bluuebunny/crossref_metadata_2025 huggingface dataset:
α1,4‐Linked N‐acetylglucosamine suppresses gastric cancer development by inhibiting Mucin‐1‐mediated signaling
Authors: Fujii Chifumi , Harumiya Satoru , Sato Yoshiko , Kawakubo Masatomo , Matoba Hisanori , Nakayama Jun
Published: August 2022

Gastric cancer is the second leading cause of cancer deaths worldwide, and more understanding of its molecular basis is urgently needed. Gastric gland mucin secreted from pyloric gland cells, mucous neck cells, and cardiac gland cells of the gastric mucosa harbors unique O‐glycans carrying terminal α1,4‐linked N‐acetylglucosamine (αGlcNAc) residues. We previously reported that αGlcNAc loss correlated positively with poor outcomes for patients with differentiated‐type gastric cancer. However, the molecular mechanisms underlying these outcomes remained poorly understood. Here, we examined the effects of upregulated αGlcNAc expression on malignant phenotypes of the differentiated‐type gastric cancer cell lines, AGS and MKN7. Upregulation of αGlcNAc following ectopic expression of its biosynthetic enzyme attenuated cell proliferation, motility, and invasiveness of AGS and MKN7 cells in vitro. Moreover, AGS cell tumorigenicity was significantly suppressed by αGlcNAc overexpression in a xenograft model. To define the molecular mechanisms underlying these phenotypes, we investigated αGlcNAc binding proteins in AGS cells and identified Mucin‐1 (MUC1) and podocalyxin. Both proteins were colocalized with αGlcNAc on human gastric cancer cells. We also found that αGlcNAc was bound to MUC1 in murine normal gastric mucosa. When we assessed the effects of αGlcNAc binding to MUC1, we found that αGlcNAc blocked galectin‐3 binding to MUC1, phosphorylation of the MUC1 C‐terminus, and recruitment of Src and β‐catenin to that C‐terminus. These results suggest that αGlcNAc regulates cancer cell phenotypes by dampening MUC1 signal transduction.
Glaucoma drainage implant exposure: A review of aetiology, risks and repair considerations
Authors: Lun Katherine W. , Chew Paul T. K. , Lim Dawn K. A.
Published: August 2022

In recent years, there has been a paradigm shift in glaucoma surgical procedures. Glaucoma drainage implant (GDI) surgeries are being performed much more commonly. Thus, it is important for surgeons to be cognisant of potential complications and their management. Exposure of a GDI is a well‐known complication, and prompt recognition and treatment are required to prevent endophthalmitis, a potentially blinding condition. In this review, we discuss the mechanisms and risk factors for GDI exposure, highlight important considerations for repair, and discuss repair techniques, with the aim of improving patient outcomes and minimising the risk of re‐exposure.
Insect herbivores drive sex allocation in angiosperm flowers
Authors: Fonseca Carlos Roberto , Gossner Martin M. , Kollmann Johannes , Brändle Martin , Paterno Gustavo Brant
Published: August 2022

Why sex has evolved and is maintained is an open question in evolutionary biology. The Red Queen hypothesis predicts that host lineages subjected to more intense parasite pressure should invest more in sexual reproduction to continuously create novel defences against their rapidly evolving natural enemies. In this comparative study across the angiosperms, we show that hermaphrodite plant species associated with higher species richness of insect herbivores evolved flowers with higher biomass allocation towards the male sex, an indication of their greater outcrossing effort. This pattern remained robust after controlling for key vegetative, reproductive and biogeographical traits, suggesting that long‐term herbivory pressure is a key factor driving the selfing–outcrossing gradient of higher plants. Although flower evolution is frequently associated with mutualistic pollinators, our findings support the Red Queen hypothesis and suggest that insect herbivores drive the sexual strategies of flowering plants and their genetic diversity.
An epidemiological overview of the equine influenza epidemic in Great Britain during 2019
Authors: Whitlock Fleur , Grewar John , Newton Richard
Published: August 2022

Background

During 2019, an epidemic of equine influenza (EI) occurred in Europe.

Objectives

To describe the epidemiology of the 2019 EI epidemic within Great Britain (GB).

Study design

Retrospective descriptive study of laboratory confirmed EI cases.

Methods

Epidemiological data were obtained from veterinary surgeons referring samples for EI virus testing. Where available, data on confirmed cases and their wider resident population on EI‐infected premises were collated and described. On a national level, spatial and temporal representations, consisting of choropleth maps and epidemic curves, described the spread of EI. EI‐infected premises‐level factors associated with the first of two epidemic phases were investigated using ordinary logistic regression analysis.

Results

There were 412 confirmed cases and 234 EI‐infected premises, with the first of two epidemic phases occurring between January and April, followed by a second phase through to August. The median age of confirmed cases was 5 years and Sports horses (24%) and Cobs (16%) made up the highest proportions by general horse type and breed. Among confirmed cases 72% were unvaccinated and 18% were vaccinated against EI. New horses arriving within 2 weeks of a confirmed case were reported by 42% of EI‐infected premises. Investigation of EI‐infected premises biosecurity measures indicated that 23% quarantined new arrivals, 37% had isolation facilities and 57% of resident horses were vaccinated. EI‐infected premises were more likely in the first than second epidemic phase to be classified as professional, have a vaccinated confirmed case and EI confirmed in a newly arrived animal.

Main limitations

Data were collected at a single time point for each EI‐infected premises with no follow ups performed.

Conclusions

During 2019, EI‐infected premises generally had low levels of population vaccine coverage and implemented limited preventive biosecurity measures, particularly linked to horse movements. Without substantial improvements in infectious disease prevention and control, the GB equine population remains at risk of future EI epidemics.
Biological activities and safety data of kojic acid and its derivatives: A review
Authors: Zilles Júlia Capp , dos Santos Francielli Lima , Kulkamp‐Guerreiro Irene Clemes , Contri Renata Vidor
Published: August 2022

Kojic acid presents a variety of applications for human use, especially as a depigmenting agent. Its derivatives are also proposed in order to prevent chemical degradation, prevent adverse effects and improve efficacy. The aim of this study was to peer review the current scientific literature concerning the biological activities and safety data of kojic acid or its derivatives, aiming at human use and trying to elucidate the action mechanisms. Three different databases were assessed, and the word “kojic” was crossed with “toxicity,” “adverse effect,” “efficacy,” “effect,” “activity” and “safety.” Articles were selected according to pre‐defined criteria. Besides the depigmenting activity, kojic acid and derivatives can act as antioxidant, antimicrobial, anti‐inflammatory, radioprotector, anticonvulsant and obesity management agents, and present potential as antitumor substances. Depigmenting activity is due to the molecules, after penetrating the cell, binding to tyrosinase active site, regulating melanogenesis factors, leucocytes modulation and free radical scavenging activity. Hence, polarity, size and ligands are also important factors for activity. Kojic acid and derivatives present cytotoxicity to some cancerous cell lines, including melanoma, hepatocellular carcinoma, ovarian cancer, breast cancer and colon cancer. Regarding safety, kojic acid or its derivatives are safe molecules for human use in the concentrations tested. Kojic acid and its derivatives have great potential for cosmetic, pharmaceutical and medical applications.
Focusing on what matters most: Evaluating multiple challenges to stability in recreational fisheries
Authors: Golden Abigail S. , van Poorten Brett , Jensen Olaf P.
Published: August 2022

Recreational fisheries were traditionally theorized to self‐regulate in a sustainable feedback loop in which recreational anglers moderate their fishing effort in response to population declines. However, several mechanisms are hypothesized to break down this self‐regulatory process, including recruitment variability and depensatory population dynamics. Although many of these mechanisms of instability have been estimated in empirical systems and explored using modelling, we still do not know the extent to which these mechanisms can (1) erode stability at their observed strength in real systems and (2) interact to dampen or intensify each other's effects. In this study, we synthesize existing data on four of these mechanisms: (1) depensation in the stock‐recruit relationship, (2) recruitment stochasticity, (3) density‐dependent catchability and (4) the strength of anglers' responsiveness to changing catch rates. We report the range of observed values for these four mechanisms in real‐world fisheries and observe their effect on a simplified recreational fishery model. We find that at moderate fishing effort none of the mechanisms was destabilizing enough on its own to collapse the modelled population, but that an angler population that was likely to keep fishing when catch rates approached zero was a key element of interactions that caused collapse. The strongest interaction was between an angler population with this characteristic and a fish population with hyperstable catch rates. Our results highlight the need for more consistent and widespread estimation of utility‐based angler effort functions as well as the importance of interdisciplinary teams that can gather both social and ecological data.
Resolving the zinc binding capacity of honey bee vitellogenin and locating its putative binding sites
Authors: Leipart Vilde , Enger Øyvind , Turcu Diana Cornelia , Dobrovolska Olena , Drabløs Finn , Halskau Øyvind , Amdam Gro V.
Published: August 2022

The protein vitellogenin (Vg) plays a central role in lipid transportation in most egg‐laying animals. High Vg levels correlate with stress resistance and lifespan potential in honey bees (Apis mellifera). Vg is the primary circulating zinc‐carrying protein in honey bees. Zinc is an essential metal ion in numerous biological processes, including the function and structure of many proteins. Measurements of Zn2+ suggest a variable number of ions per Vg molecule in different animal species, but the molecular implications of zinc‐binding by this protein are not well‐understood. We used inductively coupled plasma mass spectrometry to determine that, on average, each honey bee Vg molecule binds 3 Zn2+‐ions. Our full‐length protein structure and sequence analysis revealed seven potential zinc‐binding sites. These are located in the β‐barrel and α‐helical subdomains of the N‐terminal domain, the lipid binding site, and the cysteine‐rich C‐terminal region of unknown function. Interestingly, two potential zinc‐binding sites in the β‐barrel can support a proposed role for this structure in DNA‐binding. Overall, our findings suggest that honey bee Vg bind zinc at several functional regions, indicating that Zn2+‐ions are important for many of the activities of this protein. In addition to being potentially relevant for other egg‐laying species, these insights provide a platform for studies of metal ions in bee health, which is of global interest due to recent declines in pollinator numbers.
Can fundamental care be advanced using the science of care framework?
Authors: Jeffs Lianne , Merkley Jane , Ronald Kara , Newton Gary , Yang Lily , Gray Carolyn Steele
Published: August 2022

Aims

This manuscript aims to provide a description of an evidence‐informed Science of Care practice‐based research and innovation framework that may serve as a guiding framework to generate new discoveries and knowledge around fundamental care in a more integrated manner.

Background

New ways of thinking about models of care and implementation strategies in transdisciplinary teams are required to accelerate inquiry and embed new knowledge and innovation into practice settings. A new way of thinking starts with an explicit articulation and commitment to the core business of the healthcare industry which is to provide quality fundamental care.

Design

This discursive paper delineates an iteratively derived Science of Care research and innovation framework (Science of Care Framework) that draws from a targeted literature review.

Method

The Science of Care Framework integrates caring science with safety and symptom sciences with implementation, improvement, innovation and team sciences. Each science dimension is described in terms of seminal and evolving evidence and theoretical explanations, focusing on how these disciplines can support fundamental care.

Conclusions

The Science of Care Framework can serve as a catalyst to guide future efforts to propel new knowledge and discoveries around fundamental care and how best to implement it into clinical practice through a transdisciplinary lens.

Impact on nursing science, practice, or disciplinary knowledge

The Science of Care Framework can accelerate nursing discipline‐specific knowledge generation alongside inter and transdisciplinary insights. The novel articulation of the Science of Care Framework can be used to guide further inquiries that are co‐designed, and led, by nurses into integrated models of care and innovations in clinical practice.
Implicit bias reduction that lasts: Putting Situational Attribution Training to the test
Authors: Stewart Tracie L. , Latu Ioana M. , Martin Tim , Walsh Seamus P. , Schmidt Allyson , Kawakami Kerry
Published: August 2022

Addressing the damaging effects of implicit stereotypes—spontaneous, awareness‐independent associations between social groups and particular traits—remains a social imperative. These biases have been linked to negative outcomes in settings ranging from the workplace to medical care facilities. However, many techniques found to reduce implicit biases have been shown to yield short‐lived effects. In the present experiment, we assessed the longevity of reduced implicit racial stereotyping resulting from an intensive training technique that focuses on weakening the fundamental attributional processes underlying implicit stereotyping. Specifically, we aimed to strengthen the likelihood of White participants to consider situational attributions for behaviors performed by Black men that might otherwise have been judged to reflect negative African American stereotypes. White participants were randomly assigned to complete either Situational Attribution Training (SAT), a technique comprised of intensive training (480 trials) to “consider the situation” when making judgments about stereotype‐consistent behaviors performed by Black men, or a control task. Implicit stereotyping was assessed 24h later via the Person Categorization Task and found to be reduced for SAT, versus control, participants even after this delay. Implications for future antibias research and practice are considered.
In‐mouth, self‐disintegrating milk protein puffs‐I: Process development
Authors: Arora Bindvi , Rizvi Syed S. H.
Published: August 2022

This study elucidated the reactive role of the supercritical fluid extrusion (SCFX) process along with calcium chelation by added sodium hexametaphosphate (SHMP) in altering the physicochemical properties of milk protein concentrate (MPC) with added sucrose (MPC‐S) to make expanded extrudates of defined microstructure that self‐disintegrate in the mouth. Calcium chelation by SHMP and temporarily induced acidity (pH 4.75) due to the formation of carbonic acid via SC‐CO2 incorporation during SCFX prevented protein–protein interactions involving calcium bridging and disulfide bonding in MPC‐S extrudates. The electrophoretic patterns demonstrated increased solubility of caseins in MPC‐S‐SHMP extrudates when compared to MPC‐S‐control. MPC‐S‐SHMP extrudates absorbed three times more water than MPC‐S‐control extrudates after 30 s of hydration. Textural analysis demonstrated that the compression strength of MPC‐S‐SHMP extrudates reduced by 93% on hydration as compared to 31% for MPC‐S‐control samples. During hydration, increased water absorption by MPC‐S‐SHMP extrudates resulted in weakened extrudate structure and decreased mechanical strength contributing to self‐disintegration in less than 30 s in the mouth which was confirmed by sensory evaluation.

Practical Applications

The developed and demonstrated process led to the manufacture of nutritious, milk protein‐based convenient and quick in‐mouth disintegrating puffs that can be used as a valuable replacement for starch‐based first finger foods intended for toddlers. They also provide the opportunity to practice baby led weaning along with being rich in protein and essential amino acids. Additionally, the developed product should be suitable for consumption by elderly as well as for patients with other conditions such as dysphagia.
Ameliorating effects of electroacupuncture on the low‐grade intestinal inflammation in rat model of diarrhea‐predominant irritable bowel syndrome
Authors: Li Xuemei , Ren Kuiyu , Hong Xiaojuan , Guo Sha , Yu Shuguang , Yang Sha
Published: August 2022

Background and Aim

We aim to investigate the effects and mechanisms of electroacupuncture (EA) at ST25 and ST37 on the intestinal low‐grade inflammation (LGI) in rat model of Diarrhea‐predominant irritable bowel syndrome (IBS‐D).

Methods

IBS‐D model rats were established by acetic acid enema combined with restraint and tail clamping. Before EA intervention, they were divided into three groups: blank 1 group, blank 2 group, and IBS‐D model group. Diarrhea symptoms and visceral pain sensitivity were evaluated. After constructed the model successfully, the remaining IBS‐D model group rats were randomly divided into model group and EA group. Local intestinal inflammation (HE staining), changes of intestinal mucosa (occludin protein and microvascular diameter) were evaluated. Differences between two groups were compared using t‐test or Mann–Whitney U–test. Differences among more than two groups were compared using one‐way ANOVA or Kruskal–Wallis test.

Results

After modeling, the results of HE staining in intestinal tract of IBS‐D model rats showed LGI. Compared with the model group, 4 h fecal moisture content (diarrhea index) and the AWR score were decreased in the EA group. The results of HE in EA group showed that the infiltration of intestinal inflammatory cells were alleviated. Additionally, EA significantly upregulated the expression of occludin protein and partially dilated the intestinal microvascular diameter. Pearson correlation analysis showed that the symptoms of IBS‐D rats were correlated with the changes of intestinal mucosa.

Conclusion

EA may treat intestinal LGI in IBS‐D rats by upregulating the expression of occludin protein and dilating the intestinal microvascular diameter.
State medicaid coverage of over‐the‐counter moisturizers: A cost‐effective management strategy for atopic dermatitis?
Authors: Scollan Margaret E. , Garzon Maria C. , Lauren Christine T.
Published: August 2022

Regular moisturizing with over‐the‐counter (OTC) treatments is considered a cornerstone of atopic dermatitis (AD) management regardless of disease severity, but OTC moisturizers are not an eligible product under most state Medicaid benefits, including those of New York (NY). Removing the financial barrier to AD management may lessen both the economic burden and emotional toll of the disease for patients and their families with the added benefit of decreasing healthcare costs. Herein, the theoretical annual cost of OTC moisturizer was calculated for a patient with AD in NY to range between $35.13 to $63.35 for infants to $175.66 to $316.75 for adults, and Medicaid reimbursement rates and reported direct and indirect costs of AD were reviewed. We conclude with a discussion of Medicaid coverage criteria for drugs, cost‐effectiveness and preventative medicine, and the role of advocacy for changes in health policy.
Distinct composition and amplification dynamics of transposable elements in sacred lotus (Nelumbo nucifera Gaertn.)
Authors: Cerbin Stefan , Ou Shujun , Li Yang , Sun Yanni , Jiang Ning
Published: August 2022

Sacred lotus (Nelumbo nucifera Gaertn.) is a basal eudicot plant with a unique lifestyle, physiological features, and evolutionary characteristics. Here we report the unique profile of transposable elements (TEs) in the genome, using a manually curated repeat library. TEs account for 59% of the genome, and hAT (Ac/Ds) elements alone represent 8%, more than in any other known plant genome. About 18% of the lotus genome is comprised of Copia LTR retrotransposons, and over 25% of them are associated with non‐canonical termini (non‐TGCA). Such high abundance of non‐canonical LTR retrotransposons has not been reported for any other organism. TEs are very abundant in genic regions, with retrotransposons enriched in introns and DNA transposons primarily in flanking regions of genes. The recent insertion of TEs in introns has led to significant intron size expansion, with a total of 200 Mb in the 28 455 genes. This is accompanied by declining TE activity in intergenic regions, suggesting distinct control efficacy of TE amplification in different genomic compartments. Despite the prevalence of TEs in genic regions, some genes are associated with fewer TEs, such as those involved in fruit ripening and stress responses. Other genes are enriched with TEs, and genes in epigenetic pathways are the most associated with TEs in introns, indicating a dynamic interaction between TEs and the host surveillance machinery. The dramatic differential abundance of TEs with genes involved in different biological processes as well as the variation of target preference of different TEs suggests the composition and activity of TEs influence the path of evolution.
Impactos sociales colaterales de Más Familias en Acción a nivel departamental (2013-2017)
Authors: Barrera Tibaduiza Gerson David
Published: August 2022

En este documento se evidencia que “Más Familias en Acción” tiene impactos sociales colaterales en los departamentos durante el periodo 2013-2017. Lo impactos evidenciados son atribuibles a la nueva metodología de clasificación de hogares pobres (SISBEN III), que fue incorporada desde el año 2013 y se basa en el estándar de calidad de vida e índice de pobreza multidimensional. El rediseño incluyó el uso de tecnologías para el monitoreo de los beneficiarios y la articulación de entidades públicas y privadas para la ejecución del programa. Así, se podrían atribuir impactos colaterales a MFA sobre indicadores socioeconómicos como Población rural, hechos victimizantes, Participación del SGP, entre otros. Indicadores que la literatura evidencia otrora se deterioraron por la presencia del drama de la pobreza y resultaron en una institucionalidad débil que aun obstaculiza el desarrollo de los departamentos y que requiere reformas estructurales para conseguir la erradicación de la pobreza.
Influence of natural vegetation conservation on the distribution of mites in rubber tree crops
Authors: Araújo Fernanda Gomes de , Lima Edgar Luiz de , Costa Edilson , Daud Rodrigo Damasco
Published: August 2022

The remnants of natural vegetation can act as reservoirs of natural enemies that control pest populations in crops, thus, optimizing agricultural production. Here, we assessed whether the conservation of native vegetation in agricultural landscapes affects the abundance and richness of mites in rubber tree plantations. For this purpose, we sampled 17 landscapes that encompassing rubber tree crops either adjacent or close to natural vegetation remnants. To infer the conservation status of vegetation remnants, we used five landscape variables. Then we used Linear Mixed Models (LMM) to test the effect of conservation status metrics on the abundance and richness of mites, density of Calacarus heveae and leaf damage. We collected 1,335 mites with phytophagous being the most abundant guild, followed by predatory and mycophagous mites. We found a negative effect of habitat fragmentation on the abundance of phytophagous mites. Predatory mites abundance in rubber tree crops was positively affected by both habitat heterogeneity and complexity, as well as by the aggregation index. Likewise, the abundance of mycophagous species was also positively correlated with habitat heterogeneity. Phytophagous and predatory species richness, C. heveae density, and symptoms of leaf damage by phytophagous were not affected by the landscape metrics tested herein. These results highlight the importance in keeping natural remnants in agricultural landscapes since native vegetation can serve as refuge and reservoir for predatory mites, which colonize crops, and can contribute to biological pest control.
A new species and a new record of Tanytydeus (Acari: Paratydeidae) from Asian Russia
Authors: Khaustov Alexander A.
Published: August 2022

Postlarval stages of a new species, Tanytydeus sakhalinensis sp. nov., are described from the bark of spruce from Sakhalin Island, Russia. Tanytydeus simplex (Delfinado and Baker) is reported from Russia for the first time. Its postlarval stages were collected from moss from Altai Republic, Russia. The protonymph, deutonymph and tritonymph of T. simplex are described for the first time and the male of this species is redescribed. An updated key to species of the genus Tanytydeus is also provided.
“We React Less. We React Differently. We React Better”: A Case Study of a Mindfulness-Based Intervention for Olympic Referee Performance
Authors: Piffaretti Mattia , Carr Benjamin
Published: August 2022

This case study details the experience and results of the first author’s work as a clinical sport psychologist contracted by the International Volleyball Federation to develop and deliver a mindfulness-based intervention to volleyball and beach volleyball referees leading up to the 2016 Summer Olympic Games. Interviews with the referee commission revealed referees’ high levels of pre- and in-game stress, which can inhibit their cognitive decision-making ability needed to perform at a high level. A five-stage (emotional intelligence, stress management skills, concentration, mental imagery, and motivation) mindfulness-based intervention was developed to address referees’ attentional skills, emotional readiness, and mindful awareness. The five stages were delivered over the 4 months preceding the Games, where the clinician was also available on-site for individual preparation. Referees completed pre- and postintervention quantitative (Five-Facet Mindfulness Questionnaire, Competitive State Anxiety Inventory-2, and Concentration Skills Self-Help Test) and qualitative surveys as well as a post-Olympics evaluation of the practical tools introduced during the mindfulness-based intervention. In-game performances were evaluated by referee delegates prior to and at the Olympics. Analysis of the data showed significant positive changes in the mindfulness factors observing and nonreaction, referees’ concentration skills, and the evaluations of in-game performances. Multiple tools were reported to be highly useful and frequently implemented, including during the Olympics.
Effects of Situated Game Teaching Through Set Plays on Middle School Students’ Soccer Skills and Game Performance
Authors: Dervent Fatih , Li Weidong , Nayır Nazım , Devrilmez Erhan
Published: August 2022

Purpose: To examine the effects of the Situated Game Teaching through Set Plays (SGTSP) curricular model on secondary school students’ soccer skills and game performance during a 10-lesson unit. Methods: A quasi-experimental design with/without a repeated measure was used to examine the effectiveness of the SGTSP model in comparison with a technique-focused approach. A convenient sample of 27 sixth graders from two classes participated in this study. Classes were randomly assigned to conditions. Data were collected from soccer skill tests and game performance coding instrument. Analysis of variance with or without a repeated measure was conducted to analyze the data. Results: Participants’ ball controlling skill significantly improved for both groups over time. Their shooting and dribbling skills did not improve for both groups over time. No statistical differences were found in participants’ changes in ball controlling, shooting, and dribbling skills over time between the two conditions. Participants in the SGTSP condition had better offensive off the ball, offensive with the ball, overall offensive decision making, and overall decision making than those in the comparison condition. Conclusions: The findings provided initial evidence supporting the effectiveness of the SGTSP model on developing students’ decision making in the game plays. Participants taught by SGTSP had similar skill performance as those taught by a technique-focused approach.
Bioinspired large Stokes shift small molecular dyes for biomedical fluorescence imaging
Authors: Chen Hao , Liu Lingjun , Qian Kun , Liu Hailong , Wang Zhiming , Gao Feng , Qu Chunrong , Dai Wenhao , Lin Daizong , Chen Kaixian , Liu Hong , Cheng Zhen
Published: August 2022

Long Stokes shift dyes that minimize cross-talk between the excitation source and fluorescent emission to improve the signal-to-background ratio are highly desired for fluorescence imaging. However, simple small molecular dyes with large Stokes shift (more than 120 nanometers) and near-infrared (NIR) emissions have been rarely reported so far. Here, inspired by the chromophore chemical structure of fluorescent proteins, we designed and synthesized a series of styrene oxazolone dyes (SODs) with simple synthetic methods, which show NIR emissions (>650 nanometers) with long Stokes shift (ranged from 136 to 198 nanometers) and small molecular weight (<450 daltons). The most promising SOD9 shows rapid renal excretion and blood-brain barrier passing properties. After functioning with the mitochondrial-targeted triphenylphosphonium (TPP) group, the resulting SOD9-TPP can be engineered for head-neck tumor imaging, fluorescence image–guided surgery, brain neuroimaging, and on-site pathologic analysis. In summary, our findings add an essential small molecular dye category to the classical dyes.
Case of idiopathic multicentric Castleman’s disease: the master mimicker
Authors: Farrukh Larabe , Lightle Andrea , Peredo-Wende Ruben , Murawski Shannon
Published: August 2022

A woman in her 20s with no medical history presented with progressive abdominal distension, right-sided abdominal discomfort, fatigue and nausea. Examination showed multifocal lymphadenopathy and hepatomegaly with tense ascites. Investigations revealed a multisystem inflammatory condition characterised by elevated acute phase reactants, anaemia, thrombocytopenia, acute kidney injury, lymphocytic ascites, hypoalbuminaemia and hypergammaglobulinaemia. HIV and human herpes virus-8 tests were both negative. In the presence of elevated ANA and SS-A/Ro antibodies, the patient was suspected to be carrying a connective tissue disease, most likely systemic lupus erythematosus (SLE). Clinical and laboratory findings fulfilled the diagnostic criteria for SLE. However, lymph node biopsy showed interfollicular plasmacytosis, associated with high interleukin 6 (IL-6) and vascular endothelial growth factor titers, together hinting towards a rare diagnosis of multicentric Castleman’s disease (MCD). As we investigated further, renal biopsy was consistent with thrombotic microangiopathy which has been previously reported in MCD. Furthermore, immune staining on the renal biopsy was negative for ‘full-house’ immunoglobulin and complement staining pattern, which is specific for lupus nephritis, helping us exclude SLE. In light of these new findings, the patient was started on anti-IL-6 therapy which provided a successful outcome.
Intentions and willingness to engage in risky driving behaviour among high school adolescents: evaluating thebstreetsmart road safety programme
Authors: Sharwood Lisa Nicole , Martiniuk A , Sarrami Foroushani Pooria , Seggie Julie , Wilson Stephanie , Hsu Jeremy , Burns Brian , Logan David Bruce
Published: August 2022

Objective

To investigate the impact of a road safety programme on adolescents’ willingness to engage in risky behaviour as probationary drivers, adjusted for covariates of interest.

Method

Thebstreetsmart is a road safety programme delivered to around 25 000 adolescent students annually in New South Wales. Using a smartphone-based app, student and teacher participation incentives, students were surveyed before and after programme attendance. Mixed-methods linear regression analysed pre/post-modified Behaviour of Young Novice Driver (BYNDS_M) scores.

Results

2360 and 1260 students completed pre-event and post-event surveys, respectively. Post-event BYNDS_M scores were around three points lower than pre-event scores (−2.99, 95% CI −3.418 to −2.466), indicating reduced intention to engage in risky driving behaviours. Covariates associated with higher stated intentions of risky driving were exposure to risky driving as a passenger (1.21, 95% CI 0.622 to 2.011) and identifying as non-binary gender (2.48, 95% CI 1.879 to 4.085), adjusting for other predictors.

Conclusions

Trauma-informed, reality-based injury prevention programmes can be effective in changing short-term stated intentions to engage in risky driving, among a pre-independent driving student population. The adolescent novice driver age group is historically challenging to engage, and injury prevention action must be multipronged to address the many factors influencing their behaviour.
058 Does prolonging duration of monitoring in epilepsy monitoring unit improve diagnostic yield?
Authors: Adenan Mohammad Hijaz , Khalil Mohamed , Loh Kai Sheng , Shukralla Arif , Kilbride Ronan , Mullins Gerrard , Widdess-Walsh Peter , Kinney Michael , Delanty Norman , El-Naggar Hany
Published: August 2022

Long-term video electroencephalographic (vEEG) monitoring is a valuable tool in the evaluation of par- oxysmal clinical events. However, vEEG itself is costly. We aimed to establish whether longer duration of monitoring (DOM) is associated with higher diagnostic yield. We performed a retrospective study of 501 patients admitted to the epilepsy monitoring unit for diagnostic evaluation. Overall, 436 (87%) patients had diagnostic studies. Of these, 67.9% patients received diagnosis within the first 7 days of monitoring with the highest during day 7. A total of 175 had DOM >7 days of which 80.1% were diagnostic. In cohort with DOM >7 days, patients with previous abnormal routine EEG, previous vEEG monitoring, earlier first event recorded and more number of events were more likely to have diagnostic studies. The most common reason for DOM >7 days was to capture more events (76%). Our study supports that longer DOM was associated with an increase in diagnostic yield. More than one third of our cohort were monitored beyond 7 days with majority of these (80.1%) were diagnostic. Our findings may guide clinicians in planning DOM and predicting likelihood of diagnostic studies in patients with prolonged DOM based on clinical char- acteristics and vEEG data.
064 Epilepsy and sociodemographic factors a review
Authors: Mitchell James , Wu Kit , Vidot Micha , Nitkunan Arani , Carr Georgina
Published: August 2022

Background

Evidence suggests there is variation in the diagnosis, management, and support for people with epilepsy (PWE). To improve equity of service, in line with the aspirations of public policy across the UK, it is imperative to understand how sociodemographic factors affect management and care of PWE.

Methods

We conducted a focused review of published literature between 2000-2021 to outline the evidence describing the relationship between the nine protected characteristics of the Equality Act 2010 and the epidemiology, diagnosis, management and outcomes of PWE. Other factors such as depriva- tion, settlement status, education and employment were also explored.

Results

There is an abundance of published literature on the relationship between age, disability, pregnancy and socioeconomic factors and epilepsy epidemiology and management. There is little evidence examining the relationship between epilepsy and gender reassignment, sexual orientation, religion, immigration and settlement status. Further work should also build on the data from the NASH audits, to examine the reasons for the geographical variation in epilepsy care in planned outpatient as well as unplanned emergency care settings.

Discussion

Better understanding of sociodemographic factors and their relationship with epilepsy epide- miology and management is key to improving equity of care. This review has identified gaps in knowledge that require further research.
069 Real-world evidence on the safety and efficacy of adjunctive perampanel across different geographical regions
Authors: Wechsler Robert , Coppola Antonietta , Rohatgi Anshu , Patten Anna , Goldman Samantha , Gentile Anna , Patil Balaji , Dash Amitabh , Ngo Leock Y , Malhotra Manoj
Published: August 2022

Background

We report data from three Phase IV, observational studies (Studies 506 [US;NCT03208660], 508 [India;NCT03836924] and 501 [Italy;NCT04257604]), which assessed real-world safety and efficacy of adjunctive perampanel across different regions.

Methods

Study 506 included patients with any seizure type. Studies 508/501 included patients with focal- onset seizures.Endpoints included: retention rate (Studies 506/501), median percent reduction in seizure frequency/28 days, seizure-freedom rates and safety.

Results

In Study 506, the 12-month retention rate was 58.5% (n=876/1498). At Months 10–12, the median percent reduction in seizure frequency/28 days was 75.0% (n=123) and the seizure-freedom rate was 30.9% (n=38/123). In Study 508, the 6-month median percent reduction in seizure frequency/28 days was 100.0% (n=174) and seizure-freedom rate was 49.4% (n=86/174). In Study 501, the 6-month median percent reduction in seizure frequency/28 days, retention rate and seizure-freedom rate were 55.4% (n=198), 72.6% (n=170/234) and 18.0% (n=36/200), respectively. Treatment-emergent adverse events occurred in 704/1703 (41.3%; Study 506), 36/199 (18.1%; Study 508) and 132/234 (56.4%; Study 501) patients; the most common was dizziness/vertigo.

Conclusions

Perampanel is efficacious and well tolerated during real-world use regardless of geographi- cal region; no unexpected safety signals emerged.

Funding

Eisai Inc., Eisai Pharmaceuticals India Pvt., Ltd., and Eisai s.r.l.
080 IIH Life A prospective longitudinal cohort study of idiopathic intracranial hypertension
Authors: Thaller Mark , Homer Victoria , Wakerley Benjamin , Mollan Susan , Sinclair Alexandra
Published: August 2022

Introduction

There is limited longitudinal data evaluating visual and headache outcomes in Idiopathic intracranial hypertension and large prospective studies are required.

Aims andMethods

To evaluate the disease course for non-surgical IIH patients, determined by their pres- entation to neuro-ophthalmology with active IIH (papilloedema present) versus those in ocular remission. Data source: the prospectively collected IIH Life database (2013-2021). Loess smoothers were used to trend measurements over time.

Results

490 patients had IIH, 98% female and mean body mass index (BMI) 38 kg/m2. Visual outcomes showed little difference in Humphrey visual field mean deviation or acuity over time, despite higher optical coherence tomography (OCT) global peripapillary retinal nerve fibre layer thickness (RNFL) in the active group. For each unit increase in BMI RNFL increased by 1.21 µm. High headache frequency was found to be determined by personal migraine history and daily headache at diagnosis. Use of ICP medications did not affect visual or headache outcomes.

Conclusions

OCT appears to be a better measure for disease activity than visual field and acuity. The headache burden was high in this cohort and required complex headache management. In this cohort we were unable to establish the long-term benefit from use of ICP lowering medications.
082 Obstructive sleep apnoea in idiopathic intracranial hypertension: a sub-study of the IIH-WT randomised controlled trial
Authors: Yiangou Andreas , Mitchell James , Nicholls Matthew , Chong Yu Jeat , Vijay Vivek , ley Benjamin Waker- , Lavery Gareth , Tahrani Abd A , Mollan Susan P , Sinclair Alexandra J
Published: August 2022

Obesity is a risk factor for idiopathic intracranial hypertension (IIH) and obstructive sleep apnoea (OSA). We aimed to determine the prevalence of OSA in IIH and evaluate the diagnostic performance of OSA screening tools in IIH. Additionally, we evaluated the relationship between weight loss, OSA and IIH over 12-months.

A sub-study of a multi-centre, randomised controlled parallel group trial comparing the impact of bariatric surgery vs. community weight management intervention (CWI) on IIH (IIH:WT). OSA was assessed using home-based polygraphy at baseline and 12-months.

Of the 66 women in the IIH:WT trial, 46 were included in this sub-study. OSA prevalence was 47% (n=19). The STOP-BANG had the highest sensitivity (84%) compared to the Epworth Sleepiness Scale (69%) and Berlin (68%) to detect OSA. Bariatric surgery resulted in greater reductions in AHI vs. CWI (-2.8 [-11.9, 0.7], p=0.017). Over 12 months there was a positive association between changes in papilloedema and AHI (r=0.543, p=0.045), despite adjustment for changes in body mass index (R2=0.522, p=0.017).

OSA is common in IIH and the STOP-BANG questionnaire was the most sensitive screening tool. Bariatric surgery improved OSA in patients with IIH. The improvement in AHI was associated with improvement in papilloedema independent of weight loss.
Atypical clinical presentations are common in TIA and minor stroke patients with DWI-MRI confirmed ischaemia
Authors: Gallogly Patrick , Best Jonathan , Werring David , Hassan J , Lee C , Cousins J , Jäger Rolf , Chandratheva Arvind
Published: August 2022

Background and Aims

Current diagnostic criteria for TIA/minor stroke disqualify several atypical clinical presentations, but pre-date DWI-MRI use. We investigated the proportion of DWI-positive patients with atypical presentations, identifying clinical factors predicting DWI positivity.

Methods

We retrospectively reviewed consecutive patients with suspected TIA/minor stroke (NIHSS<5) undergoing MRI at our comprehensive stroke centre from March 2020-February 2021. We identified pre- dictors of DWI positivity using logistic regression.

Results

Of 1615 patients, 442 DWI-positive, 39% had atypical presentations including 20% with progres- sive symptom onset. Atypical symptoms common in DWI-positive patients included headache(17%), unsteadiness(15%), positive sensory symptoms(11%), presyncope(10%), confusion(9%) and vertigo(8%). Symptoms independently associated with DWI-positivity included weakness(OR 1.30, 95% CI 1.01-1.67), dysarthria(OR 2.06, CI 1.56-2.70), and ataxia (OR 3.75, CI 2.27-6.20). Fluctuating symptoms(22%) predicted DWI positivity(OR 1.37, CI 1.00-1.81), but sudden onset(80%) did not (OR 1.05, CI 0.80-1.38). Risk factors associated with DWI positivity included increasing age(OR 1.01/year, CI 1.01-1.02), hypertension (OR 1.70, CI 1.30-2.22), diabetes(OR 1.44, CI 1.07-1.93), and smoking(OR 1.68, CI 1.19-2.39). DWI-positive patients had significantly more risk factors (mean 2.65 vs 1.95 p=<0.001).

Conclusions

Over one-third with DWI-confirmed TIA/minor stroke present atypically. The value of atypical symptoms in excluding ischaemia, particularly in patients with vascular risk factors, appears limited.
098 The prevalence of progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) in Scotland
Authors: Swallow Diane , Counsell Carl
Published: August 2022

Background and Objectives

We estimated the point prevalence of progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) at regional and national levels in Scotland, UK as there are few high- quality prevalence studies of these conditions.

Methods

Nationally, multiple methods of case ascertainment were used including clinician and nurse specialist referral, searches of ICD-10 diagnostic coding in routinely collected electronic health data (Scottish Morbidity Record), and patient self-referral. In one region we also searched GP databases and unselected hospital correspondence. Cases were verified by clinical examination or medical record review. National and regional total and age-sex stratified crude prevalence rates on 31st December 2018 were calculated.

Results

The regional crude point prevalence was 4.28 per 100,000 (95% CI 2.90, 6.31) for PSP, and 2.05 per 100,000 (95% CI 1.17, 3.59) for CBS. The national crude prevalence rates were lower due to the greater reliance on passive case ascertainment. There were no clear sex differences in the prevalence rates and peak prevalence was in the 70-79 age-group.

Discussion

The prevalence rates of PSP and CBS were similar to previous estimates with little change over the past 20 years.
Cavernomas: a randomised effectiveness (CARE) trial: treatment with versus without neurosurgery for symptomatic brain cavernoma
Authors: Harkness Kirsty , Kinsella Elaine , Wade Julia , Kitchen Neil , Salman Rustam Al-Shahi ,   CARE pilot trial collaboration
Published: August 2022

Objectives

We are conducting a feasibility and pilot phase randomised controlled trial (RCT) to address the top uncertainty about cavernomas, does treatment with surgery (neurosurgery or stereotactic radio- surgery) improve outcome, compared to treatment without surgery?

Methods

Feasibility study and pilot phase, parallel group,pragmatic RCT involving ~60 participants. Par- ticipants are randomised 1:1 to treatment with surgery or treatment without surgery. The primary clinical outcome is symptomatic intracranial haemorrhage or new persistent focal neurological deficit. Collabora- tors keep screening logs capturing characteristics of patients screened, eligible,approached, consented and randomised. A Quinte T recruitment intervention is evaluating screening logs and audio recordings of recruitment discussions and interviews with recruiters and patients.

Results

The first site opened in August 2021.14 (47%) of our target of 30 sites are currently active.Six sites are pending activation. The first patient was recruited in September 2021.on 14 January, of 35 patients screened,17 (49%) were approached to assess eligibility, 10 (29%) were eligible, and three (9% of those screened and 5% of the n=60 target ) were randomised.

Conclusions

We are grateful to neurologists for supporting this multidisciplinary collaboration to demons- trate the feasibility of resolving the top uncertainty about brain cavernoma in a definitive main phase trial.