bluuebunny/crossref_metadata_2025_split huggingface dataset:
Copy number of the X‐linked genes TLR7 and CD40L influences innate and adaptive immune responses
Authors: Sarmiento Luis , Svensson Johan , Barchetta Ilaria , Giwercman Aleksander , Cilio Corrado M. 
Published: May 2019

AbstractThe number of the X chromosome–linked genes has been previously suggested to influence immune responses and the development of autoimmune diseases. In the present study, we aimed at evaluating the level of expression of CD40L (an X‐linked gene involved in adaptive immunity) and TLR7 (an X‐linked gene involved in innate immunity) in a variety of different karyotypes. Those included males, females and patients with X chromosome aneuploidy. Healthy females (46, XX; n = 10) and healthy males (46, XY; n = 10) were compared to females with Turner syndrome (TS) (45, X; n = 11) and males with Klinefelter syndrome (KS) (47, XXY; n = 5). Stimulation of peripheral blood mononuclear cells (PBMCs) with PMA and ionomycin resulted in higher percentage of CD3 + CD40L+ T cells (P < 0.001) and higher level expression of CD40L in T cell (P < 0.001) in female and KS patients compared with male and TS patients. TLR7‐mediated IFN‐alpha production by HLADR + CD3− CD19− cells was significantly upregulated in healthy women compared with healthy males, TS and KS patients (P < 0.001). TLR7 agonist‐stimulated PBMCs from healthy females and KS patients expressed significantly higher levels of TLR7 mRNA than those from male and TS patients (P < 0.05). The increased expression of the X‐linked genes TLR7 and CD40L in healthy females and KS patients suggests that the presence of two X chromosomes plays a major role in enhancing both innate and adaptive immune responses. These results may contribute to the explanation of sex‐based differences in immune biology and the sex bias in predisposition to autoimmune diseases.
Quality wars in the North
Authors: Choi Yoonho , Choi Eun Kwan 
Published: May 2019

AbstractThis paper investigates two stylised facts about quality wars between Northern firms and a Southern copycat firm in the North. First, due to low wage, a foreign or Southern copycat firm may enter the market of a developed economy inhabited by a high‐quality firm and a low‐quality domestic copycat. When the products of the high‐quality firm and the foreign copycat are vertically differentiated, the foreign copycat firm may choose an intermediate quality between the quality levels of domestic high‐ and low‐quality firms. In the second scenario where the products of the high‐quality firm and the foreign copycat are horizontally differentiated, the quality of the foreign copycat may surpass that of the domestic high‐quality firm. As the wage gap between the developed and developing countries widens, the foreign copycat is more likely to survive in the markets of developed economies.
Gata3 is required for the functional maturation of inner hair cells and their innervation in the mouse cochlea
Authors: Bardhan Tanaya , Jeng Jing‐Yi , Waldmann Marco , Ceriani Federico , Johnson Stuart L. , Olt Jennifer , Rüttiger Lukas , Marcotti Walter , Holley Matthew C. 
Published: May 2019

Key points
The physiological maturation of auditory hair cells and their innervation requires precise temporal and spatial control of cell differentiation.
The transcription factor gata3 is essential for the earliest stages of auditory system development and for survival and synaptogenesis in auditory sensory afferent neurons.
We show that during postnatal development in the mouse inner ear gata3 is required for the biophysical maturation, growth and innervation of inner hair cells; in contrast, it is required only for the survival of outer hair cells.
Loss of gata3 in inner hair cells causes progressive hearing loss and accounts for at least some of the deafness associated with the human hypoparathyroidism, deafness and renal anomaly (HDR) syndrome.
The results show that gata3 is critical for later stages of mammalian auditory system development where it plays distinct, complementary roles in the coordinated maturation of sensory hair cells and their innervation.
AbstractThe zinc finger transcription factor gata3 regulates inner ear development from the formation of the embryonic otic placode. Throughout development, gata3 is expressed dynamically in all the major cochlear cell types. Its role in afferent formation is well established but its possible involvement in hair cell maturation remains unknown. Here, we find that in heterozygous gata3 null mice (gata3+/−) outer hair cells (OHCs) differentiate normally but their numbers are significantly lower. In contrast, inner hair cells (IHCs) survive normally but they fail to acquire adult basolateral membrane currents, retain pre‐hearing current and efferent innervation profiles and have fewer ribbon synapses. Targeted deletion of gata3 driven by otoferlin‐cre recombinase (gata3fl/flotof‐cre+/−) in IHCs does not affect OHCs or the number of IHC afferent synapses but it leads to a failure in IHC maturation comparable to that observed in gata3+/− mice. Auditory brainstem responses in gata3fl/flotof‐cre+/− mice reveal progressive hearing loss that becomes profound by 6–7 months, whilst distortion product otoacoustic emissions are no different to control animals up to this age. Our results, alongside existing data, indicate that gata3 has specific, complementary functions in different cell types during inner ear development and that its continued expression in the sensory epithelium orchestrates critical aspects of physiological development and neural connectivity. Furthermore, our work indicates that hearing loss in human hypoparathyroidism, deafness and renal anomaly (HDR) syndrome arises from functional deficits in IHCs as well as loss of function from OHCs and both afferent and efferent neurons.
It is good to feel better, but better to feel good: whether a patient finds treatment ‘successful’ or not depends on the questions researchers ask
Authors: Roos Ewa M , Boyle Eleanor , Frobell Richard B , Lohmander L Stefan , Ingelsrud Lina Holm 
Published: May 2019

IntroductionIn sports physiotherapy, medicine and orthopaedic randomised controlled trials (RCT), the investigators (and readers) focus on the difference between groups in change scores from baseline to follow-up. Mean score changes are difficult to interpret (‘is an improvement of 20 units good?’), and follow-up scores may be more meaningful. We investigated how applying three different responder criteria to change and follow-up scores would affect the ‘outcome’ of RCTs. Responder criteria refers to participants’ perceptions of how the intervention affected them.MethodsWe applied three different criteria—minimal important change (MIC), patient acceptable symptom state (PASS) and treatment failure (TF)—to the aggregate Knee injury and Osteoarthritis Outcome Score (KOOS4) and the five KOOS subscales, the primary and secondary outcomes of the KANON trial (ISRCTN84752559). This trial included young active adults with an acute ACL injury and compared two treatment strategies: exercise therapy plus early reconstructive surgery, and exercise therapy plus delayed reconstructive surgery, if needed.ResultsMIC: At 2 years, more than 90% in the two treatment arms reported themselves to be minimally but importantly improved for the primary outcome KOOS4. PASS: About 50% of participants in both treatment arms reported their KOOS4follow-up scores to be satisfactory. TF: Almost 10% of participants in both treatment arms found their outcomes so unsatisfactory that they thought their treatment had failed. There were no statistically significant or meaningful differences between treatment arms using these criteria.ConclusionWe applied change criteria as well as cross-sectional follow-up criteria to interpret trial outcomes with more clinical focus. We suggest researchers apply MIC, PASS and TF thresholds to enhance interpretation of KOOS and other patient-reported scores. The findings from this study can improve shared decision-making processes for people with an acute ACL injury.
Exploring psychiatrists’ perspectives of working with patients with dissociative seizures in the UK healthcare system as part of the CODES trial: a qualitative study
Authors: Jordan Harriet , Feehan Sarah , Perdue Iain , Murray Joanna , Goldstein Laura H 
Published: May 2019

ObjectiveThere is currently limited research exploring healthcare professionals’ (HCPs) experiences of working with patients with dissociative seizures (DS). Existing studies do not focus on the role of psychiatrists in treating this complex condition. The objective of this study was to gain an understanding of UK-based psychiatrists’ experiences of the DS patient group. Against the backdrop of a UK-wide randomised controlled trial (RCT), the focus was broadened to encompass issues arising in everyday practice with the DS patient group.Design, participants and methodsA qualitative study using semistructured interviews was undertaken with 10 psychiatrists currently working with DS patients within the context of a large RCT investigating treatments for DS. Thematic analysis was used to identify key themes and subthemes.SettingThe psychiatrists were working in Liaison or Neuropsychiatry services in England.ResultsThe key themes identified were other HCPs’ attitudes to DS and the challenges of the DS patient group. There is a clear knowledge gap regarding DS for many HCPs and other clinical services can be reluctant to take referrals for this patient group. Important challenges posed by this patient group included avoidance (of difficult emotions and help), alexithymia and interpersonal difficulties. Difficulties with alexithymia meant DS patients could struggle to identify triggers for their seizures and to express their emotions. Interpersonal difficulties raised included difficulties in attachment with both HCPs and family members.ConclusionsA knowledge gap for HCPs regarding DS has been identified and needs to be addressed to improve patient care. Given the complexity of the patient group and that clinicians from multiple disciplines will come into contact with DS patients, it is essential for any educational strategy to be implemented across the whole range of specialties, and to account for those already in practice as well as future trainees.Trial registration numberISRCTN05681227;NCT02325544; Pre-results.
Ultrasonic strain elastography for detecting abnormalities in the supraspinatus tendon: an intra- and inter-rater reliability study
Authors: Brage K , Hjarbaek John , Kjaer Per , Ingwersen Kim G , Juul-Kristensen Birgit 
Published: May 2019

ObjectivesThe reliability of ultrasonic strain elastography (SEL) used to detect abnormalities in the supraspinatus tendon is unclear. Thus, the aim of this study was to investigate the reliability of SEL in the supraspinatus tendon.DesignAn intra-rater and inter-rater reliability study.SettingA single-centre study conducted at the University of Southern Denmark.ParticipantsTwenty participants with shoulder pain and MRI-verified supraspinatus tendinosis and 20 asymptomatic participants (no MRI).Primary and secondary outcome measuresRaw values (RAW) and ratios (deltoid muscle (DELT) and gel pad (GEL) as reference tissues) were calculated and mean values of measurements from three regions of the supraspinatus tendon were reported. Colour scale ratings and number of yellow/red lesions from the three areas were also included.ResultsIntra-rater reliability showed intraclass correlation coefficients (ICCs) for RAW, DELT and GEL: 0.97 (minimal detectable change (MDC): 0.28 (6.36% of the mean)), 0.89 (MDC: 2.91 (20.37%)) and 0.73 (MDC: 1.61 (58.82%)), respectively. The ICCs for inter-rater reliability were 0.89 (MDC: 0.47 (10.53%)), 0.78 (MDC: 3.69 (25.51%)) and 0.70 (MDC: 1.75 (62.63%)), respectively.For colour scale ratings, intra-rater reliability (linear weighted kappa) ranged from 0.76 to 0.79, with the inter-rater reliability from 0.71 to 0.81. For the number of lesions, intra-rater reliability ranged from 0.40 to 0.82 and inter-rater reliability from 0.24 to 0.67.ConclusionsIntra-rater and inter-rater reliability were excellent for raw values and for ratios with deltoid muscle as the reference tissue, and good for ratios with gel pad as the reference tissue. The reliability of colour scale ratings was substantial-to-almost perfect, and for the number of lesions fair-to-almost perfect.Although high reliability was found, validity and responsiveness of these elastographic methods needs further investigation.Ethics approvalThe study protocol was approved by the Ethics Committee for the Region of South Denmark (S-20160115) and reported to the Danish Data Protection Agency (2014-41-3266).
Type of sedation and the need for unplanned interventions during ERCP: analysis of the clinical outcomes research initiative national endoscopic database (CORI-NED)
Authors: Smith Zachary L , Nickel Katelin B , Olsen Margaret A , Vargo John J , Kushnir Vladimir M 
Published: May 2019

Background and aimsRecent studies suggest that sedation provided by anaesthesia professionals may be less protective against serious adverse events than previously believed, however, data are lacking regarding endoscopic retrograde cholangiopancreatography (ERCP). Using the clinical outcomes research initiative national endoscopic database (CORI-NED), we aimed to assess whether mode of sedation was associated with rates of unplanned interventions (UIs) during ERCP.Patients and methodsAll subjects from CORI-NED undergoing ERCP from 2004 to 2014 were identified and stratified into three groups based on the initial mode of anaesthesia: endoscopist-directed sedation (EDS), monitored anaesthesia care without an endotracheal tube (MAC-WET) and general endotracheal anaesthesia (GEA). The primary outcome was UIs. To assess the impact of sedation mode on UIs, multivariable logistic regression models were created adjusting for demographic, physician and procedure-level variables.DesignPopulation-based study.Results26 698 ERCPs were analysed (7588 EDS, 8395 MAC-WET, 10 715 GEA). UIs occurred in 320 ERCPs (1.2%). EDS was associated with a higher risk of UIs compared with sedation administered by an anaesthesia professional (OR 1.86, 95% CI 1.44 to 2.42). Additional factors associated with a higher risk of UIs included ASA class IV compared with class II (OR 3.18, 95% CI 2.00 to 5.06) and ERCPs done in community (OR 1.41, 1.04 to 1.91) and health maintenance organisations (OR 3.75, 2.01 to 6.99) hospitals.ConclusionEDS is associated with a higher risk of UIs during ERCP compared with sedation administered by an anaesthesia professional. Higher ASA class and procedures performed in non-university hospitals were also associated with a higher risk of UIs. This study suggests that, when available, sedation using an anaesthesia professional should be utilised for ERCP.
Using hospital discharge data for injury research or surveillance? An observational study illustrating the impact of administrative change
Authors: Davie Gabrielle , Barson Dave , Simpson Jean C , Lilley Rebbecca , Gulliver Pauline , Cryer Colin 
Published: May 2019

IntroductionHospital discharge data provide an important basis for determining priorities for injury prevention and monitoring trends in incidence. This study aims to illustrate the impact of a recent change in administrative practice on estimates of hospitalised injury incidence and to investigate the extent to which different case selection affects trends in injury incidence rates.MethodsNew Zealand (NZ) hospital discharges (2000–2014) with a primary diagnosis of injury were identified. Additional case selection criteria included first admissions only, and for serious injury, a high threat-to-life estimate. Comparisons were made, over time and by District Health Board, between hospitalised injury incidence estimates that included, or not, short-stay emergency department (SSED) discharges.ResultsOf the 1 229 772 injury hospital discharges, 365 114 were SSED; 16% of the annual total in 2000, 38% in 2014. Identification of readmissions prior to the exclusion of SSED discharges resulted in 30 724 cases being erroneously removed. Age-standardised rates of hospitalised injury over the 15-year period increased by, on average, 2.7% per year when SSED discharges were included; there was minimal secular change (−0.2%) when SSEDs were excluded. For serious hospitalised injury, the annual increase was 2.3% when SSED was included compared with 1.1% when SSEDs were excluded.ConclusionSpurious trends in hospitalised injury incidence can result when administrative practices are not appropriately accounted for. Exclusion of SSED discharges before the identification of readmissions and the use of a severity threshold are recommended to minimise the reporting bias in NZ hospitalised injury incidence estimates.
Hippocampal network abnormalities explain amnesia after VGKCC-Ab related autoimmune limbic encephalitis
Authors: Loane Clare , Argyropoulos Georgios P D , Roca-Fernández Adriana , Lage Carmen , Sheerin Fintan , Ahmed Samrah , Zamboni Giovanna , Mackay Clare , Irani Sarosh R , Butler Christopher R 
Published: May 2019

ObjectiveLimbic encephalitis associated with antibodies to components of the voltage-gated potassium channel complex (VGKCC-Ab-LE) often leads to hippocampal atrophy and persistent memory impairment. Its long-term impact on regions beyond the hippocampus, and the relationship between brain damage and cognitive outcome, are poorly understood. We investigated the nature of structural and functional brain abnormalities following VGKCC-Ab-LE and its role in residual memory impairment.MethodA cross-sectional group study was conducted. Twenty-four VGKCC-Ab-LE patients (20 male, 4 female; mean (SD) age 63.86 (11.31) years) were recruited post-acutely along with age- and sex-matched healthy controls for neuropsychological assessment, structural MRI and resting-state functional MRI (rs-fMRI). Structural abnormalities were determined using volumetry and voxel-based morphometry; rs-fMRI data were analysed to investigate hippocampal functional connectivity (FC). Associations of memory performance with neuroimaging measures were examined.ResultsPatients showed selective memory impairment. Structural analyses revealed focal hippocampal atrophy within the medial temporal lobes, correlative atrophy in the mediodorsal thalamus, and additional volume reduction in the posteromedial cortex. There was no association between regional volumes and memory performance. Instead, patients demonstrated reduced posteromedial cortico-hippocampal and inter-hippocampal FC, which correlated with memory scores (r = 0.553; r = 0.582, respectively). The latter declined as a function of time since the acute illness (r = -0.531).ConclusionVGKCC-Ab-LE results in persistent isolated memory impairment. Patients have hippocampal atrophy with further reduced mediodorsal thalamic and posteromedial cortical volumes. Crucially, reduced FC of remaining hippocampal tissue correlates more closely with memory function than does regional atrophy.
High incidence of atrial fibrillation in patients treated with ibrutinib
Authors: Baptiste Florian , Cautela Jennifer , Ancedy Yan , Resseguier Noémie , Aurran Thérèse , Farnault Laure , Escudier Marion , Ammar Chloé , Gaubert Mélanie , Dolladille Charles , Barraud Jeremie , Peyrol Michael , Cohen Ariel , Paganelli Franck , Alexandre Joachim , Ederhy Stephane , Thuny Franck 
Published: May 2019

ObjectiveAtrial fibrillation (AF) is one of the most common side effects of ibrutinib, a drug that has dramatically improved the prognosis of chronic B-cell malignancies such as chronic lymphocytic leukaemia (CLL). The true incidence of ibrutinib-related AF (IRAF) is not well known and its therapeutic management poses unique challenges especially due to the inherent risk of bleeding. We aimed to determine the incidence and predictors of IRAF, and to analyse its management and outcome.MethodsA standardised monitoring was applied at two cardio-oncology clinics in consecutive patients referred before and during ibrutinib therapy. The primary endpoint was the incidence of IRAF. The excess of AF incidence with ibrutinib was studied by comparing the incidence of IRAF with the expected incidence of AF in general population and in patients with CLL not exposed to ibrutinib.Results53 patients were included. The incidence of IRAF was 38% at 2 years and the risk was 15-fold higher than the AF risk in both the general population and patients with CLL not exposed to ibrutinib (p<0.0001). The majority of cases occurred in asymptomatic patients within the first 6 months. Left atrial volume index ≥40 mL/m2at treatment initiation identified patients at high risk of developing IRAF. No major bleeding events occurred in patients on ibrutinib, although the majority of patients with IRAF were treated with anticoagulants.ConclusionsThis cardio-oncology study showed that the risk of IRAF was much higher than previously reported. The majority of cases occurred in asymptomatic patients justifying close monitoring.
Estimating the size of key populations for HIV in Singapore using the network scale-up method
Authors: Teo Alvin Kuo Jing , Prem Kiesha , Chen Mark I C , Roellin Adrian , Wong Mee Lian , La Hanh Hao , Cook Alex R 
Published: May 2019

ObjectivesTo develop a localised instrument and Bayesian statistical method to generate size estimates—adjusted for transmission error and barrier effects—of at-risk populations in Singapore.MethodsWe conducted indepth interviews and focus group to guide the development of the survey questionnaire. The questionnaire was administered between July and August 2017 in Singapore. Using the network scale-up method (NSUM), we developed a Bayesian hierarchical model to estimate the number of individuals in four hidden populations at risk of HIV. The method accounted for both transmission error and barrier effects using social acceptance measures and demographics.ResultsThe adjusted size estimate of the population of male clients of female sex workers was 72 000 (95% CI 51 000 to 100 000), of female sex workers 4200 (95% CI 1600 to 10 000), of men who have sex with men 210 000 (95% CI 140 000 to 300 000) and of intravenous drug users 11 000 (95% CI 6500 to 17 000).ConclusionsThe NSUM with adjustment for attitudes and demographics allows national-level estimates of multiple priority populations to be determined from simple surveys of the general population, even in relatively conservative societies.
Changes in roll-your-own tobacco and cigarette sales volume and prices before, during and after plain packaging legislation in the UK
Authors: Opazo Breton Magdalena , Britton John , Bogdanovica Ilze 
Published: May 2019

BackgroundPlain packaging and minimum pack size legislation for tobacco products was introduced in the UK in May 2016, with a 1-year sell-off period until May 2017, during which both fully branded and plain packs of various sizes were legally available. This study investigates trends in prices of roll-your-own tobacco (RYO) before, during and after implementation of this legislation, and compares trends with those observed in the cigarette market.MethodsWe used Nielsen Scantrack data for the period from March 2013 to June 2018 to describe trends in UK inflation-adjusted prices and volumes of both RYO and cigarettes, and linear regression to estimate changes in prices associated with the introduction of plain packaging and the minimum pack sizes of 30 g RYO and 20 cigarettes.ResultsIn contrast to a downward trend in cigarette sales volumes, RYO volumes rose throughout the study period. By the time plain packs accounted for 75% or more of sales, the average price of products sold in equivalent pack sizes had increased, relative to average prices in the year before implementation and with adjustment for tax changes, from 34.9 to 38.8 pence per gram for RYO (mean difference 4.26, 95% CI 3.99 to 4.53 pence, 12% increase), and from 38.6 to 41.13 pence for cigarettes (mean difference 2.53, 95% CI 2.24 to 2.83 pence, 7% increase) per cigarette.ConclusionsNew legislation resulted in higher prices for RYO and manufactured cigarettes. However, sales volumes of RYO continued to increase throughout the study period, perhaps because RYO remains a less expensive means of smoking tobacco.