bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical outcome data of anxiety patients treated with cannabis-based medicinal products in the United Kingdom: a cohort study from the UK Medical Cannabis Registry
Authors: Rifkin-Zybutz Raphael , Erridge Simon , Holvey Carl , Coomber Ross , Gaffney Jessica , Lawn Will , Barros Daniela , Bhoskar Urmila , Mwimba Gracia , Praveen Kavita , Symeon Chris , Sachdeva-Mohan Simmi , Rucker James J , Sodergren Mikael H 
Published: June 2023

Abstract
Rationale
Cannabis-based medicinal products (CBMPs) have been identified as novel therapeutics for generalised anxiety disorder (GAD) based on pre-clinical models; however, there is a paucity of high-quality evidence on their effectiveness and safety.

Objectives
This study aimed to evaluate the clinical outcomes of patients with GAD treated with dried flower, oil-based preparations, or a combination of both CBMPs.

Methods
A prospective cohort study of patients with GAD (n = 302) enrolled in the UK Medical Cannabis Registry prescribed oil or flower-based CBMPs was performed. Primary outcomes were changes in generalised anxiety disorder-7 (GAD-7) questionnaires at 1, 3, and 6 months compared to baseline. Secondary outcomes were single-item sleep quality scale (SQS) and health-related quality of life index (EQ-5D-5L) questionnaires at the same time points. These changes were assessed by paired t-tests. Adverse events were assessed in line with CTCAE (Common Terminology Criteria for Adverse Events) v4.0.

Results
Improvements in anxiety, sleep quality and quality of life were observed at each time point (p < 0.001). Patients receiving CBMPs had improvements in GAD-7 at all time points (1 month: difference −5.3 (95% CI −4.6 to −6.1), 3 months: difference −5.5 (95% CI −4.7 to −6.4), 6 months: difference −4.5 (95% CI −3.2 to −5.7)). Thirty-nine participants (12.9%) reported 269 adverse events in the follow-up period.

Conclusions
Prescription of CBMPs in those with GAD is associated with clinically significant improvements in anxiety with an acceptable safety profile in a real-world setting. Randomised trials are required as a next step to investigate the efficacy of CBMPs.
Oleoylethanolamide restores stress-induced prepulse inhibition deficits and modulates inflammatory signaling in a sex-dependent manner
Authors: González-Portilla Macarena , Montagud-Romero Sandra , Rodríguez de Fonseca Fernando , Rodríguez-Arias Marta 
Published: June 2023

Abstract
Rationale
Social stress contributes to the development of depressive and anxiety symptomatology and promotes pro-inflammatory signaling in the central nervous system. In this study, we explored the effects of a lipid messenger with anti-inflammatory properties – oleoylethanolamide (OEA) – on the behavioral deficits caused by social stress in both male and female mice.

Methods
Adult mice were assigned to an experimental group according to the stress condition (control or stress) and treatment (vehicle or OEA, 10 mg/kg, i.p.). Male mice in the stress condition underwent a protocol consisting of four social defeat (SD) encounters. In the case of female mice, we employed a procedure of vicarious SD. After the stress protocol resumed, anxiety, depressive-like behavior, social interaction, and prepulse inhibition (PPI) were assessed. In addition, we characterized the stress-induced inflammatory profile by measuring IL-6 and CX3CL1 levels in the striatum and hippocampus.

Results
Our results showed that both SD and VSD induced behavioral alterations. We found that OEA treatment restored PPI deficits in socially defeated mice. Also, OEA affected differently stress-induced anxiety and depressive-like behavior in male and female mice. Biochemical analyses showed that both male and female stressed mice showed increased levels of IL-6 in the striatum compared to control mice. Similarly, VSD female mice exhibited increased striatal CX3CL1 levels. These neuroinflammation-associated signals were not affected by OEA treatment.

Conclusions
In summary, our results confirm that SD and VSD induced behavioral deficits together with inflammatory signaling in the striatum and hippocampus. We observed that OEA treatment reverses stress-induced PPI alterations in male and female mice. These data suggest that OEA can exert a buffering effect on stress-related sensorimotor gating behavioral processing.
Improving carotenoid extraction, stability, and antioxidant activity from Citrus sinensis peels using green solvents
Authors: Viñas-Ospino Adriana , López-Malo Daniel , Esteve María José , Frígola Ana , Blesa Jesús 
Published: June 2023

AbstractCarotenoids have a wide range of applications in the food, pharmaceutical, and cosmetic industries as natural coloring agents and antioxidants. Consequently, industries are more concerned about extracting them from natural resources and by-products. The present research aimed to evaluate the extraction efficiency of carotenoids from orange peels using hydrophobic deep eutectic solvents (HDESs) as alternatives for organic solvents. The antioxidant capacity and color stability of HDESs extracts were monitored for 20 days and to intensify the extraction process, ultrasound-assisted extraction (UAE) was optimized using a response surface methodology (RSM). Menthol:Eucalyptol (Me:Eu) extract showed the highest carotenoid extraction yield [359.3 ± 3.5 mg/100 g of fresh weight (fw)], and also presented high stability during the storage period. HDESs extracts showed higher antioxidant capacity compared to hexane extracts, while Me:Eu extracts showed the lowest color variation (5.9 ± 0.2). Optimal parameters using Me:Eu were extraction time of 20 min, ultrasonic power of 120 W (60%), and solid–liquid ratio of 1:20 (g/mL) reaching a carotenoid content of 573.4 mg/100 gfw. While, C12:C8 optimal parameters were 10 min, 80 W (40%), and a solid–liquid ratio of 1:10 (g/mL), providing a carotenoid content of 183.7 mg/100 gfw. To establish if the solvents used are greener alternatives, the EcoScale was used and showed that UAE is a sustainable method to recover carotenoids using HDESs. Overall, the results showed that HDESs can improve carotenoid stability, and when combined with the intrinsic safety and edibility of their components, it makes these extracts appealing for food industry.
Use of Radiofrequency-Assisted Liposuction (BodyTite) for Upper Arms Lifting
Authors: Tettamanzi Matilde , Pili Nicola , Rodio Manuela , Serra Pietro Luciano , Trignano Claudia , Rubino Corrado , Trignano Emilio 
Published: June 2023

Abstract
Background
Body contouring surgery is increasingly requested by patients, both for aesthetic and post-bariatric purposes. There has also been a rapid increase in demand for noninvasive aesthetic treatments. While brachioplasty is burdened by numerous complications and unsatisfactory scars, and conventional liposuction is unsuitable for all patients, nonsurgical arm remodeling performed with radiofrequency-assisted liposuction (RFAL) allows to effectively treat most of patients, regardless of the amount of fat and ptosis of the skin and avoiding surgical excision.

Methods
A prospective study was conducted on 120 consecutive patients who presented to the author's private clinic and required upper arm remodeling surgery for aesthetic purposes or after weight loss. Patients were classified according to the modified classification of El Khatib and Teimourian. Pre- and posttreatment upper arm circumferences were taken after 6 months of follow-up to assess the degree of skin retraction obtained by treating the arm with RFAL. A satisfaction questionnaire regarding the appearance of the arms (Body-Q upper arm satisfaction) was administered to all patients before surgery and after 6 months of follow-up.

Results
All patients were effectively treated with RFAL, and no cases required conversion to brachioplasty. The average reduction in arm circumference was 3.75 cm at 6 months follow-up, and patients’ satisfaction increased from 35 to 87% posttreatment.

Conclusions
Radio frequency is a valid tool to treat most patients with upper limbs skin laxity, with significant aesthetic results and a high degree of patient satisfaction, regardless of the degree of skin ptosis and lipodystrophy of the arm.

Level of Evidence IV
This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
Diffuse fasciitis with eosinophilia in boys: a case-based review
Authors: Wosiak Agnieszka , Biernacka-Zielińska Małgorzata , Roszkiewicz Justyna , Smolewska Elżbieta 
Published: June 2023

AbstractDiffuse fasciitis with eosinophilia (EF) is a rare condition classified as a part of the connective tissue disorders. The clinical presentation of this condition can be diverse, however the main symptoms include symmetrical swelling and hardening of distal parts of limbs accompanied by peripheral eosinophilia. The diagnostic criteria are not specified. In inconclusions cases Magnetic Resonance Imaging (MRI) and skin to muscle biopsy may be useful. The pathogenesis and ethiology remain unknown, but extensive physical exertion, certain infectious factors, such as Borrelia burgdorferi, or medications may serve as a trigger. EF affects equally women and men, mainly in their middle age, however the disease can occur at any age. The standard therapy contents gluccocorticosteroids. As a second-line treatment, methotrexate is usually chosen. In this article we compare world reports of EF in paediatric patients with the cases of two adolescent male patients recently hospitalized in the Department of Paediatric Rheumatology.
Intrathecal kappa free light chain synthesis is associated with worse prognosis in relapsing–remitting multiple sclerosis
Authors: Rosenstein Igal , Axelsson Markus , Novakova Lenka , Malmeström Clas , Blennow Kaj , Zetterberg Henrik , Lycke Jan 
Published: June 2023

Abstract
Background
While kappa free light chain (KFLC) index has become a useful diagnostic biomarker in multiple sclerosis (MS), its prognostic properties are less explored. B cells play a crucial role in MS pathogenesis, but the impact from increased intrathecal production of immunoglobulins and KFLC remains to be determined. Recently, it has become evident that insidious worsening is not confined to progressive MS but is also common in relapsing–remitting MS (RRMS), a feature known as progression independent of relapse activity (PIRA).

Methods
We retrospectively identified 131 patients with clinically isolated syndrome or early RRMS who had determined KFLC index as part of their diagnostic workup. Demographic and clinical data were extracted from the Swedish MS registry. Associations of baseline KFLC index with evidence of disease activity (EDA) and PIRA were investigated in multivariable cox proportional hazards regression models.

Results
KFLC index was significantly higher in PIRA (median 148.5, interquartile range [IQR] 106.9–253.5) compared with non-PIRA (78.26, IQR 28.93–186.5, p = 0.009). In a multivariable cox regression model adjusted for confounders, KFLC index emerged as an independent risk factor for PIRA (adjusted hazard ratio [aHR] 1.005, 95% confidence interval [CI] 1.002–1.008, p = 0.002). Dichotomized by the cut-off value KFLC index > 100, patients with KFLC index > 100 had an almost fourfold increase in the risk for developing PIRA. KFLC index was also predictive of evidence of disease activity during follow-up.

Conclusions
Our data indicate that high KFLC index at baseline is predictive of PIRA, EDA-3, and overall worse prognosis in MS.
A novel anatomical description of the esophagus: the supracarinal mesoesophagus
Authors: Cuesta Miguel A. , van Jaarsveld Romy C. , Mingol Fernando , Bleys Ronald L. A. W. , van Hillegersberg Richard , Padules Carmen , Bruna Marcos , Ruurda Jelle P. 
Published: June 2023

Abstract
Background
During thoracoscopic esophageal resection, while performing the supracarinal lymphadenectomy along the left recurrent laryngeal nerve (LRLN) from the aortic arch to the thoracic apex, we observed a not previously described bilayered fascia-like structure, serving as prolongation of the already known mesoesophagus.

Methods
We retrospectively evaluated 70 consecutively unedited videos of thoracoscopic interventions on esophageal resections for cancer, in order to determine the validity of this finding and to describe its utility for performing a systematic and more accurate dissection of the LRLN and its adequate lymphadenectomy.

Results
After mobilization of the upper esophagus from the trachea and tilting the esophagus by means of two ribbons, a bilayered fascia was observed between the esophagus and the left subclavian artery in 63 of the 70 patients included in this study. By opening the right layer, the left recurrent nerve became visualized and could be dissected free in its whole trajectory. Vessels and branches of the LRLN were divided between miniclips. Mobilizing the esophagus to the right, the base of this fascia could be found at the left subclavian artery. After dissecting and clipping the thoracic duct, complete lymphadenectomy of 2 and 4L stations could be performed. Mobilizing the esophagus in distal direction, the fascia continued at the level of the aortic arch, where it had to be divided in order to mobilize the esophagus from the left bronchus. Here, a lymphadenectomy of the aorta-pulmonary window lymph nodes (station 8) can be performed. It seems that from there the fascia continued without interruption with the previously described mesoesophagus between the thoracic aorta and the esophagus.

Conclusions
Here we described the concept of the supracarinal mesoesophagus on the left side. Applying the description of the mesoesophagus will create a better understanding of the supracarinal anatomy, leading to a more adequate and reproducible surgery.
Clinical course and management of children with IgA vasculitis with nephritis
Authors: Stone Hillarey K. , Mitsnefes Mark , Dickinson Kimberley , Burrows Evanette K. , Razzaghi Hanieh , Luna Ingrid Y. , Gluck Caroline A. , Dixon Bradley P. , Dharnidharka Vikas R. , Smoyer William E. , Somers Michael J. , Flynn Joseph T. , Furth Susan L. , Bailey Charles , Forrest Christopher B. , Denburg Michelle , Nehus Edward 
Published: June 2023

Abstract
Background
IgA vasculitis is the most common vasculitis in children and is often complicated by acute nephritis (IgAVN). Risk of chronic kidney disease (CKD) among children with IgAVN remains unknown. This study aimed to describe the clinical management and kidney outcomes in a large cohort of children with IgAVN.

Methods
This observational cohort study used the PEDSnet database to identify children diagnosed with IgAV between January 1, 2009, and February 29, 2020. Demographic and clinical characteristics were compared among children with and without kidney involvement. For children followed by nephrology, clinical course, and management patterns were described. Patients were divided into four categories based on treatment: observation, renin–angiotensin–aldosterone system (RAAS) blockade, corticosteroids, and other immunosuppression, and outcomes were compared among these groups.

Results
A total of 6802 children had a diagnosis of IgAV, of whom 1139 (16.7%) were followed by nephrology for at least 2 visits over a median follow-up period of 1.7 years [0.4,4.2]. Conservative management was the most predominant practice pattern, consisting of observation in 57% and RAAS blockade in 6%. Steroid monotherapy was used in 29% and other immunosuppression regimens in 8%. Children receiving immunosuppression had higher rates of proteinuria and hypertension compared to those managed with observation (p < 0.001). At the end of follow-up, 2.6 and 0.5% developed CKD and kidney failure, respectively.

Conclusions
Kidney outcomes over a limited follow-up period were favorable in a large cohort of children with IgAV. Immunosuppressive medications were used in those with more severe presentations and may have contributed to improved outcomes.

Graphical abstract
Subcutaneous abatacept for the treatment of rheumatoid arthritis in routine clinical practice in Germany, Austria, and Switzerland: 2-year retention and efficacy by treatment line and serostatus
Authors: Alten Rieke , Tony Hans-Peter , Bannert Bettina , Nüßlein Hubert , Rauch Christiane , Connolly Sean E. , Chartier Melanie , Lozenski Karissa , Hackl Roland , Forster Adrian , Peichl Peter 
Published: June 2023

Abstract
Introduction/objectives
The ASCORE study on treatment for rheumatoid arthritis (RA) showed better retention and clinical response rates for abatacept as first-line versus later-line therapy. This post hoc analysis of ASCORE assessed 2-year retention, efficacy, and safety of subcutaneous (SC) abatacept in Germany, Austria, and Switzerland.

Methods
Adults with RA who initiated SC abatacept 125 mg once weekly were assessed. Primary endpoint was abatacept retention rate at 2 years. Secondary endpoints: proportions of patients with low disease activity (LDA)/remission per Disease Activity Score in 28 joints based on erythrocyte sedimentation rate (≤ 3.2), Simplified Disease Activity Index (≤ 11), and Clinical Disease Activity Index (≤ 10). Outcomes were analyzed by treatment line and serostatus.

Results
For the pooled cohort, the 2-year abatacept retention rate was 47.6%; retention was highest in biologic-naïve patients (50.5% [95% confidence interval 44.9, 55.9]). Patients seropositive for both anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF; + / +) at baseline had a higher 2-year abatacept retention rate than patients with single seropositivity for either APCA or RF or double-seronegativity (− / −), irrespective of treatment line. At 2 years, a higher proportion of patients who were biologic-naïve were in LDA/remission than patients with one or ≥ two prior biologics.

Conclusion
A higher proportion of patients with + / + RA (compared with − / − RA) had abatacept retention after 2 years. Early identification of patients with seropositive RA may facilitate a precision-medicine approach to RA treatment, leading to a higher proportion of patients in LDA/remission.

Trial registration number
NCT02090556; date registered: March 18, 2014 (retrospectively registered).

Key Points• This post hoc analysis of a German-speaking subset of European patients with RA from the global ASCORE study (NCT02090556) showed that retention of SC abatacept within this subset was 47.6%, with good clinical outcomes after 2 years.• Patients with double-seropositive RA (ACPA and RF positive) had higher retention of abatacept than patients with double-seronegative RA (ACPA and RF negative). Retention and clinical responses were highest for patients who were biologic-naïve compared with patients who had one or ≥ two prior biologic treatments.• These real-world data may be useful for clinicians in informing individualized treatment pathways for patients with RA, and fostering superior disease control and clinical outcomes.
Object use in communication of semi-wild chimpanzees
Authors: Gibson Violet , Boysen Sarah T. , Hobaiter Catherine , Davila-Ross Marina 
Published: June 2023

AbstractObject interactions play an important role in human communication but the extent to which nonhuman primates incorporate objects in their social interactions remains unknown. To better understand the evolution of object use, this study explored how objects are used in social interactions in semi-wild chimpanzees (Pan troglodytes). We used an observational approach focusing on naturally occurring object actions where we examined their use and tested whether the production of object actions was influenced by the recipients’ visual attention as well as by colony membership. The results show that chimpanzees adjusted both the type of object used, and the modality of object actions to match the visual attention of the recipient, as well as colony differences in the use of targeted object actions. These results provide empirical evidence highlighting that chimpanzees use objects in diverse ways to communicate with conspecifics and that their use may be shaped by social factors, contributing to our understanding of the evolution of human nonverbal communication, language, and tool use.
Enabling QALY estimation in mental health trials and care settings: mapping from the PHQ-9 and GAD-7 to the ReQoL-UI or EQ-5D-5L using mixture models
Authors: Franklin Matthew , Hernández Alava Monica 
Published: June 2023

Abstract
Purpose
Patient-reported outcome measures (PROMs) are commonly collected in trials and some care settings, but preference-based PROMs required for economic evaluation are often missing. For these situations, mapping models are needed to predict preference-based (aka utility) scores. Our objective is to develop a series of mapping models to predict preference-based scores from two mental health PROMs: Patient Health Questionnaire-9 (PHQ-9; depression) and Generalised Anxiety Questionnaire-7 (GAD-7; anxiety). We focus on preference-based scores for the more physical-health-focussed EQ-5D (five-level England and US value set, and three-level UK cross-walk) and more mental-health-focussed Recovering Quality-of-Life Utility Index (ReQoL-UI).

Methods
We used trial data from the Improving Access to Psychological Therapies (IAPT) mental health services (now called NHS Talking Therapies), England, with a focus on people with depression and/or anxiety caseness. We estimated adjusted limited dependent variable or beta mixture models (ALDVMMs or Betamix, respectively) using GAD-7, PHQ-9, age, and sex as covariates. We followed ISPOR mapping guidance, including assessing model fit using statistical and graphical techniques.

Results
Over six data collection time-points between baseline and 12-months, 1340 observed values (N ≤ 353) were available for analysis. The best fitting ALDVMMs had 4-components with covariates of PHQ-9, GAD-7, sex, and age; age was not a probability variable for the final ReQoL-UI mapping model. Betamix had practical benefits over ALDVMMs only when mapping to the US value set.

Conclusion
Our mapping functions can predict EQ-5D-5L or ReQoL-UI related utility scores for QALY estimation as a function of variables routinely collected within mental health services or trials, such as the PHQ-9 and/or GAD-7.
The Impact of Education and Culture on Poverty Reduction: Evidence from Panel Data of European Countries
Authors: Spada A. , Fiore M. , Galati A. 
Published: June 2023

AbstractThe 2030 Agenda has among its key objectives the poverty eradication through increasing the level of education. A good level of education and investment in culture of a country is in fact necessary to guarantee a sustainable economy, in which coexists satisfactory levels of quality of life and an equitable distribution of income. There is a lack of studies in particular on the relations between some significant dimensions, such as education, culture and poverty, considering time lags for the measurement of impacts. Therefore, this study aims to fill this gap by focusing on the relationship between education, culture and poverty based on a panel of data from 34 European countries, over a 5-year period, 2015–2019. For this purpose, after applying principal component analysis to avoid multicollinearity problems, the authors applied three different approaches: pooled-ordinary least squares model, fixed effect model and random effect model. Fixed-effects estimator was selected as the optimal and most appropriate model. The results highlight that increasing education and culture levels in these countries reduce poverty. This opens space to new research paths and policy strategies that can start from this connection to implement concrete actions aimed at widening and improving educational and cultural offer.