bluuebunny/crossref_metadata_2025_split huggingface dataset:
A scoping review, novel taxonomy and catalogue of implementation frameworks for clinical decision support systems
Authors: Wohlgemut Jared M. , Pisirir Erhan , Stoner Rebecca S. , Perkins Zane B. , Marsh William , Tai Nigel R.M. , Kyrimi Evangelia 
Published: November 2024

Abstract
Background
The primary aim of this scoping review was to synthesise key domains and sub-domains described in existing clinical decision support systems (CDSS) implementation frameworks into a novel taxonomy and demonstrate most-studied and least-studied areas. Secondary objectives were to evaluate the frequency and manner of use of each framework, and catalogue frameworks by implementation stage.

Methods
A scoping review of Pubmed, Scopus, Web of Science, PsychInfo and Embase was conducted on 12/01/2022, limited to English language, including 2000–2021. Each framework was categorised as addressing one or multiple stages of implementation: design and development, evaluation, acceptance and integration, and adoption and maintenance. Key parts of each framework were grouped into domains and sub-domains.

Results
Of 3550 titles identified, 58 papers were included. The most-studied implementation stage was acceptance and integration, while the least-studied was design and development. The three main framework uses were: for evaluating adoption, for understanding attitudes toward implementation, and for framework validation. The most frequently used framework was the Consolidated Framework for Implementation Research.

Conclusions
Many frameworks have been published to overcome barriers to CDSS implementation and offer guidance towards successful adoption. However, for co-developers, choosing relevant frameworks may be a challenge. A taxonomy of domains addressed by CDSS implementation frameworks is provided, as well as a description of their use, and a catalogue of frameworks listed by the implementation stages they address. Future work should ensure best practices for CDSS design are adequately described, and existing frameworks are well-validated. An emphasis on collaboration between clinician and non-clinician affected parties may help advance the field.
Immersive virtual reality for learning exoskeleton-like virtual walking: a feasibility study
Authors: Rodríguez-Fernández Antonio , den Berg Alex van , Cucinella Salvatore Luca , Lobo-Prat Joan , Font-Llagunes Josep M. , Marchal-Crespo Laura 
Published: November 2024

Abstract
Purpose
Virtual Reality (VR) has proven to be an effective tool for motor (re)learning. Furthermore, with the current commercialization of low-cost head-mounted displays (HMDs), immersive virtual reality (IVR) has become a viable rehabilitation tool. Nonetheless, it is still an open question how immersive virtual environments should be designed to enhance motor learning, especially to support the learning of complex motor tasks. An example of such a complex task is triggering steps while wearing lower-limb exoskeletons as it requires the learning of several sub-tasks, e.g., shifting the weight from one leg to the other, keeping the trunk upright, and initiating steps. This study aims to find the necessary elements in VR to promote motor learning of complex virtual gait tasks.

Methods
In this study, we developed an HMD-IVR-based system for training to control wearable lower-limb exoskeletons for people with sensorimotor disorders. The system simulates a virtual walking task of an avatar resembling the sub-tasks needed to trigger steps with an exoskeleton. We ran an experiment with forty healthy participants to investigate the effects of first- (1PP) vs. third-person perspective (3PP) and the provision (or not) of concurrent visual feedback of participants’ movements on the walking performance – namely number of steps, trunk inclination, and stride length –, as well as the effects on embodiment, usability, cybersickness, and perceived workload.

Results
We found that all participants learned to execute the virtual walking task. However, no clear interaction of perspective and visual feedback improved the learning of all sub-tasks concurrently. Instead, the key seems to lie in selecting the appropriate perspective and visual feedback for each sub-task. Notably, participants embodied the avatar across all training modalities with low cybersickness levels. Still, participants’ cognitive load remained high, leading to marginally acceptable usability scores.

Conclusions
Our findings suggest that to maximize learning, users should train sub-tasks sequentially using the most suitable combination of person’s perspective and visual feedback for each sub-task. This research offers valuable insights for future developments in IVR to support individuals with sensorimotor disorders in improving the learning of walking with wearable exoskeletons
Blood-brain barrier permeability increases with the differentiation of glioblastoma cells in vitro
Authors: Digiovanni Sabrina , Lorenzati Martina , Bianciotto Olga Teresa , Godel Martina , Fontana Simona , Akman Muhlis , Costamagna Costanzo , Couraud Pierre-Olivier , Buffo Annalisa , Kopecka Joanna , Riganti Chiara , Salaroglio Iris Chiara 
Published: November 2024

Abstract
Background
Glioblastoma multiforme (GBM) is an aggressive tumor, difficult to treat pharmacologically because of the blood-brain barrier (BBB), which is rich in ATP-binding cassette (ABC) transporters and tight junction (TJ) proteins. The BBB is disrupted within GBM bulk, but it is competent in brain-adjacent-to-tumor areas, where eventual GBM foci can trigger tumor relapse. How GBM cells influence the permeability of BBB is poorly investigated.

Methods
To clarify this point, we co-cultured human BBB models with 3 patient-derived GBM cells, after separating from each tumor the stem cell/neurosphere (SC/NS) and the differentiated/adherent cell (AC) components. Also, we set up cultures of BBB cells with the conditioned medium of NS or AC, enriched or depleted of IL-6. Extracellular cytokines were measured by protein arrays and ELISA. The intracellular signaling in BBB cells was measured by immunoblotting, in the presence of STAT3 pharmacological inhibitor or specific PROTAC. The competence of BBB was evaluated by permeability assays and TEER measurement.

Results
The presence of GBM cells or their conditioned medium increased the permeability to doxorubicin, mitoxantrone and dextran-70, decreased TEER, down-regulated ABC transporters and TJ proteins at the transcriptional level. These effects were higher with AC or their medium than with NS. The secretome analysis identified IL-6 as significantly more produced by AC than by NS. Notably, AC-conditioned medium treated with an IL-6 neutralizing antibody reduced the BBB permeability to NS levels, while NS-conditioned medium enriched with IL-6 increased BBB permeability to AC levels. Mechanistically, IL-6 released by AC GBM cells activated STAT3 in BBB cells. In turn, STAT3 down-regulated ABC transporter and TJ expression, increased permeability and decreased TEER. The same effects were obtained in BBB cells treated with STA-21, a pharmacological inhibitor of STAT3, or with a PROTAC targeting STAT3.

Conclusions
Our work demonstrates for the first time that the degree of GBM differentiation influences BBB permeability. The crosstalk between GBM cells that release IL-6 and BBB cells that respond by activating STAT3, controls the expression of ABC transporters and TJ proteins on BBB. These results may pave the way for novel therapeutic tools to tune BBB permeability and improve drug delivery to GBM.
Latent factors underlying the symptoms of adult-onset myotonic dystrophy type 1 during the clinical course
Authors: Zhang Yanan , Wallace Bailey , Cai Bo , Johnson Nicholas , Ciafaloni Emma , Venkatesh Yedatore Swamy , Westfield Christina , McDermott Suzanne 
Published: November 2024

Abstract
Background
Myotonic dystrophy type 1 (DM1) is a multisystem genetic disorder that classically presents with symptoms associated with myotonia, early onset cataracts, and muscular weakness, although the presentation and pattern of disease progression is quite varied. Presenting symptoms are well documented among adults with DM1. However, less is known about the co-occurrence of symptoms over time. We aimed to use factor analysis to explore the correlation pattern of signs and symptoms (S/S) that emerged during the clinical course.

Results
Clinical records of 228 individuals with adult onset DM1 were abstracted using the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) from a six-site cohort in the United States during an eight-year study period. Factor analysis was used to group the correlated S/S into latent factors. Three factors were identified. Group 1: ‘Facial Weakness/Myotonia’ includes the two most common S/S, as indicated by its name. Group 2: ‘Skeletal Muscle Weakness’ includes eight muscular S/S and is more frequently reported by males and those with older age at onset. Group 3: ‘Gastrointestinal distress/Sleepiness’ includes four non-muscular S/S and hand stiffness. The abstracted medical records reported that over 63% of individuals had S/S from all three groups. Associations of covariates with factor scores were also examined using linear regression. CTG repeat length was significantly positively associated with higher factor scores for all three factors.

Conclusions
This study identified three latent factors of S/S which accumulated during the clinical course of adult onset DM1.
Mapping the diagnostic odyssey of congenital disorders of glycosylation (CDG): insights from the community
Authors: Granjo Pedro , Pascoal Carlota , Gallego Diana , Francisco Rita , Jaeken Jaak , Moors Tristen , Edmondson Andrew C. , Kantautas Kristin A. , Serrano Mercedes , Videira Paula A. , dos Reis Ferreira Vanessa 
Published: November 2024

Abstract
Background
Congenital disorders of glycosylation (CDG) are a group of rare metabolic diseases with heterogeneous presentations, leading to substantial diagnostic challenges, which are poorly understood. Therefore, this study aims to elucidate this diagnostic journey by examining families’ and professionals’ experiences.

Results and discussion
A questionnaire was designed for CDG families and professionals, garnering 160 and 35 responses, respectively. Analysis revealed the lack of seizures as a distinctive feature between PMM2-CDG (11.2%) with Other CDG (57.7%) at symptom onset. Hypotonia and developmental disability were prevalent symptoms across all studied CDG. Feeding problems were identified as an early onset symptom in PMM2-CDG (Cramer’s V (V) = 0.30, False Discovery Rate (FDR) = 3.8 × 10− 9), and hypotonia in all studied CDG (V = 0.34, FDR = 7.0 × 10− 3). The average time to diagnosis has decreased in recent years (now ~ 3.9 years), due to advancements namely the increased use of whole genome and exome sequencing. However, misdiagnoses remain prevalent (PMM2-CDG – 44.9%, non-PMM2-CDG – 64.8%). To address these challenges, we propose adapting medical training to increase awareness of CDG and other rare diseases, ongoing education for physicians, the development of educational resources for relevant medical units, and empowerment of families through patient organizations and support networks.

Conclusion
This study emphasizes the crucial role of community-centered research, and the insights families can offer to enhance CDG management. By pinpointing existing gaps and needs, our findings can inform targeted interventions and support systems to improve the lives of those impacted by CDG.
Riboflavin transporter deficiency, the search for the undiagnosed: a retrospective data mining study
Authors: Jaeger B. , Hoytema van Konijnenburg E. , Groenveld M. A. , Langeveld M. , Wolf N. I. , Bosch A. M. 
Published: November 2024

Abstract
Background
Riboflavin transporter deficiency (RTD) is an inborn error of riboflavin transport causing progressive neurological symptoms if left untreated. While infants with symptomatic RTD rapidly deteriorate, presentation later in childhood or in adulthood is more gradual. Symptoms overlap with more common diseases, carrying a risk of misdiagnosis, and given the relatively recent discovery of the genetic basis of RTD in 2010 it is likely that older patients have not been tested. Treatment with oral riboflavin (vitamin B2) halts disease progression and can be lifesaving. We hypothesized that patients may have been left unrecognized at the time of presentation and therefore we performed a datamining study to detect undiagnosed RTD patients in a tertiary referral hospital.

Methods
A systematic search in Electronic Health Records (EHR) of all patients visiting the Amsterdam University Medical Centers between January 2004 and July 2021 was performed by a medical data text-mining tool. Pseudonymized patient records, matching pre-defined search terms (hearing loss or auditory neuropathy spectrum disorders combined with key clinical symptoms or riboflavin) were screened and included if no definitive alternative diagnosis for symptoms indicating possible RTD was found. Included patients were offered genetic testing. We documented total number of patients with possible RTD, number of patients that underwent genetic testing for RTD and results of genetic testing.

Results
EHR of 2.288.901 patients were automatically screened. Thirteen patients with possible RTD were identified and offered genetic testing. Seven patients chose not to participate. Genetic testing was performed in 6 patients and was negative. The datamining did detect all previously known RTD patients in the hospital.

Conclusions
By screening a large cohort of patients of all ages in a tertiary referral hospital in a period spanning 17 years, no new RTD patients were found. Although not all suspected patients underwent genetic testing, our findings suggest that the prevalence of RTD is low and the chance of having missed this diagnosis in a tertiary referral hospital is limited.
Paclitaxel- or sirolimus-coated balloons used for ArterioVEnous fistulas-2 (PAVE-2): study protocol for a randomised controlled trial to determine the efficacy of paclitaxel- or sirolimus-coated balloons in arteriovenous fistulas used for haemodialysis
Authors: Karunanithy Narayan , Norton Sam , Calder Francis , Das Neelanjan , Dooley Niamh , Hakobyan Lusine , Jones Robert , Padayache Soundrie , Spriggs Chloe , Steiner Kate , Suckling Rebecca , Robson Michael G. 
Published: October 2024

Abstract

Background

In view of the conflicting results from previous studies, the benefit of paclitaxel-coated balloons for arteriovenous fistulas is uncertain and equipoise remains. Although an industry-led trial testing the efficacy of sirolimus-coated balloons in AVFs is in progress, the benefit of sirolimus-coated balloons for arteriovenous fistulas is currently unknown. The purpose of this trial is to compare the efficacy of additional paclitaxel-coated or sirolimus-coated balloons on outcomes after a plain balloon fistuloplasty to preserve the patency of arteriovenous fistulae used for haemodialysis.

Methods
The study design is a multicentre randomised controlled trial. Following a successful plain balloon fistuloplasty, participants will be randomised to further treatment with a paclitaxel-coated balloon, a sirolimus-coated balloon, or an uncoated control balloon. We will recruit 642 patients, each with one or two treatment segments, over a 3-year period. Patients will remain in the trial and be followed up for 1 year. The primary endpoint is time to loss of treatment segment primary patency. Cox-proportional hazards models will be used to estimate hazard ratios for the time to loss of treatment segment primary patency for each treatment group relative to the control group. Analysis of the primary endpoint will be based on treatment segments rather than participants and a shared frailty will be estimated to account for the clustering of treatment segments within patients. Secondary endpoints are time to loss of primary patency at any treatment segment; time to end of access circuit primary patency; time to AVF abandonment; number of radiological or surgical interventions; adverse events; intima-media thickness and degree of stenosis at 3 months on ultrasound; and patient quality of life assessed by EQ-5D-5L and VASQoL.

Discussion
The three-armed design in this proposal will provide an answer on the efficacy of both paclitaxel- and sirolimus-coated balloons in the same trial. This trial is likely to provide a clear answer regarding the efficacy of drug-coated balloons for arteriovenous fistulas.

Trial registration
ISRCTN ISRCTN40182296. Registered on 4 August 2023.
Effectiveness of Virtual - Compensatory Cognitive Training (V-CCT) for improving cognition in persons with schizophrenia - a multi- centre randomized controlled trial
Authors: Sims Sonia , Kantipudi Suvarna Jyothi , Ashok Yogitha , Nisha B. , Gopal Subhashini , Joseph Elsa , Amritha S. , Venkatraman Lakshmi , Venkatasubramanian Pratiksha , Ramachandran Padmavati 
Published: November 2024

Abstract
Background
Cognitive deficits are the core component in persons with schizophrenia which impacts their socio-occupational functioning. Also, cognitive deficits cause significant impairment with the person’s quality of life [3]. Hence, targeting such a pivotal aspect in persons with schizophrenia through suitable interventions is very important. Developed countries have designed various cognitive remediation programs using computers involving high-end software which cannot be generalized to low-resource settings, like India, due to various factors including sociocultural factors, educational standards, and living standards of the patient population. Compensatory cognitive training (CCT) was developed to be “brief, practical, low-tech” and found to be effective in the west [9]. As there are no structured cognitive intervention modules in India, we have adapted the English CCT manual to be used for an urban population in Chennai, India. CCT was found to be feasible in face-to-face group sessions in our setting [12] and is found to be feasible and acceptable as virtual one–one intervention (unpublished data). Therefore, this study aims to evaluate the effectiveness of V-CCT in enhancing cognition and socio-occupational functioning.

Methods
The proposed study will be a multicenter assessor-blinded randomized controlled trial at two clinical sites in Chennai, India. The preparatory phase of the study would include translation of the manual to the local language, recruitment and training of research assistants, and pilot testing using the translated manual. The second phase will be the main randomized controlled trial (RCT), during which a total of 160 persons diagnosed with schizophrenia will be recruited from both sites. After obtaining informed consent, baseline assessments will be conducted on cognition, functioning, self-esteem, and quality of life. Participants will be randomly assigned to either the virtual CCT group or the control group using a computer-generated randomization table. End-line assessments will be conducted 6 weeks after the baseline by research assistants who are blinded to the randomization post-intervention.

Discussion
If V-CCT is found to be effective, it will be available for use in Tamil for persons with schizophrenia, and it will have an effect on their functioning, quality of life, and self-esteem.

Trial registration
The study is registered under Clinical trial registry-India (CTRI), and the registration number is CTRI/2024/04/065267. Registered on April 2024.
A novel stability-indicating chromatographic quantification of the antiparkinsonian drug safinamide in its pharmaceutical formulation employing HPTLC densitometry and ion-pair HPLC–DAD
Authors: Ibrahim Engy A. , Saad Samah S. , Hegazy Maha A. , Abdel Fattah Laila E. , Marzouk Hoda M. 
Published: November 2024

AbstractParkinson's disease (PD) emerges as a notable health concern among the elderly population. Safinamide mesylate (SAF) is a novel and emerging add-on therapy in PD treatment. The stability of innovative drug formulations and the development of appropriate stability-indicating methods are of great importance to modern pharmaceutical analysis. The current work has established novel comprehensive stability-indicating chromatographic approaches, HPTLC coupled with densitometric quantification and HPLC–DAD, for the selective assay of SAF in pharmaceutical formulation along with its synthetic precursor impurity; 4-hydroxy benzaldehyde (4-HBD) in presence of its stress induced degradation products. The stability of SAF was investigated under different stress conditions. It was found that SAF is likely to undergo acid, base hydrolysis, and oxidative degradation. Using mass spectrometry and infrared spectroscopy, the structures of the forced degradation products were confirmed and elucidated. The dissolution behavior of Parkimedine® Tablets was also monitored in the FDA suitable medium. Multiple assessment tools were used to evaluate the environmental sustainability of the proposed methods and the reported one. The greenness tools included Complex-GAPI and AGREE metrics. In addition, the innovative concepts of "blueness" and "whiteness" evaluation were incorporated through the newly introduced BAGI and RGB12 algorithms, respectively.
Ribosomal proteins in hepatocellular carcinoma: mysterious but promising
Authors: Su Qian , Sun Huizhen , Mei Ling , Yan Ying , Ji Huimin , Chang Le , Wang Lunan 
Published: November 2024

AbstractRibosomal proteins (RPs) are essential components of ribosomes, playing a role not only in ribosome biosynthesis, but also in various extra-ribosomal functions, some of which are implicated in the development of different types of tumors. As universally acknowledged, hepatocellular carcinoma (HCC) has been garnering global attention due to its complex pathogenesis and challenging treatments. In this review, we analyze the biological characteristics of RPs and emphasize their essential roles in HCC. In addition to regulating related signaling pathways such as the p53 pathway, RPs also act in proliferation and metastasis by influencing cell cycle, apoptosis, angiogenesis, and epithelial-to-mesenchymal transition in HCC. RPs are expected to unfold new possibilities for precise diagnosis and individualized treatment of HCC.
Semi-automated title-abstract screening using natural language processing and machine learning
Authors: Pilz Maximilian , Zimmermann Samuel , Friedrichs Juliane , Wördehoff Enrica , Ronellenfitsch Ulrich , Kieser Meinhard , Vey Johannes A. 
Published: November 2024

Abstract
Background
Title-abstract screening in the preparation of a systematic review is a time-consuming task. Modern techniques of natural language processing and machine learning might allow partly automatization of title-abstract screening. In particular, clear guidance on how to proceed with these techniques in practice is of high relevance.

Methods
This paper presents an entire pipeline how to use natural language processing techniques to make the titles and abstracts usable for machine learning and how to apply machine learning algorithms to adequately predict whether or not a publication should be forwarded to full text screening. Guidance for the practical use of the methodology is given.

Results
The appealing performance of the approach is demonstrated by means of two real-world systematic reviews with meta analysis.

Conclusions
Natural language processing and machine learning can help to semi-automatize title-abstract screening. Different project-specific considerations have to be made for applying them in practice.