bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiomics Analysis of Multiparametric MRI for Prediction of Synchronous Lung Metastases in Osteosarcoma
Authors: Luo Zhendong , Li Jing , Liao YuTing , Liu RengYi , Shen Xinping , Chen Weiguo 
Published: February 2022

PurposeTo establish and verify a predictive model involving multiparameter MRI and clinical manifestations for predicting synchronous lung metastases (SLM) in osteosarcoma.Materials and MethodsSeventy-eight consecutive patients with osteosarcoma (training dataset, n = 54; validation dataset, n = 24) were enrolled in our study. MRI features were extracted from the T1‐weighted image (T1WI), T2‐weighted image (T2WI), and contrast-enhanced T1-weighted image (CE-T1WI) of each patient. Least absolute shrinkage and selection operator (LASSO) regression and multifactor logistic regression were performed to select key features and build radiomics models in conjunction with logistic regression (LR) and support vector machine (SVM) classifiers. Eight individual models based on T1WI, T2WI, CE-T1WI, T1WI+T2WI, T1WI+CE-T1WI, T2WI+CE-T1WI, T1WI+T2WI+CE-T1WI, and clinical features, as well as two combined models, were built. The area under the receiver operating characteristic curve (AUC), sensitivity and specificity were employed to assess the different models.ResultsTumor size was the most significant univariate clinical indicator (1). The AUC values of the LR predictive model based on T1WI, T2WI, CE-T1WI, T1WI+T2WI, T1WI+CE-T1WI, T2WI+CE-T1WI, and T1WI+T2WI+CE-T1WI were 0.686, 0.85, 0.87, 0.879, 0.736, 0.85, and 0.914, respectively (2). The AUC values of the SVM predictive model based on T1WI, T2WI, CE-T1WI, T1WI+T2WI, T1WI +CE-T1WI, T2WI +CE-T1WI, and T1WI+T2WI+CE-T1WI were 0.629, 0.829, 0.771, 0.879, 0.643, 0.829, and 0.929, respectively (3). The AUC values of the clinical, combined 1 (clinical and LR-radiomics) and combined 2 (clinical and SVM-radiomics) predictive models were 0.779, 0.957, and 0.943, respectively.ConclusionThe combined model exhibited good performance in predicting osteosarcoma SLM and may be helpful in clinical decision-making.
Clinical Evaluation of the Inverse Planning System Utilized in Gamma Knife Lightning
Authors: Cui Taoran , Nie Ke , Zhu Jiahua , Danish Shabbar , Weiner Joseph , Chundury Anupama , Ohri Nisha , Zhang Yin , Vergalasova Irina , Yue Ning , Wang Xiao 
Published: February 2022

ObjectivesThe purpose of this study is to independently compare the performance of the inverse planning algorithm utilized in Gamma Knife (GK) Lightning Treatment Planning System (TPS) to manual forward planning, between experienced and inexperienced users, for different types of targets.Materials and MethodsForty patients treated with GK stereotactic radiosurgery (SRS) for pituitary adenoma (PA), vestibular schwannoma (VS), post-operative brain metastases (pBM), and intact brain metastases (iBM) were randomly selected, ten for each site. Three inversely optimized plans were generated for each case by two experienced planners (OptExp1 and OptExp2) and a novice planner (OptNov) using GK Lightning TPS. For each treatment site, the Gradient Index (GI), the Paddick Conformity Index (PCI), the prescription percentage, the scaled beam-on time (sBOT), the number of shots used, and dosimetric metrics to OARs were compared first between the inversely optimized plans and the manually generated clinical plans, and then among the inversely optimized plans. Statistical analyses were performed using the Student’s t-test and the ANOVA followed by the post-hoc Tukey tests.ResultsThe GI for the inversely optimized plans significantly outperformed the clinical plans for all sites. PCIs were similar between the inversely optimized and clinical plans for PA and VS, but were significantly improved in the inversely optimized plans for iBM and pBM. There were no significant differences in the sBOT between the inversely optimized and clinical plans, except for the PA cases. No significant differences were observed in dosimetric metrics, except for lower brain V12Gy and PTV D98% in the inversely optimized plans for iBM. There were no noticeable differences in plan qualities among the inversely optimized plans created by the novice and experienced planners.ConclusionInverse planning in GK Lightning TPS produces GK SRS plans at least equivalent in plan quality and similar in sBOT compared to manual forward planning in this independent validation study. The automatic workflow of inversed planning ensures a consistent plan quality regardless of a planner’s experience.
An Integrated Pan-Cancer Analysis of ADAMTS12 and Its Potential Implications in Pancreatic Adenocarcinoma
Authors: Song Caiyun , Chen Jionghuang , Zhang Chaolei , Dong Dapeng 
Published: February 2022

BackgroundA Disintegrin and Metallopeptidase with Thrombospondin Type 1 Motif 12 (ADAMTS12), a member of the ADAMTS family of multidomain extracellular protease enzymes, is involved in the progression of many tumors. However, a pan-cancer analysis of this gene has not yet been performed. Its role in pancreatic adenocarcinoma (PAAD) also remains unclear.MethodsThe Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression data (GTEx) databases were used to analyze ADAMTS12 expression in pan-cancer. We assessed the expression, clinical characteristics, prognostic significance, copy number alteration, methylation, and mutation of ADAMTS12 and its correlation with the tumor immune microenvironment. qRT-PCR and immunohistochemistry assays were also performed to validate the expression of ADAMTS12 in PAAD.ResultsThrough bioinformatics analysis and preliminary experimental verification, ADAMTS12 was found to be substantially overexpressed in PAAD. High expression level of ADAMTS12 was correlated with worse survival rates in patients with PAAD and high infiltration levels of tumor-associated macrophages, cancer-associated fibroblasts, immune checkpoint proteins, and immunosuppressive genes.ConclusionOur findings suggest ADAMTS12 as a potential prognostic biomarker in PAAD. Elevated ADAMTS12 expression may also indicate an immunosuppressive microenvironment.
Case Report: Atypical HUS Presenting With Acute Rhabdomyolysis Highlights the Need for Individualized Eculizumab Dosing
Authors: Benoit Stefanie W. , Fukuda Tsuyoshi , VandenHeuvel Katherine , Witte David , Fuller Christine , Willis Jennifer , Dixon Bradley P. , Drake Keri A. 
Published: February 2022

BackgroundAtypical hemolytic uremic syndrome (aHUS) is an ultra-rare orphan disease caused by dysregulated complement activation resulting in thrombotic microangiopathy. Although complement-mediated endothelial injury predominantly affects the renal microvasculature, extra-renal manifestations are present in a significant proportion of patients. While eculizumab has significantly improved the morbidity and mortality of this rare disease, optimizing therapeutic regimens of this highly expensive drug remains an active area of research in the treatment of aHUS.Case PresentationThis report describes the case of a previously healthy 4 year-old male who presented with rhabdomyolysis preceding the development of aHUS with anuric kidney injury requiring dialysis. Clinical stabilization required increased and more frequent eculizumab doses compared with the standardized weight-based guidelines. In the maintenance phase of his disease, pharmacokinetic analysis indicated adequate eculizumab levels could be maintained with an individualized dosing regimen every 3 weeks, as opposed to standard 2 week dosing, confirmed in this patient over a 4 year follow up period. Cost analyses show that weight-based maintenance dosing costs $312,000 per year, while extending the dosing interval to every 3 weeks would cost $208,000, a savings of $104,000 per year, relative to the cost of $72,000 from more frequent eculizumab dosing during his initial hospitalization to suppress his acute disease.ConclusionThis case exemplifies the potential of severe, multisystem involvement of aHUS presenting with extra-renal manifestations, including rhabdomyolysis as in this case, and highlights the possibility for improved clinical outcomes and higher value care with individualized eculizumab dosing in patients over the course of their disease.
Eluxadoline Versus Antispasmodics in the Treatment of Irritable Bowel Syndrome: An Adjusted Indirect Treatment Comparison Meta-analysis
Authors: Qin Di , Tao Qing-Feng , Huang Shi-Le , Chen Min , Zheng Hui 
Published: February 2022

Objective: Eluxadoline is a newly approved drug for irritable bowel syndrome (IBS), but it has rarely been compared with positive controls. We aimed to compare eluxadoline with antispasmodics in the treatment of IBS.Methods: We searched the OVID Medline, Embase, and the Cochrane Central Register of Controlled Trials databases for randomized controlled trials (RCTs) comparing eluxadoline or antispasmodics with placebo. The search was conducted from 1 January 1980, to 1 September 2020, without any language restrictions. The primary efficacy outcome was the relief of abdominal pain, defined by a reduction of pain scores of at least 30% from baseline. The secondary efficacy outcome was the relief of global IBS symptoms, defined by a composite response of a decrease in abdominal pain and improvement in stool consistency on the same day for at least 50% of the days assessed. The data were pooled using a random-effects model. Outcome estimates were pooled by using Risk Ratios (RRs) and P-scores.Results: Forty-two trials with 8,457 participants were included from 45 articles. Compared with placebo, each of drotaverine, pinaverium, alverine combined with simethicone (ACS) and eluxadoline 100 mg was highly effective in the relief of abdominal pain, with drotaverine [RR, 2.71 (95% CI, 1.70 to 4.32), P-score = 0.95] ranking first. Drotaverine, otilonium, cimetropium, pinaverium, and eluxadoline 100 mg had significantly high the relief of global IBS symptomss, for which drotaverine [RR, 2.45 (95% CI, 1.42 to 4.22), P-score = 0.95] was ranked first. No significant difference was found between these interventions. Pinaverium had a significantly higher the relief of global IBS symptoms than eluxadoline [RR, 1.72 (95% CI, 1.33 to 2.21)] on sensitivity analysis. However, no significant difference was found in the number of adverse events between each intervention and the placebo.Conclusion: Our network meta-analysis showed that eluxadoline 100 mg was at least as effective as antispasmodics in relieving abdominal pain in IBS. But eluxadoline had more reported adverse events. Antispasmodics are still the first choice for the treatment of IBS.
Revealing Calcium Signaling Pathway as Novel Mechanism of Danhong Injection for Treating Acute Myocardial Infarction by Systems Pharmacology and Experiment Validation
Authors: Guo Siyu , Tan Yingying , Huang Zhihong , Li Yikui , Liu Weiyu , Fan Xiaotian , Zhang Jingyuan , Stalin Antony , Fu Changgeng , Wu Zhishan , Wang Penglong , Zhou Wei , Liu Xinkui , Wu Chao , Jia Shanshan , Zhang Jinyan , Duan Xiaoxia , Wu Jiarui 
Published: February 2022

Introduction: Danhong injection (DHI) is a traditional Chinese medicine preparation commonly used in the clinical treatment of acute myocardial infarction (AMI). In this study, the active components of DHI and its mechanism in the treatment of AMI were investigated.Methods: The chemical components of DHI were detected by the ultra-high-performance liquid chromatography-linear trap quadrupole-orbitrap-tandem mass spectrometry (UHPLC-LTQ-Orbitrap-MS/MS), and the targets and pathways of DHI in the treatment of AMI were analyzed by systems pharmacology, which was verified by molecular docking and animal experiments.Results: A total of 12 active components of DHI were obtained, and 158 common targets of component and disease were identified by systems pharmacology. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis results showed that DHI is closely related to the calcium signaling pathway in the treatment of AMI. Molecular docking showed that the key target protein has good binding affinity to related compounds. The experimental results showed that compared with the model group, LVAWs, EF, and FS significantly (p &lt; 0.05) increased in the DHI group. The percentage of myocardial infarction significantly (p &lt; 0.01) decreased, both in the ventricular and total cardiac regions, and the pathological damage of myocardial tissue also decreased. In addition, the expression of the protein CaMK II decreased (p &lt; 0.01) and the expression of SERCA significantly increased (p &lt; 0.01).Conclusion: This study revealed that ferulic acid, caffeic acid and rosmarinic acid could inhibit AMI by regulating PLB, CaMK II, SERCA, etc. And mechanistically, calcium signaling pathway was critically involved. Combination of systems pharmacology prediction with experimental validation may provide a scientific basis for in-depth clinical investigation of the material basis of DHI.
Development of a Definition for Medical Affairs Using the Jandhyala Method for Observing Consensus Opinion Among Medical Affairs Pharmaceutical Physicians
Authors: Jandhyala Ravi 
Published: February 2022

Background: There is currently no standard definition of medical affairs, despite its increasing importance to the pharmaceutical industry. The evolution of medical affairs necessitated the development of a standardised definition to guide policy and practice to ensure that patients’ interests remain central amid shifts that have, in the past, created fertile ground for ethical violations.Objectives: The aim of this study was to use an empirical method to observe a consensus of expert opinion on the definition of medical affairs to guide policy and practice within this function.Methods: In total, 11 medical affairs pharmaceutical physicians (MAPPs) completed a qualitative online survey to identify a list of key items to define medical affairs using the Jandhyala method for generating a consensus of expert opinion. Responses were coded and scored, and aggregated responses were presented to participants in a consensus round. Participants rated their agreement with each item on a 5-point Likert scale from strongly agree to strongly disagree. Indicators that reached a consensus index of &gt;50% (CI &gt; = 0.51) were retained. Items were categorised per previously defined medical affairs functions to determine the scope of the definition. A comparative content analysis using a previous definition identified in the literature was conducted to determine the utility of the definition generated here.Results: In total, 11 MAPPs generated 15 unique items to define medical affairs. Item awareness indices ranged from 0.24 (‘communication/education’) to 1.00 (‘design/strategy’). All items had a CI of more than 0.5 and were included in the final definition. All items could be categorised per previously defined medical affairs functions. Comparative content analysis showed that our definition varied in four ways: the designation of medical affairs as a medical specialty (and its primary aim, therefore, is to protect patients), the leadership of medical affairs in medicine adoption, the generation of real-world evidence and the specification of distinct stakeholders who benefit from medical affairs.Conclusion: A standard definition of medical affairs that incorporates the key principles of medical affairs as a medical specialty that leads medicine adoption and generates real-world evidence for specific stakeholders may protect and further the interests of patients by governing practice and policy.
Hypoxia During the Consolidation Phase of Distraction Osteogenesis Promotes Bone Regeneration
Authors: Liu Yanshi , Liu Jialin , Cai Feiyu , Liu Kai , Zhang Xiaoxu , Yusufu Aihemaitijiang 
Published: February 2022

BackgroundHypoxia is the critical driving force for angiogenesis and can trigger the osteogenic-angiogenic coupling followed by the enhancement of bone regeneration. While lots of studies showed that hypoxia administration can accelerate bone formation during distraction osteogenesis (DO), the therapeutic timing for the osteogenic purpose was concentrated on the distraction phase. The outcomes of hypoxia administration in the consolidation phase stay uncertain. The purpose of this study was to determine the osteogenic effectiveness of hypoxia therapy during the consolidation phase, if any, to enhance bone regeneration in a rat femoral DO model.MethodsA total of 42 adult male Sprague-Dawley rats underwent right femoral mid-diaphysis transverse osteotomy and were randomly divided into Control (NS administration, n = 21) and Group1 (deferoxamine therapy, n = 21) after distraction. During the consolidation phase, Group1 was treated with local deferoxamine (DFO) injection into the distraction zone, while the Control underwent the same dosage of NS. Animals were sacrificed after 2, 4, and 6 weeks of consolidation. The process of bone formation and remodeling was monitored by digital radiographs, and the regenerated bone was evaluated by micro-computed tomography (micro-CT), biomechanical test, and histological analysis. The serum content of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) were measured by enzyme linked immunosorbent assay (ELISA) for further analysis.ResultsBone regeneration was significantly enhanced after hypoxia therapy during the consolidation phase. The digital radiograph, micro-CT, and biomechanical evaluation showed better effects regarding volume, continuity, and mechanical properties of the regenerated bone in Group1. The histomorphological evaluation also revealed the hypoxia treatment contributed to accelerate bone formation and remodeling during DO. The higher positive expression of angiogenic and osteogenic markers were observed in Group1 after hypoxia administration according to the immunohistochemical analysis. The serum content of HIF-1α and VEGF was also increased after hypoxia therapy as evidenced from ELISA.ConclusionHypoxia administration during the consolidation phase of distraction osteogenesis has benefits in enhancing bone regeneration, including accelerates the bone formation and remodeling.
The Role of Emotion Regulation in Eating Disorders: A Network Meta-Analysis Approach
Authors: Leppanen Jenni , Brown Dalia , McLinden Hannah , Williams Steven , Tchanturia Kate 
Published: February 2022

BackgroundPrevious theoretical models and reviews have documented a strong connection between emotion dysregulation eating disorder (ED) psychopathology among the general and clinical populations. The aim of this review was to build on this previous work by conducting a network meta-analysis to explore associations between adaptive and maladaptive emotion regulation strategies and ED psychopathology trans-diagnostically across the ED spectrum to identify areas of emotion dysregulation that have the strongest association with symptomatology.MethodologyA total of 104 studies were included in the meta-analysis and correlation coefficient representing the associations between specific emotion regulation strategies and ED symptomatology were extracted. We ran a Bayesian random effects network meta-analysis and the initial network was well-connected with each emotion regulation strategy being linked to at least one other strategy. We also conducted a network meta-regression to explore whether between-study differences in body mass index (BMI), age, and whether the sample consisted of solely female participants explained any possible network inconsistency.ResultsThe network meta-analysis revealed that ruminations and non-acceptance of emotions were most closely associated with ED psychopathology. There was no significant network inconsistency but two comparisons approached significance and thus meta-regressions were conducted. The meta-regressions revealed a significant effect of BMI such that the associations between different emotion regulation strategies and ED symptomatology were weaker among those with low BMI.DiscussionThe present findings build on previous work and highlight the role of rumination and difficulties with accepting emotions as key emotion regulation difficulties in EDs. Additionally, the finding that the associations were weaker among ED patients with low BMI may point toward a complex relationship between ED behaviors and emotion regulation. Taken together, our findings call for interventions that target emotion regulation, specifically rumination and difficulties accepting emotions, in the treatment of EDs.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021249996, PROSPERO, identifier: CRD42021249996.
Interventional Response of Hospital and Health Services to the Mental Health Effects of Viral Outbreaks on Health Professionals
Authors: Branjerdporn Grace , Bowman Candice , Kenworthy Sean , Stapelberg Nicolas J. C. 
Published: February 2022

The aim of this integrative review was to examine the impact of past viral epidemics on staff mental health interventional responses, with a specific focus on healthcare provider response in the context of the COVID-19 pandemic. Following PRISMA methodology, databases were searched for relevant articles. A total of 55 articles with a range of methodologies (e.g., commentary papers, cohort studies, qualitative studies) were included to ensure broad coverage of this rapidly emerging research area. The literature showed that many healthcare providers implemented a variety of wellbeing initiatives to support their staff during a viral outbreak. Most of these interventions, however, were not formally evaluated. Interventions included leadership/team support; online psychoeducational resources and updated information on the pandemic; respite spaces; peer support outreach; staff resilience training; telephone hotline support; staff support groups; and individual counseling. Staff were generally supportive of the initiatives offered by hospital and health services, with certain interventions being more appreciated (e.g., staff respite areas). Rapid, locally, and culturally appropriate workplace-based responses may counter the negative mental health impact on staff; but a stepped response is required for a smaller number of staff at risk of mental illness, or those with pre-existing mental illness.Systematic Review Registration: Unique Identifier: CRD42020222761.
Penile Flap Inversion Vaginoplasty in Transgender Women: Contemporary Morbidity and Learning-Curve Analysis From a High-Volume Reconstructive Center
Authors: Maurer Valentin , Howaldt Marian , Feldmann Inga , Ludwig Tim , Vetterlein Malte W. , Gild Philipp , Weis Sylvia , Marks Phillip , Soave Armin , Meyer Christian P. , Fisch Margit , Dahlem Roland , Riechardt Silke 
Published: February 2022

ObjectivesNumbers of PIV are rising. The aim of this study is to analyze the surgical learning-curve (LC) on the grounds of perioperative complications.Patients and Methods108 PIVs, performed by a single surgeon between 2015 and 2018 have been analyzed. Learning-curve analysis was based on three factors: operating time, vaginal depth and complications.ResultsThe median FU was 6.3 months. Median age at surgery was 36 years, median time of hormone treatment was 36 months. The median CI was 0.3 and the median BMI was 25 kg/cm3. Median CCI® was 8.08. 40.7% of the patients developed short-term complications, more than half of which were Clavien I. Overall only 1.9% had Clavien IIIb complications. There were no Clavien IV or V complications. 17.6% of patients had wound infections, 13% wound dehiscence, 9.3% introitus strictures, 13.9% suffered from atrophy of the neovagina, i.e. loss of depth or width, and 8.3% from meatus urethrae strictures. Duration of hormonal therapy, BMI and CI had no impact on surgical outcome. Age had a significant impact on CCI®, as younger patients had a higher risk for complications. Use of scrotal skin and surgeries performed had a significant influence. LC analysis via CUSUM analysis showed that after 32 surgeries, the PIV is performed safely.ConclusionThe PIV is a safe GAS-technique, associated with minor complications leading to low rates of revision surgery. Younger age, the use of scrotal skin and surgeon's experience has significant impact on complications. Duration of hormonal therapy, circumcision and BMI has no impact on complications.