bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Just ask me what it means to live with dementia” – people with mild dementia’s strategies and techniques shared through in‐depth qualitative interviews
Authors: Thoft Diana Schack , Ward Alison 
Published: December 2020

AbstractThis article presents results from interviews with twelve persons with mild dementia about how life had changed since they received their diagnosis, exploring their experiences of dementia and how they manage life by using different strategies and techniques.Knowledge about how people with mild dementia experience life is important to explore through their unique perspective, providing clinical practice with knowledge to improve dementia care.Twelve participants were recruited at a Danish school service for people with mild dementia where they receive cognitive stimulation. Semi‐structured interviews were conducted, video recorded, transcribed and analysed by using Max Van Manen's five lifeworld existentials: spatiality, corporeality, temporality, relationality and materiality. SRQR checklist was used.Five themes were identified, illustrating the dilemmas and challenges the participants experience, as all existentials are compromised in some way: living a social and active life regardless of difficulties; trying to look at the bright side of life with dementia; it takes time to adapt but at the same time, time is being lost; it is possible to learn, but it is challenging; to try to remember but keep forgetting.The article concludes that all existentials are negatively influenced by dementia, setting the lifeworld of the participants under pressure. However, they still try to live their lives regardless of the difficulties. The study shows it is possible for people with mild dementia to describe their lived experience of dementia and what strategies and techniques they use to manage life.The experienced dilemmas and challenges in the lifeworld of people with mild dementia are of great relevance to be aware of and address in clinical practice. To support people with dementia to identify relevant strategies and techniques, as expressed in the study, that can support them managing life with dementia.
Hepatitis C reference viruses highlight potent antibody responses and diverse viral functional interactions with neutralising antibodies
Authors: Bankwitz Dorothea , Bahai Akash , Labuhn Maurice , Doepke Mandy , Ginkel Corinne , Khera Tanvi , Todt Daniel , Ströh Luisa J , Dold Leona , Klein Florian , Klawonn Frank , Krey Thomas , Behrendt Patrick , Cornberg Markus , McHardy Alice C , Pietschmann Thomas 
Published: December 2020

ObjectiveNeutralising antibodies are key effectors of infection-induced and vaccine-induced immunity. Quantification of antibodies’ breadth and potency is critical for understanding the mechanisms of protection and for prioritisation of vaccines. Here, we used a unique collection of human specimens and HCV strains to develop HCV reference viruses for quantification of neutralising antibodies, and to investigate viral functional diversity.DesignWe profiled neutralisation potency of polyclonal immunoglobulins from 104 patients infected with HCV genotype (GT) 1–6 across 13 HCV strains representing five viral GTs. Using metric multidimensional scaling, we plotted HCV neutralisation onto neutralisation maps. We employed K-means clustering to guide virus clustering and selecting representative strains.ResultsViruses differed greatly in neutralisation sensitivity, with J6 (GT2a) being most resistant and SA13 (GT5a) being most sensitive. They mapped to six distinct neutralisation clusters, in part composed of viruses from different GTs. There was no correlation between viral neutralisation and genetic distance, indicating functional neutralisation clustering differs from sequence-based clustering. Calibrating reference viruses representing these clusters against purified antibodies from 496 patients infected by GT1 to GT6 viruses readily identified individuals with extraordinary potent and broadly neutralising antibodies. It revealed comparable antibody cross-neutralisation and diversity between specimens from diverse viral GTs, confirming well-balanced reporting of HCV cross-neutralisation across highly diverse human samples.ConclusionRepresentative isolates from six neutralisation clusters broadly reconstruct the functional HCV neutralisation space. They enable high resolution profiling of HCV neutralisation and they may reflect viral functional and antigenic properties important to consider in HCV vaccine design.
F. nucleatum targets lncRNA ENO1-IT1 to promote glycolysis and oncogenesis in colorectal cancer
Authors: Hong Jie , Guo Fangfang , Lu Shi-Yuan , Shen Chaoqin , Ma Dan , Zhang Xinyu , Xie Yile , Yan Tingting , Yu TaChung , Sun Tiantian , Qian Yun , Zhong Ming , Chen Jinxian , Peng Yanshen , Wang Cheng , Zhou Xiang , Liu Jianjun , Liu Qiang , Ma Xiong , Chen Ying-Xuan , Chen Haoyan , Fang Jing-Yuan 
Published: December 2020

ObjectiveMicrobiota disorder promotes chronic inflammation and carcinogenesis. High glycolysis is associated with poor prognosis in patients with colorectal cancer (CRC). However, the potential correlation between the gut microbiota and glucose metabolism is unknown in CRC.Design18F-FDG (18F-fluorodeoxyglucose) PET (positron emission tomography)/CT image scanning data and microbiota PCR analysis were performed to measure the correlation between metabolic alterations and microbiota disorder in 33 patients with CRC. Multiple colorectal cancer models, metabolic analysis and Seahorse assay were established to assess the role of long non-coding RNA (lncRNA) enolase1-intronic transcript 1 (ENO1-IT1) in Fusobacterium (F.) nucleatum-induced glucose metabolism and colorectal carcinogenesis. RNA immunoprecipitation and chromatin immunoprecipitation sequencing were conducted to identify potential targets of lncRNA ENO1-IT1.ResultsWe have found F. nucleatum abundance correlated with high glucose metabolism in patients with CRC. Furthermore, F. nucleatum supported carcinogenesis via increasing CRC cell glucose metabolism. Mechanistically, F. nucleatum activated lncRNA ENO1-IT1 transcription via upregulating the binding efficiency of transcription factor SP1 to the promoter region of lncRNA ENO1-IT1. Elevated ENO1-IT behaved as a guider modular for KAT7 histone acetyltransferase, specifying the histone modification pattern on its target genes, including ENO1, and consequently altering CRC biological function.ConclusionF. nucleatum and glucose metabolism are mechanistically, biologically and clinically connected to CRC. Targeting ENO1 pathway may be meaningful in treating patients with CRC with elevated F. nucleatum.
Association of socioeconomic deprivation with opioid prescribing in primary care in England: a spatial analysis
Authors: Nowakowska Magdalena , Zghebi Salwa S , Perisi Rosa , Chen Li-Chia , Ashcroft Darren M , Kontopantelis Evangelos 
Published: December 2020

BackgroundThe increasing trends in opioid prescribing and opioid-related deaths in England are concerning. A greater understanding of the association of deprivation with opioid prescribing is needed to guide policy responses and interventions.MethodsThe 2018/2019 English national primary care prescribing data were analysed spatially. Prescribing of opioids in general practice was quantified by defined daily doses (DDD) and attributed to 32 844 lower layer super output areas (LSOAs), the geographical units representing ~1500 people. Linear regression was used to model the effect of socioeconomic deprivation (quintiles) on opioid prescribing while accounting for population demographics and the prevalence of specific health conditions. Adjusted DDD estimates were compared at each deprivation level within higher organisational areas (Clinical Commissioning Groups, CCGs).ResultsIn total, 624 411 164 DDDs of opioids were prescribed. LSOA-level prescribing varied between 1.7 and 121.04 DDD/1000 population/day. Prescribing in the most deprived areas in the North of England was 1.2 times higher than the national average for areas with similar deprivation levels and 3.3 times higher than the most deprived areas in London. Prescribing in the most deprived areas was on average 9.70 DDD/1000 people/day (95% CI 9.41 to 10.00) higher than the least deprived areas. Deprivation-driven disparities varied between individual CCGs. In the most unequal CCG, prescribing in the most deprived areas was twice that in the least deprived areas.ConclusionOpioid prescribing varied substantially across England and deprivation was strongly associated with prescribing. This paper provides evidence for guiding policy interventions and allocation of resources to areas with the highest levels of opioid prescribing.
Does a physical activity supportive environment ameliorate or exacerbate socioeconomic inequities in incident coronary heart disease?
Authors: Gullon Pedro , Bilal Usama , Hirsch Jana A , Rundle Andrew G , Judd Suzanne , Safford Monika M , Lovasi Gina S 
Published: December 2020

BackgroundEfforts to reduce socioeconomic inequities in cardiovascular disease include interventions to change the built environment. We aimed to explore whether socioeconomic inequities in coronary heart disease (CHD) incidence are ameliorated or exacerbated in environments supportive of physical activity (PA).MethodsWe used data from the Reasons for Geographic and Racial Differences in Stroke study, which recruited US residents aged 45 or older between 2003 and 2007. Our analyses included participants at risk for incident CHD (n=20 808), followed until 31 December 2014. We categorised household income and treated it as ordinal: (1) US$75 000+, (2) US$35 000–US$74 000, (3) US$20 000–US$34 000 and (4) <US$20 000. We operationalised PA-supportive environments using characteristics within a 1 km residential buffer: walkable destinations density, PA facility density and proportion green land cover. We used Cox proportional hazards models to estimate the adjusted association of income with incident CHD, and tested effect modification by PA-supportive environment variables.ResultsWe found a 25% (95% CI 1.17% to 1.34%) increased hazard of CHD per 1-category decrease in household income category. Adjusting for PA-supportive environments slightly reduced this association (HR=1.24). The income–CHD association was strongest in areas without walking destinations (HR=1.57), an interaction which reached statistical significance in analyses among men. In contrast, the income–CHD association showed a trend towards being strongest in areas with the highest percentage of green land cover.ConclusionsIndicators of a PA supportive environment show divergent trends to modify socioeconomic inequities in CHD . Built environment interventions should measure the effect on socioeconomic inequities.
Phenotype and genotype spectra of a Chinese cohort with nephronophthisis-related ciliopathy
Authors: Tang Xiaoshan , Liu Cuihua , Liu Xiaorong , Chen Jing , Fan Xiaoyan , Liu Jialu , Ma Duan , Cao Guanghai , Chen Zhi , Xu Daliang , Zhu Ying , Jiang Xiaoyun , Cheng Lizhi , Wu Yubing , Hou Ling , Li Yuhong , Shao Xiaoshan , Zheng Shasha , Zhang Aihua , Zheng Bixia , Jian Shan , Rong Zanhua , Su Qingxiao , Gao Xia , Rao Jia , Shen Qian , Xu Hong ,   Chinese Children Genetic Kidney Disease Database (CCGKDD)
Published: December 2020

BackgroundNephronophthisis-related ciliopathies (NPHP-RC) account for the majority of cases of monogenetically caused end-stage renal disease (ESRD) in children. Exploring the correlation between the phenotype and genotype of NPHP-RC is helpful for early diagnosis and management. We investigated the phenotype and genotype spectra of NPHP-RC in a Chinese multicentre cohort.MethodsCrosss-ectional and longitudinal data of 60 patients from 57 families with pathogenic NPHP-RC gene mutations distributed in 22 regions of China were collected into a unified, anonymous database. The mean observation time of this cohort was 3.5±3.1 years.ResultsMutations in NPHP1 and NPHP3 were the most common genetic defects. Overall, 45% of patients presented with isolated nephronophthisis (NPH), and 55% exhibited the extrarenal phenotype, which frequently involved the liver (41.7%, n=25), central nervous system (26.7%, n=16), eyes (26.7%, n=16) and skeletal system (11.7%, n=7). Accidental detection of elevated serum creatinine and non-specific symptoms caused by chronic kidney disease occurred in 65% of patients. Patients carrying NPHP1 mutations mainly presented with isolated NPH (90%, 18/20) and progressed to ESRD at a mean age of 12.9±0.5 years. The mean age of ESRD onset in the non-NPHP1 group was lower than that in the NPHP1 group (6.2±1.4 years, p<0.001), especially for patients carrying NPHP3 mutations (3.1±1.2 years), showing a heterogeneous phenotype characterised by Bardet-Biedl syndrome (12.5%, n=5), Joubert syndrome (7.5%, n=3), COACH syndrome (2.5%, n=1), Mainzer-Saldino syndrome (2.5%, n=1), short-rib thoracic dysplasia (2.5%, n=1) and unclassified symptoms (32.5%, n=13).ConclusionsThe Chinese Children Genetic Kidney Disease Database registry characterised the spectrum of the phenotype and genotype of NPHP-RC in the Chinese population. NPHP1 and NPHP3 were the most common pathogenic genes. Rapid progression to ESRD and liver involvement were noted in patients with NPHP3 mutations.
Functional analysis of TLK2 variants and their proximal interactomes implicates impaired kinase activity and chromatin maintenance defects in their pathogenesis
Authors: Pavinato Lisa , Villamor-Payà Marina , Sanchiz-Calvo Maria , Andreoli Cristina , Gay Marina , Vilaseca Marta , Arauz-Garofalo Gianluca , Ciolfi Andrea , Bruselles Alessandro , Pippucci Tommaso , Prota Valentina , Carli Diana , Giorgio Elisa , Radio Francesca Clementina , Antona Vincenzo , Giuffrè Mario , Ranguin Kara , Colson Cindy , De Rubeis Silvia , Dimartino Paola , Buxbaum Joseph D , Ferrero Giovanni Battista , Tartaglia Marco , Martinelli Simone , Stracker Travis H , Brusco Alfredo 
Published: December 2020

IntroductionThe Tousled-like kinases 1 and 2 (TLK1 and TLK2) are involved in many fundamental processes, including DNA replication, cell cycle checkpoint recovery and chromatin remodelling. Mutations in TLK2 were recently associated with ‘Mental Retardation Autosomal Dominant 57’ (MRD57, MIM# 618050), a neurodevelopmental disorder characterised by a highly variable phenotype, including mild-to-moderate intellectual disability, behavioural abnormalities, facial dysmorphisms, microcephaly, epilepsy and skeletal anomalies.MethodsWe re-evaluate whole exome sequencing and array-CGH data from a large cohort of patients affected by neurodevelopmental disorders. Using spatial proteomics (BioID) and single-cell gel electrophoresis, we investigated the proximity interaction landscape of TLK2 and analysed the effects of p.(Asp551Gly) and a previously reported missense variant (c.1850C>T; p.(Ser617Leu)) on TLK2 interactions, localisation and activity.ResultsWe identified three new unrelated MRD57 families. Two were sporadic and caused by a missense change (c.1652A>G; p.(Asp551Gly)) or a 39 kb deletion encompassing TLK2, and one was familial with three affected siblings who inherited a nonsense change from an affected mother (c.1423G>T; p.(Glu475Ter)). The clinical phenotypes were consistent with those of previously reported cases. The tested mutations strongly impaired TLK2 kinase activity. Proximal interactions between TLK2 and other factors implicated in neurological disorders, including CHD7, CHD8, BRD4 and NACC1, were identified. Finally, we demonstrated a more relaxed chromatin state in lymphoblastoid cells harbouring the p.(Asp551Gly) variant compared with control cells, conferring susceptibility to DNA damage.ConclusionOur study identified novel TLK2 pathogenic variants, confirming and further expanding the MRD57-related phenotype. The molecular characterisation of missense variants increases our knowledge about TLK2 function and provides new insights into its role in neurodevelopmental disorders.
Psychiatrists on boards: the diversity of psychiatrists working as board directors in Mental Health Trusts in England
Authors: Cornwall Peter L , Osborne Allan 
Published: December 2020

BackgroundThe lack of diversity in healthcare leadership has been reported as a risk factor for the impact of the COVID-19 pandemic on black and ethnic minority healthcare staff. The medical workforce is increasingly diverse but not necessarily in its senior leadership.MethodsWe aimed to describe the characteristics of psychiatrists with board-level responsibility in Mental Health Trusts in England, comparing the current picture to that of 2016, using publicly available sources of data. We examined whether the psychiatric leaders were representative of the consultant workforce.ResultsPsychiatrists in senior leadership positions are unrepresentative of the consultant workforce, with UK and Irish graduates, and forensic psychiatrists being over-represented, and general adult psychiatrists being under-represented. There has been minimal change between 2016 and 2020, despite a 50% turnover in those holding board-level responsibility.ConclusionsIf greater diversity in psychiatric leadership is desired, stronger action needs to be taken to promote leadership development opportunities from under-represented groups.
Angiographic cerebral venous sinus calibers and drainage patterns in patients with normal intracranial pressure and idiopathic intracranial hypertension
Authors: Peterson Keyan A , Kittel Carol , Lee Katriel E , Garner Rebecca , Nechtman Carl Mandel , Brown Patrick , Wolfe Stacey Q , Fargen Kyle M 
Published: December 2020

BackgroundNormative venous sinus diameters are not well established. This study seeks to compare two-dimensional digital subtraction cerebral angiographic (DSA) venous sinus calibers for patients with normal intracranial pressure (ICP) and with idiopathic intracranial hypertension (IIH).MethodsPatients who underwent diagnostic cerebral angiography from 2016 to 2020 were retrospectively identified. Two independent reviewers measured venous sinus calibers from anteroposterior (AP) and lateral carotid injection delayed venous phase in patients from two groups (group 1: patients with normal ICP; group 2: patients with IIH) after receiving training in a standardized measurement protocol, with measurements obtained from the superior sagittal sinus (SSS) through the sigmoid sinuses (SS).Results97 patients from group 1 and 30 patients from group 2 were included. Interrater reliability was greater than 0.75 for all measured sites. Both groups had similar anatomical subtypes with most being right transverse sinus (TS) dominant or codominant. In group 1, men had significantly larger SSS on lateral view (p<0.001) and dominant TS calibers on AP view (p=0.02) compared with women. Both dominant TS measurements and SSS measurements (lateral plane) were significantly smaller among group 2 compared with group 1 (p<0.001 and 0.02, respectively). Patients with IIH had significantly larger dominant SS measurements (p=0.01). Bifid SSS anatomy was present in 9% of patients with mean caudal width 31 mm (range 19–49 mm).ConclusionsThis study is the first to provide two-dimensional DSA dural venous sinus calibers in patients with and without IIH and to compare anatomical drainage types and calibers among groups.
Night work and incidence of Parkinson’s disease in the Danish Nurse Cohort
Authors: Jørgensen Jeanette Therming , Schernhammer Eva , Papantoniou Kyriaki , Hansen Johnni , Westendorp Rudi G J , Stayner Leslie , Simonsen Mette Kildevæld , Andersen Zorana Jovanovic 
Published: December 2020

ObjectivesEvidence on the association between night work and Parkinson’s disease (PD) is sparse and conflicting, calling for more definitive studies.MethodsWe included 20 138 female nurses from the Danish Nurse Cohort without PD who at baseline in 1993 and/or 1999 reported their most common current work schedule (day, evening, night, and rotating (a combination of at least two of these)), including information on lifetime cumulative duration (years) of each shift in a 2009 follow-up survey. We obtained information on PD hospital contacts and PD medication until November 2018 via linkage to the Danish National Patient (inpatient from 1977 and outpatient contacts from 1995 onwards) and Prescription Registers starting in 1995. We defined the incidence of PD as the first-ever hospital contact due to PD, or the first-ever redeemed levodopa prescription, whichever came first. We used Cox regression models to calculate HRs and 95% CIs, adjusting for age, smoking status, coffee consumption and use of hormone replacement therapy.ResultsWe found no significant difference in PD risk among nurses who reported working evening (HR=0.86; 95% CI=0.55 to 1.34), night (HR=1.26; 95% CI=0.79 to 2.02) or rotating shifts (HR=0.83; 95% CI=0.56 to 1.21) at cohort baseline in 1993 or 1999, when compared with permanent day workers. Similarly, persistency of shift work (working the same work schedule for 6+ years) or duration of shift work was not associated with PD risk.ConclusionsOverall, there was little evidence for an association between various shift work schedules including night work and PD in this cohort of middle-aged female nurses.
Sharing is caring: an analysis of #FOAMed Twitter posts during the COVID-19 pandemic
Authors: Rashid Mohammed Ahmed , Yip Sharon Wing Lam , Gill Deborah , Arfeen Zakia 
Published: December 2020

AbstractPurposeFree Open Access Medical Education (FOAMed) is a worldwide social media movement designed to accelerate and democratise the sharing of medical knowledge. This study sought to investigate the content shared through FOAMed during the emerging COVID-19 pandemic.Study designTweets containing the #FOAMed hashtag posted during a 24-hour period in April 2020 were studied. Included tweets were analysed using the Wiig knowledge management cycle framework (building knowledge, holding knowledge, pooling knowledge and using knowledge).Results1379 tweets contained the #FOAMed hashtag, of which 265 met the inclusion criteria and were included in the analysis. Included tweets were posted from 208 distinct users, originated from each world continent and were in five different languages. Three overarching themes were identified: (1) signposting and appraising evidence and guidelines; (2) sharing specialist and technical advice; and (3) personal and social engagement. Among 12 subthemes within these groupings, 11 aligned to one of the four dimensions of the Wiig knowledge management cycle framework, and the other focused on building and managing social networks. Almost 40% of tweets related directly to COVID-19.Conclusion#FOAMed tweets during the COVID-19 pandemic included a broad range of resources, advice and support. Despite the geographical, language and disciplinary variation of contributing users and the lack of organisational structure uniting them, this social media medical community has been able to construct, share and use emerging technical knowledge through a time of extraordinary challenge and uncertainty for the global medical community.