bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic analysis of primary open-angle glaucoma-related risk alleles in a Korean population: the GLAU-GENDISK study
Authors: Kim Yong Woo , Lee Yun Hwan , Kim Jin-Soo , Lee Jinho , Kim Yu Jeong , Cheong Hyun Sub , Kim Seok Hwan , Park Ki Ho , Kim Dong Myung , Choi Hyuk Jin , Jeoung Jin Wook 
Published: September 2020

AimTo validate six previously known primary open-angle glaucoma (POAG)-related loci in a Korean population.MethodsRepresentative POAG-related single-nucleotide polymorphisms (SNPs) from six loci (cyclin-dependent kinase 4 inhibitor B antisense RNA 1 (CDKN2B)-AS1, sineoculis homeobox homolog 1/sineoculis homeobox homolog 6(SIX1/SIX6), atonal BHLH transcription factor 7 (ATOH7), cell division cycle 7-transforming growth factor beta receptor 3, CAV1, transmembrane and coiled-coil domain family 1 (TMCO1) were selected and genotyped from discovery (POAG=309, heathy=5400) and replication cohorts (POAG=310, healthy=5612 and POAG=221, healthy=6244, respectively). Data were analysed using logistic regression to calculate the OR for POAG risk associated with SNP.ResultsFrom the discovery cohort, rs1900004 in ATOH7 (OR=1.29, p=0.0024); rs1063192 (OR=0.69, p=0.0006), rs2157719 (OR=0.63, p=0.0007) and rs7865618 (OR=0.63, p=0.0006) in CDKN2B-AS1, and rs10483727 in SIX1/SIX6 (OR=0.68, p=7.9E–05) were nominally associated with the risk of POAG. The replication cohorts revealed nominal associations with rs2157719 (OR=0.72, p=0.0135), rs1063192 (OR=0.63, p=0.0007) and rs7865618 (OR=0.52, p=0.0004) in CDKN2B-AS1. A mega-analysis from the entire Korean population revealed significance with rs1063192 (OR=0.77, p=6.0E–05), rs2157719 (OR=0.63, p=0.0007) and rs7865618 (OR=0.58, p=1.9E–06) in CDKN2B-AS1 and with rs10483727 in SIX1/SIX6 (OR=0.79, p=9.4E–05), with the same direction of effect between the discovery association and the replication sample.ConclusionsVariants near CDKN2B-AS1 and SIX1/SIX6 may require further investigation to obtain more genetic information on POAG development in a Korean population.
Clinical and confocal imaging findings in congenital corneal anaesthesia
Authors: Guillon-Rolf Rebecca , Hau Scott , Larkin Daniel F P 
Published: September 2020

Background/Aims
Congenital corneal anaesthesia (CCA) is an uncommon cause of corneal ulceration in young patients, with a reported poor visual prognosis. We correlated clinical findings in patients with CCA with corneal sub-basal nerve plexus (SBNP) morphology and dendritiform cell density (DCD) on confocal microscopy.

Methods

A prospective, case–control study was conducted at a referral clinic. History includied presenting features in patients with CCA, clinical course and examination findings. Differences in SBNP morphology and DCD on
in vivo
confocal microscopy (IVCM) were compared in cases and control subjects with healthy corneas.

Results
Eight patients with CCA were examined, of which three had a diagnosis of familial dysautonomia. Age at initial diagnosis of corneal disease ranged from infancy to 22 years, the most common presentation being corneal ulceration. All patients with CCA except one with optic neuropathy had corrected visual acuity 6/18 (logMAR 0.35) or better in at least one eye. Measured corneal sensation was minimal in all patients. Major abnormalities were found on confocal microscopy in all patients with CCA, whether or not inherited, including statistically significant reduction in SBNP nerve fibre density, fibre length and branch density. Increased DCD in superficial cornea was found in all patients with CCA.

Conclusion
Good visual acuity can be maintained in eyes with corneal anaesthesia present from birth. IVCM provides direct evidence of a morphological correlate for measured corneal anaesthesia. Increased DCD may indicate an enhanced role for innate immune cells in superficial cornea in protection of the anaesthetic ocular surface.
Visual hallucinations and sight loss in children and young adults: a retrospective case series of Charles Bonnet syndrome
Authors: Jones Lee , Moosajee Mariya 
Published: September 2020

Background/Aims
Charles Bonnet syndrome (CBS) is a complication of sight loss affecting all ages; yet, few childhood cases have been reported. Our aim is to raise awareness of this under-reported association occurring in children and young adults in order to prevent psychological harm in this age group.

Methods
A retrospective case series reviewing medical notes of patients <25 years of age with sight loss and reported CBS at a single centre hospital eye service in London, United Kingdom. Search of electronic patient records identified 13 patients experiencing hallucinatory events over a 9-year period. Outcomes were patient demographics including ocular diagnosis, visual acuity at time of onset, characteristics of hallucinations, clinical management strategies and patient-reported affliction.

Results
Eight patients were diagnosed with progressive inherited retinal diseases, primarily Stargardt disease (N=5). Clinical history indicated patients had significantly reduced best-corrected visual acuity (BCVA) in at least one eye at onset; median (IQR) worse eye BCVA was 1.0 (0.86–1.6) logarithm of minimum angle of resolution(LogMAR). CBS significantly affected patients’ personal lives including education, diet and sleep. Clinical management was varied, mostly relating to reassurance at the point of contact.

Conclusion
We describe the clinical features of young patients with CBS, with management strategies and aspects of negative outcomes. High potential caseload and risk of psychological harm merit further research. Increased awareness among healthcare professionals and patient education to forewarn susceptible individuals may reduce the overall impact and improve coping with symptoms.
Recommendations for the management of ocular sarcoidosis from the International Workshop on Ocular Sarcoidosis
Authors: Takase Hiroshi , Acharya Nisha R , Babu Kalpana , Bodaghi Bahram , Khairallah Moncef , McCluskey Peter J , Tesavibul Nattaporn , Thorne Jennifer E , Tugal-Tutkun Ilknur , Yamamoto Joyce H , Rao Narsing A , Smith Justine R , Mochizuki Manabu 
Published: September 2020

Aims
To establish expert recommendations for the management of ocular sarcoidosis (OS).

Methods
A question-based survey on the management of OS was circulated to international uveitis experts (members of the International Uveitis Study Group and the International Ocular Inflammation Society) electronically. Subsequently, a consensus workshop was conducted at the 7th International Workshop on Ocular Sarcoidosis (IWOS) in June 2019 in Sapporo, Japan as part of the Global Ocular Inflammation Workshops. Statements on the management of OS that were supported by a two-thirds majority of 10 international panel members of the workshop, after discussion and voting, were taken as consensus agreement.

Results
A total of 98 participants from 29 countries responded to the questionnaire survey. The subsequent consensus workshop established recommendations for the management of OS in five sections. The first section concerned evaluation and monitoring of inflammation. The second, third and fourth sections described ocular manifestations that were indications for treatment, and the management of anterior uveitis, intermediate uveitis and posterior uveitis. In the fifth section, the use of systemic corticosteroids and systemic immunosuppressive drugs were detailed.

Conclusions
Recommendations for management of OS were formulated through an IWOS consensus workshop.
Protocol for the impact of CBT for insomnia on pain symptoms and central sensitisation in fibromyalgia: a randomised controlled trial
Authors: McCrae Christina S , Curtis Ashley F , Craggs Jason , Deroche Chelsea , Sahota Pradeep , Siva Chokkalingam , Staud Roland , Robinson Michael 
Published: September 2020

IntroductionApproximately 50% of individuals with fibromyalgia (a chronic widespread pain condition) have comorbid insomnia. Treatment for these comorbid cases typically target pain, but growing research supports direct interventions for insomnia (eg, cognitive behavioural treatment for insomnia (CBT-I)) in these patients. Previous research suggests sustained hyperarousal mediated by a neural central sensitisation mechanism may underlie insomnia and chronic pain symptoms in fibromyalgia. We hypothesise CBT-I will improve insomnia symptoms, improve clinical pain and reduce central sensitisation. The trial will be the first to evaluate the short-term and long-term neural mechanisms underlying insomnia and pain improvements in fibromyalgia. Knowledge obtained from this trial might allow us to develop new or modify current treatments to better target pain mechanisms, perhaps reversing chronic pain or preventing it.Methods and analysisFemale participants (n=130) 18 years of age and older with comorbid fibromyalgia (with pain severity of at least 50/100) and insomnia will be recruited from the University of Missouri in Columbia, Missouri, and surrounding areas. Participants will be randomised to 8 weeks (plus 4 bimonthly booster sessions) of CBT-I or a sleep hygiene control group (SH). Participants will be assessed at baseline, post-treatment, 6 and 12 months follow-ups. The following assessments will be completed: 2 weeks of daily diaries measuring sleep and pain, daily actigraphy, insomnia severity index, pain-related disability, single night of polysomnography recording, arousal (heart rate variability, cognitive affective arousal), structural and functional MRI to examine pain-related neural activity and plasticity and mood (depression, anxiety).Ethics and disseminationEthics approval was obtained in July 2018 from the University of Missouri. All data are expected to be collected by 2022. Full trial results are planned to be published by 2024. Secondary analyses of baseline data will be subsequently published.Trial registration numberNCT03744156.
Using the behaviour change technique taxonomy v1 (BCTTv1) to identify the active ingredients of pharmacist interventions to improve non-hospitalised patient health outcomes
Authors: Scott Claire , de Barra Mícheál , Johnston Marie , de Bruin Marijn , Scott Neil , Matheson Catriona , Bond Christine , Watson Margaret C 
Published: September 2020

ObjectivesThe aim of this study was to identify which behaviour change techniques (BCTs) were present in intervention and control groups of randomised controlled trials (RCTs) included in a Cochrane systematic review.SettingThe RCTs included were conducted in community, primary and/or ambulatory-care settings.ParticipantsThe data set was derived from 86 RCTs from an interim update of the Cochrane review of the effectiveness of pharmacist services on non-hospitalised patient outcomes.Primary and secondary outcome measuresThe primary outcome was the identification of BCTs scheduled for delivery in intervention and control groups of the RCTs. The secondary outcome measure was to identify which BCTs are not being utilised in intervention and control groups of the RCTs.ResultsThe intervention and control groups included 31 and 12 BCTs, respectively. The number of identifiable BCTs/study ranged from 0 to 12 in the intervention groups (mean 3.01 (SD 2.4)) and 0 to 6 in the control groups (mean 0.38 (SD 0.84)). The most commonly identified BCTs in the intervention groups were: instruction on how to perform the behaviour (55%, n=47) (also the most common BCT in control groups); problem solving (29%, n=25); information about health consequences (24%, n=21); social support (practical) (24%, n=21); and social support (unspecified) (23%, n=20) (the second most common BCT in control groups). Thirteen trials had no identifiable BCTs in either group.ConclusionThe pharmacist interventions presented in this study did not use the full range of available BCTs. Furthermore, the reporting of BCTs was incomplete for both intervention and control groups, thereby limiting the utility and reproducibility of the interventions. Future interventions should be designed and reported using relevant taxonomies and checklists for example, BCT taxonomy and TIDieR (the template for intervention description and replication).
Comparison of neonatal outcomes of small for gestational age and appropriate for gestational age preterm infants born at 28–36 weeks of gestation: a multicentre study in Ethiopia
Authors: Gidi Netsanet Workneh , Goldenberg Robert L , Nigussie Assaye K , McClure Elizabeth , Mekasha Amha , Worku Bogale , Siebeck Matthias , Genzel-Boroviczeny Orsolya , Muhe Lulu M 
Published: September 2020

PurposeThe aim of this study was to assess morbidity and mortality pattern of small for gestational age (SGA) preterm infants in comparison to appropriate for gestational age (AGA) preterm infants of similar gestational age.MethodWe compared neonatal outcomes of 1336, 1:1 matched, singleton SGA and AGA preterm infants based on their gestational age using data from the study ‘Causes of Illness and Death of Preterm Infants in Ethiopia (SIP)’. Data were analysed using SPSS V.23. ORs and 95% CIs and χ2tests were done, p value of <0.05 was considered statistically significant.ResultThe majority of the infants (1194, 89%) were moderate to late preterm (32–36 weeks of gestation), 763 (57%) were females. Male preterm infants had higher risk of being SGA than female infants (p<0.001). SGA infants had increased risk of hypoglycaemic (OR and 95% CI 1.6 (1.2 to 2.0), necrotising enterocolitis (NEC) 2.3 (1.2 to 4.1), polycythaemia 3.0 (1.6 to 5.4), late-onset neonatal sepsis (LOS) 3.6 (1.1 to 10.9)) and prolonged hospitalisation 2.9 (2.0 to 4.2). The rates of respiratory distress syndrome (RDS), apnoea and mortality were similar in the SGA and AGA groups.ConclusionNeonatal complications such as hypoglycaemic, NEC, LOS, polycythaemia and prolonged hospitalisation are more common in SGA infants, while rates of RDS and mortality are similar in SGA and AGA groups. Early recognition of SGA status, high index of suspicion and screening for complications associated and timely intervention to prevent complications need due consideration.
Association between physical activity, cardiorespiratory fitness and clustered cardiovascular risk in South African children from disadvantaged communities: results from a cross-sectional study
Authors: Müller Ivan , Walter Cheryl , Du Randt Rosa , Aerts Ann , Adams Larissa , Degen Jan , Gall Stefanie , Joubert Nandi , Nqweniso Siphesihle , Des Rosiers Sarah , Smith Danielle , Seelig Harald , Steinmann Peter , Wadhwani Christina , Probst-Hensch Nicole , Utzinger Jürg , Pühse Uwe , Gerber Markus 
Published: September 2020

Background/AimPhysical inactivity (PIA) is a growing global health problem and evidence suggests that PIA is a key driver for cardiovascular and chronic diseases. Recent data from South Africa revealed that only about half of the children achieved recommended daily physical activity (PA) levels. Assessing the intensity of PA in children from low socioeconomic communities in low-income and middle-income countries is important to estimate the extent of cardiovascular risk and overall impact on health.MethodsWe conducted a cross-sectional survey in eight quintile 3 primary schools in disadvantaged communities in the Port Elizabeth region, South Africa. Children aged 10–15 years were subjected to PA, blood pressure, cholesterol, blood glucose and skinfold thickness assessments. Cardiovascular risk markers were converted into standardised z-scores and summed, to obtain a clustered cardiovascular risk score.ResultsOverall, 650 children had complete data records. 40.8% of the children did not meet recommended PA levels (ie, logged <60 min of moderate-to-vigorous physical activity (MVPA) per day). If quartiles were developed based on children’s cardiorespiratory fitness (CRF) and MVPA levels, a significant difference was found in clustered cardiovascular risk among children in the highest versus lowest fitness (p<0.001) or MVPA (p<0.001) quartiles.ConclusionsCRF and objectively assessed PA are closely linked with children’s clustered cardiovascular risk. Given that 4 out of 10 South African schoolchildren from marginalised communities do not meet international PA recommendations, efforts should be made to ensure that promoting a physically active lifestyle is recognised as an important educational goal in primary schools.Trial registration numbersISRCTN68411960 and H14-HEA-HMS-002.
Postgraduate education among family and community physicians in Brazil: theTrajetórias MFCproject
Authors: Fontenelle Leonardo Ferreira , Rossi Stephani Vogt , Oliveira Miguel Henrique Moraes de , Brandão Diego José , Sarti Thiago Dias 
Published: September 2020

ObjectiveOur objective was to describe the postgraduate education trajectories of family and community physicians in Brazil, where neither primary healthcare nor family and community medicine is recognised as a knowledge area for the purpose of research and postgraduate education (master’s and PhD degrees).DesignAn observational, exploratory study, using administrative data. A nationwide list of family and community physicians as of late November 2018 was compiled from multiple sources. Data on the mode of specialisation was obtained from the same sources and were correlated with data on master’s and PhD degrees, obtained from the curricula vitae on the Lattes Platform.SettingThis study was set in Brazil.Participants6238 family and community physicians (58.3% female), of whom 2795 had earned a specialist certificate (identified from the list of physicians certified by Sociedade Brasileira de Medicina de Família e Comunidade) and 3957 had completed medical residency (identified from SisCNRM, the national information system for medical residency).ResultsA master’s degree was held by 747 (12.0%) family and community physicians, and a PhD by 170 (2.7%); most degrees were in collective health (47.0% and 42%, respectively). Men were more likely than women to hold a master’s degree (adjusted odds ratio (aOR) 1.24, 95% uncertainty interval (UI) 1.07–1.45) and even more likely to a hold PhD (aOR 1.86, 95% UI 1.35–2.59). Family and community physicians were also less likely to hold a PhD degree if their master’s degree was professional (oriented towards jobs outside academia) instead of academic (aOR 0.15, 95% UI 0.05–0.39) or in some area other than collective health or medicine (aOR 0.41, 95% UI 0.21–0.78, compared with a master’s degree in collective health). The postgraduate degree was more likely to precede specialisation for family and community physicians specialising through certification (master’s degree 39.9%, PhD 33%) than through medical residency (master’s degree 9.1%, PhD 6%).ConclusionFamily and community physicians in Brazil increasingly earn academic and professional master’s and PhD degrees, with an emphasis on collective health, even though women seemingly face barriers to advance their education. The consequences of different postgraduate trajectories should be critically examined.
Positivity for SATB2 distinguishes Islet1 positive rectal neuroendocrine tumours from pancreaticoduodenal neuroendocrine tumours
Authors: Mohanty Sambit Kumar , Tiwari Ankit , Bhardwaj Nitin , Chuang Fai , Kim Evelyn , Lugo Hector , Yuan Xiaopu , Diffalha Sameer Al , Peralta-Venturina Mariza , Balzer Bonnie , Dhall Deepti 
Published: September 2020

AimsDetermining the site of origin of a metastatic neuroendocrine tumour (NET) can be challenging and has important prognostic and therapeutic implications. An immunohistochemical (IHC) panel consisting of TTF1, CDX2, PAX8/PAX6 and Islet1 is often employed. However, there can be a significant IHC overlap among different primary sites. Herein, we sought to determine the utility of including Special AT-rich sequence binding protein-2 (SATB2) in the IHC panel that is used for determining the site of origin of a metastatic NET.MethodsParaffin tissue microarrays consisting of 137 primary NETs (26 lung, 22 jejunoileal, 8 appendix, 5 stomach, 4 duodenum, 17 rectum and 55 pancreas) were stained for SATB2, in addition to the well-described lineage-associated markers, such as TTF1, CDX2, PAX6 and Islet1. Additionally, a tissue microarray consisting of 21 metastatic NETs (1 lung, 1 stomach, 8 jejunoileal and 11 pancreas) was stained for TTF1, CDX2, SATB2 and Islet1. The results were recorded as no staining, weak staining and moderate to strong staining.ResultsAll appendiceal NETs and majority (88%) of the rectal NETs were positive for SATB2. All primary foregut NETs (stomach, pancreas, duodenum and lung) were negative for SATB2, except for one pulmonary NET with weak staining. However, among the metastatic tumours, 5 of 11 pancreatic NETs, 1 stomach NET, 1 lung NET and 2 of 8 jejunoileal NETs showed weak staining. Receiver operating characteristic analysis incorporating sensitivity and specificity data of IHC panel, considering moderate to strong staining as truly positive cases, showed that inclusion of SATB2 to the previously described NET IHC panel outperformed the panel without SATB2, raising the specificity for pancreaticoduodenal NETs from 81.2% to 100%, with a positive predictive value (PPV) of 100% and negative predictive value (NPV) of 82.22% (p<0.0001); for appendiceal NETs the specificity changed from 99.1% to 98.5% and sensitivity increased from 11.8% to 80%, with a PPV and NPV of 66.67% and 99.26%, respectively (p<0.0001); and for rectal NETs the specificity increased from 97.6% to 99.3% and sensitivity raised from 7.1% to 66.7%, with a PPV and NPV of 80% and 98.53%, respectively (p<0.0001).ConclusionsSATB2 stain is useful in differentiatingIslet1/PAX6 positive pancreatic and rectal NETs, as rectal NETs are typically moderately to strongly positive for SATB2 and pancreatic NETs are usually negative or weakly positive for SATB2. Moderate to strong staining for SATB2 is suggestive of an appendiceal or a rectal primary. SATB2 may complement the panel of CDX2, TTF1 and Islet1 in determining the site of origin of an NET in a metastatic setting.
Diagnostic concordance and discordance in digital pathology: a systematic review and meta-analysis
Authors: Azam Ayesha S , Miligy Islam M , Kimani Peter K-U , Maqbool Heeba , Hewitt Katherine , Rajpoot Nasir M , Snead David R J 
Published: September 2020

BackgroundDigital pathology (DP) has the potential to fundamentally change the way that histopathology is practised, by streamlining the workflow, increasing efficiency, improving diagnostic accuracy and facilitating the platform for implementation of artificial intelligence–based computer-assisted diagnostics. Although the barriers to wider adoption of DP have been multifactorial, limited evidence of reliability has been a significant contributor. A meta-analysis to demonstrate the combined accuracy and reliability of DP is still lacking in the literature.ObjectivesWe aimed to review the published literature on the diagnostic use of DP and to synthesise a statistically pooled evidence on safety and reliability of DP for routine diagnosis (primary and secondary) in the context of validation process.MethodsA comprehensive literature search was conducted through PubMed, Medline, EMBASE, Cochrane Library and Google Scholar for studies published between 2013 and August 2019. The search protocol identified all studies comparing DP with light microscopy (LM) reporting for diagnostic purposes, predominantly including H&E-stained slides. Random-effects meta-analysis was used to pool evidence from the studies.ResultsTwenty-five studies were deemed eligible to be included in the review which examined a total of 10 410 histology samples (average sample size 176). For overall concordance (clinical concordance), the agreement percentage was 98.3% (95% CI 97.4 to 98.9) across 24 studies. A total of 546 major discordances were reported across 25 studies. Over half (57%) of these were related to assessment of nuclear atypia, grading of dysplasia and malignancy. These were followed by challenging diagnoses (26%) and identification of small objects (16%).ConclusionThe results of this meta-analysis indicate equivalent performance of DP in comparison with LM for routine diagnosis. Furthermore, the results provide valuable information concerning the areas of diagnostic discrepancy which may warrant particular attention in the transition to DP.