bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiovascular Disease in Patients With Primary and Secondary Adrenal Insufficiency and the Role of Comorbidities
Authors: Ngaosuwan Kanchana , Johnston Desmond G , Godsland Ian F , Cox Jeremy , Majeed Azeem , Quint Jennifer K , Oliver Nick , Robinson Stephen 
Published: February 2021

Abstract

Context
Mortality studies have established that cardiovascular disease is the leading cause of death in patients with adrenal insufficiency and the risk is greater than that observed in individually matched controls.

Objective
Here we have performed a detailed analysis of cardiovascular morbidity and mortality, taking account of the role of comorbidities.

Methods
We performed a retrospective cohort study using the Clinical Practice Research Datalink (CPRD), a UK general practitioner database. The participant population comprised 6821 patients with adrenal insufficiency (primary, 2052; secondary, 3948) compared with 67 564 individually matched controls, with and without adjustment for comorbidities (diabetes, hypertension, dyslipidemia, previous cardiovascular disease, and smoking). The main outcome measures were composite cardiovascular events recorded in the CPRD and cardiovascular mortality in participants with linked national mortality data.

Results
Hazard ratios (95% CI) for composite cardiovascular events in patients with adrenal insufficiency of any cause were 1.28 (1.20-1.36, unadjusted) and 1.07 (1.01-1.14, adjusted). Increased cerebrovascular events in patients with secondary adrenal insufficiency accounted for most of the increased hazard (1.53 [1.34-1.74, adjusted]) and were associated with cranial irradiation therapy. Cardiovascular mortality data were available for 3547 patients and 34 944 controls. The adjusted hazard ratio for ischemic heart disease mortality was 1.86 (1.25-2.78) for primary adrenal insufficiency and 1.39 (1.02-1.89) for secondary.

Conclusion
Comorbidities largely accounted for the increased cardiovascular events but in secondary adrenal insufficiency, cerebrovascular events were independently increased and associated with irradiation treatment. However, the risk of cardiovascular mortality remained increased even following adjustment for comorbidities in both primary and secondary adrenal insufficiency.
Ciliopathic micrognathia is caused by aberrant skeletal differentiation and remodeling
Authors: Bonatto Paese Christian Louis , Brooks Evan C. , Aarnio-Peterson Megan , Brugmann Samantha A. 
Published: February 2021

ABSTRACT
Ciliopathies represent a growing class of diseases caused by defects in microtubule-based organelles called primary cilia. Approximately 30% of ciliopathies are characterized by craniofacial phenotypes such as craniosynostosis, cleft lip/palate and micrognathia. Patients with ciliopathic micrognathia experience a particular set of difficulties, including impaired feeding and breathing, and have extremely limited treatment options. To understand the cellular and molecular basis for ciliopathic micrognathia, we used the talpid2 (ta2), a bona fide avian model for the human ciliopathy oral-facial-digital syndrome subtype 14. Histological analyses revealed that the onset of ciliopathic micrognathia in ta2 embryos occurred at the earliest stages of mandibular development. Neural crest-derived skeletal progenitor cells were particularly sensitive to a ciliopathic insult, undergoing unchecked passage through the cell cycle and subsequent increased proliferation. Furthermore, whereas neural crest-derived skeletal differentiation was initiated, osteoblast maturation failed to progress to completion. Additional molecular analyses revealed that an imbalance in the ratio of bone deposition and resorption also contributed to ciliopathic micrognathia in ta2 embryos. Thus, our results suggest that ciliopathic micrognathia is a consequence of multiple aberrant cellular processes necessary for skeletal development, and provide potential avenues for future therapeutic treatments.
Human-specific staphylococcal virulence factors enhance pathogenicity in a humanised zebrafish C5a receptor model
Authors: Buchan Kyle D. , van Gent Michiel , Prajsnar Tomasz K. , Ogryzko Nikolay V. , de Jong Nienke W. M. , Kolata Julia , Foster Simon J. , van Strijp Jos A. G. , Renshaw Stephen A. 
Published: February 2021

ABSTRACTStaphylococcus aureus infects ∼30% of the human population and causes a spectrum of pathologies ranging from mild skin infections to life-threatening invasive diseases. The strict host specificity of its virulence factors has severely limited the accuracy of in vivo models for the development of vaccines and therapeutics. To resolve this, we generated a humanised zebrafish model and determined that neutrophil-specific expression of the human C5a receptor conferred susceptibility to the S. aureus toxins PVL and HlgCB, leading to reduced neutrophil numbers at the site of infection and increased infection-associated mortality. These results show that humanised zebrafish provide a valuable platform to study the contribution of human-specific S. aureus virulence factors to infection in vivo that could facilitate the development of novel therapeutic approaches and essential vaccines.
Human microsporidian pathogen Encephalitozoon intestinalis impinges on enterocyte membrane trafficking and signaling
Authors: Flores Juan , Takvorian Peter M. , Weiss Louis M. , Cali Ann , Gao Nan 
Published: February 2021

ABSTRACT
Microsporidia are a large phylum of obligate intracellular parasites. Approximately a dozen species of microsporidia infect humans, where they are responsible for a variety of diseases and occasionally death, especially in immunocompromised individuals. To better understand the impact of microsporidia on human cells, we infected human colonic Caco2 cells with Encephalitozoon intestinalis, and showed that these enterocyte cultures can be used to recapitulate the life cycle of the parasite, including the spread of infection with infective spores. Using transmission electron microscopy, we describe this lifecycle and demonstrate nuclear, mitochondrial and microvillar alterations by this pathogen. We also analyzed the transcriptome of infected cells to reveal host cell signaling alterations upon infection. These high-resolution imaging and transcriptional profiling analysis shed light on the impact of the microsporidial infection on its primary human target cell type.
This article has an associated First Person interview with the first authors of the paper.
Characterization of the novel mitochondrial genome segregation factor TAP110 in Trypanosoma brucei
Authors: Amodeo Simona , Kalichava Ana , Fradera-Sola Albert , Bertiaux-Lequoy Eloïse , Guichard Paul , Butter Falk , Ochsenreiter Torsten 
Published: February 2021

ABSTRACT
Proper mitochondrial genome inheritance is important for eukaryotic cell survival. Trypanosoma brucei, a protozoan parasite, contains a singular mitochondrial genome, the kinetoplast (k)DNA. The kDNA is anchored to the basal body via the tripartite attachment complex (TAC) to ensure proper segregation. Several components of the TAC have been described; however, the connection of the TAC to the kDNA remains elusive. Here, we characterize the TAC-associated protein TAP110. We find that both depletion and overexpression of TAP110 leads to a delay in the separation of the replicated kDNA networks. Proteome analysis after TAP110 overexpression identified several kDNA-associated proteins that changed in abundance, including a TEX-like protein that dually localizes to the nucleus and the kDNA, potentially linking replication and segregation in the two compartments. The assembly of TAP110 into the TAC region seems to require the TAC but not the kDNA itself; however, once TAP110 has been assembled, it also interacts with the kDNA. Finally, we use ultrastructure expansion microscopy in trypanosomes for the first time, and reveal the precise position of TAP110 between TAC102 and the kDNA, showcasing the potential of this approach.
This article has an associated First Person interview with the first author of the paper.
Identification of additional outer segment targeting signals in zebrafish rod opsin
Authors: Fang Xiaoming , Peden Andrew A. , van Eeden Fredericus J. M. , Malicki Jarema J. 
Published: February 2021

ABSTRACT
In vertebrate photoreceptors, opsins are highly concentrated in a morphologically distinct ciliary compartment known as the outer segment (OS). Opsin is synthesized in the cell body and transported to the OS at a remarkable rate of 100 to 1000 molecules per second. Opsin transport defects contribute to photoreceptor loss and blindness in human ciliopathies. Previous studies revealed that the rhodopsin C-terminal tail, of 44 amino acids, is sufficient to mediate OS targeting in Xenopus photoreceptors. Here, we show that, although the Xenopus C-terminus retains this function in zebrafish, the homologous zebrafish sequence is not sufficient to target opsin to the OS. This functional difference is largely caused by a change of a single amino acid present in Xenopus but not in other vertebrates examined. Furthermore, we find that sequences in the third intracellular cytoplasmic loop (IC3) and adjacent regions of transmembrane helices 6 and 7 are also necessary for opsin transport in zebrafish. Combined with the cytoplasmic tail, these sequences are sufficient to target opsin to the ciliary compartment.
A nuclear export sequence promotes CRM1-dependent targeting of the nucleoporin Nup214 to the nuclear pore complex
Authors: Hamed Mohamed , Caspar Birgit , Port Sarah A. , Kehlenbach Ralph H. 
Published: February 2021

ABSTRACT
Nup214 is a major nucleoporin on the cytoplasmic side of the nuclear pore complex with roles in late steps of nuclear protein and mRNA export. It interacts with the nuclear export receptor CRM1 (also known as XPO1) via characteristic phenylalanine-glycine (FG) repeats in its C-terminal region. Here, we identify a classic nuclear export sequence (NES) in Nup214 that mediates Ran-dependent binding to CRM1. Nup214 versions with mutations in the NES, as well as wild-type Nup214 in the presence of the selective CRM1 inhibitor leptomycin B, accumulate in the nucleus of Nup214-overexpressing cells. Furthermore, physiological binding partners of Nup214, such as Nup62 and Nup88, are recruited to the nucleus together with Nup214. Nuclear export of mutant Nup214 can be rescued by artificial nuclear export sequences at the C-terminal end of Nup214, leading also to a correct localization of Nup88. Our results suggest a function of the Nup214 NES in the biogenesis of the nuclear pore complex and/or in terminal steps of CRM1-dependent protein export.
Dosimetric feasibility of neurovascular bundle-sparing stereotactic body radiotherapy with periprostatic hydrogel spacer for localized prostate cancer to preserve erectile function
Authors: Hwang Mark E , Mayeda Mark , Shaish Hiram , Elliston Carl D , Spina Catherine S , Wenske Sven , Deutsch Israel 
Published: February 2021

Objective:
We aim to test the hypothesis that neurovascular bundle (NVB) displacement by rectal hydrogel spacer combined with NVB delineation as an organ at risk (OAR) is a feasible method for NVB-sparing stereotactic body radiotherapy.

Methods:
Thirty-five men with low- and intermediate-risk prostate cancer who underwent rectal hydrogel spacer placement and pre-, post-spacer prostate MRI studies were treated with prostate SBRT (36.25 Gy in five fractions). A prostate radiologist contoured the NVB on both the pre- and post-spacer T2W MRI sequences that were then registered to the CT simulation scan for NVB-sparing radiation treatment planning. Three SBRT treatment plans were developed for each patient: (1) no NVB sparing, (2) NVB-sparing using pre-spacer MRI, and (3) NVB-sparing using post-spacer MRI. NVB dose constraints include maximum dose 36.25 Gy (100%), V34.4 Gy (95% of dose) &lt;60%, V32Gy &lt;70%, V28Gy &lt;90%.

Results:
Rectal hydrogel spacer placement shifted NVB contours an average of 3.1 ± 3.4 mm away from the prostate, resulting in a 10% decrease in NVB V34.4 Gy in non-NVB-sparing plans (p &lt; 0.01). NVB-sparing treatment planning reduced the NVB V34.4 by 16% without the spacer (p &lt; 0.01) and 25% with spacer (p &lt; 0.001). NVB-sparing did not compromise PTV coverage and OAR endpoints.

Conclusions:
NVB-sparing SBRT with rectal hydrogel spacer significantly reduces the volume of NVB treated with high-dose radiation. Rectal spacer contributes to this effect through a dosimetrically meaningful displacement of the NVB that may significantly reduce RiED. These results suggest that NVB-sparing SBRT warrants further clinical evaluation.

Advances in knowledge:
This is a feasibility study showing that the periprostatic NVBs can be spared high doses of radiation during prostate SBRT using a hydrogel spacer and nerve-sparing treatment planning.
Detection and staging of radio-recurrent prostate cancer using multiparametric MRI
Authors: Kowa Jie-Ying , Soneji Neil , Sohaib S Aslam , Mayer Erik , Hazell Stephen , Butterfield Nicholas , Shur Joshua , ap Dafydd Derfel 
Published: February 2021

Objective:
We determined the sensitivity and specificity of multiparametric magnetic resonance imaging (MP-MRI) in detection of locally recurrent prostate cancer and extra prostatic extension in the post-radical radiotherapy setting. Histopathological reference standard was whole-mount prostatectomy specimens. We also assessed for any added value of the dynamic contrast enhancement (DCE) sequence in detection and staging of local recurrence.

Methods:
This was a single centre retrospective study. Participants were selected from a database of males treated with salvage prostatectomy for locally recurrent prostate cancer following radiotherapy. All underwent pre-operative prostate-specific antigen assay, positron emission tomography CT, MP-MRI and transperineal template prostate mapping biopsy prior to salvage prostatectomy. MP-MRI performance was assessed using both Prostate Imaging-Reporting and Data System v. 2 and a modified scoring system for the post-treatment setting.

Results:
24 patients were enrolled. Using Prostate Imaging-Reporting and Data System v. 2, sensitivity, specificity, positive predictive value and negative predictive value was 64%, 94%, 98% and 36%. MP-MRI under staged recurrent cancer in 63%. A modified scoring system in which DCE was used as a co-dominant sequence resulted in improved diagnostic sensitivity (61%–76%) following subgroup analysis.

Conclusion:
Our results show MP-MRI has moderate sensitivity (64%) and high specificity (94%) in detecting radio-recurrent intraprostatic disease, though disease tends to be under quantified and under staged. Greater emphasis on dynamic contrast images in overall scoring can improve diagnostic sensitivity.

Advances in knowledge:
MP-MRI tends to under quantify and under stage radio-recurrent prostate cancer. DCE has a potentially augmented role in detecting recurrent tumour compared with the de novo setting. This has relevance in the event of any future modified MP-MRI scoring system for the irradiated gland.
Supplementation of rice husk activated charcoal in feed and its effects on growth and histology of the stomach and intestines from giant trevally, Caranx ignobilis
Authors: Firdus Firdus , Samadi Samadi , Muhammadar Abdullah A. , Sarong Muhammad A. , Muchlisin Zainal A. , Sari Widya , Mellisa Siska , Satria Satria , Boihaqi Boihaqi , Batubara Agung Setia 
Published: February 2021

Background:Research on supplementing feed with rice husk activated charcoal was carried out to determine the effect of variations in the concentration of rice husk activated charcoal on the growth and histological features of the giant trevally Caranx ignobilisintestine.Methods:This study used an experimental method with a completely randomized design consisting of six treatments and four replications, including adding activated charcoal to feed at concentrations of 0%, 1%, 1.5%, 2%, 2.5%, and 3% for 42 days. The measured parameters included daily growth rate (DGR), specific growth rate (SGR), absolute growth rate (AGR), feed conversion ratio (FCR), feed efficiency (FE), survival rate (SR), length of foveola gastrica, width of foveola gastrica, length of intestinal villi, and width of intestinal villi. Data were analyzed statistically using one-way analysis of variance and Duncan’s test.Results:The results showed that supplementing fish feed with rice husk activated charcoal at different concentrations significantly affected the values of DGR, AGR, FCR, FE, SR, length of the foveola gastrica, length of the villous intestine, and width of the villous intestine, but did not significantly affect SGR or foveola gastrica width.Conclusion:The 2% rice husk activated charcoal treatment showed the best results for all parameters.
Defining and validating regenerative farm systems using a composite of ranked agricultural practices
Authors: Fenster Tommy L.D. , LaCanne Claire E. , Pecenka Jacob R. , Schmid Ryan B. , Bredeson Michael M. , Busenitz Katya M. , Michels Alex M. , Welch Kelton D. , Lundgren Jonathan G. 
Published: February 2021

Background:Ongoing efforts attempt to define farms as regenerative to aid marketers, policymakers, farmers, etc. The approach needs to balance precision with function, and must be transparent, simple, scalable, transferable, incorruptible, and replicable.Methods:We developed practice-based scoring systems to distinguish regenerative cropland and rangeland, and validate them based on whether these scores scaled with regenerative goals on actual farm operations. Study systems included cornfields of the Upper Midwest, almond orchards of California, and rangeland systems of the Northern Plains. Response variables included soil carbon and organic matter, soil micronutrients, water infiltration rates, soil microbial communities, plant community structure, invertebrate community structure, pest populations, yields, and profit.Results:Regenerative outcomes were strongly correlated with our approach to farm scoring. Soil organic matter, fine particulate organic matter, total soil carbon, total soil nitrogen, phosphorous, calcium and sulfur all increased alongside regenerative matrix scores in one or both of the cropping systems. Water infiltration rates were significantly faster in more regenerative almond orchards. Soil bacterial biomass and Haney soil health test scores were higher as cropland incorporated more regenerative practices. Plant species diversity and biomass increased significantly with the number of regenerative practices employed on almonds and rangelands. Invertebrate species diversity and richness were positively associated with regenerative practices in corn, almonds, and rangelands, whereas pest populations and almond yields were unaffected by the number of regenerative practices. Corn yields were negatively associated with more regenerative practices, while almond yields were unaffected by the number of regenerative practices. Profit was significantly higher on more regenerative corn and almond operations.Conclusions:Our scoring system scaled positively with desired regenerative outcomes, and provides the basis for predicting ecosystem responses with minimal information about the farming operation. Natural clusters in the number of regenerative practices used can be used to distinguish regenerative and conventional operations.
Avaliação do grau de implantação do Programa Academia da Saúde no município de Bezerros, Pernambuco
Authors: Silva Rafaela Niels da , Oliveira Janaína Rodrigues de , Carneiro Renata Cecília Barbosa , Farias Shirlley Jackllanny Martins de , Guarda Flávio Renato Barros da 
Published: February 2021

O objetivo deste artigo foi avaliar o grau de implantação do Programa Academia da Saúde (PAS) na cidade de Bezerros, Pernambuco. Estudo descritivo de corte transversal, o qual se caracteriza como uma avaliação normativa da implantação do PAS em suas dimensões de estrutura e processo de trabalho. O estudo foi dividido em quatro etapas: i) validação de um modelo lógico para o programa; ii) elaboração das matrizes de indicadores e julgamento; iii) validação das matrizes por especialistas, e; iv) verificação do grau de implantação através de entrevistas. Utilizou-se um sistema de escores para descrever o grau de implantação como: 1) Incipiente: 0 > 33,3%; 2) Intermediário: > 33,3 < 66,6%; 3) Avançado: > 66,6%. O grau de implantação do PAS em Bezerros foi considerado intermediário (55,0%), sendo que a dimensão estrutura obteve um escore maior (64,7%) que a de processo de trabalho (48,6%). Critérios como insumos para a realização das atividades no território e para o aumento do nível de atividade física da população obtiveram pontuação máxima na avaliação, porém, outros elementos de estrutura como a existência de protocolos de ação e monitoramento das ações, assim como de processo de trabalho relativos à mobilização da comunidade e desenvolvimento de ações nas linhas de cuidado obtiveram baixo grau de implantação. O grau de implantação verificado denota a necessidade de qualificação profissional e reorientação das intervenções visando o aperfeiçoamento das atividades de promoção da saúde, e a ampliação das possibilidades de atuação sobre os demais objetivos específicos do programa.
The role of social media in clubfoot: Information sharing and social support
Authors: Hanna Gabriel , Batko Brian D. , Potter James , Ippolito Joseph , Edobor-Osula Folorunsho 
Published: February 2021

Purpose Clubfoot is the most common congenital foot deformity in children. Caregivers often seek medical information on the internet. The aim of the study was to characterize how social media is used by caregivers to access medical information. Methods A search was performed on Facebook, Twitter and YouTube platforms. Information was quantitatively assessed. Comments were qualitatively assessed, and the Kruskal-Wallis test was used to study thematic comment distribution. Results In total, 58 Facebook groups and pages, 109 YouTube accounts and ten Twitter accounts related to clubfoot were discovered from 2007 to 2019. Facebook groups and pages had a collective 56 123 members and 80 544 total likes, respectively. YouTube had a collective 3 280 454 views, with 54 969 total comments throughout the accounts. Comment themes most commonly included sharing information and advice (38.7%), appreciation and success stories (12.8%), emotional support (12.7%) and social media as a second opinion (11.9%). Facebook groups contained a significantly higher number of comments related to ‘social media as a second opinion’ compared with Facebook pages (p = 0.001), Twitter (p = 0.016) and YouTube (p < 0.0001) while YouTube contained a significantly lower number of comments related to ‘sharing information’ compared with Facebook groups, pages and Twitter (p < 0.0001). Conclusion Social media continues to be a growing tool for information sharing and the findings of this study highlight the importance placed by caregivers on the advice of their peers. The online presence of caregivers may represent an opportunity for orthopaedic surgeons to communicate with patients and help them make informed decisions. Level of evidence IV
Testing uniform colour spaces using colour differences of a wide colour gamut
Authors: Xu Qiang , Zhao Baiyue , Cui Guihua , Luo Ming Ronnier 
Published: February 2021

An experimental dataset,WCG, was assembled. The set includes 416 pairs of samples that surround 28 colour centres and covers a wide colour gamut. The data were used to test the performance of seven colour-difference models,CIELAB,CIEDE2000,CAM16-UCS,DIN99d, OSAGP, andICTCP,Jzazbz. Colour discrimination ellipses were also fitted to compare the uniformity of the colour spaces. Different versions of the models were derived to improve the fit to the data, including parametric factors,kL, kC, and a power factor. It was found that thekLoptimisedCAM16-UCS, DIN99d, OSAGPmodels significantly outperformed the other colour models. In addition, the magnitude of the colour difference had an impact on visual assessment.