bluuebunny/crossref_metadata_2025_split huggingface dataset:
Compound heterozygous splicing CDON variants result in isolated ocular coloboma
Authors: Reis Linda M. , Basel Donald , McCarrier Julie , Weinberg David V. , Semina Elena V. 
Published: July 2020

AbstractOcular coloboma is caused by failure of optic fissure closure during development and recognized as part of the microphthalmia, anophthalmia, and coloboma (MAC) spectrum. While many genes are known to cause colobomatous microphthalmia, relatively few have been reported in coloboma with normal eye size. Genetic analysis including trio exome sequencing and Sanger sequencing was undertaken in a family with two siblings affected with bilateral coloboma of the iris, retina, and choroid. Pathogenic variants in MAC genes were excluded. Trio analysis identified compound heterozygous donor splice site variants in CDON, a cell‐surface receptor known to function in the Sonic Hedgehog pathway, c.928 + 1G > A and c.2650 + 1G > T, in both affected individuals. Heterozygous missense and truncating CDON variants are associated with dominant holoprosencephaly (HPE) with incomplete penetrance and Cdon−/− mice display variable HPE and coloboma. A homozygous nonsense allele of uncertain significance was recently identified in a consanguineous patient with coloboma and a second molecular diagnosis. We report the first compound heterozygous variants in CDON as a cause of isolated coloboma. CDON is the first HPE gene identified to cause recessive coloboma. Given the phenotypic overlap, further examination of HPE genes in coloboma is indicated.
Heavy metals and the skin: Sensitization patterns in Lithuanian metalworkers
Authors: Linauskiene Kotryna , Isaksson Marléne , Malinauskiene Laura 
Published: July 2020

AbstractBackgroundMetalworkers are exposed to many sensitizing and irritant substances. There are no published data on contact allergy in this population in the Baltic countries.ObjectivesTo detect skin symptoms related to occupational exposure and to describe the reactivity pattern to the European baseline series in workers from two metal plants in Lithuania.MethodsIn this cross‐sectional study 185 metalworkers (154 production workers and 31 office staff) filled an interviewer‐administered questionnaire. Patch testing was performed in 135 metalworkers and office staff, as a control group.ResultsMetalworkers younger than 40 years complained statistically significantly more often of skin symptoms, especially on the hands and face, than older workers. Physician‐diagnosed skin diseases were reported in 1.7% of cases. Metalworkers, working <20 years in the factory, more often had skin symptoms. Contact with chemicals at the workplace was suspected as the main factor provoking skin symptoms. Metalworkers were sensitized mainly to cobalt, and nickel was the most prevalent allergen among office staff.ConclusionYounger metalworkers more often had skin symptoms suspected of being work‐related compared to older ones. Sensitization to cobalt was more prevalent in the metalworkers than in the control group.
A pragmatic randomized clinical trial of insulin glargine 300 U/mL vs first‐generation basal insulin analogues in insulin‐naïve adults with type 2 diabetes: 6‐month outcomes of the ACHIEVE Control study
Authors: Meneghini Luigi F. , Sullivan Sean D. , Oster Gerry , Busch Robert , Cali Anna M. G. , Dauchy Arnaud , Gill Jasvinder , Bailey Timothy S. 
Published: July 2020

AbstractAimsTo compare the safety and efficacy of insulin glargine 300 U/mL (Gla‐300) versus first‐generation standard‐of‐care basal insulin analogues (SOC‐BI; insulin glargine 100 U/mL or insulin detemir) at 6 months.MethodsIn the 12‐month, open‐label, multicentre, randomized, pragmatic ACHIEVE Control trial, insulin‐naïve adults with type 2 diabetes (T2D) and glycated haemoglobin (HbA1c) 64 to 97 mmol/mol (8.0%–11.0%) after ≥1 year of treatment with ≥2 diabetes medications were randomized to Gla‐300 or SOC‐BI. The composite primary endpoint, evaluated at 6 months, was the proportion of participants achieving individualized HbA1c targets per Healthcare Effectiveness Data and Information Set (HEDIS) criteria without documented symptomatic (blood glucose ≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia at any time of the day at 6 months.ResultsOf 1651 and 1653 participants randomized to Gla‐300 and SOC‐BI, respectively, 31.3% and 27.9% achieved the composite primary endpoint at 6 months (odds ratio [OR] 1.19, 95% confidence interval [CI] 1.01–1.39; P = 0.03 for superiority); 78.4% and 75.3% had no documented symptomatic or severe hypoglycaemia (OR 1.19, 95% CI 1.01–1.41). Changes from baseline to month 6 in HbA1c, fasting plasma glucose, weight, and BI analogue dose were similar between groups.ConclusionsAmong insulin‐naïve adults with poorly controlled T2D, Gla‐300 was associated with a statistically significantly higher proportion of participants achieving individualized HEDIS HbA1c targets without documented symptomatic or severe hypoglycaemia (vs SOC‐BI) in a real‐life population managed in a usual‐care setting. The ACHIEVE Control study results add value to treatment decisions and options for patients, healthcare providers, payers and decision makers.
H2S donor improves heart function and vascular relaxation in diabetes
Authors: Dorofeyeva Natalya , Drachuk Konstantin , Rajkumar Rajasekaran , Sabnis Omkar , Sagach Vadim 
Published: July 2020

AbstractBackground and aimsDiabetes dramatically increases the risk of cardiovascular complications and mortality. Hydrogen sulphide plays an important role in reducing oxidative stress. Several studies demonstrated that hydrogen sulphide protects islet beta cells from oxidant stress damage and decreases apoptosis. The aim of the work is to investigate the effect of hydrogen sulphide donor on heart functions and endothelium‐dependent relaxation of aortic smooth muscle in diabetes.Materials and methodsRats were divided into control and diabetic groups. Diabetes mellitus was induced with a single intraperitoneally injection of streptozotocin (60 mg kg−1). The functional cardiohemodynamic indicators were registered via microcatheter and Pressure‐Volume System. The sodium hydrosulphide NaHS (15.8 mg kg−1) was administered intraperitoneally. The contractile activity of the muscle preparations of the thoracic aorta was recorded using a strain gauge.ResultsWe demonstrate that the NaHS improves pumping function and restores diastolic heart function in streptozotocin‐induced (STZ) diabetes rats. We show that pretreatment with NaHS increased the stroke volume by 43.1%, and the ejection fraction increased by 48.64%. NaHS improves the ventriculo‐arterial coupling and increases by 3.4 times acetylcholine‐induced relaxation of the aorta in diabetic rats. The inhibition of NOS activity by blocker L‐NAME abolished NaHS‐mediated vasodilatation in the intact endothelium of the aorta in diabetes. It indicates that the NaHS caused vasodilatation by a NOS‐dependent mechanism.ConclusionThe exogenous hydrogen sulphide can improve pumping function and restore diastolic heart function in diabetes. The pretreatment with NaHS can prevent endothelial dysfunction in diabetes due to the NOS‐dependent mechanism.
Lake trout growth is sensitive to spring temperature in southwest Alaska lakes
Authors: von Biela Vanessa R. , Black Bryan A. , Young Daniel B. , van der Sleen Peter , Bartz Krista K. , Zimmerman Christian E. 
Published: July 2020

AbstractIn high‐latitude lakes, air temperature is an important driver of ice cover thickness and duration, which in turn influence water temperature and primary production supporting lake consumers and predators. In lieu of multidecadal observational records necessary to assess the response of lakes to long‐term warming, we used otolith‐based growth records from a long‐lived resident lake fish, lake trout (Salvelinus namaycush), as a proxy for production. Lake trout were collected from seven deep, oligotrophic lakes in Lake Clark National Park and Preserve on in southwest Alaska that varied in the presence of marine‐derived nutrients (MDN) from anadromous sockeye salmon (Oncorhynchus nerka). Linear mixed‐effects models were used to partition variation in lake trout growth by age and calendar‐year and model comparisons tested for a mean increase in lake trout growth with sockeye salmon presence. Year effects from the best mixed‐effects model were subsequently compared to indices of temperature, lake ice, and regional indices of sockeye salmon escapement. A strong positive correlation between annual lake trout growth and temperature suggested that warmer springs, earlier lake ice break‐up, and a longer ice‐free growing season increase lake trout growth via previously identified bottom‐up increases in production with warming. Accounting for differences in the presence or annual escapement of sockeye salmon with available data did not improve model fit. Collectively with other studies, the results suggest that productivity of subarctic lakes has benefitted from warming spring temperatures and that temperature can synchronise otolith growth across lakes with and without sockeye salmon MDN.
Fatigue assessment of as‐built and heat‐treated Inconel 718 specimens produced by additive manufacturing including notch effects
Authors: Solberg Klas , Wan Di , Berto Filippo 
Published: July 2020

AbstractThe fatigue behaviour of notched and unnotched specimens produced by additively manufactured Inconel 718 were analysed in the as‐built and heat‐treated conditions. The surfaces display high roughness and defects acting as fatigue initiation sites. In the as‐built condition, fine subgrains were found, while in in the heat‐treated state, the subgrains were removed and the dislocation density recovered. SN‐curves are predicted based on tensile properties, hardness and defects obtained by fractography, using the
‐method.
Time‐dependent changes in the seroprevalence of COVID‐19 in asymptomatic liver disease outpatients in an area in Japan undergoing a second wave of COVID‐19
Authors: Suda Goki , Ogawa Koji , Kimura Megumi , Maehara Osamu , Kitagataya Takashi , Ohara Masatsugu , Tokuchi Yoshimasa , Kubo Akinori , Yamada Ren , Shigesawa Taku , Suzuki Kazuharu , Kawagishi Naoki , Nakai Masato , Sho Takuya , Natsuizaka Mitsuteru , Morikawa Kenichi , Sakamoto Naoya 
Published: July 2020

AimCoronavirus disease 2019 (COVID‐19) is a serious public health concern, with unclarified prevalence in Japan. Concomitant liver disease could increase the severity of COVID‐19 disease, and chronic liver disease patients sometimes require frequent admission and gastrointestinal endoscopy. Thus, clarifying the prevalence of asymptomatic COVID‐19 in outpatients with liver disease is essential for preventing nosocomial infections. We aimed to clarify the time‐dependent changes in COVID‐19 seroprevalence in liver disease outpatients, who were asymptomatic for COVID‐19, in an area of Japan experiencing a second wave of COVID‐19.MethodsWe included the preserved sera of 100, 300, and 300 consecutive liver disease outpatients, who were asymptomatic for COVID‐19, from May 2019, March 2020, and May 2020, respectively. The sera were analyzed immunochromatographically to detect immunoglobulin G against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) (KURABO) and by Elecsys Anti‐SARS‐CoV‐2‐assay (Roche Diagnostics).ResultsAnalysis of 100 cases from May 2019, before COVID‐19 became pandemic, revealed that the specificity of immunochromatographic tests and Elecsys were 98% (95% confidence interval [CI], 93–99.8%) and 100% (95% CI, 97–100%), respectively. Analysis of 300 cases from March 2020 revealed a seroprevalence of 0.3% (1/300; 95% CI, 0–1.8%) for COVID‐19 by Elecsys Anti‐SARS‐CoV‐2 assay. Analysis of 300 cases from May 2020 revealed a seroprevalence of 0% (0/300; 95% CI, 0–1.0%).ConclusionsThe Elecsys Anti‐SARS‐CoV‐2 assay has high specificity. The cumulative seroprevalence of COVID‐19 by the Elecsys Anti‐SARS‐CoV‐2 assay in outpatients with liver disease in Sapporo, who were asymptomatic for COVID‐19, was 0.17% (1/600; 95% CI, 0.0–0.9%) until May 2020.
Habitat preferences of the endangered diving beetleGraphoderus bilineatus: implications for conservation management
Authors: Kolar Vojtech , Boukal David S. 
Published: July 2020

AbstractPopulations of the endangered diving beetleGraphoderus bilineatusare decreasing across Europe. Evidence‐based conservation of its local populations requires good knowledge of its habitat requirements, but data from different countries are often incomplete or contradictory.Graphoderus bilineatuswas common until 1950s but then almost disappeared in the Czech Republic. Using data from a recent field survey in its core distributional area in the Czech Republic, we evaluate its habitat preferences at the habitat and microhabitat scale.We found that extensively managed fishponds can provide similarly suitable habitats forG. bilineatusas do more natural habitats including floodplain and sandpit pools, while the species is typically absent in intensively managed fishponds. All else being equal, the species is more likely found in larger water bodies surrounded by other wetlands and is more often absent at sites in agricultural landscape.We detected only weak preferences on the microhabitat scale. They suggested thatG. bilineatustends to occur in deeper water but closer to the shore and in microhabitats dominated byGlyceriaorTypha. These microhabitat associations partly differ from those reported from other countries.Moreover,G. bilineatuswas found at localities with higher species richness of large‐bodied aquatic beetles, both common and threatened, supporting the species status as an umbrella species for other aquatic macroinvertebrates.Our findings provide guidelines for conservation management of currently known localities and other potentially suitable sites, including the creation of new ones. Finally, our study reinforces the Annex II species status ofG. bilineatusin the Habitats and Species Directive.
Bullying victimization and obesogenic behaviour among adolescents aged 12 to 15 years from 54 low‐ and middle‐income countries
Authors: Smith Lee , Jacob Louis , Shin Jae Il , Tully Mark A , Pizzol Damiano , López‐Sánchez Guillermo F. , Gorely Trish , Yang Lin , Grabovac Igor , Koyanagi Ai 
Published: July 2020

SummaryBackgroundData on the association between obesogenic behaviours and bullying victimization among adolescents are scarce from low‐ and middle‐income countries.ObjectivesTo assess the associations between obesogenic behaviours and bullying victimization in 54 low‐ and middle‐income countries.MethodsCross‐sectional data from the global school‐based student health survey were analyzed. Data on bullying victimization and obesogenic behaviours were collected. The association between bullying victimization and the different types of obesogenic behaviour (anxiety‐induced insomnia, fast‐food consumption, carbonated soft‐drink consumption, no physical activity and sedentary behaviour) were assessed by country‐wise multivariable logistic regression analysis adjusting for age, sex, food insecurity and obesity with obesogenic behaviours being the outcome.ResultThe sample consisted of 153 929 students aged 12 to 15 years [mean (SD) age 13.8 (1.0) years; 49.3% girls]. Overall, bullying victimization (vs no bullying victimization) was significantly associated with greater odds for all types of obesogenic behaviour with the exception of physical activity, which showed an inverse association. Specifically, the ORs (95% CIs) were: anxiety‐induced sleep problems 2.65 (2.43‐2.88); fast‐food consumption 1.36 (1.27‐1.44); carbonated soft‐drink consumption 1.14 (1.08‐1.21); no physical activity 0.84 (0.79‐0.89); and sedentary behaviour 1.34 (1.25‐1.43).ConclusionIn this large representative sample of adolescents from low‐ and middle‐income countries, bullying victimization was found to be associated with several, but not all, obesogenic behaviours.
Regenerative treatment for male stress urinary incontinence by periurethral injection of adipose‐derived regenerative cells: Outcome of the ADRESU study
Authors: Gotoh Momokazu , Shimizu Shinobu , Yamamoto Tokunori , Ishizuka Osamu , Yamanishi Tomonori , Mizokami Atsushi , Narimoto Kazutaka , Toriyama Kazuhiro , Kamei Yuzuru , Nakayama Shinobu , Kuwatsuka Yachiyo , Mizuno Masaaki , Hirakawa Akihiro 
Published: July 2020

ObjectivesTo report the outcome of the ADRESU study, a multicenter, single‐arm, investigator‐initiated clinical trial to confirm the efficacy and safety of regenerative treatment for male patients with stress urinary incontinence.MethodsThe participants were male patients with mild‐to‐moderate stress urinary incontinence persisting for >1 year after prostatectomy. Autologous adipose‐derived regenerative cells were isolated using the Celution system from adipose tissue obtained by liposuction. Adipose‐derived regenerative cells and mixture of adipose‐derived regenerative cells with adipose tissue were transurethrally injected into the rhabdosphincter and submucosal space of the urethra, respectively. The primary end‐point was the proportion of patients with improvement of the urine leakage volume at 52 weeks (or last visit within 52 weeks). Improvement of leakage volume was defined as a decrease from baseline >50% by the 24‐h pad test. A total of 10 secondary end‐points were set.ResultsA total of 45 patients satisfying the eligibility criteria were enrolled. The primary end‐point was met; the proportion of patients with improvement in leakage volume at 52 weeks was 37.2% (95% confidence interval 23.0–53.3%). No serious adverse events with causal relationships to the adipose‐derived regenerative cells were encountered. There was a progressive improvement in secondary end‐points. In the King’s Health Questionnaire, improvement of quality of life scores showed greater improvement in responders, as compared with non‐responders.ConclusionsFindings from the ADRESU study suggest the efficacy and safety of regenerative treatment for male patients with mild‐to‐moderate stress urinary incontinence.
A collaborative approach in patient education for diabetes foot and wound care: A pragmatic randomised controlled trial
Authors: Heng Marabelle Liwen , Kwan Yu Heng , Ilya Nik , Ishak Izza Atiqa , Jin Patricia Huixia , Hogan Debbie , Carmody David 
Published: July 2020

AbstractFoot care education is an important strategy in reducing lower limb complications. There is evidence that contemporary communication approaches can improve patient education outcomes. To inform the potential of such methods in diabetic foot education, we trialled a collaborative approach in patient education counselling in a podiatry clinic. We conducted a single‐blind pragmatic randomised controlled trial on 52 diabetes patients who had an active foot ulcer. Participants were randomised to either collaborative education or traditional didactic education. Outcomes on knowledge and self‐care behaviours were collected via a pre and post study questionnaire (max score: 75). The study ended at 12 weeks or when the wound healed prior. 42 (80.7%) participants completed the study. The collaborative patient education group had a significant increase in score post‐study (38.8 ± 8.5) compared to pre‐study (32.8 ± 6.9; P < .001). The control group had no significant increase in score post study. The difference in scores between groups had a moderate effect size (d = 0.54). The use of a collaborative approach in patient education was able to produce significantly greater increase in knowledge retention and self‐care behaviours, without the need for additional consultation time in a podiatry clinic.
lncRNA MIR4435‐2HG promoted clear cell renal cell carcinoma malignant progression via miR‐513a‐5p/KLF6 axis
Authors: Zhu Kai , Miao Chenkui , Tian Ye , Qin Zhiqiang , Xue Jianxin , Xia Jiadong , Zhu Shenhao , Xu Aiming , Yang Jie , Wang Zengjun 
Published: July 2020

AbstractLong non‐coding RNAs (lncRNAs) take various biological effects in clear cell renal cell carcinoma (ccRCC) mostly through sponging with microRNAs (miRNAs). lncRNA MIR4435‐2HG is found to promote tumour progression in gastric cancer, glioblastoma and hepatocellular carcinoma. However, the role of lncRNA MIR4435‐2HG in ccRCC progression remains unknown. The purpose of this research was to investigate the potential molecular mechanism of lncRNA MIR4435‐2HG regarding the regulation of ccRCC initiation and progression. In this study, we found the up‐regulation of MIR4435‐2HG in ccRCC tissues and cell lines. Functionally, overexpression of MIR4435‐2HG promoted the proliferation as well as the metastasis in ccRCC cell lines, whereas knockdown of MIR4435‐2HG inhibited the above changes. Then, bioinformatic analysis and luciferase reporter assays confirmed the negative regulation effect of MIR4435‐2HG on miR‐513a‐5p. And further investigations showed that KLF6, which collected from the intersection of databases, was the potential conjugated mRNAs of miR‐513a‐5p. Finally, the rescue experiments revealed the relation among MIR4435‐2HG and KLF6, which showed that KLF6 could reverse the promoting effect of MIR4435‐2HG on ccRCC in vitro and in vivo. Therefore, our findings provided insight into the mechanisms of MIR4435‐2HG in ccRCC and revealed an alternative target for the clinical diagnosis and treatment of ccRCC.
Melatonin against acute ischaemic stroke dependently via suppressing both inflammatory and oxidative stress downstream signallings
Authors: Chen Kuan‐Hung , Lin Kun‐Chen , Ko Sheung‐Fat , Chiang John Y. , Guo Jun , Yip Hon‐Kan 
Published: July 2020

AbstractThis study tested the hypothesis that melatonin (Mel) therapy preserved the brain architectural and functional integrity against ischaemic stroke (IS) dependently through suppressing the inflammatory/oxidative stress downstream signalling pathways. Adult male B6 (n = 6 per each B6 group) and TLR4 knockout (ie TLR4−/−) (n = 6 per each TLR4−/− group) mice were categorized into sham control (SCB6), SCTLR4−/−, ISB6, ISTLR4−/−, ISB6 + Mel (i.p. daily administration) and ISTLR4−/− + Mel (i.p. daily administration). By day 28 after IS, the protein expressions of inflammatory (HMBG1/TLR2/TLR4/MAL/MyD88/RAM TRIF/TRAF6/IKK‐α/p‐NF‐κB/nuclear‐NF‐κB/nuclear‐IRF‐3&7/IL‐1β/IL‐6/TNF‐α/IFN‐γ) and oxidative stress (NOX‐1/NOX‐2/ASK1/p‐MKK4&7/p‐JNK/p‐c‐JUN) downstream pathways as well as mitochondrial‐damaged markers (cytosolic cytochrome C/cyclophilin D/SRP1/autophagy) were highest in group ISB6, lowest in groups SCB6 and SCTLR4−/−, lower in group ISTLR4−/− + Mel than in groups ISTLR4−/− and ISB6 + Mel and lower in group ISB6 + Mel than in group ISTLR4−/− (all P < .0001). The brain infarct volume, brain infarct area and the number of inflammatory cells in brain (CD14/F4‐88) and in circulation (MPO+//Ly6C+/CD11b+//Ly6G+/CD11b+) exhibited an identical pattern, whereas the neurological function displayed an opposite pattern of inflammatory protein expression among the six groups (all P < .0001). In conclusion, TLR inflammatory and oxidative stress signallings played crucial roles for brain damage and impaired neurological function after IS that were significantly reversed by Mel therapy.
Long non‐coding RNA HEIH suppresses the expression of TP53 through enhancer of zeste homolog 2 in oesophageal squamous cell carcinoma
Authors: Ding XinYu , Qi Chen , Min Jie , Xu ZhiFei , Huang KeNan , Tang Hua 
Published: July 2020

AbstractIt is increasingly evident that the molecular and biological functions of long non‐coding RNAs (lncRNA) are vital for understanding the molecular biology and progression of cancer. The lncRNA‐HEIH, a newly identified lncRNA, has been demonstrated to be up‐regulated in hepatocellular cancer. However, little is known about its role in oesophageal squamous cell carcinoma (ESCC). In the present study, an obvious up‐regulation of lncRNA‐HEIH was observed in ESCC compared to the adjacent normal tissues. Meanwhile, patients with high expression of lncRNA‐HEIH have significantly poorer prognosis than those with low expression. We further found that lncRNA‐HEIH was associated with enhancer of zeste homolog 2 (EZH2) and that this association led to the repression of TP53. These findings indicate that lncRNA‐HEIH may serve as a prognostic marker and a potential therapeutic target for ESCC.