Miracle-dz/UniFAR-FTUs huggingface dataset:
Effectiveness of Non-Animal Chondroitin Sulfate Supplementation in the Treatment of Moderate Knee Osteoarthritis in a Group of Overweight Subjects: A Randomized, Double-Blind, Placebo-Controlled Pilot Study

Osteoarthritis (OA) is the most common form of arthritis in the world and is characterized by pain, various disabilities and loss of quality of life. Chondroitin sulfate (CS) is recommended as first-line therapy. CS of non-animal origin is of great interest for safety and sustainability reasons. This study aims to investigate the anti-inflammatory effects, anti-pain and ability-enhancement of a short-term supplementation with non-animal CS in overweight subjects with OA. In a randomized, double-blind, placebo-controlled pilot study, 60 overweight adults with symptomatic OA were allocated to consume 600 mg of non-animal CS (n = 30) or a placebo (n = 30) daily for 12 consecutive weeks. The assessment of knee-pain, quality of life, related inflammation markers and body composition was performed at 0, 4 and 12 weeks. The Tegner Lysholm Knee Scoring (TLKS) scale of the experimental group showed a statistically significant increase (+10.64 points; confidence interval (95% confidence interval (CI) 5.57; 15.70; p < 0.01), while the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score decreased (−12.24 points; CI 95% −16.01; −8.38; p < 0.01). The results also showed a decrease in the C-reactive protein (CRP) level (−0.14 mg/dL, CI 95% −0.26; −0.04; p < 0.01) and erythrocyte sedimentation rate (ESR) level (−5.01 mm/h, CI 95% −9.18; −0.84, p < 0.01) as well as the visual analogue scale (VAS) score in both knees. In conclusion, this pilot study demonstrates the effectiveness of non-animal CS supplementation in overweight subjects with knee OA in improving knee function, pain and inflammation markers.
Diagnostic Potential of Multimodal MRI Markers in Atypical Parkinsonian Disorders.

BACKGROUND The diagnostic potential of multimodal MRI approaches to discriminate among progressive supranuclear palsy (PSP), Parkinson variant of multiple system atrophy (MSA-P) and Parkinson's disease (PD) has not been well investigated. OBJECTIVE To identify disease-specific neurodegenerative patterns and evaluate the diagnostic accuracy of dedicated MRI, iron concentration (R2*), microstructural integrity (mean diffusivity; MD and fractional anisotropy; FA) as well as volumes were analyzed in patients with PSP, MSA-P and PD. METHODS 3T MRI of 18 PSP and 16 MSA-P patients were compared with 16 PD patients matched for age and disease duration as well as 21 healthy controls. Statistical parametric mapping (SPM) was applied to objectively identify focal MRI changes throughout the whole-brain. Following dimensionality reduction of significant and multiple comparison-corrected SPM clusters through principal component analysis (PCA), stepwise receiver-operating characteristic curve analysis (ROC) was applied to determine the diagnostic potential of multimodal MRI parameters. RESULTS PCA revealed two components involving multiple regions identified from SPM analysis. The first component was primarily composed of the mean MD value of the thalamus and the mean MD and FA values of the dentatorubrothalamic tract and the corpus callosum. The second component mainly consisted of mean MD and FA values of the middle cerebellar peduncle. ROC analysis showed 92% of PSP patients were differentiated correctly from MSA-P and PD and 80% of MSA-P patients could be distinguished from PD. CONCLUSION Multimodal MRI improved the detection of disease-specific neurodegenerative patterns in PSP and MSA-P and highlights its potential to improve the diagnostic accuracy of atypical parkinsonian disorders.
An exploration of how community-dwelling older adults enhance their well-being.

AIM AND OBJECTIVES To explore community-dwelling older adults approaches to enhancing their psychological well-being. BACKGROUND Older adults who are living with long-term or chronic health conditions are particularly at risk of experiencing low psychological well-being. Little attention has been paid to preventive strategies that enhance psychological well-being and, in particular, to understanding how older adults enhance their own well-being. METHODS Using Seligman's PERMA model of well-being (2011) as an organisational framework, this qualitative study interviewed 48 older people aged between 66 and 99 years. Of these, 17 men and 20 women participated in semi-structured interviews. Additionally, 11 women, all widows with a mean age of 81 years, participated in a focus group. The data were analysed with reference to the five aspects of PERMA (Positive emotion, Engagement, Relationships, Meaning, Accomplishment) with a focus on identifying what actions the older people were taking to enhance their well-being. Further analysis involved coding the data into processes or practices and also influencing factors. FINDINGS Most participants used a range of strength-based strategies or practices to enhance their well-being. For a small number of participants (n = 3), these practices were supported by the presence of partners as carers. However, using PERMA as our conceptual model illustrated that despite Seligman's view that individuals can take positive action within each of the five aspects of PERMA to enhance well-being, external factors, for example economic circumstances or mobility, can influence the ability of older adults to undertake well-being practices. CONCLUSIONS Older adults have a range of strategies or practices that they use to enhance their well-being. However, well-being is not a static concept and it is important to recognise the influence of health, social and environmental factors as enablers and enhancers of well-being. IMPLICATIONS FOR PRACTICE Nurses can play a central role in supporting older adults who may be at risk of lower well-being. Nurses can do this by developing interventions to enhance well-being and ensuring better person-activity fit of strategies and practices. Our findings support the need for nurses to be involved in providing opportunities for older people to discuss well-being to support the development of individual, as well as community, models of well-being.
Antigen-Specific Immune Decoys Intercept and Exhaust Autoimmunity to Prevent Disease

Relapsing-remitting patterns of many autoimmune diseases such as multiple sclerosis (MS) are perpetuated by a recurring circuit of adaptive immune cells that amplify in secondary lymphoid organs (SLOs) and traffic to compartments where antigen is abundant to elicit damage. Some of the most effective immunotherapies impede the migration of immune cells through this circuit, however, broadly suppressing immune cell migration can introduce life-threatening risks for patients. We developed antigen-specific immune decoys (ASIDs) to mimic tissues targeted in autoimmunity and selectively intercept autoimmune cells to preserve host tissue. Using Experimental Autoimmune Encephalomyelitis (EAE) as a model, we conjugated autoantigen PLP139-151 to a microporous collagen scaffold. By subcutaneously implanting ASIDs after induction but prior to the onset of symptoms, mice were protected from paralysis. ASID implants were rich with autoimmune cells, however, reactivity to cognate antigen was substantially diminished and apoptosis was prevalent. ASID-implanted mice consistently exhibited engorged spleens when disease normally peaked. In addition, splenocyte antigen-presenting cells were highly activated in response to PLP rechallenge, but CD3+ and CD19+ effector subsets were significantly decreased, suggesting exhaustion. ASID-implanted mice never developed EAE relapse symptoms even though the ASID material had long since degraded, suggesting exhausted autoimmune cells did not recover functionality. Together, data suggested ASIDs were able to sequester and exhaust immune cells in an antigen-specific fashion, thus offering a compelling approach to inhibit the migration circuit underlying autoimmunity.
Are Horses (Equus caballus) Sensitive to Human Emotional Cues?

Simple Summary It is important for social animals to be sensitive to others’ emotional cues, because they can process and react to valuable social and environmental information more efficiently if they can understand others’ emotional states. Such sensitivity also seems to be adaptive in animal communication with both conspecific and heterospecific individuals, particularly for dogs and horses, because these animals have been cooperating with humans since the advent of domestication. Previous studies have demonstrated that dogs are very sensitive to human cues, such as pointing and facial or vocal expressions. However, few studies have examined whether horses exhibit a sensitivity to human emotional cues that is comparable to dogs’ sensitivity. In this study, we investigated whether horses are sensitive to human emotional cues and adjust their behavior accordingly. The results revealed that human emotional cues influenced the frequency of gaze following and the amount of time that horses looked at humans. Horses avoided following the human gaze and looked in their direction for a shorter period of time when humans displayed expressions of disgust. These findings support our hypothesis that horses exhibit sensitivity to negative human emotional cues. Abstract Emotions are important for social animals because animals’ emotions function as beneficial cues to identify valuable resources such as food or to avoid danger by providing environmental information. Emotions also enable animals to predict individuals’ behavior and determine how to behave in a specific context. Recently, several studies have reported that dogs are highly sensitive to not only conspecific but also human emotional cues. These studies suggest that domestication may have affected such sensitivity. However, there are still few studies that examine whether other domesticated animals, in addition to dogs, exhibit sensitivity to human emotional cues. In this study, we used a gaze-following task to investigate whether horses (Equus caballus) are sensitive to human emotional cues (happy, neutral, disgust) and if they adjust their behavior accordingly. In the study, the experimenter suddenly turned her head to either right or left and showed emotional cues. The results revealed that horses significantly decreased the frequency with which they followed the experimenter’s gaze and the total looking time during the gaze-emotional cue presentation in the Disgust condition compared to the Neutral condition. These results suggest the possibility that horses are sensitive to human emotional cues and behave on the basis of the meaning implied by negative human emotional cues.
PI3K (Phosphatidylinositol 3-Kinase) Activation and Endothelial Cell Proliferation in Patients with Hemorrhagic Hereditary Telangiectasia Type 1

Hemorrhagic hereditary telangiectasia (HHT) type 2 patients have increased activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway in telangiectasia. The main objective is to evaluate the activation of the PI3K pathway in cutaneous telangiectasia of HHT1 patients. A cutaneous biopsy of a digital hand telangiectasia was performed in seven HHT1 and eight HHT2 patients and compared with six controls. The study was approved by the Clinical Research Ethics Committee of our center. A histopathological pattern with more dilated and superficial vessels that pushed up the epidermis was identified in HHT patients regardless of the type of mutation and was associated with older age, as opposed to the common telangiectasia pattern. The mean proliferation index (Ki-67) was statistically higher in endothelial cells (EC) from HHT1 than in controls. The percentage of positive EC for pNDRG1, pAKT, and pS6 in HHT1 patients versus controls resulted in higher values, statistically significant for pNDRG1 and pS6. In conclusion, we detected an increase in EC proliferation linked to overactivation of the PI3K pathway in cutaneous telangiectasia biopsies from HHT1 patients. Our results suggest that PI3K inhibitors could be used as novel therapeutic agents for HHT.
Adherence and Satisfaction of Smartphone- and Smartwatch-Based Remote Active Testing and Passive Monitoring in People With Multiple Sclerosis: Nonrandomized Interventional Feasibility Study

Background Current clinical assessments of people with multiple sclerosis are episodic and may miss critical features of functional fluctuations between visits. Objective The goal of the research was to assess the feasibility of remote active testing and passive monitoring using smartphones and smartwatch technology in people with multiple sclerosis with respect to adherence and satisfaction with the FLOODLIGHT test battery. Methods People with multiple sclerosis (aged 20 to 57 years; Expanded Disability Status Scale 0-5.5; n=76) and healthy controls (n=25) performed the FLOODLIGHT test battery, comprising active tests (daily, weekly, every two weeks, or on demand) and passive monitoring (sensor-based gait and mobility) for 24 weeks using a smartphone and smartwatch. The primary analysis assessed adherence (proportion of weeks with at least 3 days of completed testing and 4 hours per day passive monitoring) and questionnaire-based satisfaction. In-clinic assessments (clinical and magnetic resonance imaging) were performed. Results People with multiple sclerosis showed 70% (16.68/24 weeks) adherence to active tests and 79% (18.89/24 weeks) to passive monitoring; satisfaction score was on average 73.7 out of 100. Neither adherence nor satisfaction was associated with specific population characteristics. Test-battery assessments had an at least acceptable impact on daily activities in over 80% (61/72) of people with multiple sclerosis. Conclusions People with multiple sclerosis were engaged and satisfied with the FLOODLIGHT test battery. FLOODLIGHT sensor-based measures may enable continuous assessment of multiple sclerosis disease in clinical trials and real-world settings. Trial Registration ClinicalTrials.gov: NCT02952911; https://clinicaltrials.gov/ct2/show/NCT02952911
Pituitary Apoplexy

Pituitary apoplexy is infarction of the pituitary gland by hemorrhage or ischemia. Although pituitary apoplexy is rare, it is a neurologic emergency and sometimes a neurosurgical and endocrine emergency that require rapid intervention to prevent severe and potentially life-threatening adrenal insufficiency, hydrocephalus, intracranial hemorrhage, or ischemic stroke.
Phase II Study of Proton Beam Radiation Therapy for Patients With Breast Cancer Requiring Regional Nodal Irradiation.

PURPOSE To evaluate the safety and efficacy of proton beam radiation therapy (RT) for patients with breast cancer who require regional nodal irradiation. METHODS Patients with nonmetastatic breast cancer who required postoperative RT to the breast/chest wall and regional lymphatics and who were considered suboptimal candidates for conventional RT were eligible. The primary end point was the incidence of grade 3 or higher radiation pneumonitis (RP) or any grade 4 toxicity within 3 months of RT. Secondary end points were 5-year locoregional failure, overall survival, and acute and late toxicities per Common Terminology Criteria for Adverse Events (version 4.0). Strain echocardiography and cardiac biomarkers were obtained before and after RT to assess early cardiac changes. RESULTS Seventy patients completed RT between 2011 and 2016. Median follow-up was 55 months (range, 17 to 82 months). Of 69 evaluable patients, median age was 45 years (range, 24 to 70 years). Sixty-three patients (91%) had left-sided breast cancer, two had bilateral breast cancer, and five had right-sided breast cancer. Sixty-five (94%) had stage II to III breast cancer. Sixty-eight (99%) received systemic chemotherapy. Fifty (72%) underwent immediate reconstruction. Median dose to the chest wall/breast was 49.7 Gy (relative biological effectiveness) and to the internal mammary nodes, 48.8 Gy (relative biological effectiveness), which indicates comprehensive coverage. Among 62 surviving patients, the 5-year rates for locoregional failure and overall survival were 1.5% and 91%, respectively. One patient developed grade 2 RP, and none developed grade 3 RP. No grade 4 toxicities occurred. The unplanned surgical re-intervention rate at 5 years was 33%. No significant changes in echocardiography or cardiac biomarkers after RT were found. CONCLUSION Proton beam RT for breast cancer has low toxicity rates and similar rates of disease control compared with historical data of conventional RT. No early cardiac changes were observed, which paves the way for randomized studies to compare proton beam RT with standard RT.
First Pediatric Experience With a Novel, Adhesive Adapter Retained, Bone Conduction Hearing Aid System.

OBJECTIVES To assess the audiological outcomes, practicalities, and impact on quality of life of a new, nonimplantable, adhesive retained bone conduction hearing aid in children. STUDY DESIGN A prospective, single-subject repeat measure, cohort study. SETTING Community and in pediatric assessment center. PATIENTS Twenty-one children aged between 5 and 15 years with a conductive hearing loss of >/=25 dB HL in the better hearing ear. INTERVENTION Audiological comparisons were made using pure-tone thresholds; unaided, with a softband aid, and with the new adhesive retained bone conducting system. MAIN OUTCOME MEASURES Comparison of hearing threshold levels. Data analysis via paired t-testing, significance set at p value <0.01. Quality of life was assessed via the Glasgow Children's Benefit Inventory and a 10 cm linear analogue scale. A hearing aid review questionnaire provided insight into practical use. RESULTS Statistically significant improvement in thresholds of 7.3 dB HL (p=0.0001) was demonstrated with the adhesive system as compared with softband aids. After 4 weeks of usage, the mean hearing thresholds for the adhesive hearing system improved from 55 dB HL ± 2.4 to 31 dB HL± 7.9 in unaided and aided conditions.Improvements in QOL were demonstrated with LAS and GCBI. Four children reported mild skin reactions. Eighty-six percent reported improved self-confidence. CONCLUSION The adhesive aid produces comparable audiological results to the commercial softband hearing aids. It provides an excellent alternative in the treatment of conductive hearing loss without the possible complications and costs of a surgical intervention. Furthermore, it preserves skin envelope over the mastoid for those who wish to proceed with an autologous pinna reconstruction in the future.
Global and local visual processing in autism – a co‐twin‐control study

Background Autism Spectrum Disorder (ASD) is associated with altered global and local visual processing. However, the nature of these alterations remains controversial, with contradictory findings and notions ranging from a reduced drive to integrate information into a coherent ‘gestalt’ (“weak central coherence” = WCC) to an enhanced perceptual functioning (EPF) in local processing. Methods This study assessed the association between autism and global/local visual processing, using a large sample of monozygotic (MZ) and dizygotic (DZ) twins (N = 290, 48% females, age = 8–31 years). The Fragmented Pictures Test (FPT) assessed global processing, whereas local processing was estimated with the Embedded Figures Test (EFT) and the Block Design Test (BDT). Autism was assessed both categorically (clinical diagnosis), and dimensionally (autistic traits). Associations between visual tasks and autism were estimated both across the cohort and within‐twin pairs where all factors shared between twins are implicitly controlled. Results Clinical diagnosis and autistic traits predicted a need for more visual information for gestalt processing in the FPT across the cohort. For clinical diagnosis, this association remained within‐pairs and at trend‐level even within MZ twin pairs alone. ASD and higher autistic traits predicted lower EFT and BDT performance across the cohort, but these associations were lost within‐pairs. Conclusions In line with the WCC account, our findings indicate an association between autism and reduced global visual processing in children, adolescents and young adults (but no evidence for EPF). Observing a similar association within MZ twins suggests a non‐shared environmental contribution.
Behavior, body composition, and vascular phenotype of homocystinuric mice on methionine‐restricted diet or enzyme replacement therapy

Classic homocystinuria (HCU) is an inherited disorder characterized by elevated homocysteine (Hcy) in plasma and tissues resulting from cystathionine β‐synthase (CBS) deficiency. There is no cure, and patients are predominantly managed by methionine‐restricted diet (MRD) to limit the production of Hcy. In this study, we used the I278T mouse model of HCU to evaluate the long‐term impact of a novel enzyme replacement therapy [truncated human CBS C15S mutant modified with linear 20‐kDa N‐hydroxysuccinimide ester polyethylene glycol (OT‐58)] on clinical end points relevant to human patients with HCU. In addition, we compared its efficacy on a background of either MRD or normal methionine intake [regular diet (REG)] to that of MRD alone. We found that, compared with untreated I278T mice, OT‐58 treatment of I278T mice fed with the REG diet resulted in a 90% decrease in plasma Hcy concentrations and correction of learning/cognition, endothelial dysfunction, hemostasis, bone mineralization, and body composition. On background of the MRD, OT‐58 performed equally well with plasma Hcy entirely normalized. The MRD alone decreased plasma Hcy by 67% and corrected the HCU phenotype in I278T mice. However, the MRD increased anxiety and reduced bone mineral content in both I278T mice and wild‐type controls. This study shows that OT‐58 is a highly efficacious novel treatment for HCU on the background of either normal or restricted methionine intake. —Majtan, T. , Park, I. , Cox, A. , Branchford, B. R. , di Paola, J., Bublil, E. M. , Kraus, J. P. Behavior, body composition, and vascular phenotype of homocystinuric mice on methionine‐restricted diet or enzyme replacement therapy. FASEB J. 33, 12477–12486 (2019). www.fasebj. org
Assessment of peritoneal elastic laminal invasion improves survival stratification of pT3 and pT4a colorectal cancer: a meta-analysis

Evaluating peritoneal elastic laminal invasion (ELI) has been proposed as an additional assessment for pT3 colorectal cancers (CRC). Its clinical significance has not yet been established. We performed a meta-analysis to investigate the prognostic impact of ELI assessment for subcategorisation of pT3 CRC. We performed a search in three electronic databases. HR and its 95% CI for overall survival (OS) and disease-free survival (DFS) were calculated using the random effects model weighted by the inverse variance method. We identified six studies that met inclusion criteria out of an original 703 studies found with our database search terms. Our meta-analysis included 1925 patients with pT3 and pT4a CRCs. The presence of ELI in pT3 CRC was associated with shortened OS compared with ELI negative pT3 CRC (HR=1.76; 95% CI 1.21 to 2.55); whereas the DFS was not statistically significant (HR=1.79; 95% CI 0.91 to 3.52). Furthermore, pT4a patients’ OS (HR=1.84; 95% CI 1.41 to 2.40) and DFS (HR=1.88; 95% CI 1.17 to 3.04) were even worse than the OS and DFS of pT3 ELI (+) patients. ELI is a useful marker for stratifying patients with pT3 or pT4a CRCs into three prognostically distinct groups. We recommend the subcategorisation of pT3 CRC by ELI for better prognostic assessment and treatment strategy of patients with CRC.