bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple sclerosis: High prevalence of the ‘central vein’ sign in white matter lesions on susceptibility-weighted images
Authors: Sparacia Gianvincenzo , Agnello Francesco , Gambino Angelo , Sciortino Martina , Midiri Massimo 
Published: March 2018

Purpose The aim of this study was to determine the occurrence and distribution of the ‘central vein’ sign in white matter lesions on susceptibility-weighted magnetic resonance images in patients with multiple sclerosis (MS) and cerebral small vessel disease (CSVD). Materials and methods T2-weighted and fluid-attenuated inversion recovery magnetic resonance images of 19 MS patients and 19 patients affected by CSVD were analysed for the presence and localisation of focal hyperintense white matter lesions. Lesions were subdivided into periventricular or non-periventricular (juxtacortical, subcortical, deep white matter and cerebellar) distributed. The number and localisation of lesions presenting with the central vein sign were recorded and compared between MS and CSVD lesions. Results A total of 313 MS patients and 75 CSVD lesions were identified on T2-weighted and fluid-attenuated inversion recovery magnetic resonance images. The central vein sign was found in 128 MS lesions (40.9%), and the majority of them (71/128, 55.5%) had a periventricular distribution. The central vein sign was found in 22 out of 75 (29.3%) CSVD lesions, and periventricular distribution was seen in six out of 22 (27.2%) CSVD lesions. The difference in the proportion of white matter hyperintense lesions that presented with the central vein sign on susceptibility-weighted images in patients with MS and CSVD was statistically different, and a significantly higher number of MS patients presented with lesions with the central vein sign compared to CSVD patients. Conclusion The presence of the central vein sign on susceptibility-weighted images for MS lesions improves the understanding of the periventricular distribution of MS lesions and could contribute as adjunctive diagnostic criteria for MS disease.
Spontaneous intracranial vertebral artery dissection with acute ischemic stroke: High-resolution magnetic resonance imaging findings
Authors: Yun Soo Young , Heo Young Jin , Jeong Hae Woong , Baek Jin Wook , Choo Hye Jung , Seo Jung Hwa , Kim Sung Tae , Lee Ji Young , Jin Sung Chul 
Published: March 2018

Background Acute ischemic stroke (AIS) more frequently develops in patients with intracranial vertebral artery dissection (VAD) than extracranial VAD, and is associated with possible poor clinical outcomes. The aim of this study is to compare high-resolution magnetic resonance imaging (HR-MRI) findings and clinical features of VAD with and without AIS. Methods Twenty-nine lesions from 27 patients (15 male and 12 female patients; age range = 28–73 years) who underwent diffusion MRI and 3T HR-MRI within seven days were included. We classified VAD according to the presence of AIS lesions on diffusion MRI. Clinical features and HR-MRI findings (angiographic patterns, presence of double lumen sign, dissecting flap, posterior inferior cerebellar artery involvement, remodeling index, length of affected vessels, T1-signal intensity, area of intramural hematoma, and grades and patterns of vessel wall enhancement) were evaluated. Results Thirteen VADs with AIS and 16 without AIS were included. There were no significant differences in the clinical parameters (sex, age, risk factors, symptoms). More VADs with AIS presented as a steno-occlusive pattern than VADs without AIS. More VADs without AIS presented with aneurysmal dilation, larger mean remodeling index and longer mean length than VADs with AIS. Presence of intramural hematoma, T1-iso-signal intensity of intramural hematoma and contrast enhancement were significantly more common in VADs with AIS than without AIS. Conclusions Our study showed some differences in HR-MRI comparing intracranial VAD patients with and without AIS. Differing findings may facilitate a better understanding of intracranial VAD and risk assessment of AIS in these patients.
Service evaluation project – Are local recommendations for onward referral to a specialist menopause clinic required to translate guidelines into practice?
Authors: Neill Anne Marie C 
Published: March 2018

Objective Referral audit – are local recommendations required to translate guideline to practice? Study design In total, 50 consecutive, anonymised referral letters reviewed during the initial consultation in a specialist menopause clinic; the reasons for referral along with the patient’s age and the source of referral were analysed. Results Several common reasons for referral were identified. Sexual dysfunction, including loss of libido and dyspareunia, resulted in 11 (22%) referrals. Ten (20%) women were troubled by persistent symptoms or side effects from HRT; 9 (18%) women were referred before hormone replacement therapy was discussed or commenced; 7 (14%) women seeking advice for their menopausal symptoms had a family or personal history of cancer; 5(10%) were migraineurs; 2(4%) women had premature ovarian insufficiency; 2(4%) were denied hormone replacement therapy because of concern about venous thromboembolism risk; and 4 (8%) had miscellaneous medical disorders. Over 25% of referrals were older than 60. Conclusion Menopausal symptoms are predominately dealt with in primary care where advice and support is needed. National Institute for Health Care and Excellence published guidance regarding onward referral to a specialist menopause clinic, which is vague and referral patterns are haphazard. Our audit highlighted areas of clinical uncertainty and formed the basis for providing local pre-referral information and advice. Some of the information provided is quite detailed and aimed at healthcare professionals with a special interest in menopause. Further training is now required to improve the quality of referrals. The diversity and complexity of some referrals illustrates the need both for a menopause specialist and clear pathways for further advice or referral within each region.
Use of Anticoagulants Remains a Significant Threat to Timely Hip Fracture Surgery
Authors: Taranu Razvan , Redclift Chelsea , Williams Patrick , Diament Marina , Tate Anne , Maddox Jamie , Wilson Faye , Eardley Will 
Published: March 2018

Introduction: Hip fracture remains the biggest single source of morbidity and mortality in the elderly trauma population, and any intervention focused on quality improvement and system efficiency is beneficial for both patients and clinicians. Two of the variables contributory to improving care and efficiency are time to theater and length of stay, with the overall goal being to improve care as reflected within the achievement of best practice tariff. One of the biggest barriers to optimizing these variables is preinjury anticoagulation. Method: Building on our previous work with warfarin in this population, we utilized a regional hip fracture collaborative network collecting prospective data through the National Hip Fracture Database with custom fields pertaining to all agents, including novel oral anticoagulants. Results: In all, 1965 hip fracture patients median age 83 years (1639 not anticoagulated) were admitted to the 5 centers over 12 months. Median length of stay was 20.71 days; time to theater 23.09 hours, and the populations (anticoagulated vs control) were evenly matched for injury. Anticoagulated patients were delayed to theater ( P ≤ .001), were inpatients for longer ( P ≤ .001) and gained less best practice tariff ( P ≤ .05). All variables per agent were noted and the impact of each assessed. Conclusions: Despite the widespread use of newer anticoagulants, popular due to unmonitored reversal and administration, patients stay longer in hospital and wait longer for surgery than nonanticoagulated patients of the same age and injury. Contemporary perioperative practices impact negatively on the ability to perform timely surgery on hip fracture patients. We propose a guideline specific to the management of anticoagulation in the hip fracture population to aid the optimum preparation of patients for theater, achievement of timely surgery, and potentially reduce length of stay.
Anthropometric and Radiologic Measurements of Coracoid Dimensions and Clinical Implications in an Indian Population
Authors: Joshi Deepak , Gupta Lalit Mohan , Tanwar Milind , Lal Ajay , Chaudhary Deepak 
Published: March 2018

Background: Recurrent shoulder dislocation and anterior instability are most commonly attributed to pathology of the capsulolabral complex with the presence of bony loss at the humeral and glenoid surfaces. Unassessed bone loss has been a cause of failure of primary soft tissue procedures or recurrence of symptoms, despite adequate address of soft tissue pathology. Purpose: To study the anthropometric and radiologic dimensions of the coracoid in relation to glenoid bone loss, its adequacy in filling glenoid defects in an Indian population, and whether the choice of surgical technique (congruent arc vs classical) and graft positioning alters the surgical results. This study also intended to establish whether computed tomography measurements correlate with actual anthropometric measurements. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A total of 64 participants with 108 healthy shoulders were included in this study. Additionally, 100 skeletally mature bone specimens of the scapula were measured to assess glenoid diameter as well as coracoid width and length in 2 perpendicular planes with a humeral subtraction 3-dimensional en face glenoid view. Results: Specimen and participant measurements proved that the congruent arc technique was able to fill up to 50% more glenoid bone loss than the classical technique in an Indian population (mean ± SD, 13.45 ± 6.97 vs 7.96 ± 4.89 mm, respectively), with computed tomography being the best and most accurate modality to study it. The mean difference in the bone block length restoration of the glenoid bony arc was 5.41 ± 2.08 mm. Radii of curvature were congruent in populations of the Indian subcontinent. Conclusion: The congruent arc technique can be performed in an Indian population but with caution and careful presurgical assessment of bone loss. However, adequate coracoid dimension to accommodate the implant for fixation without failure must be ensured, as anthropometry suggests the existence of a subset of the population in whom the graft may have compromised width for accommodating standard implants for fixation.
Clinical–insurer engagement to improve maternity safety in the UK, Ireland, Sweden and Australia
Authors: Yau Christopher W H , Quick Oliver , Draycott Timothy 
Published: March 2018

Objective To explore different models of clinical–insurer engagement around maternity safety and to understand how state insurers could and should engage with clinical staff to improve outcomes and reduce harm. Design Semi-structured interviews and focus groups were conducted with senior representatives from state insurers. Transcripts were analysed to identify different models of engagement. Themes were also elicited from the transcripts. A further one-day focus group allowed for clarification and elaboration of these themes. Participants Senior representatives from state insurers in England, Scotland, Wales, Republic of Ireland, Sweden and Victoria, Australia. Results A variety of clinical engagement activities were undertaken by the insurers. These included training on claims and risk management, hospital site visits, facilitating multi-professional network meetings and working with clinical experts to develop best practice recommendations. Some insurers engaged with frontline clinical staff through collaborative patient safety programmes. The themes (identity and size, data and research, incentivising improvement and system integration) were important for considering the role of state insurers within health systems and how insurers could engage with clinical teams. Conclusions This study identified different examples of clinical–insurer engagement. Whilst this was encouraging, the relationships between insurers and clinical teams could be developed further. Insurers and clinical staff could still collaborate more closely and work together in improving patient outcomes. Whilst not specifically their domain, insurers do have a role in patient safety. Closer clinical collaboration may strengthen this contribution.
Health, performance and conduct concerns among older doctors: A retrospective cohort study of notifications received by medical regulators in Australia
Authors: Thomas Laura A , Milligan Eleanor , Tibble Holly , Too Lay S , Studdert David M , Spittal Matthew J , Bismark Marie M 
Published: March 2018

Objectives To determine whether ‘older doctors’ (aged over 65) are at higher risk of notifications to the medical regulator than ‘younger doctors’ (aged 36–60 years) regarding their health, performance and/or conduct. Design Retrospective cohort study. Setting National dataset of 12,878 notifications lodged with medical regulators in Australia between 1 January 2011 and 31 December 2014. Participants All registered doctors in Australia aged 36–60 and >65 years during the study period. Main outcome measures Incidence rates of notifications and incidence rate ratios of notifications (older versus younger doctors). Results Older doctors had higher notification rates (90.9 compared with 66.6 per 1000 practitioner years, p < 0.001). Sex-adjusted incidence rate ratios showed that older doctors had a higher risk of notifications relating to physical illness or cognitive decline (incidence rate ratio = 15.54), inadequate record keeping (incidence rate ratio = 1.98), unlawful use or supply of medications (incidence rate ratio = 2.26), substandard certificates/reports (incidence rate ratio = 2.02), inappropriate prescribing (incidence rate ratio = 1.99), disruptive behaviours (incidence rate ratio = 1.37) and substandard treatment (incidence rate ratio = 1.24). Older doctors had lower notification rates relating to mental illness and substance misuse (incidence rate ratio = 0.58) and for performance issues relating to problems with procedures (incidence rate ratio = 0.61). Conclusions Older doctors were at higher risk for notifications relating to physical or cognitive impairment, records and reports, prescribing or supply of medicines, disruptive behaviour and treatment. They were at lower risk for notifications about mental illness or substance misuse. Incorporating knowledge of these patterns into regulatory practices, workplace adjustments and continuing education/assessment could enhance patient care.
Artificial Intelligence Approach for Variant Reporting
Authors: Zomnir Michael G. , Lipkin Lev , Pacula Maciej , Dominguez Meneses Enrique , MacLeay Allison , Duraisamy Sekhar , Nadhamuni Nishchal , Al Turki Saeed H. , Zheng Zongli , Rivera Miguel , Nardi Valentina , Dias-Santagata Dora , Iafrate A. John , Le Long P. , Lennerz Jochen K. 
Published: March 2018

Purpose Next-generation sequencing technologies are actively applied in clinical oncology. Bioinformatics pipeline analysis is an integral part of this process; however, humans cannot yet realize the full potential of the highly complex pipeline output. As a result, the decision to include a variant in the final report during routine clinical sign-out remains challenging. Methods We used an artificial intelligence approach to capture the collective clinical sign-out experience of six board-certified molecular pathologists to build and validate a decision support tool for variant reporting. We extracted all reviewed and reported variants from our clinical database and tested several machine learning models. We used 10-fold cross-validation for our variant call prediction model, which derives a contiguous prediction score from 0 to 1 (no to yes) for clinical reporting. Results For each of the 19,594 initial training variants, our pipeline generates approximately 500 features, which results in a matrix of > 9 million data points. From a comparison of naive Bayes, decision trees, random forests, and logistic regression models, we selected models that allow human interpretability of the prediction score. The logistic regression model demonstrated 1% false negativity and 2% false positivity. The final models’ Youden indices were 0.87 and 0.77 for screening and confirmatory cutoffs, respectively. Retraining on a new assay and performance assessment in 16,123 independent variants validated our approach (Youden index, 0.93). We also derived individual pathologist-centric models (virtual consensus conference function), and a visual drill-down functionality allows assessment of how underlying features contributed to a particular score or decision branch for clinical implementation. Conclusion Our decision support tool for variant reporting is a practically relevant artificial intelligence approach to harness the next-generation sequencing bioinformatics pipeline output when the complexity of data interpretation exceeds human capabilities.
Deubiquitylases USP5 and USP13 are recruited to and regulate heat-induced stress granules through their deubiquitylating activities
Authors: Xie Xuan , Matsumoto Shunsuke , Endo Akinori , Fukushima Toshiaki , Kawahara Hiroyuki , Saeki Yasushi , Komada Masayuki 
Published: March 2018

ABSTRACT
Stress granules are transient cytoplasmic foci induced by various stresses that contain translation-stalled mRNAs and RNA-binding proteins. They are proposed to modulate mRNA translation and stress responses. Here, we show that the deubiquitylases USP5 and USP13 are recruited to heat-induced stress granules. Heat-induced stress granules also contained K48- and K63-linked ubiquitin chains. Depletion of USP5 or USP13 resulted in elevated ubiquitin chain levels and accelerated assembly of heat-induced stress granules, suggesting that these enzymes regulate the stability of the stress granules through their ubiquitin isopeptidase activity. Moreover, disassembly of heat-induced stress granules after returning the cells to normal temperatures was markedly repressed by individual depletion of USP5 or USP13. Finally, overexpression of a ubiquitin mutant lacking the C-terminal diglycine motif caused the accumulation of unanchored ubiquitin chains and the repression of the disassembly of heat-induced stress granules. As unanchored ubiquitin chains are preferred substrates for USP5, we suggest that USP5 regulates the assembly and disassembly of heat-induced stress granules by mediating the hydrolysis of unanchored ubiquitin chains while USP13 regulates stress granules through deubiquitylating protein-conjugated ubiquitin chains.
This article has an associated First Person interview with the first author of the paper.
Genetic dissection of the phosphoinositide cycle in Drosophila photoreceptors
Authors: Liu Che-Hsiung , Bollepalli Murali K. , Long Samuel V. , Asteriti Sabrina , Tan Julie , Brill Julie A. , Hardie Roger C. 
Published: March 2018

ABSTRACT
Phototransduction in Drosophila is mediated by phospholipase C-dependent hydrolysis of PIP2­, and is an important model for phosphoinositide signalling. Although generally assumed to operate by generic machinery conserved from yeast to mammals, some key elements of the phosphoinositide cycle have yet to be identified in Drosophila photoreceptors. Here, we used transgenic flies expressing fluorescently tagged probes (P4M and TbR332H), which allow in vivo quantitative measurements of PI4P and PIP2 dynamics in photoreceptors of intact living flies. Using mutants and RNA interference for candidate genes potentially involved in phosphoinositide turnover, we identified Drosophila PI4KIIIα (CG10260) as the PI4-kinase responsible for PI4P synthesis in the photoreceptor membrane. Our results also indicate that PI4KIIIα activity requires rbo (the Drosophila orthologue of Efr3) and CG8325 (orthologue of YPP1), both of which are implicated as scaffolding proteins necessary for PI4KIIIα activity in yeast and mammals. However, our evidence indicates that the recently reported central role of dPIP5K59B (CG3682) in PIP2 synthesis in the rhabdomeres should be re-evaluated; although PIP2 resynthesis was suppressed by RNAi directed against dPIP5K59B, little or no defect was detected in a reportedly null mutant (dPIP5K18).
Factors targeting MED12 to drive tumorigenesis?
Authors: Bullerdiek Jörn , Rommel Birgit 
Published: March 2018

Mediator Subcomplex 12 (MED12) is part of the transcriptional preinitiation machinery. Mutations of its gene predominantly occur in two types of highly frequent benign tumors, uterine leiomyomas and fibroadenomas of the breast, where they apparently act as driver mutations. Nevertheless, their presence is not restricted to benign tumors having been found at considerable frequencies in uterine leiomyosarcomas, malignant phyllodes tumors, and chronic lymphocytic leukemia also. Most of the mutations are located within exon 2 of the gene but in rare cases the intron 1/exon 2 boundary or exon 1 are affected. As to their type, predominantly single nucleotide exchanges with a hotspot in one codon are found, but small deletions clustering around that hotspot also are not uncommon. According to their presumed classification as gain-of-function mutations, these latter deletions are leaving the open reading frame intact. As to the types of mutations, so far no apparent differences between the tumor entities affected have emerged. Interestingly, this pattern with small deletions clustered around the hotspot of single nucleotide exchanges resembles that seen as a result of targeted gene editing. In contrast to other driver mutations the percentage of MED12-mutation positive tumors of independent clonal origin increases with the number of tumors per patient suggesting unknown etiological factors supporting site specific mutagenesis. These factors may act by inducing simultaneous site-specific double strand breaks the erroneous repair of which may lead to corresponding mutations. As inducers of DNA damage and its repair such as foreign nucleic acids of the microbiome displaying sequence homology to the putative target site might play a role. Interestingly, a 16 base pair homology of the hotspot to a putative terminator base-paired hairpin sequence of a Staphylococcus aureus tRNA gene cluster has been noted which might form R-loop like structures with its target sequence thus inducing said changes.
W poszukiwaniu źródeł międzynarodowej atrakcyjności Szwecji
Authors: Kobierecka Anna , Kobierecki Michał 
Published: March 2018

In Search of the Source of International Attractiveness of Sweden. A Cultural Dimension
The aim of the article is to investigate the selected ways by which Sweden shapes its international attractiveness using culture. The research is empirical and is directed at verification of hypotheses stating that culture should be regarded as animportant factor of shaping Sweden’s brand and that the chain of IKEA stores is an extraordinary channel of enhancing Sweden’s national brand with the use of culture. The others that are worth mentioning are the Swedish Institute and thewebsite sweden.se.