bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Coronary Artery Disease and Metabolic Syndrome: Usefulness of Serum Metabolomics Approach
Authors: Jing Ziwei , Liu Liwei , Shi Yingying , Du Qiuzheng , Zhang Dingding , Zuo Lihua , Du Shuzhang , Sun Zhi , Zhang Xiaojian 
Published: September 2021

IntroductionIndividuals with metabolic syndrome (MetS) are at increasing risk of coronary artery disease (CAD). We investigated the common metabolic perturbations of CAD and MetS via serum metabolomics to provide insight into potential associations.MethodsNon-targeted serum metabolomics analyses were performed using ultra high-performance liquid chromatography coupled with Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Q-Orbitrap HRMS) in samples from 492 participants (272 CAD vs. 121 healthy controls (HCs) as cohort 1, 55 MetS vs. 44 HCs as cohort 2). Cross-sectional data were obtained when the participants were recruited from the First Affiliated Hospital of Zhengzhou University. Multivariate statistics and Student’s t test were applied to obtain the significant metabolites [with variable importance in the projection (VIP) values &gt;1.0 and p values &lt;0.05] for CAD and MetS. Logistic regression was performed to investigate the association of identified metabolites with clinical cardiac risk factors, and the association of significant metabolic perturbations between CAD and MetS was visualized by Cytoscape software 3.6.1. Finally, the receiver operating characteristic (ROC) analysis was evaluated for the risk prediction values of common changed metabolites.ResultsThirty metabolites were identified for CAD, mainly including amino acids, lipid, fatty acids, pseudouridine, niacinamide; 26 metabolites were identified for MetS, mainly including amino acids, lipid, fatty acids, steroid hormone, and paraxanthine. The logistic regression results showed that all of the 30 metabolites for CAD, and 15 metabolites for MetS remained significant after adjustments of clinical risk factors. In the common metabolic signature association analysis between CAD and MetS, 11 serum metabolites were significant and common to CAD and MetS outcomes. Out of this, nine followed similar trends while two had differing directionalities. The nine common metabolites exhibiting same change trend improved risk prediction for CAD (86.4%) and MetS (90.9%) using the ROC analysis.ConclusionSerum metabolomics analysis might provide a new insight into the potential mechanisms underlying the common metabolic perturbations of CAD and MetS.
Development and Internal Validation of a Predictive Model for Adult GH Deficiency Prior to Stimulation Tests
Authors: Bioletto Fabio , Parasiliti-Caprino Mirko , Berton Alessandro Maria , Prencipe Nunzia , Cambria Valeria , Ghigo Ezio , Grottoli Silvia , Gasco Valentina 
Published: September 2021

BackgroundThe diagnosis of adult GH deficiency (GHD) relies on a reduced GH response to provocative tests. Their diagnostic accuracy, however, is not perfect, and a reliable estimation of pre-test GHD probability could be helpful for a better interpretation of their results.MethodsEighty patients showing concordant GH response to two provocative tests, i.e. the insulin tolerance test and the GHRH + arginine test, were enrolled. Data on IGF-I values and on the presence/absence of other pituitary deficits were collected and integrated for the estimation of GHD probability prior to stimulation tests.ResultsAn independent statistically significant association with the diagnosis of GHD was found both for IGF-I SDS (OR 0.34, 95%-CI 0.18-0.65, p=0.001) and for the presence of other pituitary deficits (OR 6.55, 95%-CI 2.06-20.83, p=0.001). A low (&lt;25%) pre-test GHD probability could be predicted when IGF-I SDS &gt; +0.91 in the presence of other pituitary deficits or IGF-I SDS &gt; -0.52 in the absence of other pituitary deficits. A high (&gt;75%) pre-test GHD probability could be predicted when IGF-I SDS &lt; -0.82 in the presence of other pituitary deficits or IGF-I SDS &lt; -2.26 in the absence of other pituitary deficits.ConclusionThis is the first study that proposes a quantitative estimation of GHD probability prior to stimulation tests. Our risk class stratification represents a simple tool that could be adopted for a Bayesian interpretation of stimulation test results, selecting patients who may benefit from a second stimulation test and possibly reducing the risk of wrong GHD diagnosis.
Pathogenic and Low-Frequency Variants in Children With Central Precocious Puberty
Authors: Neocleous Vassos , Fanis Pavlos , Toumba Meropi , Gorka Barbara , Kousiappa Ioanna , Tanteles George A. , Iasonides Michalis , Nicolaides Nicolas C. , Christou Yiolanda P. , Michailidou Kyriaki , Nicolaou Stella , Papacostas Savvas S. , Christoforidis Athanasios , Kyriakou Andreas , Vlachakis Dimitrios , Skordis Nicos , Phylactou Leonidas A. 
Published: September 2021

BackgroundCentral precocious puberty (CPP) due to premature activation of GnRH secretion results in early epiphyseal fusion and to a significant compromise in the achieved final adult height. Currently, few genetic determinants of children with CPP have been described. In this translational study, rare sequence variants in MKRN3, DLK1, KISS1, and KISS1R genes were investigated in patients with CPP.MethodsFifty-four index girls and two index boys with CPP were first tested by Sanger sequencing for the MKRN3 gene. All children found negative (n = 44) for the MKRN3 gene were further investigated by whole exome sequencing (WES). In the latter analysis, the status of variants in genes known to be related with pubertal timing was compared with an in-house Cypriot control cohort (n = 43). The identified rare variants were initially examined by in silico computational algorithms and confirmed by Sanger sequencing. Additionally, a genetic network for the MKRN3 gene, mimicking a holistic regulatory depiction of the crosstalk between MKRN3 and other genes was designed.ResultsThree previously described pathogenic MKRN3 variants located in the coding region of the gene were identified in 12 index girls with CPP. The most prevalent pathogenic MKRN3 variant p.Gly312Asp was exclusively found among the Cypriot CPP cohort, indicating a founder effect phenomenon. Seven other CPP girls harbored rare likely pathogenic upstream variants in the MKRN3. Among the 44 CPP patients submitted to WES, nine rare DLK1 variants were identified in 11 girls, two rare KISS1 variants in six girls, and two rare MAGEL2 variants in five girls. Interestingly, the frequent variant rs10407968 (p.Gly8Ter) of the KISS1R gene appeared to be less frequent in the cohort of patients with CPP.ConclusionThe results of the present study confirm the importance of the MKRN3-imprinted gene in genetics of CPP and its key role in pubertal timing. Overall, the results of the present study have emphasized the importance of an approach that aligns genetics and clinical aspects, which is necessary for the management and treatment of CPP.
No Causal Association Between Adiponectin and the Risk of Rheumatoid Arthritis: A Mendelian Randomization Study
Authors: Chen Hanzhu , Mi Shuai , Zhu Jiahao , Jin Weidong , Li Yasong , Wang Tianle , Li Yingjun , Fan Chunhong 
Published: September 2021

Background: Accumulating evidence from observational studies suggested that circulating adiponectin levels are associated with the risk of rheumatoid arthritis (RA), but the causality remains unknown. We aimed to assess the causal relationship of adiponectin with RA risk.Methods: Based on summary statistics from large-scale genome-wide association studies (GWAS), we quantified the genetic correlation between adiponectin and RA. Then bidirectional Mendelian randomization (MR) analysis was performed to assess the causal relationship. Twenty single-nucleotide polymorphisms (SNPs) associated with adiponectin were selected as instrumental variables from a recent GWAS (n = 67,739). We applied theses SNPs to a large-scale GWAS for RA (14,361 cases and 43,923 controls) with replication using RA data from the FinnGen consortium (6,236 cases and 147,221 controls) and the UK Biobank (5,201 cases and 457,732 controls). The inverse-variance weighted (IVW) and multiple pleiotropy-robust methods were used for two-sample MR analyses.Results: Our analyses showed no significant genetic correlation between circulating adiponectin levels and RA [rG = 0.127, 95% confidence interval (CI): –0.012 to 0.266, P = 0.074]. In MR analyses, genetically predicted adiponectin levels were not significantly associated with the RA risk (odds ratio: 0.98, 95% CI: 0.88–1.09, P = 0.669). In the reverse direction analysis, there is little evidence supporting an association of genetic susceptibility to RA with adiponectin (β: 0.007, 95% CI: –0.003 to 0.018, P = 0.177). Replication analyses and sensitivity analyses using different models yielded consistent results.Conclusions: Our findings provided no evidence to support the causal effect of adiponectin levels on RA risk and of RA on circulating adiponectin levels.
Kidney Function in Patients With Neuromuscular Disease: Creatinine Versus Cystatin C
Authors: Screever Elles M. , Kootstra-Ros Jenny E. , Doorn Joyce , Nieuwenhuis Jellie A. , Meulenbelt Henk E. J. , Meijers Wouter C. , de Boer Rudolf A. 
Published: September 2021

Background: Accurate measurement of kidney function in patients with neuromuscular disorders is challenging. Cystatin C, a marker not influenced by skeletal muscle degradation, might be of clinical value in these patients.Methods: We consecutively enrolled 39 patients with neuromuscular disorders. We investigated the association of the eGFR, based on plasma creatinine and Cystatin C, with clinical and biochemical variables associated with kidney function, namely age and galectin-3.Results: Creatinine-based eGFR was 242 (±80) and Cystatin C-based eGFR was 110 (±23) mL/min/1.73 m2. Cystatin C-based eGFR was associated with age (β −0.63 p &lt; 0.0001) and galectin-3 levels (β −0.43 p &lt; 0.01), while creatinine-based eGFR was not (β −0.22 p = 0.20; β −0.28 p = 0.10). Sensitivity analyses in Duchenne and Becker patients revealed the same results: Cystatin C-based eGFR was associated with age (β −0.61 p &lt; 0.01) and galectin-3 levels (β −0.43 p = 0.05), while creatinine-based eGFR was not (β −0.32 p = 0.13; β −0.34 p = 0.14).Conclusions: These data indicate that estimation of renal function in patients with neuromuscular disorders cannot reliably be achieved with creatinine, while Cystatin C appears a reasonable alternative. Since a large proportion of patients with neuromuscular disorders develops heart failure, and requires heart failure medication, adequate monitoring of renal function is warranted.
At the Intersection of Gut Microbiome and Stroke: A Systematic Review of the Literature
Authors: Sharma Vishakha , Sharma Vaibhav , Shahjouei Shima , Li Jiang , Chaudhary Durgesh , Khan Ayesha , Wolk Donna M. , Zand Ramin , Abedi Vida 
Published: September 2021

Background: Ischemic and hemorrhagic stroke are associated with a high rate of long-term disability and death. Recent investigations focus efforts to better understand how alterations in gut microbiota composition influence clinical outcomes. A key metabolite, trimethylamine N-oxide (TMAO), is linked to multiple inflammatory, vascular, and oxidative pathways. The current biochemical underpinnings of microbial effects on stroke remain largely understudied. The goal of our study is to explore the current literature to explain the interactions between the human gut microbiome and stroke progression, recovery, and outcome. We also provide a descriptive review of TMAO.Methods: A systematic literature search of published articles between January 1, 1990, and March 22, 2020, was performed on the PubMed database to identify studies addressing the role of the microbiome and TMAO in the pathogenesis and recovery of acute stroke. Our initial investigation focused on human subject studies and was further expanded to include animal studies. Relevant articles were included, regardless of study design. The analysis included reviewers classifying and presenting selected articles by study design and sample size in a chart format.Results: A total of 222 titles and abstracts were screened. A review of the 68 original human subject articles resulted in the inclusion of 24 studies in this review. To provide further insight into TMAO as a key player, an additional 40 articles were also reviewed and included. Our findings highlighted that alterations in richness and abundance of gut microbes and increased plasma TMAO play an important role in vascular events and outcomes. Our analysis revealed that restoration of a healthy gut, through targeted TMAO-reducing therapies, could provide alternative secondary prevention for at-risk patients.Discussion: Biochemical interactions between the gut microbiome and inflammation, resulting in metabolic derangements, can affect stroke progression and outcomes. Clinical evidence supports the importance of TMAO in modulating underlying stroke risk factors. Lack of standardization and distinct differences in sample sizes among studies are major limitations.
Trend of Sudden Unexpected Death in Epilepsy Incidence Rate in Rural West China
Authors: Wang Haijiao , Chen Deng , He Jun , He Yujin , Liu Ling , Zhou Dong 
Published: September 2021

Objectives: To explore the trend of sudden unexpected death in epilepsy (SUDEP) incidence rate over time in rural west China.Methods: We scanned probable SUDEP patients from the epilepsy program between 2010 and 2019 in rural West China and performed a verbal autopsy for each eligible patient. We calculated the crude and sex-adjusted incidence rate of SUDEP per person-year over a calendar year and the year of follow-up. We calculated the incidence rate ratio with the Poisson model in STATA 12.0 and calculated the annual percentage change (APC) and average annual percentage change in Joinpoint Trend Analysis Software 4.8.0.1 to analyze the trend of SUDEP incidence rate.Results: In 2010–2019, 44 probable SUDEPs were identified from 10,128 patients with a total person-year of 31,347. The crude and sex-adjusted incidence rates of SUDEP were 1.40 and 1.45%0. Twenty-five (56.8%) of the 44 probable SUDEPs had no generalized tonic-clonic seizure 3 months before their death. The incidence of probable SUDEP decreased significantly in the calendar year [APC = −11.7, 95% confidence interval (CI): −21.7 to −0.3] and in time of follow-up (average annual percentage change = −21.2, 95% CI: −34.3 to −5.4). Comparing the first 5 years in follow-up with the subsequent 3 years, the incidence rate of SUDEP decreased significantly (estimated incidence rate ratio = 0.4, 95% CI: 0.2 to 0.8).Significance: SUDEP happened to 1.4 cases per thousand patient-years in convulsive epilepsy in rural west China between 2010 and 2019. The incidence rate of SUDEP presented a downward trend over the time of follow-up.
Rehabilitation Needs of Head and Neck Cancer Patients and Stakeholders: Case Study
Authors: Karampela Maria , Porat Talya , Mylonopoulou Vasiliki , Isomursu Minna 
Published: September 2021

BackgroundThe incidents of Head and Neck Cancer (HNC) are rising worldwide, suggesting that this type of cancer is becoming more common. The foreseen growth of incidents signifies that future rehabilitation services will have to meet the needs of a wider population.ObjectiveThe aim of this paper is to explore the needs of patients, caregivers and healthcare professionals during HNC rehabilitation.MethodsThis paper reports the empirical findings from a case study that was conducted in a cancer rehabilitation center in Copenhagen to elicit the needs of HNC cancer patients, informal caregivers and healthcare professionals.ResultsFour areas of needs during the rehabilitation process were identified: service delivery, emotional, social and physical needs. Service delivery needs and emotional needs have been identified as the most prevalent.ConclusionsStakeholders’ needs during the rehabilitation process were found to be interrelated. All stakeholders faced service delivery challenges in the form of provision and distribution of information, including responsibilities allocation between municipalities, hospitals and rehabilitation services. Emotional and social needs have been reported by HNC patients and informal caregivers, underlining the importance of inclusion of all actors in the design of future healthcare interventions. Connected Health (CH) solutions could be valuable in provision and distribution of information.
The Prognostic Significance of the Continuous Administration of Anti-PD-1 Antibody via Continuation or Rechallenge After the Occurrence of Immune-Related Adverse Events
Authors: Fujisaki Toshiya , Watanabe Satoshi , Ota Takeshi , Kushiro Kohei , Sato Yusuke , Takahashi Miho , Ohtsubo Aya , Shoji Satoshi , Nozaki Koichiro , Ichikawa Kosuke , Hokari Satoshi , Kondo Rie , Miyabayashi Takao , Abe Tetsuya , Miura Satoru , Tanaka Hiroshi , Okajima Masaaki , Terada Masaki , Matsumoto Naoya , Ishida Takashi , Iwashima Akira , Sato Kazuhiro , Yoshizawa Hirohisa , Aoki Nobumasa , Hayashi Masachika , Ohshima Yasuyoshi , Koya Toshiyuki , Kikuchi Toshiaki 
Published: September 2021

ObjectivesAlthough immune checkpoint inhibitors (ICIs) have been shown to improve overall survival (OS) in advanced non-small-cell lung cancer (NSCLC) patients, ICIs sometimes cause various types of immune-related adverse events (irAEs), which lead to the interruption of ICI treatment. This study aims to evaluate the clinical significance of the continuation of ICIs in NSCLC patients with irAEs and to assess the safety and efficacy of the readministration of ICIs after their discontinuation due to irAEs.MethodsWe retrospectively identified patients with advanced NSCLC who were treated with first- to third-line anti-programmed cell death-1 (PD-1) therapy from January 2016 through October 2017 at multiple institutions belonging to the Niigata Lung Cancer Treatment Group. Progression-free survival (PFS) and OS from the initiation of ICI treatment were analyzed in patients with and without irAEs, with and without ICI interruption, and with and without ICI readministration. A 6-week landmark analysis of PFS and OS was performed to minimize the lead-time bias associated with time-dependent factors.ResultsOf 231 patients who received anti-PD-1 antibodies, 93 patients (40%) developed irAEs. Of 84 eligible patients with irAEs, 32 patients (14%) continued ICIs, and OS was significantly longer in patients who continued ICIs than that in patients who discontinued ICIs [not reached (95% CI: NE-NE) vs. not reached (95% CI: 22.4–NE); p = 0.025]. Of 52 patients who discontinued ICIs, 14 patients (6.1%) readministered ICIs, and OS in patients with ICI readministration was significantly longer than that in patients without ICI readministration [not reached (95% CI: NE-NE) vs. not reached (95% CI: 8.4–NE); p = 0.031].ConclusionThe current study demonstrated that both the continuation and readministration of ICIs after irAE occurrence improved OS compared to the permanent interruption of ICIs in NSCLC patients with ICI-related irAEs.
Lymph Node Dissections for T3T4 Stage Penile Cancer Patients Without Preoperatively Detectable Lymph Node Metastasis Bring More Survival Benefits: A Propensity Matching Analysis
Authors: Li Han , Ma Yucheng , Jian Zhongyu , Jin Xi , Xiang Liyuan , Li Hong , Wang Kunjie 
Published: September 2021

Background and AimsThe current guidelines for the treatment of penile cancer patients with clinically non-invasive normal inguinal lymph nodes are still broad, so the purpose of this study is to determine which patients are suitable for lymph node dissection (LND).MethodsHistologically confirmed penile cancer patients (primary site labeled as C60.9-Penis) from 2004 to 2016 in the Surveillance, Epidemiology, and Results database were included in this analysis. Univariate and multivariate Cox regression analyses were applied to determine an overall estimate of LND on overall survival and cancer-specific survival. A 1:1 propensity matching analysis (PSM) was applied to enroll balanced baseline cohort, and further Kaplan–Meier (KM) survival analysis was used to get more reliable results.ResultsOut of 4,458 histologically confirmed penile cancer patients with complete follow-up information, 1,052 patients were finally enrolled in this analysis. Age, pathological grade, T stage, and LND were identified as significant predictors for overall survival (OS) in the univariate Cox analysis. In the multivariate Cox regression, age, pathological grade, T stage, and LND were found significant. The same results were also found in the univariate and multivariate Cox regression analyses for cancer-specific survival (CSS). After the successful PSM, further KM analysis revealed that LND could bring significant OS and CSS benefits for T3T4 patients without lymph node metastasis.ConclusionLymph node dissection may bring survival benefits for penile cancer patients without preoperatively detectable lymph node metastasis, especially for T3T4 stage patients. Further randomized control trial is needed.
In-House, Open-Source 3D-Software-Based, CAD/CAM-Planned Mandibular Reconstructions in 20 Consecutive Free Fibula Flap Cases: An Explorative Cross-Sectional Study With Three-Dimensional Performance Analysis
Authors: Ritschl Lucas M. , Kilbertus Paul , Grill Florian D. , Schwarz Matthias , Weitz Jochen , Nieberler Markus , Wolff Klaus-Dietrich , Fichter Andreas M. 
Published: September 2021

BackgroundMandibular reconstruction is conventionally performed freehand, CAD/CAM-assisted, or by using partially adjustable resection aids. CAD/CAM-assisted reconstructions are usually done in cooperation with osteosynthesis manufacturers, which entails additional costs and longer lead time. The purpose of this study is to analyze an in-house, open-source software-based solution for virtual planning.Methods and MaterialsAll consecutive cases between January 2019 and April 2021 that underwent in-house, software-based (Blender) mandibular reconstruction with a free fibula flap (FFF) were included in this cross-sectional study. The pre- and postoperative Digital Imaging and Com munications in Medicine (DICOM) data were converted to standard tessellation language (STL) files. In addition to documenting general information (sex, age, indication for surgery, extent of resection, number of segments, duration of surgery, and ischemia time), conventional measurements and three-dimensional analysis methods (root mean square error [RMSE], mean surface distance [MSD], and Hausdorff distance [HD]) were used.ResultsTwenty consecutive cases were enrolled. Three-dimensional analysis of preoperative and virtually planned neomandibula models was associated with a median RMSE of 1.4 (0.4–7.2), MSD of 0.3 (-0.1–2.9), and HD of 0.7 (0.1–3.1). Three-dimensional comparison of preoperative and postoperative models showed a median RMSE of 2.2 (1.5–11.1), MSD of 0.5 (-0.6–6.1), and HD of 1.5 (1.1–6.5) and the differences were significantly different for RMSE (p &lt; 0.001) and HD (p &lt; 0.001). The difference was not significantly different for MSD (p = 0.554). Three-dimensional analysis of virtual and postoperative models had a median RMSE of 2.3 (1.3–10.7), MSD of -0.1 (-1.0–5.6), and HD of 1.7 (0.1–5.9).ConclusionsOpen-source software-based in-house planning is a feasible, inexpensive, and fast method that enables accurate reconstructions. Additionally, it is excellent for teaching purposes.