bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Randomized Clinical Trial to Evaluate the Effects of Safinamide on Apathetic Non-demented Patients With Parkinson's Disease
Authors: Kulisevsky Jaime , Martínez-Horta Saul , Campolongo Antonia , Pascual-Sedano Berta , Marín-Lahoz Juan , Bejr-kasem Helena , Aracil-Bolaños Ignacio , Horta-Barba Andrea , Puig-Davi Arnau , Pagonabarraga Javier 
Published: June 2022

BackgroundApathy is highly prevalent and disabling in Parkinson's disease (PD). Pharmacological options for its management lack sufficient evidence.ObjectiveWe studied the effects of safinamide on apathy in PD.MethodsProspective, 24-week, two-site, randomized, double-blind, placebo-controlled, parallel-group exploratory study in non-demented PD on stable dopaminergic therapy randomized 1:1 to adjunct safinamide (50 mg/day for 2 weeks and 100 mg/day for 22 weeks) or placebo. The primary endpoint was the mean change from baseline to week 24 on the Apathy Scale (AS) total score. Secondary endpoints included changes in cognition, activities of daily living, motor scores, the impression of change, and safety and tolerability measures.ResultsIn total, 30 participants (active treatment = 15; placebo = 15; 80% showing clinically significant apathetic symptoms according to the AS) were enrolled, and included in the intention-to-treat analysis. Change in AS (ANOVA) showed a trend to significance [p = 0.059] mediated by a more marked decrease in AS score with safinamide (−7.5 ± 6.9) than with placebo (−2.8 ± 5.7). Post-hoc analysis (paired t-test) showed a significant positive change in the AS score between 12-week and 24-week [p = 0.001] only in the active group. No significant or trend changes were found for any of the secondary outcome variables. Adverse events were few and only mild in both treatment groups.ConclusionsSafinamide was safe and well-tolerated, but failed to provide evidence of improved apathy. The positive trend observed in the post-hoc analyses deserves to be studied in depth in larger studies.Trial RegistrationEudraCT 2017-003254-17.
Immune–Inflammatory Biomarkers Predict Cognition and Social Functioning in Patients With Type 2 Diabetes Mellitus, Major Depressive Disorder, Bipolar Disorder, and Schizophrenia: A 1-Year Follow-Up Study
Authors: Garés-Caballer Marta , Sánchez-Ortí Joan Vicent , Correa-Ghisays Patricia , Balanzá-Martínez Vicent , Selva-Vera Gabriel , Vila-Francés Joan , Magdalena-Benedito Rafael , San-Martin Constanza , Victor Victor M. , Escribano-Lopez Irene , Hernandez-Mijares Antonio , Vivas-Lalinde Juliana , Vieta Eduard , Leza Juan C. , Tabarés-Seisdedos Rafael 
Published: June 2022

BackgroundSystemic, low-grade immune–inflammatory activity, together with social and neurocognitive performance deficits are a transdiagnostic trait of people suffering from type 2 diabetes mellitus (T2DM) and severe mental illnesses (SMIs), such as schizophrenia (SZ), major depressive disorder (MDD), and bipolar disorder (BD). We aimed to determine if immune–inflammatory mediators were significantly altered in people with SMIs or T2DM compared with healthy controls (HC) and whether these biomarkers could help predict their cognition and social functioning 1 year after assessment.MethodsWe performed a prospective, 1-year follow-up cohort study with 165 participants at baseline (TB), including 30 with SZ, 42 with BD, 35 with MDD, 30 with T2DM, and 28 HC; and 125 at 1-year follow-up (TY), and determined executive domain (ED), global social functioning score (GSFS), and peripheral blood immune–inflammatory and oxidative stress biomarkers.ResultsParticipants with SMIs and T2DM showed increased peripheral levels of inflammatory markers, such as interleukin-10 (p &lt; 0.01; η2p = 0.07) and tumor necrosis factor-α (p &lt; 0.05; η2p = 0.08); and oxidative stress biomarkers, such as reactive oxygen species (ROS) (p &lt; 0.05; η2p = 0.07) and mitochondrial ROS (p &lt; 0.01; η2p = 0.08). The different combinations of the exposed biomarkers anticipated 46–57.3% of the total ED and 23.8–35.7% of GSFS for the participants with SMIs.LimitationsParticipants' treatment, as usual, was continued without no specific interventions; thus, it was difficult to anticipate substantial changes related to the psychopharmacological pattern.ConclusionPeople with SMIs show significantly increased levels of peripheral immune–inflammatory biomarkers, which may contribute to the neurocognitive and social deficits observed in SMIs, T2DM, and other diseases with systemic immune–inflammatory activation of chronic development. These parameters could help identify the subset of patients who could benefit from immune–inflammatory modulator strategies to ameliorate their functional outcomes.
Toward Improved Diagnosis Accuracy and Treatment of Children, Adolescents, and Young Adults With Ependymoma: The International SIOP Ependymoma II Protocol
Authors: Leblond Pierre , Massimino Maura , English Martin , Ritzmann Timothy A. , Gandola Lorenza , Calaminus Gabriele , Thomas Sophie , Pérol David , Gautier Julien , Grundy Richard G. , Frappaz Didier 
Published: June 2022

Background:The clinical management of ependymoma in childhood and adolescence is complex and the clinicobiopathological correlates of outcome remain poorly understood. This international SIOP Ependymoma II (SIOP EPII) trial aims to improve the outcome of patients with ependymoma.MethodsSIOP EPII includes any patient &lt;22 years at diagnosis with ependymoma, stratified by age, tumor location, and outcome of the initial surgery. Centralized pathology and imaging is required for diagnosis confirmation. SIOP EPII included three randomized studies according to age, postoperative residue, and suitability to receive radiotherapy. Patients ineligible for interventional strata are followed-up in an observational study. The staging phase aims to determine if central neurosurgical and radiological postoperative MRI reviews increase the resection rate. Patients ≥12 months with (i) no residual disease are randomly assigned in a phase III trial to evaluate the efficacy of post-radiation 16-week chemotherapy (VEC + CDDP) on PFS (stratum I); (ii) centrally confirmed measurable inoperable residual disease are allocated to randomized frontline chemotherapy phase II study (VEC vs. VEC + high-dose methotrexate) and considered for a second-look surgery (stratum II). If second-look surgery is not feasible or tumor residuum remains, patients receive 8 Gy-boost radiotherapy after conformal radiotherapy (phase I). (iii) Patients &lt; 12 months (18 months in the UK) or not eligible to receive radiotherapy are randomized in a phase II study to receive chemotherapy (alternated myelosuppressive and nonmyelosuppressive chemotherapy), with or without valproate (stratum III). To overcome the limitations encountered in the preliminary conclusions of the ACNS-0831 study, a SIOP EPII dedicated on-study amendment has been planned to definitively conclude the relevance of maintenance chemotherapy in stratum I. Secondary outcomes include overall survival, quality of life, neuropsychological and neuroendocrine outcomes, safety, and identification of key prognostic biomarkers (BIOMECA).Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT02265770.
Retrospective Analysis of Task-Specific Effects on Brain Activity After Stroke: A Pilot Study
Authors: Demers Marika , Varghese Rini , Winstein Carolee 
Published: June 2022

BackgroundEvidence supports cortical reorganization in sensorimotor areas induced by constraint-induced movement therapy (CIMT). However, only a few studies examined the neural plastic changes as a function of task specificity. This retrospective analysis aims to evaluate the functional brain activation changes during a precision and a power grasp task in chronic stroke survivors who received 2-weeks of CIMT compared to a no-treatment control group.MethodsFourteen chronic stroke survivors, randomized to CIMT (n= 8) or non-CIMT (n= 6), underwent functional MRI (fMRI) before and after a 2-week period. Two behavioral measures, the 6-item Wolf Motor Function Test (WMFT-6) and the Motor Activity Log (MAL), and fMRI brain scans were collected before and after a 2-week period. During scan runs, participants performed two different grasp tasks (precision, power). Pre to post changes in laterality index (LI) were compared by group and task for two predetermined motor regions of interest: dorsal premotor cortex (PMd) and primary motor cortex (MI).ResultsIn contrast to the control group, the CIMT group showed significant improvements in the WMFT-6. For the MAL, both groups showed a trend toward greater improvements from baseline. Two weeks of CIMT resulted in a relative increase in activity in a key region of the motor network, PMd of the lesioned hemisphere, under precision grasp task conditions compared to the non-treatment control group. No changes in LI were observed in MI for either task or group.ConclusionThese findings provide preliminary evidence for task-specific effects of CIMT in the promotion of recovery-supportive cortical reorganization in chronic stroke survivors.
Effects of Noisy Galvanic Vestibular Stimulation on the Muscle Activity and Joint Movements in Different Standing Postures Conditions
Authors: Mitsutake Tsubasa , Taniguchi Takanori , Nakazono Hisato , Yoshizuka Hisayoshi , Sakamoto Maiko 
Published: June 2022

ObjectiveNoisy galvanic vestibular stimulation (nGVS) is an effective method for stabilizing posture; however, little is known regarding the detailed muscle activity and joint movement in the standing posture. This study aimed to clarify the changes in the lower limb muscle activity and joint angular velocity by nGVS intervention using the simultaneous assessment method of inertial measurement units and surface electromyography (EMG).MethodsSeventeen healthy participants were assessed for their physical responses under four conditions (standing on a firm surface with eyes-open/eyes-closed, and a foam surface with eyes-open/eyes-closed) without stimulation (baseline) and with stimulation (sham or nGVS). Noise stimuli were applied for 30 s at a level below the perceptual threshold. The body control response was evaluated using EMG activity and angular velocity of the lower limbs.ResultRegarding the change from baseline for each parameter, there was a significant interactive effect of EMG activity in the muscle type × intervention and EMG activity and angular velocity in the condition × intervention. Post hoc analysis revealed that the angular velocity was significantly decreased in the abduction-adduction direction in the standing on a foam surface with eyes-closed condition compared to that with eyes-open in the nGVS intervention.ConclusionOur results suggest that nGVS altered physical responses in different standing postural conditions. The present study is exploratory and therefore the evidence should be investigated in future studies specifically target those muscle activities and joint motion parameters.
Adherence to Mediterranean Diet of Breastfeeding Mothers and Fatty Acids Composition of Their Human Milk: Results From the Italian MEDIDIET Study
Authors: Di Maso Matteo , Bravi Francesca , Ferraroni Monica , Agostoni Carlo , Eussen Simone R. B. M. , Decsi Tamás , Quitadamo Pasqua A. , Tonetto Paola , Peila Chiara , Profeti Claudio , Salvatori Guglielmo , Kazmierska Iwona , Decarli Adriano , Vacca Elisabetta , Bertino Enrico , Stahl Bernd , Moro Guido E. 
Published: June 2022

Background and AimsThe content of fatty acids (FA) in human milk may be influenced by maternal nutrition. We evaluated the role of a Mediterranean diet in influencing the content of FA in human milk among 282 breastfeeding mothers participating in the MEDIDIET study.Materials and MethodsMediterranean Diet Score (MDS), a composite index, was used to evaluate adherence to the Mediterranean diet. It includes 9 components (i.e., vegetables, fruit, cereals, legumes, monounsaturated to saturated FA ratio – MUFA/SFA, fish, dairy products, meat, and alcohol) and therefore potentially ranges from 0 (no adherence) to 9 (complete adherence) points. None of the mothers obtained the highest score due to the low alcohol consumption in the study population. Mothers were categorized in approximate tertiles of adherence: 0–3 (34.4%), 4 (26.2%), and 5–8 points (39.4%). The mean content of FA across categories of MDS was compared using ANOVA and test for trend.ResultsA high adherence of breastfeeding mothers to the Mediterranean diet was associated with lower content of SFA in human milk (42.58 ± 4.36 for MDS = 0–3, 42.58 ± 4.89 for MDS = 4, and 40.92 ± 5.22% of fats for MDS = 5–8 points; p ANOVA and p for trend = 0.02). Conversely, a high adherence was associated with higher content of MUFA in human milk (43.27 ± 4.27 for MDS = 0–3, 43.27 ± 4.47 for MDS = 4, and 45.24 ± 5.22% of fats for MDS = 5–8 points; p ANOVA and p for trend &lt; 0.01), ω-3 FA (1.07 ± 0.25 for MDS = 0–3, 1.22 ± 0.49 for MDS = 4, and 1.31 ± 0.51% of fats for MDS = 5–8 points; p ANOVA and p for trend &lt; 0.01), and the major types of ω-3 FA (i.e., α-linolenic acid – ALA, eicosapentaenoic acid – EPA, docosahexaenoic acid – DHA, docosapentaenoic acid – DPA). These associations were mainly driven by the adherence to the vegetables, MUFA/SFA, fish, and dairy products components of the Mediterranean diet.ConclusionA high adherence to the Mediterranean diet was associated with human milk showing a lower content of SFA and higher content of MUFA and ω-3 FA, including DHA. The Mediterranean diet may contribute in human milk production with higher content of specific FA which is directly involved in infant’s neural and visual development, as reported by previous studies.
A Pilot Study of Radiomics Models Combining Multi-Probe and Multi-Modality Images of 68Ga-NOTA-PRGD2 and 18F-FDG PET/CT for Differentiating Benign and Malignant Pulmonary Space-Occupying Lesions
Authors: Xie Fei , Zheng Kun , Liu Linwen , Jin Xiaona , Fu Lilan , Zhu Zhaohui 
Published: June 2022

BackgroundThis is a pilot study of radiomics based on 68Ga-NOTA-PRGD2 [NOTA-PEG4-E[c(RGDfK)]2)] and 18F-FDG PET/CT to (i) evaluate the diagnostic efficacy of radiomics features of 68Ga-NOTA-PRGD2 PET in the differential diagnosis of benign and malignant pulmonary space-occupying lesions and (ii) compare the diagnostic efficacy of multi-modality and multi-probe images.MethodsWe utilized a dataset of 48 patients who participated in 68Ga-NOTA-PRGD2 PET/CT and 18F-FDG PET/CT clinical trials to extract image features and evaluate their diagnostic efficacy in the differentiation of benign and malignant lesions by the Mann-Whitney U test. After feature selection with sequential forward selection, random forest models were developed with tenfold cross-validation. The diagnostic performance of models based on different image features was visualized by receiver operating characteristic (ROC) curves and compared by permutation tests.ResultsFourteen of the 68Ga-NOTA-PRGD2 PET features between benign and malignant pulmonary space-occupying lesions had significant differences (P&lt;0.05, Mann-Whitney U test). Eighteen of the 68Ga-NOTA-PRGD2 PET features demonstrated higher AUC values than all CT features in the differential diagnosis of pulmonary lesions. The AUC value (0.908) ​​of the three-modal feature model was significantly higher (P&lt;0.05, permutation test) than those of the single- and dual-modal models.Conclusion68Ga-NOTA-PRGD2 PET features have better diagnostic capacity than CT features for pulmonary space-occupying lesions. The combination of multi-modality and multi-probe images can improve the diagnostic efficiency of models. Our preliminary clinical hypothesis of using radiomics based on 68Ga-NOTA-PRGD2 PET images and multimodal images as a diagnostic tool warrants further validation in a larger multicenter sample size.
Construction of m6A-Related lncRNA Prognostic Signature Model and Immunomodulatory Effect in Glioblastoma Multiforme
Authors: Xie Pan , Yan Han , Gao Ying , Li Xi , Zhou Dong-Bo , Liu Zhao-Qian 
Published: June 2022

BackgroundGlioblastoma multiforme (GBM), the most prevalent and aggressive of primary malignant central nervous system tumors (grade IV), has a poor clinical prognosis. This study aimed to assess and predict the survival of GBM patients by establishing an m6A-related lncRNA signaling model and to validate its validity, accuracy and applicability.MethodsRNA sequencing data and clinical data of GBM patients were obtained from TCGA data. First, m6A-associated lncRNAs were screened and lncRNAs associated with overall survival in GBM patients were obtained. Subsequently, the signal model was established using LASSO regression analysis, and its accuracy and validity are further verified. Finally, GO enrichment analysis was performed, and the influence of this signature on the immune regulation response and anticancer drug sensitivity of GBM patients was discussed.ResultsThe signature constructed by four lncRNAs AC005229.3, SOX21-AS1, AL133523.1, and AC004847.1 is obtained. Furthermore, the signature proved to be effective and accurate in predicting and assessing the survival of GBM patients and could function independently of other clinical characteristics (Age, Gender and IDH1 mutation). Finally, Immunosuppression-related factors, including APC co-inhibition, T-cell co-inhibition, CCR and Check-point, were found to be significantly up-regulated in GBM patients in the high-risk group. Some chemotherapeutic drugs (Doxorubicin and Methotrexate) and targeted drugs (AZD8055, BI.2536, GW843682X and Vorinostat) were shown to have higher IC50 values in patients in the high-risk group.ConclusionWe constructed an m6A-associated lncRNA risk model to predict the prognosis of GBM patients and provide new ideas for the treatment of GBM. Further biological experiments can be conducted on this basis to validate the clinical value of the model.
Reference Values for and Correlation Analysis of the Anogenital Distance of Chinese Han Full-Term Singleton Neonates
Authors: Cao Wei , Ding Xiaowei , Dong Zhiya , Tang Haiting 
Published: June 2022

BackgroundAnogenital distance (AGD) is a biomarker used for the evaluation of fetal androgen action. The disruption of fetal androgen action can affect the development of the reproductive system and adversely affect future reproductive functions. However, AGD may differ by race. Currently, there is a lack of data regarding the evaluation of AGD in large Han Chinese samples.ObjectiveAGD for neonates in Shanghai, China, was measured, and relevant factors that influenced AGD were analyzed.MethodsThe AGD of full-term singleton neonates was measured within 3 days of birth, and the results were grouped according to gestational age and body weight at birth. In addition, relevant factors that influenced AGD were investigated.ResultsA total of 1,867 full-term singleton neonates were enrolled in this study. All the neonates were Han Chinese; among them, 986 were male, and 881 were female. Male AGD was 23.18 ± 3.17 mm, and female AGD was 11.65 ± 1.53 mm. Male AGD was 1.99 times longer than female AGD. With the increase in gestational age and body weight, AGD gradually increased. AGD was correlated with gestational age, body weight, and head circumference. The correlation between body weight at birth and AGD was highly significant.ConclusionThis study, for the first time, reported AGD measurement data for Chinese Han neonates. The results indicated that AGD was correlated with gestational age, body weight, and head circumference. The correlation between body weight at birth and AGD was highly significant.
Gastrodin From Gastrodia elata Enhances Cognitive Function and Neuroprotection of AD Mice via the Regulation of Gut Microbiota Composition and Inhibition of Neuron Inflammation
Authors: Fasina Opeyemi B. , Wang Jianyu , Mo Jianxia , Osada Hiroyuki , Ohno Hiroshi , Pan Wensheng , Xiang Lan , Qi Jianhua 
Published: June 2022

Gastrodin (Gas) is known to exhibit neuroprotective effects in Alzheimer’s disease (AD). However, the detailed mechanism of action is still unclear. In the present study, we focused on the microbiome–gut–brain axis to investigate the mechanism of action of Gas using a D-galactose (Dgal)–induced AD model. Gas reversed the memory dysfunction of Dgal-administered mice. Neurons in the cerebral cortex and hippocampus were reduced in the Dgal-administered group, and the decrease of neurons was suppressed in 90 and 210 mg/kg Gas treatment groups. 16S rRNA sequence analysis was carried out to explore the composition of gut microbiota in fecal samples of mice. Gas treatment had a positive correlation with Firmicutes and had a negative correlation with Cyanobacteria, Proteobacteria, and Deferribaceters. Importantly, the LPS and proinflammatory cytokines in the brain increased in Dgal-administered mice, but these parameters recovered to normal levels after oral administration of Gas. To determine whether the microbiota–gut–brain axis is involved in the neuroprotective effect of Gas, the mice were given antibiotic cocktail before and during the trial period to decrease the gut microbiota of mice. The antibiotic cocktail partially eliminated the neuroprotective effect of Gas by changing the gut microbiome composition. These results indicated that Gas improves the memory of the AD mouse model via partly targeting the microbiota–gut–brain axis and mitigating neuron inflammation.
Key Considerations for Phase 2 or 3 Clinical Study Design of Anti-Inflammatory Agent for COVID-19 Treatment
Authors: Park Yewon , Na Joo Young , Cho Joo-Youn , Oh Jaeseong , Rhee Su-jin 
Published: June 2022

Purpose: Current understanding of COVID-19 disease progression suggests a major role for the “cytokine storm” as an important contributor to COVID-19 mortality. To prevent an exaggerated immune response and improve COVID-19 patient endpoints, anti-inflammatory therapeutics have been proposed as clinically useful in severe patients with COVID-19. The purpose of this study was to propose a clinical trial design for the development of anti-inflammatory agents for the treatment of COVID-19, taking into account the physiological and immunological process of COVID-19 and the treatment mechanism of anti-inflammatory agents.Methods: We reviewed and analyzed the guidelines for the development of COVID-19 treatments and the treatment of COVID-19 by regulatory agencies and previously conducted clinical trials on anti-inflammatory drugs for COVID-19. Finally, after discussing with an advisory group, a synopsis was presented for an example protocol for a COVID-19 anti-inflammatory agent phase 2 or 3 study that considers the drug mechanism and the disease progression of COVID-19.Results: A randomized, placebo-controlled, double-blind parallel-group design was suggested as a phase 2 or 3 trial design for developing an anti-inflammatory agent as a COVID-19 treatment. A key item of the example protocol specific to anti-inflammatory agents was the inclusion and exclusion criteria, taking into account the immunosuppressive effects of the drug, clinical time course of COVID-19 disease, and treatment guidelines for COVID-19. Time to recovery is the primary endpoint associated with clinical efficacy and is generally well accepted by many experts.Conclusion: Through this suggested phase 2 or 3 study design of an anti-inflammatory drug for COVID-19, we provide a basis for a study design that can be utilized in clinical development by pharmaceutical companies which are developing a potential anti-inflammatory agent for COVID-19.