bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacy-based screening to detect persons at elevated risk of type 2 diabetes: a cost-utility analysis
Authors: Jalkanen Kari , Aarnio Emma , Lavikainen Piia , Lindström Jaana , Peltonen Markku , Laatikainen Tiina , Martikainen Janne 
Published: September 2021

AbstractBackgroundEarly identification of people at elevated risk of type 2 diabetes (T2D) is an important step in preventing or delaying its onset. Pharmacies can serve as a significant channel to reach these people. This study aimed to assess the potential health economic impact of screening and recruitment services in pharmacies in referring people to preventive interventions.MethodsA decision analytic model was constructed to perform a cost-utility analysis of the expected national health economic consequences (in terms of costs and quality-adjusted life years, QALYs) of a hypothetical pharmacy-based service where people screened and recruited through pharmacies would participate in a digital lifestyle program. Cost-effectiveness was considered in terms of net monetary benefit (NMB). In addition, social return on investment (SROI) was calculated as the ratio of the intervention and recruitment costs and the net present value of expected savings. Payback time was the time taken to reach the break-even point in savings. In the base scenario, a 20-year time horizon was applied. Probabilistic and deterministic sensitivity analyses were applied to study robustness of the results.ResultsIn the base scenario, the expected savings from the pharmacy-based screening and recruitment among the reached target cohort were 255.3 m€ (95% CI − 185.2 m€ to 717.2 m€) in pharmacy visiting population meaning 1412€ (95% CI − 1024€ to 3967€) expected savings per person. Additionally, 7032 QALYs (95% CI − 1344 to 16,143) were gained on the population level. The intervention had an NMB of 3358€ (95% CI − 1397€ to 8431€) using a cost-effectiveness threshold of 50,000 €/QALY. The initial costs were 122.2 m€ with an SROI of 2.09€ (95% CI − 1.52€ to 5.88€). The expected payback time was 10 and 8 years for women and men, respectively. Results were most sensitive for changes in effectiveness of the intervention and selected discount rate.ConclusionsT2D screening and recruitment to prevention programs conducted via pharmacies was a dominant option providing both cost savings and QALY gains. The highest savings can be potentially reached by targeting recruitment at men at elevated risk of T2D.
The association between first-time accreditation and the delivery of recommended care: a before and after study in the Faroe Islands
Authors: Bergholt Maria Daniella , Falstie-Jensen Anne Mette , Hibbert Peter , Eysturoy Barbara Joensen , Guttesen Gunnvá , Róin Tóra , Valentin Jan Brink , Braithwaite Jeffrey , von Plessen Christian , Johnsen Søren Paaske 
Published: September 2021

Abstract
Background
Significant resources are spent on hospital accreditation worldwide. However, documentation of the effects of accreditation on processes, quality of care and outcomes in healthcare remain scarce. This study aimed to examine changes in the delivery of patient care in accordance with clinical guidelines (recommended care) after first-time accreditation in a care setting not previously exposed to systematic quality improvement initiatives.

Methods
We conducted a before and after study based on medical record reviews in connection with introducing first-time accreditation. We included patients with stroke/transient ischemic attack, bleeding gastric ulcer, diabetes, chronic obstructive pulmonary disease (COPD), childbirth, heart failure and hip fracture treated at public, non-psychiatric Faroese hospitals during 2012–2013 (before accreditation) or 2017–2018 (after accreditation). The intervention was the implementation of a modified second version of The Danish Healthcare Quality Program (DDKM) from 2014 to 2016 including an on-site accreditation survey in the Faroese hospitals. Recommended care was assessed using 63 disease specific patient level process performance measures in seven clinical conditions. We calculated the fulfillment and changes in the opportunity-based composite score and the all-or-none score.

Results
We included 867 patient pathways (536 before and 331 after). After accreditation, the total opportunity-based composite score was marginally higher though the change did not reach statistical significance (adjusted percentage point difference (%): 4.4%; 95% CI: − 0.7 to 9.6). At disease level, patients with stroke/transient ischemic attack, bleeding gastric ulcer, COPD and childbirth received a higher proportion of recommended care after accreditation. No difference was found for heart failure and diabetes. Hip fracture received less recommended care after accreditation. The total all-or-none score, which is the probability of a patient receiving all recommended care, was significantly higher after accreditation (adjusted relative risk (RR): 2.32; 95% CI: 2.03 to 2.67). The improvement was particularly strong for patients with COPD (RR: 16.22; 95% CI: 14.54 to 18.10).

Conclusion
Hospitals were in general more likely to provide recommended care after first-time accreditation.
Case report: hepatitis in a child infected with SARS-CoV-2 presenting toll-like receptor 7 Gln11Leu single nucleotide polymorphism
Authors: Pessoa Natália Lima , Bentes Aline Almeida , de Carvalho Andrea Lucchesi , de Souza Silva Thaís Bárbara , Alves Pedro Augusto , de Sousa Reis Erik Vinicius , Rodrigues Tayse Andrade , Kroon Erna Geessien , Campos Marco Antônio 
Published: September 2021

Abstract
Background
Covid-19 has the respiratory tract as the main target of infection, and patients present mainly dyspnea, pneumonia, dry cough, and fever. Nevertheless, organs outside the respiratory tract had been reported in recent studies, including the gastrointestinal tract and liver. The host innate immune system recognizes pathogen-associated molecular patterns (PAMPs) through their pattern recognition receptor (PRRs). Toll-like receptor 7 (TLR-7) is a pattern recognition receptor recognizing ssRNA (SARS-CoV-2 is an ssRNA). Polymorphisms are characterized by two or more alternative forms of a distinct phenotype in the same population. Polymorphisms in tlrs genes can negatively influence the immune response to infectious diseases. There are several references in the literature to non-synonymous single nucleotide (rs) polymorphisms related to several genes. Some of them are important for the innate immunity, as rs 179008 (tlr-7), rs3775291 (tlr3), rs8177374 (tir domain-containing adaptor protein, tirap), rs1024611 (monocyte chemoattractant protein-1, mcp-1) and rs61942233 (2′-5′-oligoadenylate synthase-3, oas-3).

Case presentation
We identified a 5-year-old-male child with gastrointestinal symptoms and fever presenting acholic stool and jaundice, who was positive for SARS-CoV-2 IgM, IgA, and IgG and presenting the Gln11Leu rs 179008 in tlr-7. The child presented high levels of aspartate aminotransferase, alanine aminotransferase, bilirubin, C-reactive protein, D-dimer, gamma-glutamyl transferase, alkaline phosphatase, and was negative for serological tests for hepatitis A, B, C, E, HIV 1 and 2, herpes virus, cytomegalovirus, Epstein–Barr virus, and negative for RTqPCR for Influenza A and B, RSV and SARS-CoV-2. We also investigated other SNPs in the tlr-3 (rs3775291), tirap (rs8177374), mcp-1 (rs1024611), and oas-3 (rs61942233) genes, and no mutation was detected. After an interview with the child's caregivers, any possible accidental ingestion of drugs or hepatotoxic substances was ruled out.

Conclusion
To our knowledge, this is the first report of a SARS-CoV-2 caused hepatitis in a male child that has the tlr-7 Gln11Leu rs 179008, which could impair an efficient initial immune response. The knowledge of the patient's immune deficiency could improve the treatment to correct this deficiency with specific medications.
Quality of life and treatment-related burden during ocular proton therapy: a prospective trial of 131 patients with uveal melanoma
Authors: Gollrad Johannes , Rabsahl Christopher , Riechardt Aline-Isabel , Heufelder Jens , Stroux Andrea , Goerling Ute , Joussen Antonia , Budach Volker , Boehmer Dirk 
Published: September 2021

Abstract
Background
Proton beam therapy is a well-established treatment option for patients with uveal melanoma (UM). The treatment procedure, in general, includes placing radiopaque clips to ensure exact eye-positioning during radiotherapy, followed by the delivery of proton irradiation.
The short-term burden associated with proton therapy in patients with UM has rarely been addressed. In this prospective study, we investigated the physiological and psychological aspects of proton therapy that might affect the well-being of patients during the different stages of treatment.

Methods
During the treatment procedure, we conducted longitudinal assessments of the Quality of life (QOL), organ-specific symptoms, and psychological aspects in patients with UM with three questionnaires (EORTC QLQ-C30, EORTC QLQ-OPT30, and GAD-7). Patients completed questionnaires before clip surgery (T0), before proton therapy (T1), after completing treatment (T2), and three months after treatment completion (T3). We also collected data on tumor characteristics and socio-demographics to identify potential risk factors associated with high treatment burdens.

Results
We prospectively included 131 consecutive patients. Questionnaire data showed a significant, temporary decline in global QOL and an increase in eye-related symptoms, as a result of the clip surgery (T0–T1). After treatment completion (T2), global QOL improved gradually, and none of the eye-related symptoms significantly deteriorated over the course of proton therapy. The global QOL returned to baseline levels three months after treatment (T3). We identified baseline anxiety as an independent risk factor for experiencing an acute treatment-related burden. Furthermore, we found interactions between GAD7 and patient sex showing that anxiety had a more pronounced effect on QOL outcome in female patients.

Conclusion
The short-term treatment-related burden of ocular proton therapy appeared to be largely associated with the preceding clip surgery, rather than the irradiation procedure. We found that anxiety was strongly associated with experiencing QOL issues during the treatment procedure. Our findings could contribute to the development of future strategies for improving the treatment process and psycho-oncologic patient care.
Anthropometric measurements of non-arthritic knees in an Egyptian population: an MRI-based study
Authors: Abdelnasser Mohammad Kamal , Khalifa Ahmed A. , Bassem Micheal , Abdelhameed Mohammed Anter , Adam Mahmoud Faisal , Bakr Hatem M. , Khalifa Yaser E. 
Published: September 2021

Abstract
Background
Knee anthropometric characteristics were evaluated for different ethnicities; however, data from North African populations are deficient. The primary aim was to investigate the Egyptian knees’ anthropometric characteristics as a representative of North African populations. Secondary aims are as follows: (1) to study the anthropometric gender difference, (2) to compare results with other ethnic groups, and (3) to study the mismatch in comparison to geometric characteristics of modern TKA implant designs.

Methods
Two hundred normal knee MRI scans (100 females and 100 males, aging from 18 to 60) were obtained for analysis. Linear measurements (anteroposterior (AP), mediolateral (ML), and aspect ratio (AR)) of the planned cut surface of the distal femur (f) and the proximal tibia (t) were evaluated.

Results
A significant difference between both sexes was found, males had larger measurements in anteroposterior [fAP: 60.97 ± 3.1 vs 54.78 ± 3.3 (P < 0.001), tAP: 46.89 ± 3.0 vs 41.35 ± 2.9 (P < 0.001)] and mediolateral [fML: 74.89 ± 3.2 vs 67.29 ± 3.7 (P < 0.001), tML: 76.01 ± 3.0 vs 67.26 ± 3.2 (P < 0.001)], the mean femoral and tibial AP and ML measurements were different from other ethnic groups. None of the seven studied TKA systems matched the largest ML or the smallest AP dimensions of the distal femur in the current study population.

Conclusion
A significant difference was found between males’ and females’ knee anthropometric characteristics. Some of the commonly used TKA implants in our area could not provide a perfect fit and coverage.

Trial registration
ClinicalTrials.gov identifier: NCT03622034, registered on July 28, 2018.
Histological regional analysis of the aortic root and thoracic ascending aorta: a complete analysis of aneurysms from root to arch
Authors: Surman Timothy Luke , Abrahams John Matthew , Manavis Jim , Finnie John , O’Rourke Dermot , Reynolds Karen Jane , Edwards James , Worthington Michael George , Beltrame John 
Published: September 2021

Abstract
Background
Although aortic root and ascending aortic aneurysms are treated the same, they differ in embryological development and pathological processes. This study examines the microscopic structural differences between aortic root and ascending aortic aneurysms, correlating these features to the macroscopic pathophysiological processes.

Methods
We obtained surgical samples from ascending aortic aneurysms (n = 11), aortic root aneurysms (n = 3), and non-aneurysmal patients (n = 7), Aortic collagen and elastin content were examined via histological analysis, and immunohistochemistry techniques used to determine collagen I, III, and IV subtypes. Analysis was via observational features, and colour deconvolution quantification techniques.

Results
Elastin fiber disruption and fragmentation was the most extensive in the proximal aneurysmal regions. Medial fibrosis and collagen density increased in proximal aneurysmal regions and aortic root aneurysms (p < 0.005). Collagen I was seen in highest quantity in aortic root aneurysms. Collagen I content was greatest in the sinus tissue regions compared to the valvular and ostial regions (p < 0.005) Collagen III and IV quantification did not vary greatly. The most susceptible regions to ultrastructural changes in disease are the proximal ascending aorta and aortic root.

Conclusions
The aortic root differs histologically from the ascending aorta confirming its unique composition in aneurysm pathology. These findings should prompt further evaluation on the influence of this altered structure on function which could potentially guide clinical management.
Methylphenidate for attention-deficit/hyperactivity disorder in patients with Smith–Magenis syndrome: protocol for a series of N-of-1 trials
Authors: Müller A. R. , Zinkstok J. R. , Rommelse N. N. J. , van de Ven P. M. , Roes K. C. B. , Wijburg F. A. , de Rooij-Askes E. , Linders C. , Boot E. , van Eeghen A. M. 
Published: September 2021

AbstractBackgroundSmith–Magenis syndrome (SMS) is a rare genetic neurodevelopmental disorder characterized by intellectual disability and severe behavioural and sleep disturbances. Often, patients with SMS are diagnosed with attention-deficit/hyperactivity disorder (ADHD). However, the effectiveness of methylphenidate (MPH), the first-line pharmacological treatment for ADHD, in patients with SMS is unclear. Our objective is to examine the effectiveness of MPH for ADHD symptoms in individuals with SMS, proposing an alternative trial design as traditional randomized controlled trials are complex in these rare and heterogeneous patient populations.Methods and analysisWe will initiate an N-of-1 series of double-blind randomized and placebo-controlled multiple crossover trials in six patients aged ≥ 6 years with a genetically confirmed SMS diagnosis and a multidisciplinary established ADHD diagnosis, according to a power analysis based on a summary measures analysis of the treatment effect. Each N-of-1 trial consists of a baseline period, dose titration phase, three cycles each including randomized intervention, placebo and washout periods, and follow-up. The intervention includes twice daily MPH (doses based on age and body weight). The primary outcome measure will be the subscale hyperactivity/inattention of the Strengths and Difficulties Questionnaire (SDQ), rated daily. Secondary outcome measures are the shortened version of the Emotion Dysregulation Inventory (EDI) reactivity index, Goal Attainment Scaling (GAS), and the personal questionnaire (PQ). Statistical analysis will include a mixed model analysis. All subjects will receive an assessment of their individual treatment effect and data will be aggregated to investigate the effectiveness of MPH for ADHD in SMS at a population level.ConclusionsThis study will provide information on the effectiveness of MPH for ADHD in SMS, incorporating personalized outcome measures. This protocol presents the first properly powered N-of-1 study in a rare genetic neurodevelopmental disorder, providing a much-needed bridge between science and practice to optimize evidence-based and personalized care.Trial registrationThis study is registered in the Netherlands Trial Register (NTR9125).
Minhee Analysis Package: an integrated software package for detection and management of spontaneous synaptic events
Authors: Kim Yong Gyu , Shin Jae Jin , Kim Sang Jeong 
Published: September 2021

AbstractTo understand the information encoded in a connection between the neurons, postsynaptic current (PSC) has been widely measured as a primary index of synaptic strength in the field of neurophysiology. Although several automatic detection methods for PSCs have been proposed to simplify a workflow in the analysis, repetitive steps such as quantification and management of PSC data should be still performed with much effort. Here, we present Minhee Analysis Package, an integrated standalone software package that is capable of detecting, sorting, and quantifying PSC data. First, we developed a stepwise exploratory algorithm to detect PSC and validated our detection algorithm using the simulated and experimental data. We also described all the features and examples of the package so that users can use and follow them properly. In conclusion, our software package is expected to improve the convenience and efficiency of neurophysiologists to analyze PSC data by simplifying the workflow from detection to quantification. Minhee Analysis Package is freely available to download from http://www.github.com/parkgilbong/Minhee_Analysis_Pack.
Matching-adjusted indirect treatment comparison of liso-cel versus axi-cel in relapsed or refractory large B cell lymphoma
Authors: Maloney David G. , Kuruvilla John , Liu Fei Fei , Kostic Ana , Kim Yeonhee , Bonner Ashley , Zhang Yixie , Fox Christopher P. , Cartron Guillaume 
Published: September 2021

Abstract
Background
In the absence of randomized studies directly comparing chimeric antigen receptor T cell therapies, this study used matching-adjusted indirect comparisons (MAIC) to evaluate the comparative efficacy and safety of lisocabtagene maraleucel (liso-cel) versus axicabtagene ciloleucel (axi-cel) in patients with relapsed or refractory large B cell lymphoma (LBCL).

Methods
Primary data sources included individual patient data from the TRANSCEND NHL 001 study (TRANSCEND [NCT02631044]; N = 256 for efficacy set, N = 269 for safety set) for liso-cel and summary-level data from the ZUMA-1 study (NCT02348216; N = 101 for efficacy set, N = 108 for safety set) for axi-cel. Inter-study differences in design, eligibility criteria, baseline characteristics, and outcomes were assessed and aligned to the extent feasible. Clinically relevant prognostic factors were adjusted in a stepwise fashion by ranked order. Since bridging therapy was allowed in TRANSCEND but not ZUMA-1, the initial efficacy and safety analyses included bridging therapy use as a matching factor (TRANSCEND patients who received bridging therapy were removed). Subsequent sensitivity analyses excluded this matching factor.

Results
The initial analysis showed similar MAIC-weighted efficacy outcomes between TRANSCEND and ZUMA-1 for overall and complete response rates (odds ratio [95% confidence interval (CI)], 1.40 [0.56–3.49] and 1.21 [0.56–2.64], respectively) and for overall survival and progression-free survival (hazard ratio [95% CI], 0.81 [0.44–1.49] and 0.95 [0.58–1.57], respectively). MAIC-weighted safety outcomes favored liso-cel, with significantly lower odds of all-grade and grade ≥ 3 cytokine release syndrome (odds ratio [95% CI], 0.03 [0.01–0.07] and 0.08 [0.01–0.67], respectively) and study-specific neurological events (0.16 [0.08–0.33] and 0.05 [0.02–0.15], respectively). Efficacy and safety outcomes remained similar in sensitivity analyses, which did not include use of bridging therapy as a matching factor.

Conclusions
After matching and adjusting for clinically relevant prognostic factors, liso-cel demonstrated comparable efficacy and a more favorable safety profile compared with axi-cel in patients with third- or later-line relapsed or refractory LBCL.
Trial registration: NCT02631044 and NCT02348216
Alkaloid profiling and antimicrobial activities of Papaver glaucum and P. decaisnei
Authors: Jafaar Hawraz Jawdat , Isbilen Ovgu , Volkan Ender , Sariyar Gunay 
Published: September 2021

Abstract
Objective
Papaver decaisnei Hochst. & Steud. Ex Elkan and Papaver glaucum Boiss. & Hausskn. growing wild in Northern Iraq have been historically used for medicinal purposes. In this study, both species were evaluated for their alkaloid content and antimicrobial activities.

Results
Alkaloids were extracted and isolated by preparative thin-layer chromatography (TLC). Identification was carried out by comparing spectral data (UV and 1H-NMR) and TLC Rf values with those of authentic samples. Two alkaloids, proapaorphine-type mecambrine and aporphine-type roemerine were isolated from P. decaisnei. Two benzylisoquinoline type alkaloids papaverine (major alkaloid) and palaudine as well as aporphine-type N-methylasimilobine have been obtained in P. glaucum. Both P. glaucum and P. decaisnei extracts revealed strong antimicrobial activity on Pseudomonas aeruginosa ATCC 27853 and Enterococcus faecalis ATCC 29212. Collectively these results indicate that P. glaucum and P. decaisnei are promising sources of alkaloids that could further be investigated for medicinal purposes.
Sun-health behaviours and attitudes towards sun safety amongst Australian teenagers: a qualitative update
Authors: Gamage Nisali , Nguyen Rebecca , Clare Isabelle M. , Lucas Robyn M. , Strickland Mark , Granich Joanna , Gorman Shelley 
Published: September 2021

Abstract
Objective
This study aimed to explore current attitudes towards sun protection, and sun-seeking behaviour among young Australian adolescents. It was done as part of a larger project aiming to develop a digital resource to support young people in making informed sun-health decisions.

Results
Ten (4 male, 6 female) adolescents (12–13 years of age) living in Perth (Western Australia) were recruited through a social media-based strategy. Each participant engaged in a semi-structured telephone interview which explored their sun-health decision-making, with interview transcripts assessed qualitatively using NVivo. Three major themes (and eight sub-themes) were identified: (1) ‘personal sun health considerations’; (2) ‘attitudes towards sun protection’; and (3) ‘recommendations’. The importance of sun protection was appreciated by participants. However, females were more diligent in the use of sun protection while males were indifferent. Behaviours were influenced by parental input, the school environment and engagement in sport. Adolescents had limited knowledge of the UV Index and its implications for sun protection, and the health importance of sun-derived vitamin D. Overall, the importance of sun protection was acknowledged but did not consistently translate into sun protective behaviours.