bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiobiological modeling analysis of the optimal fraction scheme in patients with peripheral non-small cell lung cancer undergoing stereotactic body radiotherapy
Authors: Huang Bao-Tian , Lu Jia-Yang , Lin Pei-Xian , Chen Jian-Zhou , Li De-Rui , Chen Chuang-Zhen 
Published: December 2015

AbstractThis study aimed to determine the optimal fraction scheme (FS) in patients with small peripheral non-small cell lung cancer (NSCLC) undergoing stereotactic body radiotherapy (SBRT) with the 4 × 12 Gy scheme as the reference. CT simulation data for sixteen patients diagnosed with primary NSCLC or metastatic tumor with a single peripheral lesion ≤3 cm were used in this study. Volumetric modulated arc therapy (VMAT) plans were designed based on ten different FS of 1 × 25 Gy, 1 × 30 Gy, 1 × 34 Gy, 3 × 15 Gy, 3 × 18 Gy, 3 × 20 Gy, 4 × 12 Gy, 5 × 12 Gy, 6 × 10 Gy and 10 × 7 Gy. Five different radiobiological models were employed to predict the tumor control probability (TCP) value. Three other models were utilized to estimate the normal tissue complication probability (NTCP) value to the lung and the modified equivalent uniform dose (mEUD) value to the chest wall (CW). The 1 × 30 Gy regimen is recommended to achieve 4.2% higher TCP and slightly higher NTCP and mEUD values to the lung and CW compared with the 4 × 12 Gy schedule, respectively. This regimen also greatly shortens the treatment duration. However, the 3 × 15 Gy schedule is suggested in patients where the lung-to-tumor volume ratio is small or where the tumor is adjacent to the CW.
Versatile microscale screening platform for improving recombinant protein productivity in Chinese hamster ovary cells
Authors: Hansen Henning Gram , Nilsson Claes Nymand , Lund Anne Mathilde , Kol Stefan , Grav Lise Marie , Lundqvist Magnus , Rockberg Johan , Lee Gyun Min , Andersen Mikael Rørdam , Kildegaard Helene Faustrup 
Published: December 2015

AbstractChinese hamster ovary (CHO) cells are widely used as cell factories for the production of biopharmaceuticals. In contrast to the highly optimized production processes for monoclonal antibody (mAb)-based biopharmaceuticals, improving productivity of non-mAb therapeutic glycoproteins is more likely to reduce production costs significantly. The aim of this study was to establish a versatile target gene screening platform for improving productivity for primarily non-mAb glycoproteins with complete interchangeability of model proteins and target genes using transient expression. The platform consists of four techniques compatible with 96-well microplates: lipid-based transient transfection, cell cultivation in microplates, cell counting and antibody-independent product titer determination based on split-GFP complementation. We were able to demonstrate growth profiles and volumetric productivity of CHO cells in 96-half-deepwell microplates comparable with those obtained in shake flasks. In addition, we demonstrate that split-GFP complementation can be used to accurately measure relative titers of therapeutic glycoproteins. Using this platform, we were able to detect target gene-specific increase in titer and specific productivity of two non-mAb glycoproteins. In conclusion, the platform provides a novel miniaturized and parallelisable solution for screening target genes and holds the potential to unravel genes that can enhance the secretory capacity of CHO cells.
Lysosomal Cholesterol Accumulation Sensitizes To Acetaminophen Hepatotoxicity by Impairing Mitophagy
Authors: Baulies Anna , Ribas Vicent , Núñez Susana , Torres Sandra , Alarcón-Vila Cristina , Martínez Laura , Suda Jo , Ybanez Maria D. , Kaplowitz Neil , García-Ruiz Carmen , Fernández-Checa Jose C. 
Published: December 2015

AbstractThe role of lysosomes in acetaminophen (APAP) hepatotoxicity is poorly understood. Here, we investigated the impact of genetic and drug-induced lysosomal cholesterol (LC) accumulation in APAP hepatotoxicity. Acid sphingomyelinase (ASMase)−/−mice exhibit LC accumulation and higher mortality after APAP overdose compared to ASMase+/+littermates. ASMase−/−hepatocytes display lower threshold for APAP-induced cell death and defective fusion of mitochondria-containing autophagosomes with lysosomes, which decreased mitochondrial quality control. LC accumulation in ASMase+/+hepatocytes caused by U18666A reproduces the susceptibility of ASMase−/−hepatocytes to APAP and the impairment in the formation of mitochondria-containing autolysosomes. LC extraction by 25-hydroxycholesterol increased APAP-mediated mitophagy and protected ASMase−/−mice and hepatocytes against APAP hepatotoxicity, effects that were reversed by chloroquine to disrupt autophagy. The regulation of LC by U18666A or 25-hydroxycholesterol did not affect total cellular sphingomyelin content or its lysosomal distribution. Of relevance, amitriptyline-induced ASMase inhibition in human hepatocytes caused LC accumulation, impaired mitophagy and increased susceptibility to APAP. Similar results were observed upon glucocerebrosidase inhibition by conduritol β-epoxide, a cellular model of Gaucher disease. These findings indicate that LC accumulation determines susceptibility to APAP hepatotoxicity by modulating mitophagy and imply that genetic or drug-mediated ASMase disruption sensitizes to APAP-induced liver injury.
Variant fatty acid-like molecules Conjugation, novel approaches for extending the stability of therapeutic peptides
Authors: Li Ying , Wang Yuli , Wei Qunchao , Zheng Xuemin , Tang Lida , Kong Dexin , Gong Min 
Published: December 2015

AbstractThe multiple physiological properties of glucagon-like peptide-1 (GLP-1) make it a promising drug candidate for the treatment of type 2 diabetes. However, the in vivo half-life of GLP-1 is short due to rapid degradation by dipeptidyl peptidase-IV (DPP-IV) and renal clearance. The poor stability of GLP-1 has significantly limited its clinical utility; however, many studies are focused on extending its stability. Fatty acid conjugation is a traditional approach for extending the stability of therapeutic peptides because of the high binding affinity of human serum albumin for fatty acids. However, the conjugate requires a complex synthetic approach, usually involving Lys and occasionally involving a linker. In the current study, we conjugated the GLP-1 molecule with fatty acid derivatives to simplify the synthesis steps. Human serum albumin binding assays indicated that the retained carboxyl groups of the fatty acids helped maintain a tight affinity to HSA. The conjugation of fatty acid-like molecules improved the stability and increased the binding affinity of GLP-1 to HSA. The use of fatty acid-like molecules as conjugating components allowed variant conjugation positions and freed carboxyl groups for other potential uses. This may be a novel, long-acting strategy for the development of therapeutic peptides.
One-step Synthesis of Few-layer WS2 by Pulsed Laser Deposition
Authors: Loh Tamie A. J. , Chua Daniel H. C. , Wee Andrew T. S. 
Published: December 2015

AbstractAtomically thin tungsten disulfide (WS2) has attracted much attention in recent years due its indirect-to-direct band gap transition, band gap tunability and giant spin splitting. However, the fabrication of atomically thin WS2 remains largely underdeveloped in comparison to its structural analogue MoS2. Here we report the direct fabrication of highly crystalline few-layer WS2 on silver substrates by pulse laser deposition at the relatively low temperature of 450 °C. The growth takes places by conventional epitaxy, through the in-situ formation of nearly lattice-matching Ag2S on the silver surface. Intriguingly, it was observed that the resulting film was composed of not only the usual semiconducting 2H-WS2 structure but also the less common metallic 1T-WS2. Modifications of the synthesis parameters allow for control over the crystalline quality, film thickness and crystal phase composition of the resulting WS2 film.
pH-Triggered Molecular Alignment for Reproducible SERS Detection via an AuNP/Nanocellulose Platform
Authors: Wei Haoran , Vikesland Peter J. 
Published: December 2015

AbstractThe low affinity of neutral and hydrophobic molecules towards noble metal surfaces hinders their detection by surface-enhanced Raman spectroscopy (SERS). Herein, we present a method to enhance gold nanoparticle (AuNP) surface affinity by lowering the suspension pH below the analyte pKa. We developed an AuNP/bacterial cellulose (BC) nanocomposite platform and applied it to two common pollutants, carbamazepine (CBZ) and atrazine (ATZ) with pKa values of 2.3 and 1.7, respectively. Simple mixing of the analytes with AuNP/BC at pH < pKa resulted in consistent electrostatic alignment of the CBZ and ATZ molecules across the nanocomposite and highly reproducible SERS spectra. Limits of detection of 3 nM and 11 nM for CBZ and ATZ, respectively, were attained. Tests with additional analytes (melamine, 2,4-dichloroaniline, 4-chloroaniline, 3-bromoaniline and 3-nitroaniline) further illustrate that the AuNP/BC platform provides reproducible analyte detection and quantification while avoiding the uncontrolled aggregation and flocculation of AuNPs that often hinder low pH detection.
A dual role of transient receptor potential melastatin 2 channel in cytotoxicity induced by silica nanoparticles
Authors: Yu Peilin , Li Jin , Jiang Jialin , Zhao Zunquan , Hui Zhaoyuan , Zhang Jun , Zheng Yifan , Ling Daishun , Wang Lie , Jiang Lin-Hua , Luo Jianhong , Zhu Xinqiang , Yang Wei 
Published: December 2015

AbstractSilica nanoparticles (NPs) have remarkable applications. However, accumulating evidence suggests NPs can cause cellular toxicity by inducing ROS production and increasing intracellular Ca2+ ([Ca2+]i), but the underlying molecular mechanism is largely unknown. Transient receptor potential melastatin 2 (TRPM2) channel is known to be a cellular redox potential sensor that provides an important pathway for increasing the [Ca2+]i under oxidative stress. In this study, we examined the role of TRPM2 channel in silica NPs-induced oxidative stress and cell death. By quantitation of cell viability, ROS production, [Ca2+]i and protein identification, we showed that TRPM2 channel is required for ROS production and Ca2+ increase induced by silica NPs through regulating NADPH oxidase activity in HEK293 cells. Strikingly, HEK293 cells expressing low levels of TRPM2 were more susceptible to silica NPs than those expressing high levels of TRPM2. Macrophages from young mice showed significantly lower TRPM2 expression than those from senescent mice and had significantly lower viability after silica NPs exposure than those from senescent ones. Taken together, these findings demonstrate for the first time that TRPM2 channel acts as an oxidative stress sensor that plays a dual role in silica NPs-induced cytotoxicity by differentially regulating the NADPH oxidase activity and ROS generation.
A random interacting network model for complex networks
Authors: Goswami Bedartha , Shekatkar Snehal M. , Rheinwalt Aljoscha , Ambika G. , Kurths Jürgen 
Published: December 2015

AbstractWe propose a RAndom Interacting Network (RAIN) model to study the interactions between a pair of complex networks. The model involves two major steps: (i) the selection of a pair of nodes, one from each network, based on intra-network node-based characteristics and (ii) the placement of a link between selected nodes based on the similarity of their relative importance in their respective networks. Node selection is based on a selection fitness function and node linkage is based on a linkage probability defined on the linkage scores of nodes. The model allows us to relate within-network characteristics to between-network structure. We apply the model to the interaction between the USA and Schengen airline transportation networks (ATNs). Our results indicate that two mechanisms: degree-based preferential node selection and degree-assortative link placement are necessary to replicate the observed inter-network degree distributions as well as the observed inter-network assortativity. The RAIN model offers the possibility to test multiple hypotheses regarding the mechanisms underlying network interactions. It can also incorporate complex interaction topologies. Furthermore, the framework of the RAIN model is general and can be potentially adapted to various real-world complex systems.
Information-theoretic model comparison unifies saliency metrics
Authors: Kümmerer Matthias , Wallis Thomas S. A. , Bethge Matthias 
Published: December 2015

SignificanceWhere do people look in images? Predicting eye movements from images is an active field of study, with more than 50 quantitative prediction models competing to explain scene viewing behavior. Yet the rules for this competition are unclear. Using a principled metric for model comparison (information gain), we quantify progress in the field and show how formulating the models probabilistically resolves discrepancies in other metrics. We have also developed model assessment tools to reveal where models fail on the database, image, and pixel levels. These tools will facilitate future advances in saliency modeling and are made freely available in an open source software framework (www.bethgelab.org/code/pysaliency).
Bimodal rheotactic behavior reflects flagellar beat asymmetry in human sperm cells
Authors: Bukatin Anton , Kukhtevich Igor , Stoop Norbert , Dunkel Jörn , Kantsler Vasily 
Published: December 2015

Significance
Successful sperm navigation is essential for sexual reproduction, yet we still understand relatively little about how sperm cells are able to adapt their swimming motion in response to chemical and physical cues. This lack of knowledge is owed to the fact that it has been difficult to observe directly the full 3D dynamics of the whip-like flagellum that propels the cell through the fluid. To overcome this deficiency, we apply a new algorithm to reconstruct the 3D beat patterns of human sperm cells in experiments under varying flow conditions. Our analysis reveals that the swimming strokes of human sperm are considerably more complex than previously thought, and that sperm may use their heads as rudders to turn right or left.
Rapid increases in immature synapses parallel estrogen-induced hippocampal learning enhancements
Authors: Phan Anna , Suschkov Sarah , Molinaro Luke , Reynolds Kathryn , Lymer Jennifer M. , Bailey Craig D. C. , Kow Lee-Ming , MacLusky Neil J. , Pfaff Donald W. , Choleris Elena 
Published: December 2015

Significance
Estrogens are known to rapidly affect learning and memory, but how they do so is not well understood. Here we identify the hippocampus as a brain structure responsible for rapid estradiol-induced improvement of general discrimination learning in female mice, which coincides with a substantial increase in hippocampal dendritic spines, the postsynaptic sites of excitatory synapses. Until now, it had been assumed that estradiol-induced increases in hippocampal synapses would result in increased excitatory input into the neuron. Surprisingly, we find the opposite: increases in hippocampal spines are associated with a decrease in the excitatory glutamatergic input. This finding suggests that estradiol improves learning through inducing the formation of silent or immature synapses, which provide the substrate for storing new memories.
Clinical Reasoning Tasks and Resident Physicians: What Do They Reason About?
Authors: McBee Elexis , Ratcliffe Temple , Goldszmidt Mark , Schuwirth Lambert , Picho Katherine , Artino Anthony R. , Masel Jennifer , Durning Steven J. 
Published: December 2015

Purpose
A framework of clinical reasoning tasks thought to occur in a clinical encounter was recently developed. It proposes that diagnostic and therapeutic reasoning comprise 24 tasks. The authors of this current study used this framework to investigate what internal medicine residents reason about when they approach straightforward clinical cases.

Method
Participants viewed three video-recorded clinical encounters portraying common diagnoses. After each video, participants completed a post encounter form and think-aloud protocol. Two authors analyzed transcripts from the think-aloud protocols using a constant comparative approach. They conducted iterative coding of the utterances, classifying each according to the framework of clinical reasoning tasks. They evaluated the type, number, and sequence of tasks the residents used.

Results
Ten residents participated in the study in 2013–2014. Across all three cases, the residents employed 14 clinical reasoning tasks. Nearly all coded tasks were associated with framing the encounter or diagnosis. The order in which residents used specific tasks varied. The average number of tasks used per case was as follows: Case 1, 4.4 (range 1–10); Case 2, 4.6 (range 1–6); and Case 3, 4.7 (range 1–7). The residents used some tasks repeatedly; the average number of task utterances was 11.6, 13.2, and 14.7 for, respectively, Case 1, 2, and 3.

Conclusions
Results suggest that the use of clinical reasoning tasks occurs in a varied, not sequential, process. The authors provide suggestions for strengthening the framework to more fully encompass the spectrum of reasoning tasks that occur in residents’ clinical encounters.
Does Fentanyl Lead to Opioid-induced Hyperalgesia in Healthy Volunteers?
Authors: Mauermann Eckhard , Filitz Joerg , Dolder Patrick , Rentsch Katharina M. , Bandschapp Oliver , Ruppen Wilhelm 
Published: December 2015

AbstractAbstract
High-dose (10 μg/kg) fentanyl infusion can increase cold pressor test pain threshold and tolerance 4.5 to 6.5 h after infusion. Simultaneously, high-dose fentanyl infusion can increase the area of hyperalgesia caused by electrical burn.
Supplemental Digital Content is available in the text.

Background
Although opioids in general and remifentanil in particular have been shown to induce hyperalgesia, data regarding fentanyl are scarce. Thus, the authors investigated the effect of fentanyl dosing on pain perception and central sensitization in healthy volunteers using established pain models.

Methods
Twenty-one healthy, male volunteers were included in this randomized, double-blind, crossover study and received either intravenous low-dose (1 μg/kg) or high-dose (10 μg/kg) fentanyl. Pain intensities and hyperalgesia were assessed by intracutaneous electrical stimulation, and cold pressor pain was used as an additional measure of acute pain. The primary outcome was hyperalgesia from 4.5 to 6.5 h after fentanyl administration.

Results
A higher dose of fentanyl led to significantly decreased pain scores as measured by the numeric rating scale (0.83 units lower [95% CI, 0.63 to 1.02]; P < 0.001) but increased areas of hyperalgesia (+30.5% [95% CI, 16.6 to 44.4%]; P < 0.001) from 4.5 to 6.5 h after fentanyl administration. Allodynia did not differ between groups (+4.0% [95% CI, −15.4 to 23.5%]; P = 0.682).The high dose also led to both increased cold pressor pain threshold (+43.0% [95% CI, 29.7 to 56.3%]; P < 0.001) and tolerance (+32.5% [95% CI, 21.7 to 43.4%]; P < 0.001) at 4.5 to 6.5h. In the high-dose group, 19 volunteers (90%) required reminders to breathe, 8 (38%) required supplemental oxygen, and 12 (57%) experienced nausea.

Conclusions
A higher dose of fentanyl increased hyperalgesia from 4.5 to 6.5 h in healthy volunteers while simultaneously decreasing pain scores.
Triggered EMG Potentials in Determining Neuroanatomical Safe Zone for Transpsoas Lumbar Approach
Authors: Sarwahi Vishal , Pawar Abhijit , Sugarman Etan , Legatt Alan D. , Dworkin Aviva , Thornhill Beverly , Lo Yungtai , Wendolowski Stephen F. , Gecelter Rachel C. , Moguilevitch Marina 
Published: December 2015

Study Design.

In vivo analysis in swine model.

Objective.
The purpose of this study was to determine the accuracy of triggered EMG (t-EMG) and its reliability in lateral lumbar interbody fusions surgery. We also aim to document changes in psoas muscle produced during the approach.

Summary of Background Data.
Lateral lumbar interbody fusions is preferred over direct anterior approach because of lower complications, blood loss, and shorter recovery time. Threshold-EMGs are utilized for real-time feedback about nerve location; however, neurological deficits are widely reported, and are unique to this approach. Multiple factors have been hypothesized including neuropraxia from retractors and compression from psoas hematoma/edema. The variable reports of neurological complication even with t-EMGs indicate the need to study them further.

Methods.
Eight swines underwent left-sided retroperitoneal approach. The nerve on the surface of the psoas was identified and threshold-EMGs were obtained utilizing a ball-tip, and needle probe. First EMG and threshold responses required to elicit 20-μV responses were recorded for 2 mm incremental distances up to 10 mm. In the second part, a K-wire was inserted into the mid-lumbar disc space, and a tubular retractor docked and dilated adequately. Postmortem CT scans were carried out to evaluate changes in psoas muscle.

Results.
A t-EMG stimulus threshold of <5 mA indicates a higher probability that the probe is close to or on the nerve, but this was not proportional to the distance suggesting limitations for nerve mapping. Negative predictive value of t-EMGs is 76.5% with the ball-tipped probe and 80% with the needle probe for t-EMG ≥10 mA and indicates that even with higher thresholds, the nerve may be much closer than anticipated. Postoperative hematoma was not seen on CT scans.

Conclusion.
Threshold measurements are unreliable in estimating distance from the nerve in an individual subject and higher values do not always correspond to a ‘safe zone.”

Level of Evidence: 5
SEVERE PANUVEITIS, RETINAL VASCULITIS, AND OPTIC DISK GRANULOMA SECONDARY TO SARCOIDOSIS
Authors: Patterson Michael , Bergstrom Chris S. , Clark W. Lloyd , Grossniklaus Hans E. , Payne John F. 
Published: December 2015

Purpose:
To report a case of panuveitis, retinal vasculitis, and optic disk granuloma due to sarcoidosis.

Methods:
Case report and literature review.

Results:
A 26-year-old previously healthy African American male presented with four months of gradual progressive visual decline in the right eye. Clinical examination revealed severe panuveitis, retinal vasculitis, and large optic nerve mass lesion. Diffuse supraclavicular lymphadenopathy was also present. Histopathologic examination of the lymph node biopsy revealed granulomatous inflammation with some areas of caseous necrosis consistent with sarcoidosis.

Conclusion:
Sarcoidosis is a common cause of uveitis and retinal vasculitis. In rare cases, an optic disk granuloma may occur and can be treated with immunosuppressive therapy.