bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unmeasurable small size superficial and deep foveal avascular zone in nanophthalmos: the Collaborative Nanophthalmos OCTA Study
Authors: Mansour Ahmad M , Stewart Michael W , Yassine Salma W , Mehanna Carl-Joe Z , Casella Antonio Marcelo B , Hamam Rola N , Chhablani Jay , Lima Luiz H , Shinojima Ari , Kaneko Hiroyuki , Younis Muhammad H , Shahin Hasan K , Jalali Subhadra , Kucukerdonmez Cem , Saatci Ali O , Chakurkar Renuka , Shields Carol L 
Published: October 2018

AimTo study the macular structure and vasculature in consecutive nanophthalmic eyes using optical coherence tomography angiography.MethodsThis is a prospective, multicentre, cross-sectional study of patients with nanophthalmos (one or both eyes). The superficial and deep foveal avascular zones (FAZ) were measured both manually and with the machine’s built-in automated measurement tool. Correlations between best corrected visual acuity (BCVA), central macular thickness (CMT) and subfoveolar choroidal thickness (SFCT) were calculated.ResultsSixty-five eyes of 35 subjects (16 men and 19 women) with a mean age of 37.4 years were analysed. The mean±SD of refractive error was 14.3±3.2 dioptres, axial length was 16.4±1.6 mm, CMT was 410.2±128.3 µm and SFCT was 450.1±108.3 µm. FAZ was unmeasurable small size in both the superficial and deep capillary plexus in all eyes, along with tortuosity of the superficial foveal capillaries and large vessels. Foveal folds were present in 29 eyes. Disc drusen was detected in 27 eyes and was absent in 31 eyes, while fundus autofluorescence was positive in 17 and negative in 24 eyes. BCVA varied from 20/20 to 20/800, with a mean of 20/76. Using Spearman’s correlation, logarithm of the minimum angle of resolution BCVA correlated negatively with axial length (r=−0.30; p=0.015).ConclusionsFAZ attenuation, capillary tortuosity, foveal folds and thickened subfoveal choroid characterise the nanophthalmic macula. These findings may result from a redundant retina and the absence of apoptotic foveolar retraction because of developmental arrest of the optic vesicle after closure of the embryonic fissure.
Normothermic versus hypothermic cardiopulmonary bypass in low-risk paediatric heart surgery: a randomised controlled trial
Authors: Caputo Massimo , Pike Katie , Baos Sarah , Sheehan Karen , Selway Kathleen , Ellis Lucy , Stoica Serban , Parry Andrew , Clayton Gemma , Culliford Lucy , Angelini Gianni D , Pandey Ragini , Rogers Chris A 
Published: October 2018

ObjectiveTo compare normothermic (35°C–36°C) versus hypothermic (28°C) cardiopulmonary bypass (CPB) in paediatric patients undergoing open heart surgery to test the hypothesis that normothermic CPB perfusion maintains the functional integrity of major organ systems leading to faster recovery.MethodsTwo single-centre, randomised controlled trials (known as Thermic-1 and Thermic-2, respectively) were carried out to compare the effectiveness and acceptability of normothermic versus hypothermic CPB in children with congenital heart disease undergoing open heart surgery. In both studies, the co-primary clinical outcomes were duration of inotropic support, intubation time and postoperative hospital stay.ResultsIn total, 200 participants were recruited; 59 to the Thermic-1 study and 141 to the Thermic-2 study. 98 patients received normothermic CPB and 102 patients received hypothermic CPB. There were no significant differences between the treatment groups for any of the co-primary outcomes: inotrope duration HR=1.01, 95% CI (0.72 to 1.41); intubation time HR=1.14, 95% CI (0.86 to 1.51); postoperative hospital stay HR=1.06, 95% CI (0.80 to 1.40). Differences favouring normothermia were found in urea nitrogen at 2 days geometric mean ratio (GMR)=0.86 95% CI (0.77 to 0.97); serum creatinine at 3 days GMR=0.89, 95% CI (0.81 to 0.98); urinary albumin at 48 hours GMR=0.32, 95% CI (0.14 to 0.74) and neutrophil gelatinase-associated lipocalin at 4 hours GMR=0.47, 95% CI (0.22 to 1.02), but not at other postoperative time points.ConclusionsNormothermic CPB is as safe and effective as hypothermic CPB and can be routinely adopted as a perfusion strategy in low-risk infants and children undergoing open heart surgery.Trial registration numberISRCTN93129502.
Cortical correlates of behavioural change in amyotrophic lateral sclerosis
Authors: Consonni Monica , Cappa Stefano F , Dalla Bella Eleonora , Contarino Valeria Elisa , Lauria Giuseppe 
Published: October 2018

BackgroundBehavioural changes in amyotrophic lateral sclerosis (ALS) are heterogeneous. The study aim was to identify the behavioural profiles of non-demented patients with ALS and their neuroimaging correlates and to elucidate if they are comparable to those reported in studies of the behavioural-variant of frontotemporal dementia (bvFTD).MethodsBehavioural changes of 102 non-demented patients with ALS were assessed through the Frontal Behavioural Inventory (FBI), a 24-item scale assessing different behavioural modifications, mainly chosen from the core clinical features of FTD. Principal component analysis (PCA) was used to detect distinct clusters of behavioural changes based on FBI subscores. The cortical thinning related to each behavioural profile was analysed in 29 patients with ALS. Cronbach’s α was used to test the reliability of bvFTD-related FBI clustering in our cohort.ResultsSixty patients with ALS had FBI score≥1. PCA identified three phenotypic clusters loading on disinhibited/hostile, dysexecutive and apathetic FBI subscores. Imaging analyses revealed that the thinning of bilateral orbitofrontal cortex was related to apathy, the right frontotemporal and cingular cortex to the disinhibited/hostile profile and the left precuneus cortex to the dysexecutive behaviours. The bvFTD-associated aggressive profile reliably applied to our cohort.ConclusionsIn non-demented patients with ALS, different behavioural profiles could be identified. The right frontotemporal and cingular cortex thinning was the hallmark of the behavioural profile mostly overlapping that described in bvFTD. Our findings provide the unbiased identification of determinants relevant for a novel stratification of patients with ALS based on their behavioural impairment, which might be useful as proxy of cognitive decline.
Risk of asthma and chronic obstructive pulmonary disease in a large historical cohort of Danish firefighters
Authors: Pedersen Julie Elbæk , Ugelvig Petersen Kajsa , Ebbehøj Niels Erik , Bonde Jens Peter , Hansen Johnni 
Published: October 2018

ObjectiveFirefighters are exposed to numerous respiratory hazards, but large studies on the risk of pulmonary disease are scarce. The objective of this study was to examine incidence of asthma and chronic obstructive pulmonary disease (COPD) in a nationwide cohort of Danish firefighters.MethodsWe used individual historical employment records on 11 968 Danish male firefighters primarily supplied by trade unions and fire agencies. Furthermore, we used the Supplementary Pension Fund Register to form an occupational reference group consisting of military employees. Information on respiratory incidence was retrieved from the nationwide Danish National Patient Registry. Age and calendar time standardised incidence ratio (SIR) and Poisson regression analyses (incidence rate ratio) were used for estimation of risks, including 95% CIs.ResultsCompared with military employees, the overall age and calendar-time adjusted risk for asthma was significantly increased among full-time firefighters (SIR=1.58, 95% CI 1.32 to 1.88), but not among part-time/volunteer firefighters. Full-time firefighters’ risk for asthma did not vary by duration of employment. No consistent evidence of an increased risk for chronic obstructive pulmonary disease was detected.ConclusionDanish firefighters have an increased risk of asthma, but the causes, whether occupational or not, remain to be established.
Provincial-level cancer burden attributable to active and second-hand smoking in China
Authors: Xia Changfa , Zheng Rongshou , Zeng Hongmei , Zhou Maigeng , Wang Lijun , Zhang Siwei , Zou Xiaonong , Sun Kexin , Yang Zhixun , Li He , Parascandola Mark , Islami Farhad , Chen Wanqing 
Published: October 2018

BackgroundUnderstanding disparities in the burden of cancer attributable to smoking is crucial to inform and improve tobacco control measures. In this report, we estimate the population attributable fraction (PAF) of cancers deaths attributable to smoking at the national and provincial levels in China.MethodsUsing cancer mortality data from 978 counties, smoking data from a nationwide survey and relative risks from a prospective study of 0.5 million adults in China, we calculated the absolute (non-standardised) and standardised numbers and proportions of cancer deaths among adults 30 years and older attributable to active and second-hand smoking in 2014 across all 31 provinces in Mainland China.ResultsThe estimated number of cancer deaths attributable to smoking in China in 2014 was 342 854 among men and 40 313 among women, of which second-hand smoking accounted for 1.8% and 50.0%, respectively. Among men, the absolute PAF in China was 23.8%, ranging from 14.6% in Xinjiang to 26.8% in Tianjin; the overall standardised PAF was 22.2%, ranging from 15.7% in Xinjiang to 26.0% in Guizhou. Among women, the overall absolute and standardised PAFs were 4.8% and 4.0%, ranging from 1.8% and 1.6% in Jiangxi to 14.9% and 9.6% in Heilongjiang, respectively. Overall, provinces with the highest standardised PAFs among men were located in Southwest China and among women in the Northeast.ConclusionsComprehensive smoke-free policies in China should expand to all provinces, notably those with a higher burden of cancer attributable to smoking, instead of being mostly limited to Beijing and some other metropolitan areas.
Palliative limb‐sparing photodynamic therapy with chemotherapy in a dog with osteosarcoma of the proximal tibia
Authors: Osaki Tomohiro , Murahata Yusuke , Yamashita Masamichi , Isao Sakata , Okamoto Yoshiharu 
Published: October 2018

Canine osteosarcoma conveys a poor prognosis. This long‐term follow‐up report describes using photodynamic therapy with intra‐arterial chemotherapy as palliation in canine osteosarcoma of the proximal tibia. A 10‐year‐old male Boston terrier dog presented with right hindlimb lameness; osteosarcoma of the right tibia was diagnosed. The owner chose palliative limb‐sparing photodynamic therapy with intra‐arterial chemotherapy. Right hindlimb lameness disappeared 24 days after the first treatment. In total, 210 days after the first treatment, post‐contrast T1‐weighted MRI showed a decreased gadolinium‐enhancing area within the tumour. And 254 days after the first treatment, the dog underwent the tenth treatment. Then 287 days after the first treatment, abdominal radiography showed an approximately 6‐ cm iliac lymph node. The dog died 321 days after the first treatment; lameness did not recur. Palliative photodynamic therapy with chemotherapy can be viable and feasible in osteosarcoma of the proximal tibia; more research is needed.
James Robert Temple Hazell: A Pioneer of African Hydrogeology
Authors: Adekile Dotun , Carter Richard 
Published: October 2018

Abstract
James Robert Temple Hazell, known to many as Robin Hazell, passed away in March 2017, in Bodmin, Cornwall, aged 89, after a professional life spanning close to 70 years. Robin's main contributions addressed the exploration for and development of groundwater especially in hard rock areas. Much of this work was undertaken in the country of his first overseas posting, Nigeria, and was primarily spent in the field. He started his career in south and east Nigeria mapping groundwater resources and uncovering links between geology, baseflow and the likelihood of surface water being contaminated. In northern Nigeria he developed conceptual models for how groundwater existed in fractured rocks, and the importance of mineralogy and fractures, and used this knowledge to help site many thousands of successful boreholes. Perhaps Robin's greatest legacy, however, was his generosity in teaching and mentoring other hydrogeologists. Robin's last public contribution was his paper at the conference on Groundwater in Fractured Rocks, the subject of this Special Publication.
Plasma Exchange Can Be an Alternative Therapeutic Modality for Severe Cytokine Release Syndrome after Chimeric Antigen Receptor-T Cell Infusion: A Case Report
Authors: Xiao Xia , He Xiaoyuan , Li Qing , Zhang Huan , Meng Juanxia , Jiang Yanyu , Deng Qi , Zhao Mingfeng 
Published: October 2018

Abstract

Background:
Tumor immunotherapy with chimeric antigen receptor-T cells (CAR-T) is a promising new treatment for B-cell malignancies and has produced exciting results. However, cytokine release syndrome (CRS) is the most significant toxicity associated with this treatment and can be life-threatening.

Case Presentation:
A 23-year-old male patient had been diagnosed with relapsed and refractory B-cell acute lymphocytic leukemia. The patient was recruited into our CAR-T clinical trial, and 1 × 106/kg of engineered anti-CD19 CAR-T cells was administered. After infusion of CAR-T cells (day 0), the patient underwent a typical CRS reaction, with increases in fever, muscle soreness, and inflammatory cytokines. He was treated with antiallergic and antipyretic drugs, glucocorticoids, and tocilizumab (4 mg/kg, days 3 and 5). However, CRS was not under control, and his condition rapidly deteriorated. He was transferred to the intensive care unit, where dexamethasone 10 mg q6h was administered, and plasma exchange was performed, with 3,000 mL of plasma replaced by fresh frozen plasma per day for 3 consecutive days. His symptoms gradually improved, and the CRS-related symptoms were relieved. Additionally, a bone marrow smear showed no lymphoblast cells, and minimal residual disease was negative on day 28. The patient was eventually discharged in a normal condition.

Conclusions:
CRS is caused by an exaggerated systemic immune response, potentially resulting in organ damage that can be fatal. Although therapeutic plasma exchange is not included in CRS management guidelines, this case shows that plasma exchange is feasible in at least some patients with severe CRS.
Ketoconazole and Posaconazole Selectively Target HK2-expressing Glioblastoma Cells
Authors: Agnihotri Sameer , Mansouri Sheila , Burrell Kelly , Li Mira , Mamatjan Yasin , Liu Jeff , Nejad Romina , Kumar Sushil , Jalali Shahrzad , Singh Sanjay K. , Vartanian Alenoush , Chen Eric Xueyu , Karimi Shirin , Singh Olivia , Bunda Severa , Mansouri Alireza , Aldape Kenneth D. , Zadeh Gelareh 
Published: October 2018

Abstract

Purpose:
Hexokinase II (HK2) protein expression is elevated in glioblastoma (GBM), and we have shown that HK2 could serve as an effective therapeutic target for GBM. Here, we interrogated compounds that target HK2 effectively and restrict tumor growth in cell lines, patient-derived glioma stem cells (GSCs), and mouse models of GBM.
Experimental Design: We performed a screen using a set of 15 drugs that were predicted to inhibit the HK2-associated gene signature. We next determined the EC50 of the compounds by treating glioma cell lines and GSCs. Selected compounds showing significant impact in vitro were used to treat mice and examine their effect on survival and tumor characteristics. The effect of compounds on the metabolic activity in glioma cells was also assessed in vitro.

Results:
This screen identified the azole class of antifungals as inhibitors of tumor metabolism. Among the compounds tested, ketoconazole and posaconazole displayed the greatest inhibitory effect on GBM both in vitro and in vivo. Treatment of mice bearing GBM with ketoconazole and posaconazole increased their survival, reduced tumor cell proliferation, and decreased tumor metabolism. In addition, treatment with azoles resulted in increased proportion of apoptotic cells.

Conclusions:
Overall, we provide evidence that azoles exert their effect by targeting genes and pathways regulated by HK2. These findings shed light on the action of azoles in GBM. Combined with existing literature and preclinical results, these data support the value of repurposing azoles in GBM clinical trials.
The Increased Expression of Estrogen-Related Receptor α Correlates with Wnt5a and Poor Prognosis in Patients with Glioma
Authors: Zhang Liudi , Zhu Yingfeng , Cheng Haixia , Zhang Jinsen , Zhu Yuqian , Chen Haifei , Chen Lu , Qi Huijie , Ren Guoqiang , Tang Jianmin , Zhong Mingkang , Hua Wei , Shi Xiaojin , Li Qunyi 
Published: October 2018

Abstract
Malignant glioma is an often fatal type of cancer. Elevated expression of the orphan nuclear receptor estrogen-related receptor alpha (ERRα) is an unfavorable factor for malignant progression and poor prognosis in several cancers, although the mechanism by which this receptor affects the pathophysiology of cancers remains obscure. However, few studies have been conducted in regard to the role of ERRα in glioma. In the current study, we found that elevated expression of ERRα was observed in 107 glioma cases by means of IHC. Clinically, high expression of ERRα was associated with later stages of disease progression and clinical outcome of patients with glioma. ERRα had the ability to promote cell proliferation and migration in glioma cell lines. Moreover, in a xenograft model, we also found that silencing ERRα had an inhibitory effect on the growth of glioma. Further investigation confirmed that ERRα was involved in the carcinogenesis of glioma via the regulation of the Wnt5a signal pathway in vitro and in vivo. Our study was first to show the overexpression of ERRα in glioma tissues and a direct correlation between ERRα expression and clinical prognosis of glioma. Together, these data reveal that ERRα has prognostic significance in glioma, and targeting ERRα may provide a reliable therapeutic strategy for the treatment for human glioma.
KRAS and EGFR Amplifications Mediate Resistance to Rociletinib and Osimertinib in Acquired Afatinib-Resistant NSCLC Harboring Exon 19 Deletion/T790M in EGFR
Authors: Nakatani Kaori , Yamaoka Toshimitsu , Ohba Motoi , Fujita Ken-Ichi , Arata Satoru , Kusumoto Sojiro , Taki-Takemoto Iori , Kamei Daisuke , Iwai Shinichi , Tsurutani Junji , Ohmori Tohru 
Published: October 2018

Abstract
The critical T790M mutation in EGFR, which mediates resistance to first- and second-generation EGFR tyrosine kinase inhibitors (TKI; gefitinib, erlotinib, and afatinib), has facilitated the development of third-generation mutation-selective EGFR TKIs (rociletinib and osimertinib). We previously reported heterogeneous afatinib-resistant mechanisms, including emergence of T790M-EGFR, and responses to third-generation EGFR TKIs. Here, we used afatinib-resistant lung adenocarcinoma cells [AfaR (formerly AFR3) cells], carrying exon 19 deletion/T790M in EGFR. To identify the novel resistance mechanisms in post-afatinib treatment, RocR1/RocR2 and OsiR1/OsiR2 cells were established using increasing concentrations of rociletinib and osimertinib, respectively. Attenuation of exon 19 deletion and T790M was confirmed in both rociletinib-resistant cells; in addition, EGFR and KRAS amplification was observed in RocR1 and RocR2, respectively. Significant KRAS amplification was observed in the osimertinib-resistant cell lines, indicating a linear and reversible increase with increased osimertinib concentrations in OsiR1 and OsiR2 cells. OsiR1 cells maintained osimertinib resistance with KRAS amplification after osimertinib withdrawal for 2 months. OsiR2 cells exhibited KRAS attenuation, and osimertinib sensitivity was entirely recovered. Phospho-EGFR (Y1068) and growth factor receptor–bound protein 2 (GRB2)/son of sevenless homolog 1 (SOS1) complex was found to mediate osimertinib resistance in OsiR1 cells with sustained KRAS activation. After 2 months of osimertinib withdrawal, this complex was dissociated, and the EGFR signal, but not the GRB2/SOS1 signal, was activated. Concomitant inhibition of MAPK kinase and EGFR could overcome osimertinib resistance. Thus, we identified a heterogeneous acquired resistance mechanism for third-generation EGFR TKIs, providing insights into the development of novel treatment strategies.
Neuroregeneration and Vascular Protection by Citalopram in Acute Ischemic Stroke (TALOS)
Authors: Kraglund Kristian Lundsgaard , Mortensen Janne Kaergaard , Damsbo Andreas Gammelgaard , Modrau Boris , Simonsen Sofie Amalie , Iversen Helle Klingenberg , Madsen Morten , Grove Erik Lerkevang , Johnsen Søren Paaske , Andersen Grethe 
Published: October 2018

Background and Purpose—
Recent studies indicate a possible beneficial effect on neuroregeneration and vascular protection of selective serotonin reuptake inhibitors after stroke. We conducted a national multicentre study to explore these effects.

Methods—
The TALOS study (The Efficacy of Citalopram Treatment in Acute Stroke) is a Danish placebo-controlled, randomized, double-blind study of citalopram started within 7 days after symptom onset to detect improvement in functional outcomes and cardiovascular protection in nondepressed, first-ever ischemic stroke. Study medication was given as add-on to standard medical care and treatment duration and follow-up was 6 months. There were 2 coprimary outcomes: changes in functional disability from 1 to 6 months on the modified Rankin Scale, and a composite vascular end point of transient ischemic attack/stroke, myocardial infarction, or vascular mortality during the first 6 months.

Results—

We enrolled 642 patients randomized to either citalopram (n=319) or placebo (n=323). Median National Institutes of Health Stroke Scale was 5.3 (range, 0–27) versus 4.8 (range, 0–28) at admission. Improvement in functional recovery from 1 to 6 months occurred in 160 (50%) patients on citalopram and 136 (42%) on placebo (odds ratio, 1.27; 95% CI, 0.92–1.74;
P
=0.057). When dropouts before 31 days were excluded (n=90), the analysis population showed an odds ratio of 1.37 (95% CI, 0.97–1.91;
P
=0.07). During a median follow-up of 150 days, 23 (7%) patients in the citalopram group and 26 (8%) patients in the placebo group had a primary, vascular end point (hazard ratio, 0.89; 95% CI, 0.50–1.60;
P
=0.24). A total of 28 patients (4%) died (16 versus 12;
P
=0.42) during the study.

Conclusions—
Early citalopram treatment did not improve functional recovery in nondepressed ischemic stroke patients within the first 6 months, although a borderline statistical significant effect was observed in the analysis population. The risk of cardiovascular events was similar between treatment groups, and citalopram treatment was well tolerated.

Clinical Trial Registration—

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01937182. URL:
https://www.clinicaltrialsregister.eu/
. EudraCT number: 2013-002253-30.