bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delphi study to identify consensus on patient selection for hydrogel rectal spacer use during radiation therapy for prostate cancer in the UK
Authors: Payne Heather Ann , Jain Suneil , Peedell Clive , Edwards Albert , Thomas James Andrew , Das Prantik , Hansson Hedblom Amanda , Woodward Emily , Saunders Rhodri , Bahl Amit 
Published: July 2022

ObjectivesTo identify consensus on patient prioritisation for rectal hydrogel spacer use during radiation therapy for the treatment of prostate cancer in the UK.DesignDelphi study consisting of two rounds of online questionnaires, two virtual advisory board meetings and a final online questionnaire.SettingRadical radiation therapy for localised and locally advanced prostate cancer in the UK.ParticipantsSix leading clinical oncologists and one urologist from across the UK.InterventionsRectal hydrogel spacer.Primary and secondary outcome measuresNone reported.ResultsThe panel reached consensus on the importance of minimising toxicity for treatments with curative intent and that even low-grade toxicity-related adverse events can significantly impact quality of life. There was agreement that despite meeting rectal dose constraints, too many patients experience rectal toxicity and that rectal hydrogel spacers in eligible patients significantly reduces toxicity-related adverse events. However, as a consequence of funding limitations, patients need to be prioritised for spacer use. A higher benefit of spacers can be expected in patients on anticoagulation and in patients with diabetes or inflammatory bowel disease, but consensus could not be reached regarding patient groups expected to benefit less. While radiation therapy regimen is not a main factor determining prioritisation, higher benefit is expected in ultrahypofractionated regimens.ConclusionThere is a strong and general agreement that all patients with prostate cancer undergoing radical radiation therapy have the potential to benefit from hydrogel spacers. Currently, not all patients who could potentially benefit can access hydrogel spacers, and access is unequal. Implementation of the consensus recommendations would likely help prioritise and equalise access to rectal spacers for patients in the UK.
Protocol for a qualitative study to explore acceptability, barriers and facilitators of the implementation of new teleophthalmology technologies between community optometry practices and hospital eye services
Authors: Blandford Ann , Abdi Sarah , Aristidou Angela , Carmichael Josie , Cappellaro Giulia , Hussain Rima , Balaskas Konstantinos 
Published: July 2022

IntroductionNovel teleophthalmology technologies have the potential to reduce unnecessary and inaccurate referrals between community optometry practices and hospital eye services and as a result improve patients’ access to appropriate and timely eye care. However, little is known about the acceptability and facilitators and barriers to the implementations of these technologies in real life.Methods and analysisA theoretically informed, qualitative study will explore patients’ and healthcare professionals’ perspectives on teleophthalmology and Artificial Intelligence Decision Support System models of care. A combination of situated observations in community optometry practices and hospital eye services, semistructured qualitative interviews with patients and healthcare professionals and self-audiorecordings of healthcare professionals will be conducted. Participants will be purposively selected from 4 to 5 hospital eye services and 6–8 affiliated community optometry practices. The aim will be to recruit 30–36 patients and 30 healthcare professionals from hospital eye services and community optometry practices. All interviews will be audiorecorded, with participants’ permission, and transcribed verbatim. Data from interviews, observations and self-audiorecordings will be analysed thematically and will be informed by normalisation process theory and an inductive approach.Ethics and disseminationEthical approval has been received from London-Bromley research ethics committee. Findings will be reported through academic journals and conferences in ophthalmology, health services research, management studies and human-computer interaction.
COVID-19 and children with congenital anomalies: a European survey of parents’ experiences of healthcare services
Authors: Latos-Bieleńska Anna , Marcus Elena , Jamry-Dziurla Anna , Rankin Judith , Barisic Ingeborg , Cavero- Carbonell Clara , Den Hond Elly , Garne Ester , Genard Lucas , João Santos Ana , Lutke L Renée , Matias Dias Carlos , Neergaard Pedersen Christina , Neville Amanda , Niemann Annika , Odak Ljubica , Páramo-Rodríguez Lucía , Pierini Anna , Rissmann Anke , Morris Joan K 
Published: July 2022

ObjectiveTo survey parents and carers of children with a congenital anomaly across Europe about their experiences of healthcare services and support during the COVID-19 pandemic.DesignCross-sectional study.SettingOnline survey in 10 European countries, open from 8 March 2021 to 14 July 2021.Population1070 parents and carers of children aged 0–10 years with a cleft lip, spina bifida, congenital heart defect (CHD) requiring surgery and/or Down syndrome.Main outcome measuresParental views about: the provision of care for their child (cancellation/postponement of appointments, virtual appointments, access to medication), the impact of disruptions to healthcare on their child’s health and well-being, and satisfaction with support from medical sources, organisations and close relationships.ResultsDisruptions to healthcare appointments were significantly higher (p<0.001) in the UK and Poland, with approximately two-thirds of participants reporting ‘cancelled or postponed’ tests (67/101; 256/389) and procedures compared with approximately 20% in Germany (13/74) and Belgium/Netherlands (11/55). A third of participants in the UK and Poland reported ‘cancelled or postponed’ surgeries (22/72; 98/266) compared with only 8% in Germany (5/64). In Poland, 43% (136/314) of parents reported that changes to their child’s ongoing treatment had moderately to severely affected their child’s health, significantly higher than all other countries (p<0.001). Satisfaction ratings for support from general practitioners were lowest in the UK and Poland, and lowest in Poland and Italy for specialist doctors and nurses.ConclusionA large proportion of participants reported disruptions to healthcare during the pandemic, which for some had a significant impact on their child’s health. Regional differences in disruptions raise questions about the competence of certain healthcare systems to meet the needs of this vulnerable group of patients and indicate improvements should be strived for in some regions.
Prevalence of intestinal parasites and associated factors among food handlers in food establishments in the Lideta subcity of Addis Ababa, Ethiopia: an institution-based, cross-sectional study
Authors: Abera Woinishet , Gintamo Binyam , Shitemaw Tewoderos , Mekuria Zelalem Negash , Gizaw Zemichael 
Published: July 2022

ObjectiveThis study was conducted to assess the prevalence of intestinal parasites and the associated factors among food handlers in the Lideta subcity of Addis Ababa, Ethiopia.DesignAn institution-based, cross-sectional study design was used. Stool samples were collected from food handlers and examined using direct wet mount and formalin-ether concentration techniques. Personal and establishment-related information was collected using a pretested questionnaire, with a structured observation. Multivariable binary logistic regression was used to identify factors associated with the prevalence of intestinal parasites on the basis of adjusted OR (AOR) and 95% CI and p values <0.05.SettingFood establishments in the Lideta subcity of Addis Ababa, Ethiopia.Participants411 food handlers participated in the study.Outcome measuresThe primary outcome was the prevalence of intestinal parasites, defined as the presence of one or more intestinal parasitic species in stool samples.ResultsOne or more intestinal parasites were detected in 171 (41.6%; 95% CI 36.6% to 46.4%) stool samples. The most common intestinal parasites were Entamoeba histolytica/dispar (12.7%), Giardia duodenalis (11.2%) and Ascaris lumbricoides (8.3%). The presence of intestinal parasites among food handlers was associated with low monthly income (AOR: 2.83, 95% CI 1.50 to 8.84), untrimmed fingernails (AOR: 4.36, 95% CI 1.98 to 11.90), no food safety training (AOR: 2.51, 95% CI 1.20 to 5.58), low level of education (AOR: 3.13, 95% CI 1.34 to 7.44), poor handwashing practice (AOR: 2.16, 95% CI 1.03 to 4.22) and lack of medical check-up (AOR: 2.31, 95% CI 1.18 to 6.95).ConclusionThe prevalence of intestinal parasites among food handlers in food establishments in the Lideta subcity of Addis Ababa was high. The presence of intestinal parasites was linked to socioeconomic conditions, poor hand hygiene conditions and absence of food safety training. It is crucially important to promote handwashing practices and provide food hygiene and safety training in these settings.
Prevalence and determinants of atrial fibrillation progression in paroxysmal atrial fibrillation
Authors: Nguyen Bao-Oanh , Weberndorfer Vanessa , Crijns Harry JGM , Geelhoed Bastiaan , Ten Cate Hugo , Spronk Henri , Kroon Abraham , De With Ruben , Al-Jazairi Meelad , Maass Alexander H , Blaauw Yuri , Tieleman Robert G , Hemels Martin E W , Luermans Justin , de Groot Joris , Allaart Cornelis P , Elvan Arif , De Melis Mirko , Scheerder Coert , van Zonneveld Anton Jan , Schotten Ulrich , Linz Dominik , Van Gelder Isabelle , Rienstra Michiel 
Published: July 2022

ObjectiveAtrial fibrillation (AF) often progresses from paroxysmal AF (PAF) to more permanent forms. To improve personalised medicine, we aim to develop a new AF progression risk prediction model in patients with PAF.MethodsIn this interim-analysis of the Reappraisal of AF: Interaction Between HyperCoagulability, Electrical Remodelling, and Vascular Destabilisation in the Progression of AF study, patients with PAF undergoing extensive phenotyping at baseline and continuous rhythm monitoring during follow-up of ≥1 year were analysed. AF progression was defined as (1) progression to persistent or permanent AF or (2) progression of PAF with >3% burden increase. Multivariable analysis was done to identify predictors of AF progression.ResultsMean age was 65 (58–71) years, 179 (43%) were female. Follow-up was 2.2 (1.6–2.8) years, 51 of 417 patients (5.5%/year) showed AF progression. Multivariable analysis identified, PR interval, impaired left atrial function, mitral valve regurgitation and waist circumference to be associated with AF progression. Adding blood biomarkers improved the model (C-statistic from 0.709 to 0.830) and showed male sex, lower levels of factor XIIa:C1-esterase inhibitor and tissue factor pathway inhibitor, and higher levels of N-terminal pro-brain natriuretic peptide, proprotein convertase subtilisin/kexin type 9 and peptidoglycan recognition protein 1 were associated with AF progression.ConclusionIn patients with PAF, AF progression occurred in 5.5%/year. Predictors for progression included markers for atrial remodelling, sex, mitral valve regurgitation, waist circumference and biomarkers associated with coagulation, inflammation, cardiomyocyte stretch and atherosclerosis. These prediction models may help to determine risk of AF progression and treatment targets, but validation is needed.Trial registration numberNCT02726698.
Suicidal ideation and suicide attempts among older recipients of public welfare assistance in Japan
Authors: Kino Shiho , Stickley Andrew , Nishioka Daisuke , Ueno Keiko , Saito Masashige , Ojima Toshiyuki , Kondo Naoki 
Published: July 2022

BackgroundThe high suicide rate among older adults is an important public health issue. Financial insecurity has been linked to suicidal behaviour. Despite this, as yet, there has been little research on suicide-related behaviours among older recipients of public welfare. This study will examine if suicidal ideation and suicide attempts are more prevalent in older recipients of public welfare assistance in Japan.MethodsThis cross-sectional study analysed data from 16 135 adults aged ≥65 years who participated in the 2019 wave of the Japan Gerontological Evaluation Study. Information was obtained on receiving public welfare assistance, lifetime suicidal ideation and attempts, and a variety of covariates. Poisson regression analysis with robust variance estimates was used to examine associations.ResultsSuicidal ideation was reported by 4.8% of the participants, while the corresponding figure for attempted suicide was 2.2%. In fully adjusted analyses public welfare recipients had an almost 1.5 times higher prevalence of lifetime suicidal ideation (prevalence ratio, PR 1.47, 95% CI 1.02 to 2.13), and an almost two times higher prevalence of attempted suicide (PR 1.91, 95% CI 1.20 to 3.04) when compared with their counterparts not receiving public welfare assistance.ConclusionOlder recipients of public welfare have a higher prevalence of suicidal behaviour in Japan. An urgent focus is now warranted on this vulnerable population to determine the specific factors underlying this association.
Colocalized targeting of TGF-β and PD-L1 by bintrafusp alfa elicits distinct antitumor responses
Authors: Lan Yan , Yeung Tsz-Lun , Huang Hui , Wegener Ansgar A , Saha Somdutta , Toister-Achituv Mira , Jenkins Molly H , Chiu Li-Ya , Lazorchak Adam , Tarcic Ohad , Wang Hong , Qi Jin , Locke George , Kalimi Doron , Qin Guozhong , Marelli Bo , Yu Huakui , Gross Alec W , Derner Melissa G , Soloviev Maria , Botte Mathieu , Sircar Aroop , Ma Hong , Sood Vanita D , Zhang Dong , Jiang Feng , Lo Kin-Ming 
Published: July 2022

BackgroundBintrafusp alfa (BA) is a bifunctional fusion protein designed for colocalized, simultaneous inhibition of two immunosuppressive pathways, transforming growth factor-β (TGF-β) and programmed death-ligand 1 (PD-L1), within the tumor microenvironment (TME). We hypothesized that targeting PD-L1 to the tumor by BA colocalizes the TGF-β trap (TGF-βRII) to the TME, enabling it to sequester TGF-β in the tumor more effectively than systemic TGF-β blockade, thereby enhancing antitumor activity.MethodsMultiple technologies were used to characterize the TGF-β trap binding avidity. BA versus combinations of anti-PD-L1 and TGF-β trap or the pan-TGF-β antibody fresolimumab were compared in proliferation and two-way mixed lymphocyte reaction assays. Immunophenotyping of tumor-infiltrating lymphocytes (TILs) and RNA sequencing (RNAseq) analysis assessing stromal and immune landscape following BA or the combination therapy were performed in MC38 tumors. TGF-β and PD-L1 co-expression and their associated gene signatures in MC38 tumors and human lung carcinoma tissue were studied with single-cell RNAseq (scRNAseq) and immunostaining. BA-induced internalization, degradation, and depletion of TGF-β were investigated in vitro.ResultsBA and fresolimumab had comparable intrinsic binding to TGF-β1, but there was an ~80× avidity-based increase in binding affinity with BA. BA inhibited cell proliferation in TGF-β-dependent and PD-L1-expressing cells more potently than TGF-β trap or fresolimumab. Compared with the combination of anti-PD-L1 and TGF-β trap or fresolimumab, BA enhanced T cell activation in vitro and increased TILs in MC38 tumors, which correlated with efficacy. BA induced distinct gene expression in the TME compared with the combination therapy, including upregulation of immune-related gene signatures and reduced activities in TGF-β-regulated pathways, such as epithelial-mesenchymal transition, extracellular matrix deposition, and fibrosis. Regulatory T cells, macrophages, immune cells of myeloid lineage, and fibroblasts were key PD-L1/TGF-β1 co-expressing cells in the TME. scRNAseq analysis suggested BA modulation of the macrophage phenotype, which was confirmed by histological assessment. PD-L1/TGF-β1 co-expression was also seen in human tumors. Finally, BA induced TGF-β1 internalization and degradation in the lysosomes.ConclusionBA more effectively blocks TGF-β by targeting TGF-β trap to the tumor via PD-L1 binding. Such colocalized targeting elicits distinct and superior antitumor responses relative to single agent combination therapy.
ELK3 modulates the antitumor efficacy of natural killer cells against triple negative breast cancer by regulating mitochondrial dynamics
Authors: Park Joo Dong , Kim Kwang-Soo , Choi Seung Hee , Jo Gae Hoon , Choi Jin-Ho , Park Si-Won , Ko Eun-Su , Lee Minwook , Lee Dae-Keum , Jang Hye Jung , Hwang Sohyun , Jung Hae-Yun , Park Kyung-Soon 
Published: July 2022

BackgroundTriple negative breast cancer (TNBC) is the most lethal subtype of breast cancer due to its aggressive behavior and frequent development of resistance to chemotherapy. Although natural killer (NK) cell-based immunotherapy is a promising strategy for overcoming barriers to cancer treatment, the therapeutic efficacy of NK cells against TNBC is below expectations. E26 transformation-specific transcription factor ELK3 (ELK3) is highly expressed in TNBCs and functions as a master regulator of the epithelial-mesenchymal transition.MethodsTwo representative human TNBC cell lines, MDA-MB231 and Hs578T, were exposed to ELK3-targeting shRNA or an ELK3-expressing plasmid to modulate ELK3 expression. The downstream target genes of ELK3 were identified using a combined approach comprising gene expression profiling and molecular analysis. The role of ELK3 in determining the immunosensitivity of TNBC to NK cells was investigated in terms of mitochondrial fission–fusion transition and reactive oxygen species concentration both in vitro and in vivo.ResultsELK3-dependent mitochondrial fission–fusion status was linked to the mitochondrial superoxide concentration in TNBCs and was a main determinant of NK cell-mediated immune responses. We identified mitochondrial dynamics proteins of 51 (Mid51), a major mediator of mitochondrial fission, as a direct downstream target of ELK3 in TNBCs. Also, we demonstrated that expression of ELK3 correlated inversely with that of Mid51, and that the ELK3-Mid51 axis is associated directly with the status of mitochondrial dynamics. METABRIC analysis revealed that the ELK3-Mid51 axis has a direct effect on the immune score and survival of patients with TNBC.ConclusionsTaken together, the data suggest that NK cell responses to TNBC are linked directly to ELK3 expression levels, shedding new light on strategies to improve the efficacy of NK cell-based immunotherapy of TNBC.
Teaching poster design to enhance research presentation quality at academic conferences: a guide for educators
Authors: Belilos Eleanor , Kamande Stanley , Morrison Mike , Malmut Laura 
Published: July 2022

Abstract

Poster sessions are one of the most common platforms for presenting research at academic conferences, yet posters are often inefficient at transferring knowledge to their readers due to suboptimal design and content selection. Physician trainees may not receive education on constructing posters as a traditional part of their residency curriculum. The purpose of this work is to propose a curriculum that will provide residents foundational knowledge and skills needed for designing high-quality research posters. The curriculum uses the flipped classroom model, a pedagogical approach that reverses the traditional learning environment by delivering instructional content outside of the classroom and moves activities into the classroom. Preparatory work includes watching an educational video on ‘how to create a better research poster in less time’ and preparing a poster to be presented at an upcoming conference. An 1-hour workshop is conducted during protected resident didactic time. It incorporates a 10-min slide show presentation on poster design and 50 min of active learning. During the active learning component, learners are asked to ‘think–pair–share’ to construct a research poster rubric using the information they just learnt. The learners work as a group to evaluate sample research posters. The class is then broken down into small groups of 2–3 learners to spend time working on their own posters and provide peer feedback. Following the workshop, residents continue to develop their research posters for conference presentation. This curriculum has the potential to enhance the quality of resident research posters presented at academic conferences, advance research education and ultimately improve dissemination of research within academic communities. The lesson plan outlined in this work can be used as a guide for teaching poster design to physician trainees in a number of specialties and may encourage programmes to consider integrating poster design as a formal part of the residency curriculum.

Research questions
Impact of varying degrees of peripheral nerve blockade on experimental pressure and ischemic pain: adductor canal and sciatic nerve blocks in a human model of compartment syndrome pain
Authors: Chen Yun-Yun Kathy , Lirk Philipp , Flowers K Mikayla , Colebaugh Carin A , Wilson Jenna M , Zeballos Jose , Von Keudell Arvind , Barrett Karyn E , Vlassakov Kamen , Schreiber Kristin L 
Published: July 2022

IntroductionEarly diagnosis of acute extremity compartment syndrome is crucial to timely surgical management. Pain is commonly used as an early diagnostic sign for acute extremity compartment syndrome, making regional anesthesia after lower extremity surgery controversial. This randomized study tested whether different concentrations of local anesthetics, or combinations of nerve blocks, would differentially impact the perception of acute extremity compartment syndrome-like pressure and ischemic pain.MethodsHealthy volunteers underwent quantitative sensory testing, including determination of pressure pain thresholds and prolonged pressure/ischemic pain in the leg using a variable cuff inflation system. Subjects were randomized to receive (1) adductor canal block alone (ACB), (2) ACB with low-concentration sciatic nerve block (ACB +LC SNB), or (3) ACB with high-concentration SNB (ACB +HC SNB). For the primary outcome, we assessed block-induced increases in pressure threshold to reach 6/10 pain, and compared the degree of increase between the three groups. The main secondary outcome was a comparison of average pain score during a 5 min hold at the 6/10 pressure pain threshold between the three groups.ResultsAll blocks raised pressure pain threshold and decreased ischemic pain, but to variable extents. Specifically, the amount the block increased pressure pain threshold was significantly different among ACB, ACB+LC SNB, and ACB+HC SNB groups (mean±SD: 24±32 mm Hg, 120±103 mm Hg, 159±93 mm Hg; p=0.002), with post hoc testing revealing ACB as less than the other two groups. Similarly, average pain scores during a prolonged/ischemic cuff hold differed among the groups (4.2±1.4, 1.4±1.7, 0.4±0.7; p<0.001), with post hoc testing revealing ACB as significantly higher.DiscussionThis study suggests the possible utility of titrating regional anesthesia, to provide some analgesia while still allowing acute extremity compartment syndrome detection.Trial registration numberNCT04113954.