European Union before or during the 2008–2018 period and involving 15 rare diseases, were included in the study. The monitored population included patients with one of the conditions surveilled by the population-based Tuscany Registry of Rare Diseases and diagnosed between 2000–2018. A multi-database approach was applied, by linking data from the registry with information collected in drug prescriptions databases. The prevalence and intensity of use were estimated for the selected orphan drugs and other non-orphan medications, used to treat the same rare disease and for which a change in the prevalence of use was hypothesized after authorization of the orphan drug.Results: For some diseases (acquired aplastic anemia, tuberous sclerosis complex, most metabolic diseases) a low prevalence of orphan drugs use was observed (range between 1.1–12.5%). Conversely, orphan drugs were frequently used in hemophilia B, Wilson disease and idiopathic pulmonary fibrosis (maximum of 78.3, 47.6 and 41.8%, respectively). For hemophilia B and Leber’s hereditary optic neuropathy, there are currently no other medications used in clinical practice in addition to orphan drugs. Six orphan drugs were used for the treatment of pulmonary arterial hypertension, appearing the elective therapy for this disease, albeit with different utilization profiles (range of prevalence 1.7–55.6%).Conclusion: To the best of our knowledge, this is the first study investigating the utilization profile of orphan drugs prescribed in a defined geographical area, and providing relevant information to monitor over time potential changes in the prevalence of these medications as well as in the health care decision making.
How Sensitive is Sensitivity Analysis?: Evaluation of Pharmacoeconomic Submissions in Korea
Authors: Bae SeungJin , Lee Joohee , Bae Eun-Young 
Published: May 2022

Purpose: We aimed to describe the types of uncertainties examined in the economic evaluations submitted for reimbursement in Korea and their impact on the incremental cost-effectiveness ratio (ICER).Method: Fifty dossiers were submitted by pharmaceutical companies to the economic subcommittee of the Pharmaceutical Benefit Coverage Advisory Committee (PBCAC) from January 2014 to December 2018. The types of uncertainties were categorized as structural and parametric, and the frequencies of the sensitivity analysis per variables were analyzed. The impact of uncertainties was measured by the percent variance of the ICER relative to that of the base case analysis.Results: Of the 50 submissions, varying discount rate (44 submissions), followed by time horizon (38 submissions) and model assumptions (29 submissions), were most frequently used to examine structural uncertainty, while utility (42 submissions), resource use (41 submissions), and relative effectiveness (26 submissions) were used to examine parametric uncertainty. A total of 1,236 scenarios (a scenario corresponds to a case where a single variable is varied by a single range) were presented in the one-way sensitivity analyses, where parametric and structural sensitivity analyses comprised 679 and 557 scenarios, respectively. Varying drug prices had the highest impact on ICER (median variance 19.9%), followed by discount rate (12.2%), model assumptions (11.9%), extrapolation (11.8%), and time horizon (10.0%).Conclusions: Variables related to long-term assumptions, such as model assumptions, time horizon, extrapolation, and discounting rate, were related to a high level of uncertainty. Caution should be exercised when using immature data.