bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel insights into potential therapeutic targets and biomarkers using integrated multi-omicsapproaches for dilated and ischemic cardiomyopathies
Authors: Kanapeckaitė Austė , Burokienė Neringa
Published: December 2020

At present heart failure treatment targets symptoms based on the left ventricle dysfunction severity; however, lack of systemic studies and available biological data to uncover heterogeneous underlying mechanisms on the scale of genomic, transcriptional and expressed protein level signifies the need to shift the analytical paradigm toward network centric and data mining approaches. This study, for the first time, aimed to investigate how bulk and single cell RNA-sequencing as well as the proteomics analysis of the human heart tissue can be integrated to uncover heart failure specific networks and potential therapeutic targets or biomarkers. Furthermore, it was demonstrated that transcriptomics data in combination with minded data from public databases can be used to elucidate specific gene expression profiles. This was achieved using machine learning algorithms to predict the likelihood of the therapeutic target or biomarker tractability based on a novel scoring system also introduced in this study. The described methodology could be very useful for the target selection and evaluation during the pre-clinical therapeutics development stage. Finally, the present study shed new light into the complex etiology of the heart failure differentiating between subtle changes in dilated and ischemic cardiomyopathy on the single cell, proteome and whole transcriptome level.

HIGHLIGHTS

First report of an integrated multi-omics analysis for dilated and ischemic cardiomyopathies.

Identification of metabolic and regulatory network differences for the two types of cardiomyopathies.

Introduction of a new scoring system to evaluate genes based on the size of their network and disease association.

Two-step machine learning pipeline to uncover potential therapeutic target clusters.
Striatal dopamine D1 receptors control motivation to respond, but not interval timing, during the timing task
Authors: Kamada Taisuke , Hata Toshimichi
Published: December 2020

Dopamine plays a critical role in behavioral tasks requiring interval timing (time perception in a seconds-to-minutes range). Although some studies demonstrate the role of dopamine receptors as a controller of the speed of the internal clock, other studies demonstrate their role as a controller of motivation. Both D1 dopamine receptors (D1DRs) and D2 dopamine receptors (D2DRs) within the dorsal striatum may play a role in interval timing because the dorsal striatum contains rich D1DRs and D2DRs. However, relative to D2DRs, the precise role of D1DRs within the dorsal striatum in interval timing is unclear. To address this issue, rats were trained on the peak-interval 20-sec procedure, and D1DR antagonist SCH23390 was infused into the bilateral dorsocentral striatum before behavioral sessions. Our results showed that the D1DR blockade drastically reduced the maximum response rate and increased the time to start responses with no effects on the time to terminate responses. These findings suggest that the D1DRs within the dorsal striatum are required for motivation to respond, but not for modulation of the internal clock speed.
Development and assessment of CootVR, a virtual reality computer program for model building
Authors: Todd Hamish , Emsley Paul
Published: December 2020

Biological macromolecules have complex three-dimensional shapes that are experimentally examined using X-ray crystallography and electron cryo-microscopy. Interpreting the data that these methods yield involves building 3D atomic models. With almost every data set, some portion of the time put into creating these models must be spent manually modifying the model in order to make it consistent with the data; this is difficult and time-consuming, in part because the data are `blurry' in three dimensions. This paper describes the design and assessment of CootVR (available at http://hamishtodd1.github.io/cvr), a prototype computer program for performing this task in virtual reality, allowing structural biologists to build molecular models into cryo-EM and crystallographic data using their hands. CootVR was timed against Coot for a very specific model-building task, and was found to give an order-of-magnitude speedup for this task. A from-scratch model build using CootVR was also attempted; from this experience it is concluded that currently CootVR does not give a speedup over Coot overall.
Effect of artificial liver blood purification treatment on the survival of critical ill COVID‐19 patients
Authors: Dai Xiahong , Zhang Yimin , Yu Liang , Jiang Ying‐an , Chen Liang , Chen Ye , Li Ming , Gao Chunming , Shang Jia , Xiang Shulin , Li Yongguo , Li Jianzhou , Zhou Chenliang , Zhou Xiaoyang , Chen Nan , Liu Yuanchun , Liu Jing , Zhang Yuanyuan , Chen Xiaobei , Zhu Danhua , Gao Hainv , Tang Lingling , Zhu Mengfei , Li Lanjuan
Published: December 2020

Our aim was to investigate the effect of artificial liver blood purification treatment on the survival of severe/critical patients with coronavirus disease 2019 (COVID‐19). A total of 101 severe and critical patients with coronavirus SARS‐CoV‐2 infection were enrolled in this open, case‐control, multicenter, prospective study. According to the patients’ and their families’ willingness, they were divided into two groups. One was named the treatment group, in which the patients received artificial liver therapy plus comprehensive treatment (n = 50), while the other was named the control group, in which the patients received only comprehensive treatment (n = 51). Clinical data and laboratory examinations, as well as the 28‐day mortality rate, were collected and analyzed. Baseline data comparisons on average age, sex, pre‐treatment morbidity, initial symptoms, vital signs, pneumonia severity index score, blood routine examination and biochemistry indices etc. showed no difference between the two groups. Cytokine storm was detected, with a significant increase of serum interleukin‐6 (IL‐6) level. The serum IL‐6 level decreased from 119.94 to 20.49 pg/mL in the treatment group and increased from 40.42 to 50.81 pg/mL in the control group (P < .05), indicating that artificial liver therapy significantly decreased serum IL‐6. The median duration of viral nucleic acid persistence was 19 days in the treatment group (ranging from 6 to 67 days) and 17 days in the control group (ranging from 3 to 68 days), no significant difference was observed (P = .36). As of 28‐day follow‐up,17 patients in the treatment group experienced a median weaning time of 24 days, while 11 patients in the control group experienced a median weaning time of 35 days, with no significant difference between the two groups (P = .33). The 28‐day mortality rates were 16% (8/50) in the treatment group and 50.98% (26/51) in the control group, with a significant difference (z = 3.70, P < .001). Cytokine storm is a key factor in the intensification of COVID‐19 pneumonia. The artificial liver therapy blocks the cytokine storm by clearing inflammatory mediators, thus preventing severe cases from progressing to critically ill stages and markedly reducing short‐term mortality.
Intravitreal anti‐vascular endothelial growth factors, panretinal photocoagulation and combined treatment for proliferative diabetic retinopathy: a systematic review and network meta‐analysis
Authors: Fallico Matteo , Maugeri Andrea , Lotery Andrew , Longo Antonio , Bonfiglio Vincenza , Russo Andrea , Avitabile Teresio , Pulvirenti Alfredo , Furino Claudio , Cennamo Gilda , Barchitta Martina , Agodi Antonella , Reibaldi Michele
Published: December 2020

Purpose

To conduct a systematic review with network meta‐analysis (NMA) of randomized clinical trials (RCTs) comparing panretinal photocoagulation (PRP) versus anti‐vascular endothelial growth factor (VEGF) treatment alone or in combination with PRP, for proliferative diabetic retinopathy (PDR).

Methods

PubMed, Medline and Embase databases were searched for RCTs comparing PRP versus intravitreal anti‐VEGF therapy and/or combined PRP and intravitreal anti‐VEGF for PDR. The primary outcome measures were the mean best corrected visual acuity (BCVA) change and the regression of neovascularization. Mean change of central macular thickness (CMT), the subgroup analyses of patients without diabetic macular oedema (DME) and the rate of vitreous haemorrhage and vitrectomy were secondary outcomes. Frequentist NMAs were performed.

Results

Twelve RCTs were included. For the 12‐month mean BCVA change, NMA showed a better visual outcome in both the anti‐VEGF group and combined group compared to PRP [anti‐VEGF vs PRP, mean difference (MD) = 3.42; standard error (SE) = 1.5; combined vs PRP, MD = 3.92; SE = 1.65], with no difference between combined group and anti‐VEGF (MD = −0.50; SE = 1.87). No difference in neovascularization regression was found between PRP and anti‐VEGF alone or in combination with PRP, but there was significant inconsistency (p = 0.016). Subgroup analyses in patients without DME yielded no difference for the 12‐month visual outcome between the three interventions, but with significant inconsistency (p = 0.005).

Conclusion

This NMA showed limited evidence of comparable efficacy in terms of neovascularization regression between PRP and anti‐VEGF therapy alone or in combination with PRP, but better visual outcomes were associated with anti‐VEGF use. Intravitreal anti‐VEGF therapy could be a valid therapeutic option in association with PRP.
Insights into multiple sclerosis‐associated uveitis: a scoping review
Authors: Casselman Pauline , Cassiman Cathérine , Casteels Ingele , Schauwvlieghe Pieter‐Paul
Published: December 2020

Purpose

This paper is a scoping review of research on multiple sclerosis (MS)‐associated uveitis to determine its epidemiology, pathophysiology, clinical features and treatment.

Methods

A comprehensive search of the medical databases MEDLINE (PubMed), EMBASE, Web of Science and Cochrane was carried out on 25 November 2019, to identify papers published between 1980 and 2019 that focus on patients with MS‐associated uveitis.

Results

Based on large cohort studies (n ≥ 1000), the prevalence of uveitis in patients with MS is estimated to be 0.53–1.34% (mean = 0.83%), and MS is diagnosed in 0.52–3.20% (mean = 1.30%) of patients with uveitis. The condition is most frequent among middle‐aged women. Patients usually complain of floaters and/or blurred vision, with bilateral intermediate uveitis (with retinal vasculitis) as the most frequent ophthalmological finding. Both MS and intermediate uveitis are associated with HLA‐DRB1*15:01 and IL‐2RA gene polymorphism rs2104286 A > G, suggesting a common genetic background. T cells, and possibly B cells, play an important role in both autoimmune disorders. Multiple sclerosis (MS)‐related uveitis is classically treated as non‐infectious uveitis, with corticosteroids as the first treatment step. Other treatments include immunosuppressants, cryotherapy, laser photocoagulation and vitrectomy. These treatment options have a limited, if any, effect on the course of MS and can be complicated by side‐effects. As treatment strategies for MS have increased in the last decade, it would be interesting to evaluate the efficacy of these new treatments during the course of uveitis. Moreover, the correlation between retinal periphlebitis and MS could be established more accurately with the recently developed techniques of wide‐field fluorescein angiography in a large cohort of MS patients.

Conclusion

MS‐associated uveitis is a rare, highly discussed pathology about which much is still unknown. Large epidemiological studies and extrapolation of new MS treatments to this condition are warranted.
Climate change adaptation in the Canadian wine industry: Strategies and drivers
Authors: Jobin Poirier Emilie , Plummer Ryan , Pickering Gary
Published: December 2020

The wine industry is and will continue to be impacted by climate change. The adaptation of vineyards and winery practices is therefore paramount to the success of winegrowing operations around the globe. We surveyed winegrowers across Canada to assess their adaptation status, the strategies they currently use or plan to implement to cope with the effects of climate change, and the drivers that influence the adoption of adaptation measures. We found that Canadian winegrowers are most adapted to weather events associated with precipitation and drought and less adapted to other extreme weather events. Our results also show that winegrowers' concern about climate change exerts a small, but significant, positive effect on both climate change adaptation and the willingness to adapt in the future. Moreover, winegrowers with smaller operations are less likely to be adapted to some weather events associated with climate change. This research provides an overview of the state of climate change adaptation by winegrowers in Canada and supports the implementation of context‐specific adaptations in wine regions throughout the country.
“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

This 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.
Jahn–Teller distorted Cu1−xNixCr2O4 (x = 0, 0.5, 1) nanoparticles
Authors: Rubengo Farai , Prinsloo Aletta R. E. , Carleschi Emanuela , Mohanty Pankaj , Doyle Bryan P. , Sheppard Charles J.
Published: December 2020

In this report, x-ray photoelectron spectroscopy data for three types of Cu-doped nickel chromite nanoparticles are presented. CuCr2O4, Cu0.5Ni0.5Cr2O4, and NiCr2O4 were prepared using the citric acid-assisted sol-gel method. All samples were amorphous after the initial gel preparations were dried, but after calcination at temperatures higher than 700 °C, the samples crystallized in a spinel structure. X-ray diffraction patterns for the samples were well fitted with the I41/amd space group. Survey scans were conducted as well as detailed scans of Cu 2p, Ni 2p, Cr 2p, and O 1s levels. The O 1s core level was well-fitted with three components, including lattice oxygen (low binding energy) and two higher binding energy components, which corresponded to surface-absorbed hydroxyl groups originating from water and alcohol used in the synthesis of the particles. The line shape of the Cu 2p core level was compatible with mixed 2+ and 1+/0+ oxidation states for Cu ions in these nanoparticles. The strong intensity of the high binding energy satellite indicated that the majority of the Cu 2p ions were in 2+ oxidation state. Finally, Ni 2p showed a mixed 3+/2+ oxidation state for Ni ions in these nanoparticles.
Method for Measuring Phenotypic Colistin Resistance in Escherichia coli Populations from Chicken Flocks
Authors: Nhung Nguyen Thi , Yen Nguyen Thi Phuong , Thien Nguyen Van Ky , Cuong Nguyen Van , Kiet Bach Tuan , Campbell James , Thwaites Guy , Baker Stephen , Geskus Ronald B. , Carrique-Mas Juan
Published: December 2020

Colistin (polymyxin E) is an antimicrobial with poor solubility in agar-based media, and therefore, broth microdilution is the only available method for determining phenotypic resistance. However, estimating colistin resistance in mixed
Escherichia coli
populations is laborious, since it requires individual colony isolation, identification, and susceptibility testing.
Integrated Transcriptome Sequencing (RNA-seq) and Proteomic Studies Reveal Resource Reallocation towards Energy Metabolism and Defense in
Skeletonema marinoi
in Response to CO
2
Increase
Authors: Zhang Mei , Zhen Yu , Mi Tiezhu , Lin Senjie
Published: December 2020

Rising atmospheric CO
2
concentrations are causing ocean acidification with significant consequences for marine organisms. Chain-forming centric diatoms of
Skeletonema
is one of the most successful groups of eukaryotic primary producers with widespread geographic distribution.
Genomes of the “
Candidatus
Actinomarinales” Order: Highly Streamlined Marine Epipelagic Actinobacteria
Authors: López-Pérez Mario , Haro-Moreno Jose M. , Iranzo Jaime , Rodriguez-Valera Francisco
Published: December 2020

Microbiology is in a new age in which sequence databases are primary sources of information about many microbes. However, in-depth analysis of environmental genomes thus retrieved is essential to substantiate the new knowledge.
Supplemental Material: An integrated structural and GPS study of the Jalpatagua fault, southeastern Guatemala
Authors: Garnier B. , al. et
Published: December 2020

Complete 40Ar/39Ar results.
Supplemental Material: Metamorphic P-T-t evolution of amphibolite in the north Hengshan terrane, North China Craton: Insights into the late Paleoproterozoic tectonic processes from initial collision to final exhumation
Authors: Qian Jiahui , al. et
Published: December 2020

Table S1: Selected microprobe analyses for amphibolite from the north Hengshan terrane; Table S2: Bulk-rock compositions and their normalized mole-proportions of amphibolite from the north Hengshan terrane; Table S3: Zircon U-Pb isotopic data obtained by LA-ICP-MS for amphibolite sample H1718 from the north Hengshan terrane; Table S4: Titanium and ree compositions (ppm) of zircons for amphibolite sample H1718 from the north Hengshan terrane.
Supplemental Material: High-latitude ice and climate control on sediment supply across SW Gondwana during the late Carboniferous and early Permian
Authors: Griffis Neil
Published: December 2020

Concordia plots and isotopic data for each sample, field photographs of outcrops and analytical methods are provided in the data repository.
How do deployed general surgeons acquire relevant skill sets and competencies and mitigate skill fade?
Authors: Cant Matthew Robert , Naumann D N , König T C , Bowley D M
Published: December 2020

There are recognised difficulties internationally with acquisition and retention of skills among deployed military general surgeons. These are compounded by reduced trauma workload in non-deployed roles or during low tempo or limited activity deployments, and the winding-down of combat operations in Iraq and Afghanistan. We summarise the relevant military-run courses, military-civilian collaborations and potential future strategies that have been used to address skill sets and competencies of deployed surgeons. We use examples from the American, British, Danish, French, German and Swedish Armed Forces. There is variation between nations in training, with a combination of didactic lectures, simulation training and trauma placements in civilian settings at home and overseas. Data regarding effectiveness of these techniques are sparse. It is likely that combat surgical skill-set acquisition and maintenance requires a combination of employment at a high-volume trauma centre during a surgeon’s non-deployed role, together with military-specific courses and high-fidelity simulation to fill skill gaps. There are multiple newer modalities of training that require further evaluation if they are to prove effective in the future. We aimed to summarise the current methods used internationally to ensure acquisition and retention of vital skill sets for these surgeons.
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

Objective

Neutralising 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.

Design

We 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.

Results

Viruses 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.

Conclusion

Representative 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

Objective

Microbiota 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.

Design

18F-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.

Results

We 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.

Conclusion

F. 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.
Pathology of IgG4-related sclerosing mastitis
Authors: Erivwo Polycarp , Turashvili Gulisa
Published: December 2020

Immunoglobulin G4-related sclerosing mastitis (IgG4-RM) is a recently recognised member of the IgG4-related disease (IgG4-RD) family, a multisystem fibroinflammatory condition that can affect any organ system. IgG4-RM is rare and predominantly occurs in middle-aged women. It may present with painless palpable mass and/or lymphadenopathy thereby mimicking breast cancer. Although there is an abundance of literature describing the clinicopathological characteristics of IgG4-RD in a variety of organs, data on IgG4-RM are limited due to its rarity. This review describes the manifestation of the disease in the breast based on reported cases, emphasising the clinicopathological features, pathophysiology, differential diagnosis, treatment and prognosis.
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

Background

The 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.

Methods

The 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).

Results

In 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.

Conclusion

Opioid 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

Background

Efforts 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).

Methods

We 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.

Results

We 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.

Conclusions

Indicators 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

Background

Nephronophthisis-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.

Methods

Crosss-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.

Results

Mutations 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).

Conclusions

The 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

Introduction

The 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.

Methods

We 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.

Results

We 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.

Conclusion

Our 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

Background

The 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.

Methods

We 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.

Results

Psychiatrists 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.

Conclusions

If greater diversity in psychiatric leadership is desired, stronger action needs to be taken to promote leadership development opportunities from under-represented groups.
'On the different Species of Phobia’ and ‘On the different Species of Mania’ (1786): from popular furies to mental disorders in America
Authors: Janssen Diederik F
Published: December 2020

Benjamin Rush’s twin 1786 letters on the different species of phobia and mania sit at an extended historical juncture at which an early modern quasi-medical troping of mental disorder in American social commentary sobered up to mental medicine. The letters’ satirical drive hinged on a perennial problem still occupying George Beard almost a century onward: which idiosyncratic trepidation or ill-grounded idea warranted the nomination of national and epochal ill? Rush’s mania letter exemplified an established genre identifying popular and especially political crazes; at the same time, it foreshadowed the early 19th-century rise and mid-century fall of monomania as forensic-nosological stopgap. The phobia text established the term’s dictionary (OED) sense of specific morbid fears, but did so in the form of a mobilisation of nosological jargon for social diagnostics purposes: an ambivalent prelude to Rush’s later formal engagement with unreasonable fears and follies. Both letters draw attention to a pervasive duality in early modern and Enlightenment conceptions of hydrophobia, aerophobia, syphilophobia and lyssophobia, between public-health and mental-hygienic follies.
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

Background

Normative 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).

Methods

Patients 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).

Results

97 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).

Conclusions

This 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

Objectives

Evidence on the association between night work and Parkinson’s disease (PD) is sparse and conflicting, calling for more definitive studies.

Methods

We 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.

Results

We 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.

Conclusions

Overall, 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

Purpose

Free 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 design

Tweets 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).

Results

1379 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.
Does the presence of cranial contrast spread during a sacroiliac joint injection predict short-term outcome?
Authors: Vandervennet Wout , Van Boxem Koen , Peene Laurens , Mesotten Dieter , Buyse Klaas , Devooght Pieter , Mestrum Roel , Puylaert Martine , Vanlantschoot Astrid , Vanneste Thibaut , Van Zundert Jan
Published: December 2020

Background

The innervation of the sacroiliac joint (SIJ) is complex, with a dual innervation originating from the lumbosacral plexus anteriorly as well as the sacral lateral branches posteriorly. Nociceptors are found in intra-articular structures as well as periarticular structures. In patients with SIJ pain, a fluoroscopy-guided SIJ injection is usually performed posteriorly into the bottom one-third of the joint with local anesthetic and corticosteroids, but this does not always reach all intra-articular structures. The correlation between a cranial contrast spread and clinical success is undetermined in patients with SIJ pain.

Methods

In a tertiary referral pain center, electronic medical records of patients who underwent an SIJ injection were retrospectively analyzed. Only patients with at least three positive provocation maneuvers for SIJ pain were selected. Contrast images of the SIJ were classified as with or without cranial spread on fluoroscopy as a marker of intra-articular injection. Clinical success was defined as ≥50% improvement in the patient’s global perceived effect after 3–4 weeks. The primary outcome was defined as the correlation between cranial contrast spread and clinical success after an SIJ injection.

Results

128 patients in total were included. In 68 patients (53.1%) fluoroscopy showed cranial contrast spread. Clinical success was higher in patients with cranial spread of contrast (55 of 68, 81%) versus those without (35 of 60, 58%) (p=0.0067). In a multivariable analysis with age, gender, presence of rheumatoid arthritis, side, and number of positive provocation maneuvers, the cranial spread of contrast remained the only independent factor of clinical success (p=0.006; OR 3.2, 95% CI 1.4 to 7.7).

Conclusion

In patients with SIJ pain, identified by positive pain provocation maneuvers, cranial contrast spread as a marker of intra-articular injection, with subsequent injection of 3 mL of local anesthetic and methylprednisolone 40 mg, was significantly correlated with clinical success up to 4 weeks. Therefore, attempts should be made to reach this final needle position before injecting local anesthetic and corticosteroids. This result needs to be confirmed in a high-quality prospective trial.