bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time for a general approval of growth hormone treatment in adults with Prader–Willi syndrome
Authors:   The Clinical and Scientific Advisory Board of The International Prader-Willi Syndrome Organisation, Höybye Charlotte , Holland Anthony J. , Driscoll Daniel J. 
Published: February 2021

AbstractPrader-Willi syndrome (PWS) is a complex, multi-system, neurodevelopmental disorder characterised by neonatal muscular hypotonia, short stature, high risk of obesity, hypogonadism, intellectual disabilities, distinct behavioural/psychiatric problems and abnormal body composition with increased body fat and a deficit of lean body mass. Growth hormone (GH) deficiency and other hormone deficiencies are common due to hypothalamic dysfunction. In children with PWS GH treatment has been widely demonstrated to improve body composition, normalise height and improve psychomotor development. In adults with PWS, GH’s main effects are to maintain normal body structure and metabolism. The positive effects of GH treatment on body composition, physical fitness and beneficial effects on cardiovascular risk markers, behaviour and quality of life in adults with PWS are also well established from several studies. GH treatment is approved for treatment of children with PWS in many countries, but until recently not as a treatment in young adults in the transition period or for adults in general. In this commentary we want to draw attention to the uneven global use of GH treatment, specifically in adults with PWS, and advocate for GH treatment to be approved internationally, not just for children, but also for adults with PWS and based only on the diagnosis of genetically confirmed PWS.
Results of a Patient Reported Experience Measure (PREM) to measure the rare disease patients and caregivers experience: a Spanish cross-sectional study
Authors: Guilabert Mercedes , Martínez-García Alba , Sala-González Marina , Solas Olga , Mira José Joaquín 
Published: February 2021

AbstractObjectiveTo measure the experience of the person having a rare disease in order to identify objectives for optimal care in the health care received by these patients. Methods. A cross-sectional study was conducted in Spain involving patients associated with the Spanish Rare Diseases Federation [Federación Española de Enfermedades Raras] (FEDER). A modified version of the PREM IEXPAC [Instrumento para evaluar la Experiencia del Paciente Crónico] instrument was used (IEXPAC-rare-diseases). Scores ranged between 0 (worst experience) and 10 (best experience).ResultsA total of 261 caregivers (in the case of paediatric population) and patients with rare diseases (response rate 54.4%) replied. 232 (88.9%) were adult patients and 29 (11.1%) caregivers of minor patients. Most males, 227 (87%), with an average age of 38 (SD 13.6) years. The mean time since confirmation of diagnosis was 7.8 (SD 8.0) years. The score in this PREM was 3.5 points out to 10 (95%CI 3.2–3.8, SD 2.0). Caregivers of paediatric patients scored higher, except for coordination of social and healthcare services.ConclusionsThere are wide and important areas for improvement in the care of patients with rare diseases. This study involves a first assesment of the experience of patients with rare diseases in Spain.
Adapting evidence-based clinical practice guidelines for people with attention deficit hyperactivity disorder in Saudi Arabia: process and outputs of a national initiative
Authors: Bashiri Fahad A. , Albatti Turki H. , Hamad Muddathir H. , Al-Joudi Haya F. , Daghash Hadeel F. , Al-Salehi Saleh M. , Varnham Jeremy L. , Alhaidar Fatimah , Almodayfer Omar , Alhossein Abdulkarim , Aldhalaan Hesham , Ad-Dab’bagh Yasser A. , Al Backer Nouf , Altwaijri Waleed , Alburikan Khalid , Buraik Maysaa W. , Ghaziuddin Mohammad , Nester Michael J. , Wahabi Hayfaa A. , Alhabib Samia , Jamal Amr A. , Amer Yasser S. 
Published: February 2021

AbstractBackgroundWe recently adapted the published National Institute for Health and Care Excellence (NICE) Attention deficit hyperactivity disorder (ADHD) diagnosis and management guideline to the Saudi Arabian context. It has been postulated that adaptation of evidence-based clinical practice guidelines to the local healthcare context rather than de-novo development will improve their adoption and implementation without imposing a significant burden on resources. The objective of this paper is to describe the adaptation process methodology utilized for the generation of the first national guideline for management of people with ADHD in Saudi Arabia.MethodsWe used the KSU-Modified-ADAPTE methodology for the guideline adaptation process. We describe the full process in detail including the three phases of set-up, adaptation, and finalization. The process was conducted by a multidisciplinary guideline adaptation group in addition to an external review for the clinical content and methodology.ResultsThe group adapted ten main categories of recommendations from one source CPG (NICE). The recommendations include: (i) service organisation and training, (ii) recognition, identification and referral, (iii) diagnosis, (iv) support, (v) managing ADHD, (vi) dietary advice, (vii) medication, (viii) maintenance and monitoring, (ix) adherence to treatment, and (x) review of medication and discontinuation. Several implementation tools were compiled and developed to enhance implementability including a clinical algorithm, quality measures, coding system, medication tables, translations, patient information, and online resources.ConclusionsThe finalized clinical practice guideline provides healthcare providers with applicable evidence-based guidance for the management of people with ADHD in Saudi Arabia. The project also demonstrated the effectiveness of KSU-Modified-ADAPTE, and emphasized the value of a collaborative clinical and methodological expert group for adaptation of national guidelines.
Childhood multisystem inflammatory syndrome associated with COVID-19 (MIS-C): a diagnostic and treatment guidance from the Rheumatology Study Group of the Italian Society of Pediatrics
Authors:   on behalf of the Rheumatology Study Group of the Italian Society of Pediatrics, Cattalini Marco , Taddio Andrea , Bracaglia Claudia , Cimaz Rolando , Paolera Sara Della , Filocamo Giovanni , La Torre Francesco , Lattanzi Bianca , Marchesi Alessandra , Simonini Gabriele , Zuccotti Gianvincenzo , Zunica Fiammetta , Villani Alberto , Ravelli Angelo 
Published: February 2021

Abstract
Background
Italy was the first Western country to be hit by the SARS-CoV-2 epidemic. There is now mounting evidence that a minority of children infected with SARS-CoV2 may experience a severe multisystem inflammatory syndrome, called Multisystem inflammatory Syndrome associated with Coronavirus Disease 2019 (MIS-C). To date no universally agreed approach is available for this disease.

Main body
as Italy is now facing a second hity of COVID-19 cases, we fear a recrudescence of MIS-C cases. We have, therefore, decided to prepare a report that will help clinicians to face this novel and challenging disease. We propose a diagnostic algorithm, to help case definition and guide work-up, and a therapeutic approach. MIS-C should be promptly recognized, based on the presence of systemic inflammation and specific organ involvement. Early treatment is crucial, and it will be based on the combined use of corticosteroids, high-dose immunoglobulins and anti-cytokine treatments, depending on the severity of the disease. Ancillary treatments (such as. aspirin and thrombo-profilaxis) will be also discussed.

Conclusions
we propose a document that will help physicians to diagnose and treat MIS-C patients. Given the level of evidence available and the methodology used, this document should not be interpreted as a guideline; the final decision about the optimal management should still be taken by the caring physician, on an individual basis.
COHESION: core outcomes in neonatal encephalopathy (protocol)
Authors: Quirke Fiona A. , Healy Patricia , Bhraonáin Elaine Ní , Daly Mandy , Biesty Linda , Hurley Tim , Walker Karen , Meher Shireen , Haas David M. , Bloomfield Frank H. , Kirkham Jamie J. , Molloy Eleanor J. , Devane Declan 
Published: February 2021

Abstract
Background
Neonatal encephalopathy is a complex syndrome in infants that predominantly affects the brain and other organs. The leading cause is a lack of oxygen in the blood reaching the brain. Neonatal encephalopathy can result in mortality or complications later in life, including seizures, movement disorders and cerebral palsy. Treatment options for neonatal encephalopathy are limited mainly to therapeutic hypothermia, although other potential treatments are emerging. However, evaluations of the effectiveness of treatments are challenging because of heterogeneity and inconsistency in outcomes measured and reported between trials. In this paper, we detail how we will develop a core outcome set to standardise outcomes measured and reported upon for interventions for the treatment of neonatal encephalopathy.

Methods
We will systematically review the literature to identify outcomes reported previously in randomised trials and systematic reviews of randomised trials. We will identify outcomes important to parents or caregivers of infants diagnosed with and who have received treatment for neonatal encephalopathy. We will do this by conducting in person or by video teleconferencing interviews with parents or caregivers in high-income and low- to middle-income countries. Stakeholders with expertise in neonatal encephalopathy (parents/caregivers, healthcare providers and researchers) will rate the importance of identified outcomes in an online Delphi survey using either a three-round Delphi survey or a “Real-Time” Delphi survey to which stakeholders will be allocated at random. Consensus meetings will take place by video conference to allow for an international group of stakeholder representatives to discuss and vote on the outcomes to include in the final core outcome set (COS).

Discussion
More research is needed on treatments for neonatal encephalopathy. Standardising outcomes measured and reported in evaluations of the effectiveness of interventions for the treatment of neonatal encephalopathy will improve evidence synthesis and improve results reported in systematic reviews and meta-analysis in this area. Overall, this COS will allow for improved treatments to be identified, heterogeneity in research to be reduced, and overall patient care to be enhanced.

Trial registration
This study is registered in the Core Outcome Measures for Effectiveness (COMET) database http://www.comet-initiative.org/Studies/Details/1270.
Decreased insulin resistance in diabetic patients by influencing Sirtuin1 and Fetuin-A following supplementation with ellagic acid: a randomized controlled trial
Authors: Ghadimi Mahnaz , Foroughi Farshad , Hashemipour Sima , Nooshabadi Mohammadreza Rashidi , Ahmadi Mohammad Hossein , Yari Mojtaba Ghadimi , Kavianpour Maria , Haghighian Hossein Khadem 
Published: February 2021

Abstract
Background
The beneficial effects of polyphenols have been reported. This study aimed to investigate the effect of oral Ellagic acid (EA) supplement on insulin resistance (IR) and Fetuin-A and serum sirtuin1 (SIRT1) in type 2 diabetics.

Methods
In this double-blind, randomized clinical trial, 44 diabetic patients were selected. Patients were assigned to the intervention group (22 subjects) and placebo (22 subjects) and received a capsule containing 180 mg of EA per day or placebo for eight weeks, respectively. At the beginning and end of the study, anthropometric indices, fasting plasma glucose (FPG), plasma insulin level, IR, Fetuin-A, and SIRT1 were measured. Statistical analysis was performed using SPSS software.

Results
At the beginning and end of the study, there was no significant difference between the two groups regarding anthropometric indices (P > 0.05). At the end of the survey, EA supplementation significantly reduced FPG, insulin, IR, and Fetuin-A and increased SIRT1 levels compared with the placebo group (P < 0.05). However, these changes were not significant in the placebo group (P > 0.05).

Conclusion
EA with antioxidant properties plays an essential role in reducing the macrovascular and microvascular complications of diabetes by reducing inflammation and insulin resistance.
Trial registration The protocol of this clinical trial is registered with the Iranian Registry of Clinical Trials (http://www.IRCT.IR, identifier: IRCT20141025019669N13)
Assessing the feasibility of heart rate variability as an objective indicator of anxiety in older adults with dementia living in care homes
Authors: Quinci Milena A. , Astell Arlene J. 
Published: February 2021

Abstract
Objective
Anxiety is reportedly prevalent in older adults with dementia living in care homes and, within this population, is most often assessed through caregiver reports. Heart rate variability (HRV) is a physiological indicator of autonomic function, whereby reduced vagally-mediated HRV is associated with a variety of anxiety symptoms and disorders. This study evaluates the feasibility of collecting HRV data within this population, presents HRV data for older adults with dementia living in a care home, and examines HRV in the context of self-reported anxiety. These data were collected during a larger study examining an exercise intervention.

Results
HRV data, in the form of log-transformed root mean square of the successive differences (lnRMSSD), were in line with transformed data from previous research. These data provide a promising direction for the use of wrist-worn devices in future HRV research with people living with dementia in care homes.
Inhibition of Ref(2)P, the Drosophila homologue of the p62/SQSTM1 gene, increases lifespan and leads to a decline in motor function
Authors: Hurley Emily P. , Staveley Brian E. 
Published: February 2021

Abstract
Objective
Sequestosome 1 (p62/SQSTM1) is a multifunctional scaffold/adaptor protein encoded by the p62/SQSTM1 gene with function in cellular homeostasis. Mutations in the p62/SQSTM1 gene have been known to be associated with patients with amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Parkinson disease (PD). The aim of the present study was to create a novel model of human neurogenerative disease in Drosophila melanogaster by altering the expression of Ref(2)P, the Drosophila orthologue of the human p62/SQSTM1 gene. Ref(2)P expression was altered in all neurons, the dopaminergic neurons and in the motor neurons, with longevity and locomotor function assessed over time.

Results
Inhibition of Ref(2)P resulted in a significantly increased median lifespan in the motor neurons, followed by a severe decline in motor skills. Inhibition of Ref(2)P in the dopaminergic neurons resulted in a significant, but minimal increase in median lifespan, accompanied by a drastic decline in locomotor function. Inhibition of Ref(2)P in the ddc-Gal4-expressing neurons resulted in a significant increase in median lifespan, while dramatically reducing motor function.
Shifts in soil and plant functional diversity along an altitudinal gradient in the French Alps
Authors: Stokes Alexia , Angeles Guillermo , Anthelme Fabien , Aranda-Delgado Eduardo , Barois Isabelle , Bounous Manon , Cruz-Maldonado Nereyda , Decaëns Thibaud , Fourtier Stéphane , Freschet Grégoire T. , Gabriac Quentin , Hernández-Cáceres Daniel , Jiménez Leonor , Ma Jing , Mao Zhun , Marín-Castro Beatriz Eugenia , Merino-Martín Luis , Mohamed Awaz , Piedallu Christian , Pimentel-Reyes Carlos , Reijnen Hans , Reverchon Frédérique , Rey Hervé , Selli Lavinia , Siebe-Grabach Christina Desireé , Sieron Katrin , Weemstra Monique , Roumet Catherine 
Published: February 2021

AbstractObjectivesAltitude integrates changes in environmental conditions that determine shifts in vegetation, including temperature, precipitation, solar radiation and edaphogenetic processes. In turn, vegetation alters soil biophysical properties through litter input, root growth, microbial and macrofaunal interactions. The belowground traits of plant communities modify soil processes in different ways, but it is not known how root traits influence soil biota at the community level. We collected data to investigate how elevation affects belowground community traits and soil microbial and faunal communities. This dataset comprises data from a temperate climate in France and a twin study was performed in a tropical zone in Mexico.Data descriptionThe paper describes soil physical and chemical properties, climatic variables, plant community composition and species abundance, plant community traits, soil microbial functional diversity and macrofaunal abundance and diversity. Data are provided for six elevations (1400–2400 m) ranging from montane forest to alpine prairie. We focused on soil biophysical properties beneath three dominant plant species that structure local vegetation. These data are useful for understanding how shifts in vegetation communities affect belowground processes, such as water infiltration, soil aggregation and carbon storage. Data will also help researchers understand how plant communities adjust to a changing climate/environment.
Cerebrospinal fluid N-224 tau helps discriminate Alzheimer’s disease from subjective cognitive decline and other dementias
Authors: Cicognola Claudia , Hansson Oskar , Scheltens Philip , Kvartsberg Hlin , Zetterberg Henrik , Teunissen Charlotte E. , Blennow Kaj 
Published: February 2021

Abstract
Background
Elevated cerebrospinal fluid (CSF) concentrations of total tau (T-tau) and phosphorylated tau at Thr181 (P-tau181) protein are typical of Alzheimer’s disease (AD). However, the T-tau assay measures only the mid-region of the protein, while tau in CSF is instead composed of a series of fragments. One fragment species in particular, N-224, shows increased levels in AD compared to controls. In this multicentre study, we performed a clinical validation of the N-224 assay in cohorts including patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), AD, non-AD dementias and controls.

Methods
Cohorts consisted of 30 SCD and 30 probable AD from the Amsterdam Dementia Cohort (cohort 1) and 539 controls, 195 SCD, 232 MCI, 137 AD and 253 non-AD from the Swedish BioFINDER study (cohort 2). All samples had AD core biomarkers (Aβ42, T-tau, P-tau181) measurements. N-224 was measured with an in-house ultrasensitive Simoa assay.

Results
N-224 levels were significantly higher in AD compared to SCD (cohort 1: p = 0.003) and in AD compared to all other diagnostic groups in cohort 2 (control, SCD, MCI and non-AD, p < 0.0001). Within the non-AD group, N-224 showed significantly lower concentrations compared to AD in Parkinson’s disease (PD, p < 0.0001), Parkinson’s disease dementia (PDD, p = 0.004), progressive supranuclear palsy (PSP, < 0.0001), multiple system atrophy (MSA, p = 0.002) and parkinsonisms not otherwise specified (NOS, p = 0.007). In cohort 1, higher concentrations of N-224 were associated to lower Mini-Mental State Examination (MMSE) scores (R2 = 0.318, β = 0.564, p ≤ 0.0001) and could accurately identify a pathological (< 24) MMSE score (p < 0.0001, AUC = 0.824).

Conclusions
N-224 tau can distinguish AD subjects from SCD and can discriminate subgroups of non-AD dementias from AD. Therefore, N-224 may be a useful addition to the tau biomarker toolbox for the study of tau species in CSF and for better understanding disease pathogenesis.
RETRACTED ARTICLE: Preservation of dendritic spine morphology and postsynaptic signaling markers after treatment with solid lipid curcumin particles in the 5xFAD mouse model of Alzheimer’s amyloidosis
Authors: Maiti Panchanan , Bowers Zackary , Bourcier-Schultz Ali , Morse Jarod , Dunbar Gary L. 
Published: February 2021

Abstract
Background
Synaptic failure is one of the principal events associated with cognitive dysfunction in Alzheimer’s disease (AD). Preservation of existing synapses and prevention of synaptic loss are promising strategies to preserve cognitive function in AD patients. As a potent natural anti-oxidant, anti-amyloid, and anti-inflammatory polyphenol, curcumin (Cur) shows great promise as a therapy for AD. However, hydrophobicity of natural Cur limits its solubility, stability, bioavailability, and clinical utility for AD therapy. We have demonstrated that solid lipid curcumin particles (SLCP) have greater therapeutic potential than natural Cur in vitro and in vivo models of AD. In the present study, we have investigated whether SLCP has any preservative role on affected dendritic spines and synaptic markers in 5xFAD mice.

Methods
Six- and 12-month-old 5xFAD and age-matched wild-type mice received oral administration of SLCP (100 mg/kg body weight) or equivalent amounts of vehicle for 2 months. Neuronal morphology, neurodegeneration, and amyloid plaque load were investigated from prefrontal cortex (PFC), entorhinal cortex (EC), CA1, CA3, and the subicular complex (SC). In addition, the dendritic spine density from apical and basal branches was studied by Golgi-Cox stain. Further, synaptic markers, such as synaptophysin, PSD95, Shank, Homer, Drebrin, Kalirin-7, CREB, and phosphorylated CREB (pCREB) were studied using Western blots. Finally, cognitive and motor functions were assessed using open-field, novel object recognition (NOR) and Morris water maze (MWM) tasks after treatment with SLCP.

Results
We observed an increased number of pyknotic and degenerated cells in all these brain areas in 5xFAD mice and SLCP treatment partially protected against those losses. Decrease in dendritic arborization and dendritic spine density from primary, secondary, and tertiary apical and basal branches were observed in PFC, EC, CA1, and CA3 in both 6- and 12-month-old 5xFAD mice, and SLCP treatments partially preserved the normal morphology of these dendritic spines. In addition, pre- and postsynaptic protein markers were also restored by SLCP treatment. Furthermore, SLCP treatment improved NOR and cognitive function in 5xFAD mice.

Conclusions
Overall, these findings indicate that use of SLCP exerts neuroprotective properties by decreasing amyloid plaque burden, preventing neuronal death, and preserving dendritic spine density and synaptic markers in the 5xFAD mice.