bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epstein–Barr virus (EBV) encoded microRNA BART8‐3p drives radioresistance‐associated metastasis in nasopharyngeal carcinoma
Authors: Zhou Xiaohan , Lin Yanling , Chen Yuting , Wang Lingzhi , Peng Xiaohong , Liao Jinrong , Zeng Hanyi , Luo Wenxiao , Wu Dehua , Cai Longmei 
Published: March 2021

AbstractRadiotherapy plays an important role in the treatment of nasopharyngeal carcinoma (NPC), however, 20% of patients with NPC exhibit unusual radioresistance. Patients with radioresistance are at risk of recurrence, so it is imperative to explore the mechanism of resistance to radiotherapy. In the past, studies on the mechanism of radioresistance have been restricted to DNA damage and related cell cycle remodeling or apoptosis. So far, no studies have explored the relationship between radioresistance and metastasis. Through the analysis of clinical samples, we observed that the metastasis rate of recurrent NPC was much higher than that of primary patients. In vitro and in vivo experiments showed that NPC cells with acquired radioresistance exhibited a stronger ability for invasion and metastasis. Mechanistically, we found that the Epstein–Barr virus (EBV)‐encoded miRNA BART8‐3p was increased in patients with NPC, and its expression was positively correlated with adverse prognostic factors, such as radioresistance. Besides this, miR‐BART8‐3p promoted the epithelial–mesenchymal transition, invasion, and metastasis of radioresistant NPC cells by targeting and inhibiting their PAG1 host gene. These findings suggested a novel role for EBV‐miR‐BART8‐3p in promoting NPC radioresistance‐associated metastasis and highlighted its potential value as a prognostic indicator or therapeutic target.
Long non‐coding RNA ADAMTS9‐AS1 inhibits the progression of prostate cancer by modulating the miR‐142‐5p/CCND1 axis
Authors: Zhou Zhien , Wu Xingcheng , Zhou Yi , Yan Weigang 
Published: March 2021

AbstractBackgroundEmerging evidence has implied the importance of long non‐coding RNAs in cancer development, including prostate cancer (PCa). Bioinformatic analyses have identified that ADAMTS9‐AS1 may play a role in cancer progression.MethodsA quantitative real‐time polymerase chain reaction was conducted to measure ADAMTS9‐AS1 expression level at messenger RNA level. In vitro functional analyses were performed to investigate cell behaviors status under different conditions. Moreover, rescue assays were conducted to explore the potential mechanisms of ADAMTS9‐AS1 in PCa progression.ResultsADAMTS9‐AS1 expression is down‐regulated in PCa. Forcing ADAMTS9‐AS1 expression impedes PCa cell proliferation via initiating cell apoptosis. Importantly, microRNA‐142‐5p (miR‐142‐5p) mimic and small‐interfering RNA targeting cyclin D1 (CCND1, si‐CCND1) could attenuate the inhibitory effects of ADAMTS9‐AS1 overexpression on PCa cell growth.ConclusionsCollectively, our results indicate that ADAMTS9‐AS1 suppresses PCa progression by regulating the miR‐142‐5p/CCND1 axis, which provides a new mechanism for the progression of PCa.
Effectiveness of retreatment with ombitasvir/paritaprevir/ritonavir and dasabuvir+sofosbuvir+ribavirin in patients with chronic hepatitis C, subtype 1b, and cirrhosis, who failed previous treatment with first‐ and second‐generation NS5A inhibitors
Authors: Fedorchenko Sergii V. , Martynovych Tatiana , Klimenko Zhanna , Solianyk Iryna 
Published: March 2021

AbstractThe use of direct‐acting antiviral agents (DAAs) in patients with chronic HCV genotype (GT) 1 infection results in sustained virologic response (SVR) rates of 95%–97%, but 3%–5% of patients experience virologic failure. We observed 41 patients infected with HCV subtype 1b who failed previous treatment with DAAs, including 37 subjects (90.2%) with liver cirrhosis. In total, 30 (73.2%) subjects previously received NS5A inhibitors of the first generation (ledipasvir, daclatasvir, or ombitasvir) and 11 subjects (26.8%) received NS5A inhibitors of the second generation (velpatasvir). All patients received retreatment with a combination of ombitasvir/paritaprevir/ritonavir and dasabuvir (3D) with sofosbuvir (SOF) and ribavirin (RBV). We compared SVR12 rates depending on fibrosis stage, presence of just single or double NS5A mutation (L31M/V/I and/or Y93H), and the generation of previously used NS5A inhibitors. Observed SVR12 rates were as follows: 97.6% (40/41 patients) overall; 100% in patients without cirrhosis (n = 4) versus 97.3% in those with cirrhosis (n = 37); 100% with single L31M/V/I or Y93H mutation (n = 22) versus 94.4% with double mutations (n = 18); 100% in patients who failed previous treatment with first‐generation (n = 30) versus 90.9% in those who failed previous treatment with second‐generation NS5A inhibitors (n = 11). Retreatment with 3D + SOF + RBV was highly effective and safe in patients with chronic HCV GT1b infection, including those with liver cirrhosis, who failed previous treatment with DAA containing NS5A inhibitors. Fibrosis stage and single or simultaneous presence of NS5A RASs L31M/V/I and Y93H at the baseline, as well as the generation of previously used NS5A inhibitors, did not impact SVR12 rates.
Severity of RSV infection in Southern European elderly patients during two consecutive winter seasons (2017–2018)
Authors: Boattini Matteo , Almeida André , Christaki Eirini , Marques Torcato Moreira , Tosatto Valentina , Bianco Gabriele , Iannaccone Marco , Tsiolakkis Georgios , Karagiannis Christos , Maikanti Panagiota , Cruz Lourenço , Antão Diogo , Moreira Maria Inês , Cavallo Rossana , Costa Cristina 
Published: March 2021

AbstractIn Europe, the respiratory syncytial virus (RSV) surveillance system is very heterogeneous and there is growing evidence of the importance of RSV infections resulting in hospitalization of elderly patients. The aim of this study was to assess the severity of RSV infection in the elderly living in the aged Southern European countries. We conducted a retrospective study of elderly patients ( ≥65‐year old) admitted for laboratory‐confirmed RSV infection in three tertiary hospitals in Portugal, Italy, and Cyprus over two consecutive winter seasons (2017–2018). Uni‐multivariable analyses were carried out to evaluate the effect of clinical variables on radiologically confirmed pneumonia, use of noninvasive ventilation (NIV), and in‐hospital death (IHD). A total of 166 elderly patients were included. Pneumonia was evident in 29.5%. NIV was implemented in 16.3%, length of stay was 11.8 ± 12.2 days, and IHD occurred in 12.1%. Multivariable analyses revealed that the risk of pneumonia was higher in patients with chronic kidney disease (CKD) (odds ratio [OR]: 2.57; 95% confidence interval [CI]: 1.12–5.91); the use of NIV was higher in patients with obstructive sleep apnea or obesity hypoventilation syndrome (OSA or OHS) (OR: 5.38; 95% CI: 1.67–17.35) and CKD (OR: 2.52; 95% CI: 1.01–6.23); the risk of IHD was higher in males (OR: 3.30; 95% CI: 1.07–10.10) and in patients with solid neoplasm (OR: 9.06; 95% CI: 2.44–33.54) and OSA or OHS (OR: 8.39; 95% CI: 2.14–32.89). Knowledge of factors associated with RSV infection severity may aid clinicians to set priorities and reduce disease burden. Development of effective antiviral treatment and vaccine against RSV is highly desirable.
Influence of the MJO on daily surface air temperature over Iran
Authors: Pourasghar Farnaz , Oliver Eric C. J. , Holbrook Neil J. 
Published: March 2021

AbstractThe influence of the Madden‐Julian Oscillation (MJO) on surface air temperature over Iran is examined using daily data from meteorological stations from 1979 to 2015. Composites of daily surface air temperature anomalies are positive in MJO phases 1 and 8 and negative in MJO phases 3–4 with broader region positive tendencies also in MJO phases 2 and 7, and negative tendencies in MJO phases 5–6. This variability is associated with horizontal temperature advection, whereby the southerly (northward) winds act to heat and the northerly (southward) winds cool Iran, in association with the MJO. Further, we find that daily minimum surface air temperatures respond more strongly to the MJO than do daily maximum surface temperatures. These signals correspond to cloudy and humid conditions.
Technologies for the Crystal LED display system
Authors: Biwa Goshi , Aoyagi Akiyoshi , Doi Masato , Tomoda Katsuhiro , Yasuda Atsushi , Kadota Hisashi 
Published: March 2021

AbstractWe have developed novel active matrix driving technology integrating red–green–blue (RGB) microscale light emitting diodes (micro LEDs) and a microscale integrated circuit (micro IC) in each pixel for the Crystal LED display system. The small size and closely placed RGB subpixels of micro LEDs enabled us to achieve an outstanding contrast ratio even in a bright environment. We also achieved superior luminance linearity and chromaticity stability using accurate pulse width modulation (PWM) driving by micro ICs in the active matrix system. To integrate micro LEDs and micro ICs into a scalable display system, an additional fine‐patterned layer was applied to a conventional printed circuit board (PCB). In addition, with precise tiling technology, we could produce a large‐scale image providing an immersive visual experience.
Current trend of antibiotic prescription and management for peritonsillar abscess: A cross‐sectional study
Authors: Wu Vincent , Manojlovic Kolarski Mirko , Kandel Christopher E. , Monteiro Eric , Chan Yvonne 
Published: March 2021

AbstractObjectiveThere are no consensus guidelines for managing peritonsillar abscess (PTA) despite its prevalence. In order to devise best practice guidelines, current practice patterns must first be established.MethodsThis was a cross‐sectional study, surveying Otolaryngology—Head & Neck Surgery trainees (residents and fellows) and consultant (academic and community). The primary outcome was the type and duration of outpatient antibiotic prescription. Secondary outcomes included differences in workup, management, prescription, and follow‐up.ResultsThere were 57 respondents to the survey; 24 (42%) trainees (residents/fellows) and 33 (58%) consultants. On average, each respondent managed an average of 15.2 (SD 11.2) PTAs within the last year. All respondents prescribed oral antibiotics, with amoxicillin—clavulanic acid being the most common (61%). Trainees prescribed amoxicillin—clavulanic acid more often than consultants (n = 21, 88% vs n = 14, 42%, P = .0084), respectively. Duration of antibiotic therapy ranged from 5 to 14 days. Most commonly, a 10‐day course of antibiotics was prescribed (n = 31, 54%). Regarding the management of PTAs, a majority of respondents requested blood work (n = 39, 68%), performed needle aspiration (n = 42, 72%) and performed incision and drainage (n = 52, 91%). Culture and sensitivity of the aspirate/drainage fluid was frequently performed (n = 41, 72%). Patients were often provided non‐opioid analgesics (n = 46, 81%), but more than half still received prescription opioids (n = 36, 63%). The majority of clinicians arranged for follow‐up (n = 42, 74%), most often with Otolaryngology – Head & Neck Surgery (n = 27, 64%), with an average follow‐up of 12.5 (SD 8.2) days.ConclusionWe found heterogeneity in the management of PTAs, with variability in the outpatient antibiotic prescription. This study highlighted the wide range of management strategies employed along with differences in workup, investigation, post‐discharge analgesic prescription, and follow‐up arrangements.Level of Evidence5.
Clinical benefit of neoadjuvant anti‐PD‐1/PD‐L1 utilization among different tumors
Authors: Li Zhiyang , Wu Xin , Zhao Yanjie , Xiao Yinan , Zhao Yunuo , Zhang Ting , Li Hui , Sha Fushen , Wang Yating , Deng Lei , Ma Xuelei 
Published: March 2021

AbstractPD‐1/PD‐L1 (programmed cell death‐1 and programmed death‐ligand 1) inhibitors utilization in neoadjuvant therapy has been assessed in tumors. This study focused on the clinical benefits of neoadjuvant anti‐PD‐1/PD‐L1 therapy. A comprehensive search was conducted in electronic databases to identify eligible studies. Major response rate (MRR) and complete response rate (CRR) were pooled in this analysis to assess the efficacy of neoadjuvant anti‐PD‐1/PD‐L1 utilization, all grades and high‐grade adverse events (AEs) were pooled to evaluate its safety. Twenty studies were included in this meta‐analysis, with 828 patients suffering from different tumors. The pooled CRR of triple‐negative breast cancer was 0.569 (95% CI 0.514, 0.624, I2 = 0%) and the pooled MRR of lung cancer was 0.471 (95% CI 0.267, 0.575, I2 = 0%). The most frequent adverse event was fatigue (0.272 95% CI 0.171, 0.402, I2 = 87%), and the most common high‐grade adverse event was febrile neutropenia (0.084 95% CI 0.063, 0.112, I2 = 85%). In conclusion, neoadjuvant anti‐PD‐1/PD‐L1 therapy received satisfactory clinical results in these tumors included.
Classification of tolerable/intolerable mucosal toxicity of head‐and‐neck radiotherapy schedules with a biomathematical model of cell dynamics
Authors: Pardo‐Montero Juan , Parga‐Pazos Martín , Fenwick John D. 
Published: March 2021

PurposeThe purpose of this study is to present a biomathematical model based on the dynamics of cell populations to predict the tolerability/intolerability of mucosal toxicity in head‐and‐neck radiotherapy.Methods and MaterialsOur model is based on the dynamics of proliferative and functional cell populations in irradiated mucosa, and incorporates the three As: Accelerated proliferation, loss of Asymmetric proliferation, and Abortive divisions. The model consists of a set of delay differential equations, and tolerability is based on the depletion of functional cells during treatment. We calculate the sensitivity (sen) and specificity (spe) of the model in a dataset of 108 radiotherapy schedules, and compare the results with those obtained with three phenomenological classification models, two based on a biologically effective dose (BED) function describing the tolerability boundary (Fowler and Fenwick) and one based on an equivalent dose in 2 Gy fractions (EQD2) boundary (Strigari). We also perform a machine learning‐like cross‐validation of all the models, splitting the database in two, one for training and one for validation.ResultsWhen fitting our model to the whole dataset, we obtain predictive values (sen + spe) up to 1.824. The predictive value of our model is very similar to that of the phenomenological models of Fowler (1.785), Fenwick (1.806), and Strigari (1.774). When performing a k = 2 cross‐validation, the specificity and sensitivity in the validation dataset decrease for all models, from ˜1.82 to ˜1.55–1.63. For Fowler, the worsening is higher, down to 1.49.ConclusionsOur model has proved useful to predict the tolerability/intolerability of a dataset of 108 schedules. As the model is more mechanistic than other available models, it could prove helpful when designing unconventional dose fractionations, schedules not covered by datasets to which phenomenological models of toxicity have been fitted.
Evaluation of a variable‐aperture full‐ring SPECT system using large‐area pixelated CZT modules: A simulation study for brain SPECT applications
Authors: Huh Yoonsuk , Yang Jaewon , Dim Odera U. , Cui Yonggang , Tao Weijie , Huang Qiu , Gullberg Grant T. , Seo Youngho 
Published: March 2021

PurposeSingle photon emission computed tomography (SPECT) scanners using cadmium zinc telluride (CZT) offer compact, lightweight, and improved imaging capability over conventional NaI(Tl)‐based SPECT scanners. The main purpose in this study is to propose a full‐ring SPECT system design with eight large‐area CZT detectors that can be used for a broad spectrum of SPECT radiopharmaceuticals and demonstrate the performance of our system in comparison to the reference conventional NaI(Tl)‐based two‐head Anger cameras.MethodsA newly designed full‐ring SPECT system is composed of eight large‐area CZT cameras (128 mm × 179.2 mm effective area) that can be independently swiveled around their own axes of rotation independently and can have radial motion for varying aperture sizes that can be adapted to different sizes of imaging volume. Extended projection data were generated by conjoining projections of two adjacent detectors to overcome the limited field‐of‐view (FOV) by each CZT camera. Using Monte Carlo simulations, we evaluated this new system design with digital phantoms including a Derenzo hot rod phantom and a Zubal brain phantom. Comparison of performance metrics such as spatial resolution, sensitivity, contrast‐to‐noise ratio (CNR), and contrast‐recovery ratio was made between our design and conventional SPECT scanners having different pixel sizes and radii of rotation (one clinically well‐known type and two arbitrary types matched to our proposed CZT‐SPECT geometries).ResultsThe proposed scanner could result in up to about three times faster in acquisition time over conventional scan time at same acquisition time per step. The spatial resolution improvement, or deterioration, of our proposed scanner compared to the clinical‐type scanner was dependent upon the location of the point source. However, there were overall performance improvements over the three different setups of the conventional scanner particularly in volume sensitivity (approximately up to 1.7 times). Overall, we successfully reconstructed the phantom image for both 99mTc‐based perfusion and 123I‐based dopamine transporter (DaT) brain studies simulated for our new design. In particular, the striatal/background contrast‐recovery ratio in 3‐to‐1 reference ratio was over 0.8 for the 123I‐based DaT study.ConclusionsWe proposed a variable‐aperture full‐ring SPECT system using combined pixelated CZT and energy‐optimized parallel‐hole collimator modules and evaluated the performance of this scanner using relevant digital phantoms and MC simulations. Our studies demonstrated the potential of our new full‐ring CZT‐SPECT design, showing reduced acquisition time and improved sensitivity with acceptable CNR and spatial resolution.
Evaluation of Visual Implant Elastomer, PIT, and p-Chip Tagging Methods in a Small-Bodied Minnow Species
Authors: Moore Desiree M. , Brewer Shannon K. 
Published: March 2021

Abstract
Reliable fish tagging methods are needed to conduct studies (e.g., movement, habitat, abundance) that inform conservation and management decisions; however, dependable tagging approaches are lacking for many small-bodied fishes. Therefore, our study objective was to determine survival, tag retention (visible implant elastomer [VIE], PIT, or light-activated microtransponder [“p-Chip”]) and tagging effects on short-term growth of the federally threatened Arkansas River Shiner Notropis girardi. We also examined the use of anesthesia to reduce fish mortality (i.e., reduce handling time) and improve tagging efficiency. Fish tagged with p-Chips had the highest survival (87%), whereas VIE-tagged fish had the second highest survival (67%). Visible implant elastomer tags were retained in our fish 88% of the time, and retention was also high using p-Chips (72%). Location of the VIE tag did not significantly affect survival or retention rates. Survival of PIT-tagged fish significantly increased from 53% to 83% when handling time was reduced; however, tag retention was relatively low in both cases (50% and 45%, respectively). The majority of tagged fish across experiments (83–100%) gained weight regardless of tag type. If the research or management goal is to tag Arkansas River Shiner or similar species with individual identification, p-Chips appear to be an appropriate tag. Particularly if cost is limiting or higher tag retention is needed, VIE tags would also be appropriate for batch tagging (i.e., no individual identification). Additional studies to broaden application of tagging to other small-bodied species would be beneficial.
Physiologically‐based pharmacokinetic modeling to predict drug interactions of lemborexant with CYP3A inhibitors
Authors: Ueno Takashi , Miyajima Yukiko , Landry Ishani , Lalovic Bojan , Schuck Edgar 
Published: March 2021

AbstractLemborexant, a recently approved dual orexin receptor antagonist for treatment of adults with insomnia, is eliminated primarily by cytochrome P450 (CYP)3A metabolism. The recommended dose of lemborexant is 5 mg once per night, with a maximum recommended dose of 10 mg once daily. A physiologically‐based pharmacokinetic (PBPK) model for lemborexant was developed and applied to integrate data obtained from in vivo drug–drug interaction (DDI) assessments, and to further explore lemborexant interaction with CYP3A inhibitors and inducers. The model predictions were in good agreement with observed pharmacokinetic data and with DDI results from clinical studies with CYP3A inhibitors, itraconazole and fluconazole. The model further predicted that DDI effects of weak CYP3A inhibitors (fluoxetine and ranitidine) are weak, and effects of moderate inhibitors (erythromycin and verapamil) are moderate. Based on the PBPK simulations and clinical efficacy and safety data, the maximum daily recommended lemborexant dose when administered with weak CYP3A inhibitors is 5 mg; co‐administration of moderate and strong inhibitors should be avoided except in countries where 2.5 mg has been approved.
Accounting for moist processes in a sub‐grid orographic drag scheme
Authors: Smith Samantha 
Published: March 2021

AbstractA method for estimating the effective moist stability within a sub‐grid orographic drag scheme is described. It accounts for latent heat effects during low‐level saturated sub‐grid orographic ascent, with the lifting condensation level determining how much of the assumed sub‐grid ascents are saturated. The scheme has been verified for two cases with moist south to southwesterly low‐level flow impinging on mountain ranges of the USA and India, within both low‐resolution global simulations and high‐resolution limited‐area model simulations with degraded orography. It produces significant improvements to the model wind fields in both regions. In particular, the amount of low‐level orographic blocking predicted by the orographic drag scheme is reduced, particularly at low resolution, as are the associated large negative near‐surface wind biases over the mountains. Precipitation is shifted slightly downstream. A suite of 24 five‐day global NWP forecasts at N320 resolution was used to demonstrate that these results are robust, and that similar effects are seen over a number of mountain ranges. Over India, the convection scheme is very active in the global simulations, and has a larger effect on the winds at all levels than the orographic drag scheme. However the two schemes interact. Reducing the sub‐grid low‐level orographic blocking drag resulted in a reduction in the convergence occurring as the westerly flow decelerates towards the mountains. This decreased the amount of convection occurring over the sea upstream and along the coast, reducing the associated negative low‐level wind bias there, as well as reducing the negative wind biases over land.