bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disease Activity Indices in Rheumatoid Arthritis: Comparative Performance to Detect Changes in Function, IL-6 Levels, and Radiographic Progression
Authors: Rodriguez-García Sebastián C. , Montes Nuria , Ivorra-Cortes José , Triguero-Martinez Ana , Rodriguez-Rodriguez Luis , Castrejón Isabel , Carmona Loreto , González-Álvaro Isidoro 
Published: May 2021

Objective:To compare the capacity of various disease activity indices to evaluate changes in function, IL-6 levels, and radiographic progression in early and established rheumatoid arthritis (RA).Methods:Secondary data analysis of a clinical trial assessing the efficacy of tocilizumab in patients with established RA (ACT-RAY) and a longitudinal prospective register of early arthritis (PEARL). Targeted outcomes were changes in physical function, measured with the health assessment questionnaire (HAQ), IL-6 serum levels, and radiographic progression. The “Hospital Universitario La Princesa Index” (HUPI), DAS28 using erythrocyte sedimentation rate and SDAI were the disease activity indices compared. Models adjusted for age and sex were fitted for each outcome and index and ranked based on theR2parameter and the quasi-likelihood under the independence model criterion.Results:Data from 8,090 visits (550 patients) from ACT-RAY and 775 visits (534 patients) from PEARL were analyzed. The best performing models for HAQ were the HUPI (R2= 0.351) and SDAI ones (R2= 0.329). For serum IL-6 levels, the SDAI (R2= 0.208) followed by the HUPI model (R2= 0.205). For radiographic progression in ACT-RAY, the HUPI (R2= 0.034) and the DAS28 models (R2= 0.026) performed best whereas the DAS28 (R2= 0.030) and HUPI models (R2= 0.023) did so in PEARL.Conclusions:HUPI outperformed other indices identifying changes in HAQ and radiographic progression and performed similarly to SDAI for IL-6 serum levels.
Intrauterine Growth Restriction Promotes Postnatal Airway Hyperresponsiveness Independent of Allergic Disease
Authors: Kalotas Jack O. , Wang Carolyn J. , Noble Peter B. , Wang Kimberley C. W. 
Published: May 2021

Introduction: Intrauterine growth restriction (IUGR) is associated with asthma. Murine models of IUGR have altered airway responsiveness in the absence of any inflammatory exposure. Given that a primary feature of asthma is airway inflammation, IUGR-affected individuals may develop more substantial respiratory impairment if subsequently exposed to an allergen. This study used a maternal hypoxia-induced mouse model of IUGR to determine the combined effects of IUGR and allergy on airway responsiveness.Methods: Pregnant BALB/c mice were housed under hypoxic conditions (10.5% O2) from gestational day (GD) 11-GD 17.5 (IUGR group; term = GD 21). Following hypoxic exposure, mice were returned to a normoxic environment (21% O2). A second group of pregnant mice were housed under normoxic conditions throughout pregnancy (Control). All offspring were sensitized to ovalbumin (OVA) and assigned to one of four treatment groups: Control – normoxic and saline challenge; IUGR – hypoxic and saline challenge; Allergy – normoxic and OVA challenge; and IUGR + Allergy – hypoxic and OVA challenge. At 8 weeks of age, and 24 h post-aerosol challenge, mice were tracheostomised for methacholine challenge and assessment of lung mechanics by the forced oscillation technique, and lungs subsequently fixed for morphometry.Results: IUGR offspring were lighter than Control at birth and in adulthood. Both Allergy and IUGR independently increased airway resistance after methacholine challenge. The IUGR group also exhibited an exaggerated increase in tissue damping and elastance after methacholine challenge compared with Control. However, there was no incremental effect on airway responsiveness in the combined IUGR + Allergy group. There was no impact of IUGR or Allergy on airway structure and no effect of sex on any outcome.Conclusion: IUGR and aeroallergen independently increased bronchoconstrictor response, but when combined the pathophysiology was not worsened. Findings suggest that an association between IUGR and asthma is mediated by baseline airway responsiveness rather than susceptibility to allergen.
Comparisons Between Serum Levels of Hepcidin and Leptin in Male College-Level Endurance Runners and Sprinters
Authors: Nirengi Shinsuke , Taniguchi Hirokazu , Ishibashi Aya , Fujibayashi Mami , Akiyama Nao , Kotani Kazuhiko , Ishihara Kengo , Sakane Naoki 
Published: May 2021

Background: Hepcidin-25 is a 25 amino acid hepatokine and a key regulator of iron metabolism related to iron deficiency anemia. Recent studies have suggested that an elevated hepcidin level is correlated with low energy availability. Leptin is an appetite-suppressing adipokine and has been reported to stimulate hepcidin production in animals and cultured cells. While leptin is modulated by exercise, it is known that endurance runners and sprinters practice different types of exercise. This study investigated and compared the relationships between hepcidin and leptin levels, iron status, and body fat to understand better the risk of iron deficiency anemia in endurance runners and sprinters.Methods: Thirty-six male college track and field athletes (15 endurance runners and 21 sprinters) were recruited for this study. Dietary intake, body composition, and blood levels of ferritin, hepcidin-25, leptin, and adiponectin were measured. Correlations between hepcidin levels and ferritin, body fat, leptin, and adiponectin were evaluated using Pearson's correlation coefficient for each group.Results: The endurance runners had lower hepcidin levels and higher leptin and adiponectin levels compared with sprinters. Ferritin was positively correlated with hepcidin-25 levels in both the endurance and sprinter groups. A positive correlation was observed between hepcidin-25 and body fat or leptin levels only in sprinters.Conclusion: This is the first study investigating the relationship between blood levels of hepcidin and leptin in athletes. The positive correlation between hepcidin-25 and leptin was observed in sprinters but not endurance runners.
Assessing the Contribution of Relative Macrophage Frequencies to Subcutaneous Adipose Tissue
Authors: Kalafati Marianthi , Lenz Michael , Ertaylan Gökhan , Arts Ilja C. W. , Evelo Chris T. , van Greevenbroek Marleen M. J. , Blaak Ellen E. , Adriaens Michiel , Kutmon Martina 
Published: May 2021

Background: Macrophages play an important role in regulating adipose tissue function, while their frequencies in adipose tissue vary between individuals. Adipose tissue infiltration by high frequencies of macrophages has been linked to changes in adipokine levels and low-grade inflammation, frequently associated with the progression of obesity. The objective of this project was to assess the contribution of relative macrophage frequencies to the overall subcutaneous adipose tissue gene expression using publicly available datasets.Methods: Seven publicly available microarray gene expression datasets from human subcutaneous adipose tissue biopsies (n = 519) were used together with TissueDecoder to determine the adipose tissue cell-type composition of each sample. We divided the subjects in four groups based on their relative macrophage frequencies. Differential gene expression analysis between the high and low relative macrophage frequencies groups was performed, adjusting for sex and study. Finally, biological processes were identified using pathway enrichment and network analysis.Results: We observed lower frequencies of adipocytes and higher frequencies of adipose stem cells in individuals characterized by high macrophage frequencies. We additionally studied whether, within subcutaneous adipose tissue, interindividual differences in the relative frequencies of macrophages were reflected in transcriptional differences in metabolic and inflammatory pathways. Adipose tissue of individuals with high macrophage frequencies had a higher expression of genes involved in complement activation, chemotaxis, focal adhesion, and oxidative stress. Similarly, we observed a lower expression of genes involved in lipid metabolism, fatty acid synthesis, and oxidation and mitochondrial respiration.Conclusion: We present an approach that combines publicly available subcutaneous adipose tissue gene expression datasets with a deconvolution algorithm to calculate subcutaneous adipose tissue cell-type composition. The results showed the expected increased inflammation gene expression profile accompanied by decreased gene expression in pathways related to lipid metabolism and mitochondrial respiration in subcutaneous adipose tissue in individuals characterized by high macrophage frequencies. This approach demonstrates the hidden strength of reusing publicly available data to gain cell-type-specific insights into adipose tissue function.
Ketogenic Metabolic Therapy, Without Chemo or Radiation, for the Long-Term Management of IDH1-Mutant Glioblastoma: An 80-Month Follow-Up Case Report
Authors: Seyfried Thomas N. , Shivane Aditya G. , Kalamian Miriam , Maroon Joseph C. , Mukherjee Purna , Zuccoli Giulio 
Published: May 2021

Background: Successful treatment of glioblastoma (GBM) remains futile despite decades of intense research. GBM is similar to most other malignant cancers in requiring glucose and glutamine for growth, regardless of histological or genetic heterogeneity. Ketogenic metabolic therapy (KMT) is a non-toxic nutritional intervention for cancer management. We report the case of a 32-year-old man who presented in 2014 with seizures and a right frontal lobe tumor on MRI. The tumor cells were immunoreactive with antibodies to the IDH1 (R132H) mutation, P53 (patchy), MIB-1 index (4–6%), and absent ATRX protein expression. DNA analysis showed no evidence of methylation of the MGMT gene promoter. The presence of prominent microvascular proliferation and areas of necrosis were consistent with an IDH-mutant glioblastoma (WHO Grade 4).Methods: The patient refused standard of care (SOC) and steroid medication after initial diagnosis, but was knowledgeable and self-motivated enough to consume a low-carbohydrate ketogenic diet consisting mostly of saturated fats, minimal vegetables, and a variety of meats. The patient used the glucose ketone index calculator to maintain his Glucose Ketone Index (GKI) near 2.0 without body weight loss.Results: The tumor continued to grow slowly without expected vasogenic edema until 2017, when the patient opted for surgical debulking. The enhancing area, centered in the inferior frontal gyrus, was surgically excised. The pathology specimen confirmed IDH1-mutant GBM. Following surgery, the patient continued with a self-administered ketogenic diet to maintain low GKI values, indicative of therapeutic ketosis. At the time of this report (May 2021), the patient remains alive with a good quality of life, except for occasional seizures. MRI continues to show slow interval progression of the tumor.Conclusion: This is the first report of confirmed IDH1-mutant GBM treated with KMT and surgical debulking without chemo- or radiotherapy. The long-term survival of this patient, now at 80 months, could be due in part to a therapeutic metabolic synergy between KMT and the IDH1 mutation that simultaneously target the glycolysis and glutaminolysis pathways that are essential for GBM growth. Further studies are needed to determine if this non-toxic therapeutic strategy could be effective in providing long-term management for other GBM patients with or without IDH mutations.
Agreement of Single-Frequency Electrical Bioimpedance in the Evaluation of Fat Free Mass and Fat Mass in Peritoneal Dialysis Patients
Authors: Reis Nayrana Soares do Carmo , Vaninni Francieli Cristina Delatim , Silva Maryanne Zilli Canedo , de Oliveira Rogério Carvalho , Reis Fabrício Moreira , Costa Fabiana Lourenço , Martin Luis Cuadrado , Barretti Pasqual 
Published: May 2021

Background: Protein-energy wasting is related to impairment of quality of life and lower survival of end-stage kidney disease (ESKD) patients. The evaluation of body composition, especially fat free mass (FFM) and fat mass (FM), is important for the prediction of outcomes in these individuals. The aim of this study was to compare the FFM and FM measurements obtained by single-frequency bioimpedance (SF-BIA) and by a multiple frequency bioimpedance (MF-BIA) device, using dual energy X-ray absorptiometry (DXA) peritoneal dialysis (PD) patients.Methods: This was a cross-sectional study involving adult patients undergoing regular PD, in which we performed SF-BIA, MF-BIA, and DXA at the same visit. To compare the bioimpedance values with DXA, we used: Person correlation (r), intraclass correlation coefficient (ICC), and Bland-Altman concordance analysis.Results: The sample consisted of 50 patients in the PD, with mean age of 55.1 ± 16.3 years. Both bioimpedance methods showed a strong correlation (r &gt; 0.7) and excellent reproducibility (ICC &gt; 0.75) compared to DXA. According to the Bland-Altman diagram, SF-BIA showed agreement in body compartment measurements, with no proportionality bias (p &gt; 0.05), without systematic bias for FFM (−0.5 ± 4.9, 95% CI −1.8 to 0.9, p = 0.506), and for FM (0.3 ± 4.6, p = 0.543). MF-BIA did not present a proportionality bias for the FFM, but it underestimated this body compartment by 2.5 ± 5.4 kg (p = 0.002). In addition, MF-BIA presented proportionality bias for FM.Conclusion: SF-BIA was a more accurate assessing method than MBIA for FFM and FM measurements in PD patients. Because it is a low-cost, non-evaluator-dependent measurement and has less systematic bias, it can also be recommended for fat mass and free-fat mass evaluation in PD patients.
Case Report: Rechallenge With BRAF and MEK Inhibitors in Metastatic Melanoma: A Further Therapeutic Option in Salvage Setting?
Authors: Stagno Anna , Vari Sabrina , Annovazzi Alessio , Anelli Vincenzo , Russillo Michelangelo , Cognetti Francesco , Ferraresi Virginia 
Published: May 2021

BackgroundThe combination of BRAF and MEK inhibitors represents the standard of care treatment for patients with metastatic BRAF-mutated melanoma, notwithstanding the high frequency of emergent resistance. Moreover, therapeutic options outside clinical trials are scarce when patients have progressed after both targeted therapy and therapy with immune checkpoint inhibitors. In this article, we report our experience with targeted therapy rechallenging with BRAF and MEK inhibitors in patients with metastatic BRAF-mutated melanoma after progression with kinase inhibitors and immunotherapy.MethodsFour patients with metastatic BRAF-mutated melanoma were rechallenged with BRAF and MEK inhibitors after progression with targeted therapy and subsequent immunotherapy (checkpoint inhibitors).ResultsTwo patients (one of them was heavily pretreated) had partial response over 36 months (with local treatment on oligoprogression disease) and 10 months, respectively. A third patient with multisite visceral disease and high serum levels of lactate dehydrogenase had a short-lived clinical benefit rapidly followed by massive progression of disease (early progressor). The fourth patient, currently on treatment with BRAF/MEK inhibitors, is showing a clinical benefit and radiological stable disease over 3 months of therapy. Adverse events were manageable, similar to those reported during the first targeted therapy; the treatment was better tolerated at rechallenge compared with the first treatment by two out of four patients.
Multiparametric MRI Features Predict the SYP Gene Expression in Low-Grade Glioma Patients: A Machine Learning-Based Radiomics Analysis
Authors: Xiao Zheng , Yao Shun , Wang Zong-ming , Zhu Di-min , Bie Ya-nan , Zhang Shi-zhong , Chen Wen-li 
Published: May 2021

PurposeSynaptophysin (SYP) gene expression levels correlate with the survival rate of glioma patients. This study aimed to explore the feasibility of applying a multiparametric magnetic resonance imaging (MRI) radiomics model composed of a convolutional neural network to predict the SYP gene expression in patients with glioma.MethodUsing the TCGA database, we examined 614 patients diagnosed with glioma. First, the relationship between the SYP gene expression level and outcome of survival rate was investigated using partial correlation analysis. Then, 7266 patches were extracted from each of the 108 low-grade glioma patients who had available multiparametric MRI scans, which included preoperative T1-weighted images (T1WI), T2-weighted images (T2WI), and contrast-enhanced T1WI images in the TCIA database. Finally, a radiomics features-based model was built using a convolutional neural network (ConvNet), which can perform autonomous learning classification using a ROC curve, accuracy, recall rate, sensitivity, and specificity as evaluation indicators.ResultsThe expression level of SYP decreased with the increase in the tumor grade. With regard to grade II, grade III, and general patients, those with higher SYP expression levels had better survival rates. However, the SYP expression level did not show any significant association with the outcome in Level IV patients.ConclusionOur multiparametric MRI radiomics model constructed using ConvNet showed good performance in predicting the SYP gene expression level and prognosis in low-grade glioma patients.
Survival Outcomes and Treatment Decision by Human Papillomavirus Status Among Patients With Stage IVC Head and Neck Squamous Cell Carcinoma
Authors: Zhou Ping , Yu Yi-Feng , Lian Chen-Lu , Wang Jun , Zhuo Ren-Gong , Wu San-Gang 
Published: May 2021

PurposeTo investigate the influence of human papillomavirus (HPV) status on survival outcomes and treatment decisions for patients with de novo stage IV head and neck squamous cell cancers (HNSCC).MethodsPatients initially diagnosed with de novo stage IVC HNSCC between 2010 and 2015 were identified from the Surveillance, Epidemiology, and End Results database. Cox multivariable analyses were performed to determine prognostic factors associated with head and neck cancers specific survival (HNCSS) and overall survival (OS).ResultsWe identified 303 patients who received chemotherapy in this study, including 52.5% of them had HPV-positive disease. HPV-positive HNSCC had better HNCSS (P &lt; 0.001) and OS (P &lt; 0.001) compared to those with HPV-negative disease. The results of Cox multivariable analyses showed that HPV-negative status (P = 0.007), N3 stage (P = 0.004), bone metastases (P &lt; 0.001), and lung metastases (P = 0.003) were associated with worse HNCSS. Similar results were found regarding the OS. The sensitivity analyses indicated that HPV-positive HNSCC patients who were treated with radiotherapy had better survival outcomes. However, no survival benefits were found in those with HPV-positive disease receiving surgery. For HPV-negative patients, no survival benefit was observed among those treated with radiotherapy or surgery.ConclusionsApproximately half of the stage IVC HNSCC patients are HPV-related. The presence of HPV infection appears to be strongly associated with the survival outcome in patients with de novo stage IV HNSCC. Determination of HPV status may help guide clinicians in prognostic assessment and treatment decision-making in this population.
Newborn Screening for Biotinidase Deficiency. The Experience of a Regional Center in Italy
Authors: Maguolo Alice , Rodella Giulia , Dianin Alice , Monge Irene , Messina Martina , Rigotti Erika , Pellegrini Francesca , Molinaro Grazia , Lupi Fiorenzo , Pasini Andrea , Campostrini Natascia , Ion Popa Florina , Teofoli Francesca , Vincenzi Monica , Camilot Marta , Piacentini Giorgio , Bordugo Andrea 
Published: May 2021

Introduction: Biotinidase deficiency (BD) is an autosomal recessive disease causing a defect in the biotin-releasing enzyme. Newborn screening (NBS) allows early diagnosis and treatment, ensuring excellent prognosis. The aim of this study was to describe our experience in the diagnosis, treatment, and follow-up showing key strategies and unsolved questions of the management of BD patients.Methods: We analyzed data of patients identified by the Regional Centre for Newborn Screening of Verona and followed by the Inherited Metabolic Disease Unit of Verona and Neonatal Intensive Care Unit of Bolzano, Italy, from 2014 to 2020.Results: Thirty-seven patients were diagnosed by NBS (five profound and 32 partial BD), with a total incidence of 1:5,996. All were started on biotin at diagnosis and presented no symptoms at follow-up. Analysis of parents and siblings led to identification of five asymptomatic patients with partial BD: one asymptomatic parent and four young siblings. Genetic analysis of the BTD gene identified 17 different genotypes and one mutation not previously known.Discussion: Our data confirm that NBS introduction had a dramatic impact on BD diagnosis, and the incidence has increased significantly compared to other areas. Partial defects are more common than profound and have a distinctive genotype. Partial BD treatment is still controversial even at what dose of biotin and for how long. At the end, BD treatment is very easy and inexpensive and prevents severe neurological damage. Sharing experiences is essential to achieving guidelines for treatment and follow-up and a better genotype–phenotype correlation.
Laser-Induced Control of the Optical Response of Aluminum Phthalocyanine Chloride Complexes Dissolved in Ethanol
Authors: da Costa Castanheira Carina , Persch Andreas , Birk Paul , Ott Christian , Pfeifer Thomas 
Published: May 2021

We show that absorption spectra of aluminum chloride phthalocyanine (AlClPc) in the liquid phase can be dynamically modified through the time-resolved interaction with a second laser pulse during a time window on the order of 100 fs. The observed effects can be explained by laser-induced coherent coupling dynamics between the ground state and a bath of excited states as reproduced by a few-level toy model. The presented results help to understand how intense laser fields interact with complex molecules in solution, but in their laser-controlled response still much alike isolated atoms in the gas phase. This understanding can, in the future, be used to modify and control the dynamics in complex systems.