bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cascade biotransformation of estrogens by Isaria fumosorosea KCh J2
Authors: Kozłowska Ewa , Dymarska Monika , Kostrzewa-Susłow Edyta , Janeczko Tomasz 
Published: July 2019

AbstractEstrone, estradiol, ethynylestradiol and estrone 3-methyl ether underwent a biotransformation process in the submerged culture of Isaria fumosorosea KCh J2. Estrone was transformed into seven metabolites, four of which were glycosylated. Estradiol was selectively glycosylated at C-3 and then transformed to D-ring lactone. Ethynylestradiol was coupled with methylglucoside and 6β-hydroxyderivative was obtained. Estrone 3-methyl ether was not transformed indicating that a free hydroxyl group at C-3 is necessary for glycosylation. Baeyer–Villiger oxidation combined with hydroxylation and glycosylation was observed. All glycosides obtained in this study are 3-O-β-methylglucosides.
Multimodal structural disease progression of retinitis pigmentosa according to mode of inheritance
Authors: Jauregui Ruben , Takahashi Vitor K. L. , Park Karen Sophia , Cui Xuan , Takiuti Julia T. , Lima de Carvalho Jose Ronaldo , Tsang Stephen H. 
Published: July 2019

AbstractWe analyze disease progression in retinitis pigmentosa (RP) according to mode of inheritance by quantifying the progressive decrease of the ellipsoid zone (EZ) line width on spectral domain optical coherence tomography (SD-OCT) and of the dimensions of the hyperautofluorescent ring on short-wave fundus autofluorescence (SW-FAF). In this retrospective study of 96 patients, average follow-up time was 3.2 ± 1.9 years. EZ line width declined at a rate of −123 ± 8 µm per year, while the horizontal diameter and ring area declined at rates of −131 ± 9 µm and −0.5 ± 0.05 mm2 per year, respectively. Disease progression was found to be slowest for autosomal dominant RP and fastest for X-linked RP, with autosomal recessive RP progression rates between those of adRP and XLRP. EZ line width and ring diameter rates of disease progression were significantly different between each mode of inheritance. By using EZ line width and horizontal diameter as parameters of disease progression, our results confirm that adRP is the slowest progressing form of RP while XLRP is the fastest. Furthermore, the reported rates can serve as benchmarks for investigators of future clinical trials for RP and its different modes of inheritance.
Discovery of novel inhibitors of ribosome biogenesis by innovative high throughput screening strategies
Authors: Scull Catherine E. , Zhang Yinfeng , Tower Nichole , Rasmussen Lynn , Padmalayam Indira , Hunter Robert , Zhai Ling , Bostwick Robert , Schneider David A. 
Published: July 2019

Abstract
Over the past two decades, ribosome biogenesis has emerged as an attractive target for cancer treatment. In this study, two high-throughput screens were used to identify ribosome biogenesis inhibitors. Our primary screen made use of the HaloTag selective labeling strategy to identify compounds that decreased the abundance of newly synthesized ribosomes in A375 malignant melanoma cells. This screen identified 5786 hit compounds. A subset of those initial hit compounds were tested using a secondary screen that directly measured pre-ribosomal RNA (pre-rRNA) abundance as a reporter of rRNA synthesis rate, using quantitative RT-PCR. From the secondary screen, we identified two structurally related compounds that are potent inhibitors of rRNA synthesis. These two compounds, Ribosome Biogenesis Inhibitors 1 and 2 (RBI1 and RBI2), induce a substantial decrease in the viability of A375 cells, comparable to the previously published ribosome biogenesis inhibitor CX-5461. Anchorage-independent cell growth assays further confirmed that RBI2 inhibits cell growth and proliferation. Thus, the RBI compounds have promising properties for further development as potential cancer chemotherapeutics.
Cisplatin contributes to programmed death-ligand 1 expression in bladder cancer through ERK1/2-AP-1 signaling pathway
Authors: Tsai Te-Fu , Lin Ji-Fan , Lin Yi-Chia , Chou Kuang-Yu , Chen Hung-En , Ho Chao-Yen , Chen Po-Chun , Hwang Thomas I-Sheng 
Published: July 2019

Abstract
Bladder cancer (BC) is the second most common urologic malignancy and the ninth most common malignancy worldwide. Surgical resection is the mainstay of treatment for patients with early-stage disease, whereas therapeutic options are limited for patients with advanced-stage or residual BC. Programmed cell death ligand-1 (PD-L1) is an important target for immunotherapy. It is known that PD-L1 is overexpressed in BC; a clinical trial involving PD-L1 immune checkpoint inhibitors in advanced BC is ongoing. In the present study, we used Western blot and quantitative real-time PCR (qPCR) to define the expression level of PD-L1 after cisplatin treatment in BC-derived cell lines. The signal activation was also evaluated by Western blot in BC-derived cell lines. We found that chemotherapeutic drug cisplatin can induce PD-L1 but not PD-L2 expression in BC-derived cell lines. Furthermore, the expression level of PD-L1 was increased in a dose- and time-dependent manner after cisplatin treatment. The cisplatin-induced PD-L1 expression is mainly mediated by ERK1/2 but not Akt/mTOR signal pathway. Moreover, we found that cisplatin activates transcription factor activator protein-1 (AP-1) to regulate PD-L1 expression. The chemotherapy drug such as cisplatin may trigger resistance of BC through PD-L1 up-regulation. The present study suggests that PD-L1 antibody should be used concomitantly with chemotherapy in the setting of advanced and metastatic BC.
RAS in pancreatic cancer
Authors: Lanfredini Simone , Thapa Asmita , O'Neill Eric 
Published: July 2019

Abstract
The pancreas is a gland composed mainly by endocrine and exocrine cells, giving rise to three main tumour types. Pancreatic neuroendocrine tumour or PNET arise from the endocrine portion of the pancreas. On the contrary, pancreatic exocrine neoplasms include pancreatic ductal adenocarcinoma (PDAC) and acinar cell carcinoma. PDAC is the most common type of pancreatic cancer and one of the leading causes of cancer-related death. It has been shown that less than 3% of PDAC patients have an overall survival of up to 5 years in the U.K. This mainly arises since the majority of patients diagnosed with PDAC present with advanced unresectable disease, which is highly resistant to all forms of chemotherapy and radiotherapy. Activating mutations of an isoform of the RAS protein, KRAS, are found in almost all PDAC cases and occur during early stages of malignant transformation. KRAS mutations play a critical role as they are involved in both initiating and maintaining PDAC development. The interaction of RAS with GDP/GTP along with its recruitment to the membrane affects transduction of its activating signals to downstream effectors. In this review, we aim to summarise different mutations of RAS and their prevalence in pancreatic cancer along with other RAS-induced tumours. In addition, we briefly discuss the genetically engineered mouse models that have been developed to study KRAS-mutated adenocarcinomas in the pancreas. These provide an opportunity to also address the importance of targeting RAS for better treatment response in PDAC patients along with the challenges incurred herein.
Is there a role for prostanoid-mediated inhibition of IL-6trans-signalling in the management of pulmonary arterial hypertension?
Authors: Durham Gillian A. , Palmer Timothy M. 
Published: July 2019

AbstractInflammation has been highlighted as a key factor in pulmonary arterial hypertension (PAH) development, particularly interleukin-6 (IL-6). IL-6 activates JAK-STAT signalling to induce transcription of pro-inflammatory and pro-angiogenic genes, enabling PAH progression, as well as the transcription of suppressor of cytokine signalling 3 (SOCS3) which limits IL-6 signalling. Current PAH therapies include prostanoid drugs which induce vasodilation via stimulating intracellular 3′,5′-cyclic adenosine monophosphate (cAMP) levels. cAMP can also inhibit IL-6-mediated endothelial dysfunction via the induction of SOCS3. Thus, we propose that an important mechanism by which cAMP-mobilising prostanoid drugs limit PAH is by inhibiting IL-6-mediated pulmonary inflammation and remodelling via SOCS3 inhibition of IL-6 signalling. Further clarification may result in effective strategies with which to target the IL-6/JAK-STAT signalling pathway in PAH.
A Comparison of the Prevalence Rates of Language Impairment Before and After Response-to-Intervention Implementation
Authors: Hall-Mills Shannon 
Published: July 2019

Purpose
This research note presents a secondary data analysis of language impairment (LI) prevalence rates of children in public schools before and after a statewide mandate for response-to-intervention (RTI) implementation.

Method
Statewide and district-level LI prevalence rates were compared across 10 school years. Prevalence data from 67 school districts located in 1 state in the United States are reported as the proportion of the general student population (students ages 3–21 years) who were identified with a primary disability of LI.

Results
The mandated implementation of RTI within special education prereferral, evaluation, and eligibility processes coincided with significant changes in LI prevalence as a primary disability for most of the school districts. The majority of school districts experienced an increase in LI prevalence within 1 school year following RTI implementation. However, the degree and direction of change in prevalence rates varied across some of the school districts. Similar degrees of change were not evident across the other years of prevalence data review, suggesting the systemic change that occurred via RTI requirements coincided with fluctuations in the LI prevalence rates for the majority of school districts in the state.

Conclusion
A causal relation between RTI and LI prevalence cannot be established with the current data; however, this study establishes a temporal connection between the timing of RTI implementation and changes in LI prevalence in public schools of 1 very large state. Implications are presented for further research investigating the potential impact of systemic mandates on the identification of school-age children with LI.

Supplemental Material

https://doi.org/10.23641/asha.8968676
Properties of extragalactic thick discs recovered from ultra-deep Stripe82 imaging
Authors: Martínez-Lombilla C. , Knapen J. H. 
Published: July 2019

Context. Thick discs can give invaluable information on the formation and evolution history of galaxies as most, if not all, disc galaxies have a thin (classical) disc and a thick disc.
Aims. We study the structure of thick discs in extraordinary depth by reaching a surface brightness limit of μrdeep ∼ 28.5−29 mag arcsec−2 with combined g, r, i band images from the IAC Stripe 82 Legacy Project.
Methods. We present the characterisation of the thick discs in a sample of five edge-on galaxies. A study of the radial and vertical surface brightness profiles is presented by comparing our data with point spread function (PSF) deconvolved models. Our method begins with an analysis of the background and masking processes. Then we consider the effects of the PSF through galaxy modelling. The galaxy disc components are fitted considering that the thin and thick discs are two stellar fluids that are gravitationally coupled in hydrostatic equilibrium.
Results. We find that effects due to the PSF are significant when low surface brightness is reached, especially in the vertical profiles, but it can be accounted for by careful modelling. The galaxy outskirts are strongly affected by the faint wings of the PSF, mainly by PSF-redistributed light from the thin disc. This is a central problem for ultra-deep imaging. The thick-disc component is required to reach satisfactory fit results in the more complex galaxies in our sample, although it is not required for all galaxies. When the PSF is ignored, the brightness of these structures may be overestimated by up to a factor of ∼4.
Conclusions. In general, our results are in good agreement with those of previous works, although we reach deeper surface brightness levels, so that the PSF effects are stronger. We obtain scale heights and mass ratios of thin and thick discs (zt, zT, and MT/Mt), which provide excellent agreement with previous studies. Our small initial sample provides evidence for aspects of a wide variety of formation theories for the thick discs in disc galaxies.
The 6Li/7Li isotopic ratio in the metal-poor binary CS22876–032
Authors: González Hernández J. I. , Bonifacio P. , Caffau E. , Ludwig H.-G. , Steffen M. , Monaco L. , Cayrel R. 
Published: July 2019

Aims. We present high-resolution and high-quality UVES spectroscopic data of the metal-poor double-lined spectroscopic binary CS 22876–032 ([Fe/H] approximately −3.7 dex). Our goal is to derive the 6Li/7Li isotopic ratio by analysing the Li I λ 670.8 nm doublet.
Methods. We co-added all 28 useful spectra normalised and corrected for radial velocity to the rest frame of the primary star. We fitted the Li profile with a grid of the 3D non-local thermodynamic equilibrium (NLTE) synthetic spectra to take into account the line profile asymmetries induced by stellar convection, and performed Monte Carlo simulations to evaluate the uncertainty of the fit of the Li line profile.
Results. We checked that the veiling factor does not affect the derived isotopic ratio, 6 Li/7Li, and only modifies the Li abundance, A(Li), by about 0.15 dex. The best fit of the Li profile of the primary star provides A(Li) = 2.17 ± 0.01 dex and 6 Li/7Li = 8−5+2% at 68% confidence level. In addition, we improved the Li abundance of the secondary star at A(Li) = 1.55 ± 0.04 dex, which is about 0.6 dex lower than that of the primary star.
Conclusions. The analysis of the Li profile of the primary star is consistent with no detection of 6 Li and provides an upper limit to the isotopic ratio of 6 Li/7Li < 10% at this very low metallicity, about 0.5 dex lower in metallicity than previous attempts for detection of 6 Li in extremely metal poor stars. These results do not solve or worsen the cosmological 7 Li problem, nor do they support the need for non-standard 6Li production in the early Universe.
Feasibility of endoscopic submucosal dissection of lesions at anastomosis site post-colorectal surgery: a case series
Authors: Krutsri Chonlada , Toyonaga Takashi , Ishida Tsukasa , Hoshi Namiko , Baba Shinichi , Miyajima Nelson Tomio , Kodama Yuzo 
Published: July 2019

Abstract
Background and study aims Patients who have undergone colorectal surgery for resection of cancer and benign lesions are at risk for recurrent, residual, or metachronous lesions at the anastomosis site. Surgical resection of such lesions is difficult because of adhesions, and a stoma may be required as there are risks for leakage after resection. The feasibility and safety of endoscopic submucosal dissection (ESD) for these lesions remain unknown. Therefore, this case series aimed to examine the feasibility and safety of ESD by evaluating the clinical outcomes.
Patients and methods We retrospectively investigated five patients who underwent ESD by a single expert for superficial neoplastic lesions at the anastomosis site after previous colorectal surgery.
Results R0 resections were achieved for all lesions. Mean procedure time was 160.6 minutes. Mean dimensions of the resected specimen and tumor were 52.4 mm and 31.8mm, respectively. None of the patients had complications or recurrence after surveillance colonoscopy 1-year post-resection.
Conclusions In an expert’s hands, ESD at the anastomosis site might be feasible minimally invasive treatment for superficial neoplastic lesions.
Outcomes of an international multicenter registry on EUS-guided gallbladder drainage in patients at high risk for cholecystectomy
Authors: Teoh A.Y. , Perez-Miranda Manuel , Kunda Rastislav , Lee Sang Soo , Irani Shayan , Yeaton Paul , Sun Siyu , Baron Todd Huntley , Moon Jong Ho , Holt Bronte , Khor Christopher J.L. , Rerknimitr Rungsun , Bapaye Amol , Chan Shannon Melissa , Choi Hyun Jong , James Theodore William , Kongkam Pradermchai , Lee Yun Nah , Parekh Parth , Ridtitid Wiriyaporn , Serna-Higuera Carlos , Tan Damien M.Y. , Torres-Yuste Raul 
Published: July 2019

Abstract
Background and study aims The aim of the current study was to review the outcomes of a large-scale international registry on endoscopic ultrasound-guided gallbladder drainage (EGBD) that encompasses different stent systems in patients who are at high-risk for cholecystectomy.
Patients and methods This was a retrospective international multicenter registry on EGBD created by 13 institutions around the world. Consecutive patients who received EGBD for several indications were included. Outcomes include technical and clinical success, unplanned procedural events (UPE), adverse events (AEs), mortality, recurrent cholecystitis and learning curve of the procedure.
Results Between June 2011 and November 2017, 379 patients were recruited to the study. Technical and clinical success were achieved in 95.3 % and 90.8 % of the patients, respectively. The 30-day AE rate was 15.3 % and 30-day mortality was 9.2 %. UPEs were significantly more common in patients with EGBD performed for conversion of cholecystostomy and symptomatic gallstones (P < 0.001); and by endoscopists with experience of fewer than 25 procedures (P = 0.033). Both presence of clinical failure (P = 0.014; RR 8.69 95 %CI [1.56 – 48.47]) and endoscopist experience with fewer than 25 procedures (P = 0.002; RR 4.68 95 %CI [1.79 – 12.26]) were significant predictors of 30-day AEs. Presence of 30-day AEs was a significant predictor of mortality (P < 0.001; RR 103 95 %CI [11.24 – 944.04]).
Conclusion EGBD was associated with high success rates in this large-scale study. EGBD performed for indications other than acute cholecystitis was associated with higher UPEs. The number of cases required to gain competency with the technique by experienced interventional endosonographers was 25 procedures.
Investigation of Radiation Exposure of Patients with Acute Ischemic Stroke during Mechanical Thrombectomy
Authors: Bärenfänger Felix , Block Andreas , Rohde Stefan 
Published: July 2019

Purpose In radiological interventions, the skin is the most exposed organ. The aim of this study was to investigate the local dose exposure and the resulting risk of deterministic radiation effects for patients who underwent mechanichal thrombectomy.
Materials and Methods The examination protocols of 50 consecutive stroke patients who underwent mechanical thrombectomy from September 2016 to April 2017 were evaluated in this study. All procedures were performed on a biplanar angiographic suite. The local skin equivalent dose H
P(0.07) was calculated retrospectively using the recorded radiation data and previously measured conversion factors. The in-vitro determination of the conversion factors was performed with a silicon semiconductor detector on the surface of an Alderson-Rando head phantom depending on the radiation quality.
Results Vessel occlusion was located in the M1 and M2 segments of the cerebral artery media (n = 32), the internal carotid artery or carotid-T (n = 12) and the basilar artery (n = 6). The fluoroscopy times ranged from 5.7 minutes to 137.3 minutes with an average value of 39.5 ± 4.1 minutes. The determined skin equivalent dose values ranged from 0.16 ± 0.02 Gy to 4.80 ± 0.51 Gy, with the mean value being 1.00 ± 0.14 Gy. In 3 out of 50 cases (6 %), the threshold value for skin reactions of 3 Gy published by the German Radiation Protection Commission was exceeded. A further 15 patients (36 %) were exposed to a dose of 1–3 Gy. The highest dose values were achieved during long procedures with occlusions in the posterior circulation and carotid occlusions. In addition, a local dose reference level of 1.24 ± 0.15 Gy could be determined for the skin equivalent dose in mechanical thrombectomies for our center.
Conclusion Even during a modern neuroradiological intervention, such as mechanical thrombectomy, radiation doses to the patient are produced and can lead to deterministic radiation damage to the skin in approximately 6 % of cases. Systematic monitoring of local dose quantities, such as H
P(0.07), seems appropriate. Possibilities for recording and reducing the local dose load should be developed by the interventional teams in cooperation with a medical physics expert.
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Carotid Artery Injury during Transsphenoidal Pituitary Surgery: Lessons from a 15-Year Modern Microsurgery Cohort
Authors: Meyer Jenna , Perry Avital , Graffeo Christopher S. , Carlstrom Lucas P. , Marcellino Christopher R. , Burrows Anthony , Bancos Irina , Driscoll Colin , Meyer Fredric B. 
Published: July 2019

Background Internal carotid artery (ICA) injury is a rare but potentially catastrophic complication of transsphenoidal resection (TSR) of pituitary tumors, potentially resulting in a host of deficits due to the risk of hemorrhage, ischemia, or even death. The endoscopic endonasal approach (EEA) has gained considerable popularity in the modern era, with few busy neurosurgeons remaining committed to practicing transnasal pituitary microsurgery. Our objective was therefore to characterize the overall incidence of ICA injury in a large, longitudinal, single-surgeon microscopic TSR series conducted during the modern EEA era.Methods Retrospective case series.Results Overall TSR volume by the senior author (F.B.M.) was 817 pituitary tumors during the study period, 2002 to 2017. Within that cohort, two instances of ICA injury were identified (0.2%), including one each with Cushing's disease and acromegaly, both of whom ultimately recovered without residual neurologic deficit. No pediatric injuries were identified.Conclusion Vascular injury is an exceedingly rare complication of transsphenoidal pituitary surgery. Adjuncts to prevent this complication include careful review of the coronal magnetic resonance imaging, identification of the midline, as needed use of the Doppler, and initial caudal opening of the sellar dura. Although potentially disastrous, good neurologic outcomes may be obtained, with immediate judicious packing followed by immediate digital subtraction angiography to assess vessel patency and secondary complications such as pseudoaneurysm.