bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contextual interference in children with brain lesions: a pilot study investigating blocked vs. random practice order of an upper limb robotic exergame
Authors: Graser Judith V. , Bastiaenen Caroline H. G. , Gut Anja , Keller Urs , van Hedel Hubertus J. A. 
Published: June 2021

Abstract
Introduction
Evidence about contextual interference in children with brain lesions when practising motor tasks is lacking. Our main objective was to evaluate the feasibility of a randomised controlled trial (RCT) comparing blocked with random practice order of an upper limb robotic exergame to improve reaching in children with neuromotor disorders with a pilot trial.

Methods
We recruited children with brain lesions and impaired upper limb functions who underwent a 3-week schedule that consisted of baseline assessments, intervention period (participants were randomised to a blocked or random order group), and follow-up assessment. We evaluated ten feasibility criteria, including the practicability of the inclusion/exclusion criteria, recruitment rate, feasibility of randomisation, scheduling procedure, and the participants’ programme adherence.

Results
The inclusion/exclusion criteria were not completely feasible as patients who were not able to perform the exergames were included. Twelve participants were recruited, and six datasets were used for analysis. The scheduling and randomisation procedures were generally feasible, but the procedure was only partially feasible for the participants, as some sessions were aborted due to lack of motivation and fatigue.

Conclusion
An RCT following this study protocol is not feasible. We formulated suggestions for future studies that aim to investigate contextual interference as in this pilot study.

Trial registration
ClinicalTrials.gov Identifier: NCT02443857, registered on May 14, 2015
Studying visual search without an eye tracker: an assessment of artificial foveation
Authors: Matzen Laura E. , Stites Mallory C. , Gastelum Zoe. N. 
Published: June 2021

AbstractEye tracking is a useful tool for studying human cognition, both in the laboratory and in real-world applications. However, there are cases in which eye tracking is not possible, such as in high-security environments where recording devices cannot be introduced. After facing this challenge in our own work, we sought to test the effectiveness of using artificial foveation as an alternative to eye tracking for studying visual search performance. Two groups of participants completed the same list comparison task, which was a computer-based task designed to mimic an inventory verification process that is commonly performed by international nuclear safeguards inspectors. We manipulated the way in which the items on the inventory list were ordered and color coded. For the eye tracking group, an eye tracker was used to assess the order in which participants viewed the items and the number of fixations per trial in each list condition. For the artificial foveation group, the items were covered with a blurry mask except when participants moused over them. We tracked the order in which participants viewed the items by moving their mouse and the number of items viewed per trial in each list condition. We observed the same overall pattern of performance for the various list display conditions, regardless of the method. However, participants were much slower to complete the task when using artificial foveation and had more variability in their accuracy. Our results indicate that the artificial foveation method can reveal the same pattern of differences across conditions as eye tracking, but it can also impact participants’ task performance.
Rhino-orbital mucormycosis in COVID-19 patients—a new threat?
Authors: Awal Sandeep Singh , Biswas Som Subhro , Awal Sampreet Kaur 
Published: June 2021

Abstract
Background
Coronavirus disease 2019 (COVID-19) is known to be associated with a myriad of viral, fungal, and bacterial co-infections. Rhino-orbital mucormycosis is a rare angio-invasive fungal infection which has shown a rising trend in the setting of COVID-19.

Case presentation
We describe the imaging findings in 3 cases of rhino-orbital mucormycosis in patients with history of COVID-19. All cases had varying involvement of paranasal sinuses extending into the orbital compartment while case 3 had intracranial extension of infection.

Conclusions
Rhino-orbital mucormycosis can have aggressive necrosis of the involved paranasal sinuses and orbits with or without cerebral extension. Hence, the correct diagnosis is imperative as prompt antifungal drugs and surgical debridement can significantly reduce mortality and morbidity.
Harm minimisation for the management of self-harm: a mixed-methods analysis of electronic health records in secondary mental healthcare
Authors: Cliffe Charlotte , Pitman Alexandra , Sedgwick Rosemary , Pritchard Megan , Dutta Rina , Rowe Sarah 
Published: June 2021

Background
Prevalence of self-harm in the UK was reported as 6.4% in 2014. Despite sparse evidence for effectiveness, guidelines recommend harm minimisation; a strategy in which people who self-harm are supported to do so safely.

Aims
To determine the prevalence, sociodemographic and clinical characteristics of those who self-harm and practise harm minimisation within a London mental health trust.

Method
We included electronic health records for patients treated by South London and Maudsley NHS Trust. Using an iterative search strategy, we identified patients who practise harm minimisation, then classified the approaches using a content analysis. We compared the sociodemographic characteristics with that of a control group of patients who self-harm and do not use harm minimisation.

Results
In total 22 736 patients reported self-harm, of these 693 (3%) had records reporting the use of harm-minimisation techniques. We coded the approaches into categories: (a) ‘substitution’ (>50% of those using harm minimisation), such as using rubber bands or using ice; (b) ‘simulation’ (9%) such as using red pens; (c) ‘defer or avoid’ (7%) such as an alternative self-injury location; (d) ‘damage limitation’ (9%) such as using antiseptic techniques; the remainder were unclassifiable (24%). The majority of people using harm minimisation described it as helpful (>90%). Those practising harm minimisation were younger, female, of White ethnicity, had previous admissions and were less likely to have self-harmed with suicidal intent.

Conclusions
A small minority of patients who self-harm report using harm minimisation, primarily substitution techniques, and the large majority find harm minimisation helpful. More research is required to determine the acceptability and effectiveness of harm-minimisation techniques and update national clinical guidelines.
Phase II Trial of Pembrolizumab Plus Gemcitabine, Vinorelbine, and Liposomal Doxorubicin as Second-Line Therapy for Relapsed or Refractory Classical Hodgkin Lymphoma
Authors: Moskowitz Alison J. , Shah Gunjan , Schöder Heiko , Ganesan Nivetha , Drill Esther , Hancock Helen , Davey Theresa , Perez Leslie , Ryu Sunyoung , Sohail Samia , Santarosa Alayna , Galasso Natasha , Neuman Rachel , Liotta Brielle , Blouin William , Kumar Anita , Lahoud Oscar , Batlevi Connie L. , Hamlin Paul , Straus David J. , Rodriguez-Rivera Ildefonso , Owens Colette , Caron Philip , Intlekofer Andrew M. , Hamilton Audrey , Horwitz Steven M. , Falchi Lorenzo , Joffe Erel , Johnson William , Lee Christina , Palomba M. Lia , Noy Ariela , Matasar Matthew J. , Pongas Georgios , Salles Gilles , Vardhana Santosha , Sanin Beatriz Wills , von Keudell Gottfried , Yahalom Joachim , Dogan Ahmet , Zelenetz Andrew D. , Moskowitz Craig H. 
Published: June 2021

PURPOSE We conducted a phase II study evaluating pembrolizumab plus gemcitabine, vinorelbine, and liposomal doxorubicin (pembro-GVD) as second-line therapy for relapsed or refractory (rel/ref) classical Hodgkin lymphoma (cHL) (ClinicalTrials.gov identifier: NCT03618550 ). METHODS Transplant eligible patients with rel/ref cHL following first-line therapy were treated with two to four cycles of pembrolizumab (200 mg intravenous [IV], day 1), gemcitabine (1,000 mg/m2 IV, days 1 and 8), vinorelbine (20 mg/m2 IV, days 1 and 8), and liposomal doxorubicin (15 mg/m2, days 1 and 8), given on 21-day cycles. The primary end point was complete response (CR) following up to four cycles of pembro-GVD. Patients who achieved CR by labeled fluorodeoxyglucose-positron emission tomography (Deauville ≤ 3) after two or four cycles proceeded to high-dose therapy and autologous hematopoietic cell transplantation (HDT/AHCT). HDT/AHCT was carried out according to institutional standards, and brentuximab vedotin maintenance was allowed following HDT/AHCT. RESULTS Of 39 patients enrolled, 41% had primary ref disease and 38% relapsed within 1 year of frontline treatment. 31 patients received two cycles of pembro-GVD, and eight received four cycles. Most adverse events were grade 1 or two, whereas few were grade 3 and included transaminitis (n = 4), neutropenia (n = 4), mucositis (n = 2), thyroiditis (n = 1), and rash (n = 1). Of 38 evaluable patients, overall and CR rates after pembro-GVD were 100% and 95%, respectively. Thirty-six (95%) patients proceeded to HDT/AHCT, two received pre-HDT/AHCT involved site radiation, and 13 (33%) received post-HDT/AHCT brentuximab vedotin maintenance. All 36 transplanted patients are in remission at a median post-transplant follow-up of 13.5 months (range: 2.66-27.06 months). CONCLUSION Second-line therapy with pembro-GVD is a highly effective and well-tolerated regimen that can efficiently bridge patients with rel/ref cHL to HDT/AHCT.
Second-tier Testing for 21-Hydroxylase Deficiency in the Netherlands: A Newborn Screening Pilot Study
Authors: Stroek Kevin , Ruiter An , van der Linde Annelieke , Ackermans Mariette , Bouva Marelle J , Engel Henk , Jakobs Bernadette , Kemper Evelien A , van den Akker Erica L T , van Albada Mirjam E , Bocca Gianni , Finken Martijn J J , Hannema Sabine E , Mieke Houdijk E C A , van der Kamp Hetty J , van Tellingen Vera , Paul van Trotsenburg A S , Zwaveling-Soonawala Nitash , Bosch Annet M , de Jonge Robert , Heijboer Annemieke C , Claahsen-van der Grinten Hedi L , Boelen Anita 
Published: June 2021

Abstract

Context
Newborn screening (NBS) for classic congenital adrenal hyperplasia (CAH) consists of 17-hydroxyprogesterone (17-OHP) measurement with gestational age–adjusted cutoffs. A second heel puncture (HP) is performed in newborns with inconclusive results to reduce false positives.

Objective
We assessed the accuracy and turnaround time of the current CAH NBS algorithm in comparison with alternative algorithms by performing a second-tier 21-deoxycortisol (21-DF) pilot study.

Methods
Dried blood spots (DBS) of newborns with inconclusive and positive 17-OHP (immunoassay) first HP results were sent from regional NBS laboratories to the Amsterdam UMC Endocrine Laboratory. In 2017-2019, 21-DF concentrations were analyzed by LC-MS/MS in parallel with routine NBS. Diagnoses were confirmed by mutation analysis.

Results
A total of 328 DBS were analyzed; 37 newborns had confirmed classic CAH, 33 were false-positive and 258 were categorized as negative in the second HP following the current algorithm. With second-tier testing, all 37 confirmed CAH had elevated 21-DF, while all 33 false positives and 253/258 second-HP negatives had undetectable 21-DF. The elevated 21-DF of the other 5 newborns may be NBS false negatives or second-tier false positives. Adding the second-tier results to inconclusive first HPs reduced the number of false positives to 11 and prevented all 286 second HPs. Adding the second tier to both positive and inconclusive first HPs eliminated all false positives but delayed referral for 31 CAH patients (1-4 days).

Conclusion
Application of the second-tier 21-DF measurement to inconclusive first HPs improved our CAH NBS by reducing false positives, abolishing the second HP, and thereby shortening referral time.
Type 2 Diabetes Mellitus and Amyotrophic Lateral Sclerosis: Genetic Overlap, Causality, and Mediation
Authors: Chen Haimiao , Zhang Jinhui , Wang Ting , Zhang Shuo , Lai Qingwei , Huang Shuiping , Zeng Ping 
Published: June 2021

Abstract

Context
Understanding phenotypic connection between type II diabetes (T2D) mellitus and amyotrophic lateral sclerosis (ALS) can offer valuable sight into shared disease etiology and have important implication in drug repositioning and therapeutic intervention.

Objective
This work aims to disentangle the nature of the inverse relationship between T2D mellitus and ALS.

Methods
Depending on summary statistics of T2D (n = 898 130) and ALS (n = 80 610), we estimated the genetic correlation between them and prioritized pleiotropic genes through a multiple-tissue expression quantitative trait loci–weighted integrative analysis and the conjunction conditional false discovery rate (ccFDR) method. We implemented mendelian randomization (MR) analyses to evaluate the causal relationship between the 2 diseases. A mediation analysis was performed to assess the mediating role of T2D in the pathway from T2D-related glycemic/anthropometric traits to ALS.

Results
We found supportive evidence of a common genetic foundation between T2D and ALS (rg = –0.223, P = .004) and identified 8 pleiotropic genes (ccFDR &lt; 0.10). The MR analyses confirmed that T2D exhibited a neuroprotective effect on ALS, leading to an approximately 5% (95% CI, 0% ~ 9.6%, P = .038) reduction in disease risk. In contrast, no substantial evidence was observed that supported the causal influence of ALS on T2D. The mediation analysis revealed T2D can also serve as an active mediator for several glycemic/anthropometric traits, including high-density lipoprotein cholesterol, overweight, body mass index, obesity class 1, and obesity class 2, with the mediation effect estimated to be 0.024, –0.022, –0.041, –0.016, and –0.012, respectively.

Conclusion
We provide new evidence supporting the observed inverse link between T2D and ALS, and revealed that a shared genetic component and causal association commonly drove such a relationship. We also demonstrate the mediating role of T2D standing in the pathway from T2D-related glycemic/anthropometric traits to ALS.
Whole-genome Sequencing of Follicular Thyroid Carcinomas Reveal Recurrent Mutations in MicroRNA Processing Subunit DGCR8
Authors: Paulsson Johan O , Rafati Nima , DiLorenzo Sebastian , Chen Yi , Haglund Felix , Zedenius Jan , Juhlin C Christofer 
Published: June 2021

Abstract

Background
The genomic and transcriptomic landscape of widely invasive follicular thyroid carcinomas (wiFTCs) and Hürthle cell carcinoma (HCC) are poorly characterized, and subsets of these tumors lack information on genetic driver events.

Objective
The aim of this study was to bridge this gap.

Methods
We performed whole-genome and RNA sequencing and subsequent bioinformatic analyses of 11 wiFTCs and 2 HCCs with a particularly poor prognosis, and matched normal tissue.

Results
All wiFTCs exhibited one or several mutations in established thyroid cancer genes, including TERT (n = 4), NRAS (n = 3), HRAS, KRAS, AKT, PTEN, PIK3CA, MUTYH, TSHR, and MEN1 (n = 1 each). MutSig2CV analysis revealed recurrent somatic mutations in FAM72D (n = 3, in 2 wiFTCs and in a single HCC), TP53 (n = 3, in 2 wiFTCs and a single HCC), and EIF1AX (n = 3), with DGCR8 (n = 2) as borderline significant. The DGCR8 mutations were recurrent p.E518K missense alterations, known to cause familial multinodular goiter via disruption of microRNA (miRNA) processing. Expression analyses showed reduced DGCR8 messenger RNA expression in FTCs in general, and the 2 DGCR8 mutants displayed a distinct miRNA profile compared to DGCR8 wild-types. Copy number analyses revealed recurrent gains on chromosomes 4, 6, and 10, and fusion gene analyses revealed 27 high-quality events. Both HCCs displayed hyperploidy, which was fairly unusual in the FTC cohort. Based on the transcriptome data, tumors amassed in 2 principal clusters.

Conclusion
We describe the genomic and transcriptomic landscape in wiFTCs and HCCs and identify novel recurrent mutations and copy number alterations with possible driver properties and lay the foundation for future studies.
Active Micromixer of Microfluids via Plasmonic Marangoni Convection
Authors: Agawa Hiroaki , Hasebe Koichi , Matsutani Akihiro , Isobe Toshihiro , Nakajima Akira , Matsushita Sachiko 
Published: June 2021

Abstract
Chemical reactions can be efficiently carried out in microfluidic devices using a small amount of solution, meaning that fewer resources are required and less liquid waste is generated, making them energy-efficient and eco-friendly devices. However, the microchannel of the device has a narrow channel width, so the reaction solution exhibits laminar flow. Although this laminar flow is good for transporting the solution, efficiently conducting a chemical reaction is difficult in such a flow. Therefore, the aim of the present study is to produce a micromixer in which diffusion can be easily controlled in the microchannel. In this work, efficient stirring of the fluid was achieved only under laser irradiation by utilising the local light-to-heat conversion that occurs on plasmonic metal nanostructures placed in the microchannel. The gold nanostructure that covers a two-dimensional colloidal crystal, which was easily manufactured at low cost, has a high temperature of 200 °C or more only when irradiated with a laser, and the solution is vapourised and forms bubbles with a diameter of approximately 10 µm. The temperature difference on the bubble surface causes Marangoni convection, which can be used to efficiently stir the reaction solution in the assembled microfluidic device.
Dual-Stimuli-Responsive Probes for Detection of Ovarian Cancer Cells and Quantification of Both pH and Enzyme Activity
Authors: Huo Wenting , Miki Koji , Tokunaga Daisuke , Mu Huiying , Oe Masahiro , Harada Hiroshi , Ohe Kouichi 
Published: June 2021

Abstract
Many physiological processes involve multiple coordinated chemical and/or biological events. Therefore, it is considered urgent to develop dual-responsive probes for a more comprehensive understanding of the synergistic effects between multiple analytes in complex cellular environments. In this study, we developed a dual-responsive probe βgal-BP-PMB (β-galactosyl–3,3′-dihydroxy-2,2′-bipyridyl–p-methoxybenzyl), the photoluminescence of which can be activated by β-galactosidase (β-gal) and acidic conditions. The overexpression of β-gal is an important feature of senescent and ovarian cancer cells. Single-input activatable probes for detecting β-gal activity in ovarian cancer cells can induce a false positive response from senescent cells. Because the lysosomal pH in senescent cells is increased, probe βgal-BP-PMB can be specifically activated in ovarian cancer cells, but silenced in senescent cells. Probe βgal-BP-PMB has a small molecular size, high sensitivity towards targeted stimuli and unique ratiometric properties, thereby enabling the quantification of both pH and enzyme activity. Such dual-responsive probes could earn a unique place in the field of bioimaging, where multiple analytes should be accurately and simultaneously monitored.
Catalogando Requisitos Não-Funcionais de Sistemas Embarcados
Authors: Silva Reinaldo Antônio , Castro Jaelson , Pimentel João 
Published: June 2021

As dificuldades no processo de desenvolvimento de sistemas embarcados, como o tratamento de Requisitos Não-Funcionais(RNFs), levaram os desenvolvedores a buscarem na engenharia de requisitos conceitos e aplicações que apoiassem a sua construção. Assim, este artigo aborda a complexidade no tratamento de RNFs em projetos de sistemas embarcados através de um catálogo de Requisitos Não-Funcionais para sistemas embarcados(NFR4ES). Este catálogo possui o conhecimento adquirido a partir da literatura e de especialistas do domínio, que foi organizado para a elicitação e especificação de requisitos não-funcionais para sistemas embarcados e pode ser utilizado para reúso. Este catálogo foi avaliado por uma prova de conceito e uma pesquisa com especialistas, no qual foi apontado como útil e adequado para a elicitação e especificação de RNFs em sistemas embarcados.
The Red Legs RATED tool to improve diagnosis of lower limb cellulitis in the emergency department
Authors: O'Brien Gillian , White Patricia 
Published: June 2021

Background: Lower limb cellulitis poses a significant burden for the Irish healthcare system. Accurate diagnosis is difficult, with a lack of validated evidence-based tools and treatment guidelines, and difficulties distinguishing cellulitis from its imitators. It has been suggested that around 30% of suspected lower limb cellulitis is misdiagnosed. An audit of 132 patients between May 2017 and May 2018 identified a pattern of misdiagnosis in approximately 34% of this cohort. Objective: The aim of this pilot project was to develop a streamlined service for those presenting to the emergency department with red legs/suspected cellulitis, through introduction of the ‘Red Leg RATED’ tool for clinicians. Method: The tool was developed and introduced to emergency department clinicians. Individuals (n=24) presenting with suspected cellulitis over 4 weeks in 2018 were invited to participate in data gathering. Finally, clinician questionnaire feedback regarding the tool was evaluated. Results: Fourteen participants consented, 6 female and 8 male with mean age of 65 years. The tool identified 50% (n=7) as having cellulitis, of those 57% (n=4) required admission, 43% (n=3) were discharged. The remainder who did not have cellulitis (n=7) were discharged. Before introduction of the tool, all would typically have been admitted to hospital for further assessment and management of suspected lower limb cellulitis. Overall, 72% (n=10) of patients who initially presented with suspected cellulitis were discharged, suggesting positive impact of the tool. Clinician feedback suggested all were satisfied with the tool and contents. Conclusion: The Red Leg RATED tool is user friendly and impacts positively on diagnosis treatment and discharge. Further evaluation is warranted.