bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conjunctival melanoma treatment outcomes in 288 patients: a multicentre international data-sharing study
Authors: Jain Puneet , Finger Paul T , Fili Maria , Damato Bertil , Coupland Sarah E , Heimann Heinrich , Kenawy Nihal , J Brouwer Niels , Marinkovic Marina , Van Duinen Sjoerd G , Caujolle Jean Pierre , Maschi Celia , Seregard Stefan , Pelayes David , Folgar Martin , Yousef Yacoub A , Krema Hatem , Gallie Brenda , Calle-Vasquez Alberto 
Published: September 2020

BackgroundTo relate conjunctival melanoma characteristics to local control.MethodsRetrospective, registry-based interventional study with data gathered from 10 ophthalmic oncology centres from 9 countries on 4 continents. Conjunctival melanoma patients diagnosed between January 2001 and December 2013 were enrolled in the study. Primary treatments included local excision, excision with cryotherapy and exenteration. Adjuvant treatments included topical chemotherapy, brachytherapy, proton and external beam radiotherapy (EBRT). Cumulative 5-year and 10-year Kaplan-Meier local recurrence rates were related to clinical and pathological T-categories of the eighth edition of the American Joint Committee on Cancer (AJCC) staging system.Results288 patients had a mean initial age of 59.7±16.8 years. Clinical T-categories (cT) were cT1 (n=218,75.7%), cT2 (n=34, 11.8%), cT3 (n=15, 5.2%), cTx (n=21,7.3%) with no cT4. Primary treatment included local excision (n=161/288, 55.9%) followed by excision biopsy with cryotherapy (n=108/288, 37.5%) and exenteration (n=5/288, 1.7%). Adjuvant therapies included topical mitomycin (n=107/288, 37.1%), plaque-brachytherapy (n=55/288, 19.1%), proton-beam (n=36/288, 13.5%), topical interferon (n=20/288, 6.9%) and EBRT (n=15/288, 5.2%). Secondary exenteration was performed (n=11/283, 3.9%). Local recurrence was noted in 19.1% (median=3.6 years). Cumulative local recurrence was 5.4% (3.2–8.9%), 19.3% (14.4–25.5%) and 36.9% (26.5–49.9%) at 1, 5 and 10 years, respectively. cT3 and cT2 tumors were twice as likely to recur than cT1 tumours, but only cT3 had statistically significantly greater risk of local recurrence than T1 (p=0.013). Factors such as tumour ulceration, plica or caruncle involvement and tumour thickness were not significantly associated with an increased risk of local recurrence.ConclusionThis multicentre international study showed that eighth edition of AJCC tumour staging was related to the risk of local recurrence of conjunctival melanoma after treatment. The 10-year cumulative local recurrence remains high despite current management.
Glaucoma conversion of the contralateral eye in unilateral normal-tension glaucoma patients: a 5-year follow-up study
Authors: Kim Jin-Soo , Choi Hyuk Jin , Park Ki Ho 
Published: September 2020

Background/AimsTo investigate clinical characteristics and risk factors for glaucoma conversion of the contralateral eye in unilateral normal-tension glaucoma (NTG) patients.MethodsA retrospective observational cohort study was conducted on a total of 76 subjects who had been diagnosed with unilateral NTG at the baseline and followed up for more than 5 years. Glaucoma conversion in the contralateral eye was defined as increased thinning of neuro-retinal rim, development of retinal nerve fibre layer defect and/or development of glaucomatous visual field defect.ResultsDuring the mean follow-up period of 7.3±2.4 years, 21 of 76 (27.6%) subjects were confirmed to have developed glaucoma in the non-glaucomatous contralateral eye. The 5-year rate of glaucoma conversion in contralateral eyes was 19.7%. The maximum width of β-zone parapapillary atrophy (MWβPPA)-disc diameter (DD) ratio at the baseline and the presence rate of disc haemorrhage during follow-up period were significantly greater in the contralateral eyes of the conversion group than in those of the non-conversion group (p=0.011, <0.001, respectively). A multivariate Cox-proportional hazard model revealed intraocular pressure (IOP) over 17 mm Hg (HR 5.05, p=0.031), central corneal thickness (CCT) under 491 μm (HR 4.25, p=0.025) and MWβPPA-DD ratio over 0.32 (HR 6.25, p=0.003) in contralateral eye at the baseline as the independent risk factors for glaucoma conversion.ConclusionsAmong unilateral NTG patients, those with low CCT and high MWβPPA-DD ratio as well as high IOP in the contralateral eye are more likely to develop glaucoma in that eye during long-term follow-up.
Long-term natural history of highly myopic eyes with a dome-shaped macula with or without untreated serous retinal detachment: a 4-year follow-up study
Authors: Viola Francesco , Leone Gaia , Garoli Elena , Mainetti Claudia , Galli Davide , Invernizzi Alessandro 
Published: September 2020

PurposeTo evaluate the long-term functional and morphological changes occurring in myopic eyes with a dome-shaped macula (DSM), with or without untreated serous retinal detachment (SRD).MethodsThis prospective, single-centre study enrolled consecutive cases of highly myopic patients with DSM with or without a SRD. Patients underwent complete ophthalmological examinations, optical coherence tomography, axial length measurements and autofluorescence. Follow-up visits were performed with a maximum interval of 6 months for 4 years. Eyes with choroidal neovascularisation were excluded.ResultsTwenty-six eyes from 18 patients (mean age 61.2) were included. At baseline, 13 eyes had SRD and 13 did not. The DSMs were either horizontal (69%) or round (31%). There were no significant differences in best-corrected visual acuity (BCVA) between eyes with and without SRD during the 48-month follow-up period. Multivariate analysis showed that baseline BCVA was the only parameter among those analysed (age and SRD height) to have a significant effect on the final BCVA (p<0.0001). SRD fluctuated overtime and SRD height was significantly influenced by choroidal thickness (p=0.002). The scleral bulge thickness had no effect on SRD thickness.ConclusionsBCVA remained clinically stable over 4 years without treatment despite the fluctuations and persistence of the SRDs.
Clinical outcomes of KeraVio using violet light: emitting glasses and riboflavin drops for corneal ectasia: a pilot study
Authors: Kobashi Hidenaga , Torii Hidemasa , Toda Ikuko , Kondo Shinichiro , Itoi Motozumi , Tsubota Kazuo 
Published: September 2020

Background/aimsWe developed a novel technology consisting of violet light (VL)-emitting glasses and defined the combination of VL irradiation and riboflavin treatment as KeraVio. Our goal was to evaluate the clinical results of KeraVio in patients with progressive corneal ectasia.MethodsEyes were exposed to VL (375 nm, irradiance 310 μW/cm2)-emitting glasses for 3 hours daily for 6 months, and a riboflavin solution was administered onto the corneal epithelium six times during each 3-hour VL irradiation. The primary end point was a change in the maximum keratometry (Kmax) value over 6 months compared with that over the 1 year before baseline.ResultsThe efficacy of KeraVio was evaluated in 20 eyes with severe progression, and its safety was evaluated in all 40 eyes. The mean changes in Kmax over the 1 year before baseline and during the 6-month observation period were 6.03±3.41 dioptres (D) and −0.81±3.34 D, respectively (p=0.002). At 6 months, the Kmax value decreased by more than 2 D in 4 eyes (20%), remained within 2 D in 13 eyes (65%), and increased by 2 D or more in 3 eyes (15%). The corneal stromal demarcation line was identified in 16 eyes (80%), and its depth was 206.3±54.9 μm at 1 month. No significant decrease in endothelial cell density, lenticular opacity or transient corneal haze was noted.ConclusionBased on our 6-month results, daily treatment of progressive corneal ectasia with KeraVio can halt disease progression without any safety concerns.Clinical trial registration numberjRCTs032180217.
Fractal analysis of polypoidal choroidal neovascularisation in age-related macular degeneration
Authors: Serra Rita , Coscas Florence , Pinna Antonio , Cabral Diogo , Coscas Gabriel , Souied Eric H 
Published: September 2020

AimTo describe optical coherence tomography angiography (OCTA) features of polypoidal choroidal neovascularisation (PCNV) secondary to age-related macular degeneration.MethodsA retrospective consecutive series of 51 patients with a diagnosis of PCNV, based on clinical and multimodal imaging, was analysed. All patients with PCNV underwent a comprehensive ophthalmological examination, including fluorescein and indocyanine green angiography, structural optical coherence tomography (OCT) and OCTA. Two blinded retinal specialists carefully reviewed OCTA slabs in order to assess the morphological patterns of PCNV lesions. Furthermore, fractal analysis of PCNV en face images on OCTA, including vascular perfusion density (VPD), fractal dimension (FD) and lacunarity (LAC), was performed.ResultsFifty-one PCNV eyes were included in the study. In all, the branching vascular network appeared hyper-reflective. Polyps showed two different patterns: in 34/51 (67%) eyes, they corresponded to hypo-reflective structures, whereas in the remaining 17 (33%) eyes, they appeared as hyper-reflective lesions. In all PCNV eyes, mean VPD, FD and LAC were 0.76±0.17%, 1.46±0.12 and 2.4±0.87, respectively. No significant difference was found between PCNVs showing a different OCTA pattern, in terms of quantitative OCTA parameters.ConclusionFractal analysis provides quantitative parameters demonstrating that PCNVs with different OCTA patterns share the same neovascular architecture and branching complexity. These new findings improve our ability to interpret OCTA slabs, opening new areas of discussion about this type of neovascular lesion.
Haemoglobin, iron status and lung function of adolescents participating in organised sports in the Finnish Health Promoting Sports Club Study
Authors: Toivo Kerttu , Kannus Pekka , Kokko Sami , Alanko Lauri , Heinonen Olli J , Korpelainen Raija , Savonen Kai , Selänne Harri , Vasankari Tommi , Kannas Lasse , Kujala Urho M , Villberg Jari , Niemelä Onni , Parkkari Jari 
Published: September 2020

ObjectivesTo compare laboratory test results and lung function of adolescent organised sports participants (SP) with non-participants (NP).MethodsIn this cross-sectional study, laboratory tests (haemoglobin, iron status), and flow-volume spirometry were performed on SP youths (199 boys, 203 girls) and their NP peers (62 boys, 114 girls) aged 14–17.ResultsHaemoglobin concentration <120/130 g/L was found in 5.8% of SP and 5.1% NP (OR 1.20, 95% CI 0.54 to 2.68). Ferritin concentration below 15 µg/L was found in 22.7% of both SP and NP girls. Among boys ferritin <30 µg/L was found in 26.5% of SP and 30.2% of NP (OR 0.76, 95% CI 0.40 to 1.47). Among SP iron supplement use was reported by 3.5% of girls and 1.5% of boys. In flow-volume spirometry with bronchodilation test, 7.0% of SP and 6.4% of NP had asthma-like findings (OR 1.17, 95% CI 0.54 to 2.54); those using asthma medication, that is, 9.8% of SP and 5.2% of NP were excluded from the analysis.ConclusionsScreening for iron deficiency is recommended for symptomatic persons and persons engaging in sports. Lung function testing is recommended for symptomatic persons and persons participating in sports in which asthma is more prevalent.
#OrthoTwitter: social media as an educational tool
Authors: Sahu Muhammad Arham , Goolam-Mahomed Zahrah , Fleming Simon , Ahmed Usman 
Published: September 2020

AimsThe increased use of social media creates opportunity for new, effective methods of delivering medical and clinical education. Twitter is a popular social media platform where users can post frequent updates and create threads containing related content using hashtags. This study aims to investigate and analyse the type of content relating to orthopaedic surgery that is being posted on the platform of Twitter.MethodsA retrospective search was performed for tweets containing the words ‘orthopaedic surgery’ or ‘orthopedic surgery’ or the use of the hashtag ‘#OrthoTwitter’ between November 2018 to November 2019. A total of 5243 tweets were included.ResultsTweets containing ‘orthopaedic surgery’ or ‘orthopedic surgery’ most frequently contained promotional or marketing content (30% promotional, 21% marketing), and private organisations were the category of author to which the greatest number of tweets belonged (30%). Tweets containing educational or research content were the least common among all tweets containing ‘orthopaedic surgery’ or ‘orthopedic surgery’ (11%). In contrast, of the tweets containing the hashtag ‘#OrthoTwitter’, 44% contained educational or research content, 15% contained promotional content and no tweets containing marketing content. Furthermore, 87% of all tweets using the hashtag ‘#OrthoTwitter’ were from orthopaedic surgeons, and the least number of tweets were from private organisations (2%).ConclusionTwitter is a widely used social media platform regarding orthopaedic surgery. We propose that the hashtag ‘#OrthoTwitter’ can be used to create an online community of orthopaedic surgeons where members can assist one another through sharing reliable and educational content.
Combined lifestyle factors, all-cause mortality and cardiovascular disease: a systematic review and meta-analysis of prospective cohort studies
Authors: Zhang Yan-Bo , Pan Xiong-Fei , Chen Junxiang , Cao Anlan , Xia Lu , Zhang Yuge , Wang Jing , Li Huiqi , Liu Gang , Pan An 
Published: September 2020

IntroductionUnhealthy lifestyles caused a huge disease burden. Adopting healthy lifestyles is the most cost-effective strategy for preventing non-communicable diseases. The aim was to perform a systematic review and meta-analysis to quantify the relationship of combined lifestyle factors (eg, cigarette smoking, alcohol consumption, physical activity, diet and overweight/obesity) with the risk of all-cause mortality, cardiovascular mortality and incident cardiovascular disease (CVD).MethodsPubMed and EMBASE were searched from inception to April 2019. Cohort studies investigating the association between the combination of at least three lifestyle factors and all-cause mortality, cardiovascular mortality or incidence of CVD were filtered by consensus among reviewers. Pairs of reviewers independently extracted data and evaluated study quality. Random-effects models were used to pool HRs. Heterogeneity and publication bias were tested.ResultsIn total, 142 studies were included. Compared with the participants with the least-healthy lifestyles, those with the healthiest lifestyles had lower risks of all-cause mortality (HR=0.45, 95% CI 0.41 to 0.48, 74 studies with 2 584 766 participants), cardiovascular mortality (HR=0.42, 95% CI 0.37 to 0.46, 41 studies with 1 743 530 participants), incident CVD (HR=0.38, 95% CI 0.29 to 0.51, 22 studies with 754 894 participants) and multiple subtypes of CVDs (HRs ranging from 0.29 to 0.45). The associations were largely significant and consistent among individuals from different continents, racial groups and socioeconomic backgrounds.ConclusionsGiven the great health benefits, comprehensively tackling multiple lifestyle risk factors should be the cornerstone for reducing the global disease burden.
Urinary calcium indices in primary hyperparathyroidism (PHPT) and familial hypocalciuric hypercalcaemia (FHH): which test performs best?
Authors: Arshad Muhammad Fahad , McAllister James , Merchant Azhar , Rab Edmund , Cook Jacqueline , Eastell Richard , Balasubramanian Sabapathy 
Published: September 2020

ABSTRACT

Aim
Primary hyperparathyroidism (PHPT) is much more common than familial hypocalciuric hypercalcaemia (FHH), but there is considerable overlap in biochemical features. Urine calcium indices help with the differential diagnosis, but their reliability in making this distinction is not clear. The aim of this study was to compare urinary calcium values in patients with PHPT and FHH.

Methods
This was a case–control study of patients with PHPT who had successful surgery and genetically proven FHH between 2011 and 2016. Due to low FHH numbers, patients from neighbouring hospitals and outside study period (2017–2019) were allowed to improve power. Data on demographics and urinary calcium were obtained from electronic records and compared between the two groups.

Results
During the study period, 250 patients underwent successful PHPT surgery, while in the FHH arm, 19 genetically proven cases were included. The median (IQR) 24-hour urine calcium excretion (UCE) in the PHPT group was 8.3 (5.6–11.2) mmol/24 hours compared with 3.2 (2.1–6.1) mmol/24 hour in the FHH group (p&lt;0.001). Median (IQR) calcium to creatinine clearance ratio (CCCR) in the PHPT and FHH groups was 0.020 (0.013–0.026) and 0.01 (0.002–0.02), respectively (p=0.001). The sensitivity of urinary tests for PHPT was 96% for UCE (cut-off ≥2.5 mmol/24 hour) and 47% for CCCR (cut-off &gt;0.02). The specificity of the urinary tests for FHH was 29.4% for UCE (cut-off &lt;2.5 mmol/24 hour) and 93% for CCCR (cut-off &lt;0.02).

Conclusions
24-hour UCE is more sensitive in diagnosing PHPT; however, it is less specific in ruling out FHH as compared with CCCR, when the cut-offs suggested by the International guidelines from the fourth international workshop are used. A significant proportion of patients with PHPT would have also required genetic studies if the guidelines were followed.
Recognising the spectrum of scleromyositis: HEp-2 ANA patterns allow identification of a novel clinical subset with anti-SMN autoantibodies
Authors: Landon-Cardinal Océane , Baril-Dionne Alexandra , Hoa Sabrina , Meyer Alain , Leclair Valérie , Bourré-Tessier Josiane , Mansour Anne-Marie , Zarka Farah , Makhzoum Jean-Paul , Nehme Jessica , Rich Eric , Goulet Jean-Richard , Grodzicky Tamara , Koenig Martial , Joyal France , Richard Isabelle , Hudson Marie , Targoff Ira , Satoh Minoru , Fritzler Marvin J , Troyanov Yves , Senécal Jean-Luc 
Published: September 2020

ObjectiveTo describe systemic sclerosis (SSc) with myopathy in patients without classic SSc-specific and SSc-overlap autoantibodies (aAbs), referred to as seronegative scleromyositis.MethodsTwenty patients with seronegative scleromyositis diagnosed by expert opinion were analysed retrospectively for SSc features at myositis diagnosis and follow-up, and stratified based on HEp-2 nuclear patterns by indirect immunofluorescence (IIF) according to International Consensus of Autoantibody Patterns. Specificities were analysed by protein A−assisted immunoprecipitation. Myopathy was considered an organ involvement of SSc.ResultsSSc sine scleroderma was a frequent presentation (45%) at myositis diagnosis. Myositis was the most common first non-Raynaud manifestation of SSc (55%). Lower oesophagal dysmotility was present in 10 of 11 (91%) investigated patients. At follow-up, 80% of the patients met the American College of Rheumatology/EULAR SSc classification criteria. Two-thirds of patients had a positive HEp-2 IIF nuclear pattern (all with titers ≥1/320), defining three novel scleromyositis subsets. First, antinuclear antibody (ANA)-negative scleromyositis was associated with interstitial lung disease (ILD) and renal crisis. Second, a speckled pattern uncovered multiple rare SSc-specific aAbs. Third, the nuclear dots pattern was associated with aAbs to survival of motor neuron (SMN) complex and a novel scleromyositis subset characteriszed by calcinosis but infrequent ILD and renal crisis.ConclusionsSSc skin involvement is often absent in early seronegative scleromyositis. ANA positivity, Raynaud phenomenon, SSc-type capillaroscopy and/or lower oesophagal dysmotility may be clues for scleromyositis. Using HEp-2 IIF patterns, three novel clinicoserological subsets of scleromyositis emerged, notably (1) ANA-negative, (2) ANA-positive with a speckled pattern and (3) ANA-positive with nuclear dots and anti-SMN aAbs.
Ghrelin receptor agonist hexarelin attenuates antinociceptive tolerance to morphine in rats
Authors: Baser Tayfun , Ozdemir Ercan , Filiz Ahmet Kemal , Taskiran Ahmet Sevki , Gursoy Sinan 
Published: September 2020

Ghrelin, a peptide hormone released from the gastric endocrine glands, shows analgesic activity apart from its various physiological effects. Nevertheless, the effects of ghrelin receptor (GHS-R) agonists on morphine analgesia and tolerance have not yet been elucidated. The purpose of this study was to evaluate the effects of the ghrelin receptor agonist hexarelin and antagonist [d-Lys3]-GHRP-6 on morphine antinociception and tolerance in rats. A total of 104 Wistar albino male adult rats (weighing approximately 220–240 g) were used in the experiments. To induce morphine tolerance, a three-day cumulative dose regimen was used in the rats. Then, randomly selected rats were evaluated for morphine tolerance on day 4. The analgesic effects of hexarelin (0.2 mg·kg–1), [d-Lys3]-GHRP-6 (10 mg·kg–1), and morphine (5 mg·kg–1) were measured at 30-min intervals (0, 30, 60, 90, and 120 min) by tail-flick and hot-plate analgesia tests. The findings suggest that hexarelin in combination with morphine attenuates analgesic tolerance to morphine. On the other hand, ghrelin receptor antagonist [d-Lys3]-GHRP-6 has no significant analgesic activity on the morphine tolerance in analgesia tests. Furthermore, co-administration of hexarelin and morphine increases the analgesic effect. In conclusion, these data indicate that administration of GHS-R agonist hexarelin with morphine enhances the antinociception and attenuates morphine tolerance.
TMEM98, a novel secretory protein, promotes endothelial cell adhesion as well as vascular smooth muscle cell proliferation and migration
Authors: Li Mei , Zhu Hongmei , Hu Xiaoyan , Gao Fuhua , Hu Xinxin , Cui Ying , Wei Xiaoqing , Xie Ce , Lv Guangxin , Zhao Ying , Gao Ying 
Published: September 2020

Transmembrane protein 98 (TMEM98) is a novel gene, and its function has not been well investigated. In a prior study, we have shown that siRNA-mediated knockdown of TMEM98 inhibited interleukin-8 (IL-8) promoted endothelial cell (EC) adhesion, as well as vascular smooth muscle cell (VSMC) proliferation and migration in the vascular endothelial and smooth muscle cell dysfunction. Herein, we used gain- and loss-of-function approaches combined with biochemical techniques to further explore the role of TMEM98 in the vascular wall cell. The expression and secretion of TMEM98 was increased in cultured human umbilical vein endothelial cells (HUVECs) and VSMCs treated with IL-8 and platelet-derived growth factor-BB (PDGF-BB). Also, PDGF-BB secretion was increased in TMEM98-treated HUVECs and VSMCs. Thus, it appears that TMEM98 and PDGF-BB form a positive feedback loop in potentiation of EC adhesion, as well as VSMC proliferation and migration. Knockdown of TMEM98 mediated by siRNA inhibited PDGF-BB-promoted EC adhesion by downregulating the expression of ICAM-1 and VCAM-1, as well as impaired the proliferation and migration of VSMCs by suppressing the AKT/GSK3β/cyclin D1 signaling pathway and reducing the expression of β-catenin. Hence, TMEM98 promoted EC adhesion by inducing the expression of ICAM-1/VCAM-1 and triggered VSMC proliferation and migration by activating the ERK and AKT/GSK3β signaling pathways. Taken together, TMEM98 may serve as a potential therapeutic target for the clinical treatment of vascular endothelial and smooth muscle cell dysfunction.